(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 Choice

Harvard https://www.health.harvard.edu/blog/gene-testing-to-guide-antidepressant-treatment-has-its-time-arrived-2019100917964

First prime

As 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

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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.

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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.0279166

Vitamin 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 were

Unadjusted 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 suicide

Clearly this isn’t a universal answer but possible

Another thought is

the 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 placebo

D'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: <7.5%, 7.5% to 9%, and >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 me

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.

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

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.

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

Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence | NEJM

N 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.

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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=1

https://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/NEJMp038207

study 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;67:853–62

A 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

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coffee saves your life-- maybe, careful for confounders

heart failure hospital admission is really hard to prevent

moderate dose statin is most important..but ezetmibe and moderate dose is equal to high dose statin

I think we should take out all kidney stones and the evidence says there will be lest hospitalizations if we do that

EHR can help us and remind us to check and PTH

robotic surgery is not all that is seems to be-- or at least not yet

vit. D and fish oil dont help dry eyes....or much of anything for that matter

stop injecting Hyaluronic acid into the knee

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skin exam, ddp4, IUD, oral hypertension medication

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https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.122.059410?af=R

The Biomarkers say REDUCE-IT was a scam

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2791663

NO! Just NO-- stick with the calculator for now

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.059038

start the SLGT-2 inhibitors early! maybe an early discharge

https://pubmed.ncbi.nlm.nih.gov/35849407/

If we could get the EMR to do it automatically else you cant expect providers to

https://pubmed.ncbi.nlm.nih.gov/35727595/

the head CT for psych stuff can probably be put on hold

https://eprints.whiterose.ac.uk/180135/

continue the disease modifying agents

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mammograms and pink ribbons-- lets talk evidence

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mammograms-- we all know them, but lets discuss

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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 Network

careful what you believe and always question medicine- even if it is about covid vaccine

Use 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.

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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.

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a couple points over the last podcast

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Acute low back pain, chronic low back pain, back pain with sciatica

in the end
unless red flags hold on imaging for 6weeks
NSAIDS for acute low back pain
exercise and spinal manipulative therapy for chronic low back pain
be conservative and don't write for drugs that don't work like gabapentin or pregablin

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

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European Heart Journal

Bariatric surgery and cardiovascular disease: a systematic review and meta-analysis

Eur 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.1

And 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.

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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/00006562-199701000-00009

https://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 titled

Torasemide 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 titled

Torsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysisWhich 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.

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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.

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https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00572-9/fulltext
Old calculators use old studies and can over exaggerate the calculated effect

https://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 anticoagulation

https://pubmed.ncbi.nlm.nih.gov/34074830/
2 Kiwi a day will increase your bowel movements

https://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 there

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01063-1/fulltext
DAPT following a stent-- but then just maybe we should stay with plavix and not aspirin

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https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2782015

coffee is ok with atrial fibrillation -- just don't go crazy is probably good advice

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781351

Hearing loss sucks and can really change your whole physical function

https://www.bmj.com/content/374/bmj.n1511

elective orthopedic procedures with good evidence are limited

https://jamanetwork.com/journals/jama/fullarticle/2781859

PRP injections -- work about as well as vitamin D-- just stop

https://www.bmj.com/content/374/bmj.n1446

muscle relaxants for back pain improve pain at 2 weeks 8 points on 100 point scale

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2781311

STOP GIVING LEVOTHYROXINE to a majority of normal or subclinical normal people

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2781806

antibiotics will always be given if they are always given

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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-DM

Effect 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 Network

BIG TIME ARTICLE—FINALLY WE HAVE EVIDENCE cause nothing worse than saying—we have no evidence for that

advances 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.

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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 ARAHE

The number needed to treat (NNT) to prevent one case of ARAHE was 4

EVEN 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 delay

START 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.

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https://pubmed.ncbi.nlm.nih.gov/33734980/
if you lay flat with a blood draw you may have psuedoanemia

https://jamanetwork.com/journals/jama/fullarticle/2782300
Men and UTI-- 7 days

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2782461
don't get a UA prior to a procedure for screening

https://www.nejm.org/doi/full/10.1056/NEJMoa2026845
cardiogenic shock- dobutamine vs milrinone

https://pubmed.ncbi.nlm.nih.gov/34259820/
Dont use a CAC

https://pubmed.ncbi.nlm.nih.gov/33637192/
CKD = SBP <120

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2782564
men are still more professional than women no matter what they wear-- or at least that is the perception among 36yr old patients

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

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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 Gold

STUDY DESIGN

This 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.

IMPLICATIONS

The 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% expiration

That 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.

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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.

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 great

But 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.

Cardiovascular risk prediction in type 2 diabetes before and after widespread screening: a derivation and validation study - ClinicalKey

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

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 article

Kelly 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.

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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 disease

Reduce it trial---

The big trial which showed all the promise used mineral oil as a placebo

AND then we have evaporate trial—which showed steady plaque

The 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 blinded

The placebo group had higher CRP and dramatically worse cholesterol panels after taking mineral oil

Then 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 everyone

Given 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 decline

Please 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.A10589

Results: 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 least\

Zhou 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 take

should 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.

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DYSh out information on DYSlipidemia: An Evidence-based Update on Cholesterol Management

Please contact me for more information: Andrew Buelt, D.O.

andrewbuelt@gmail.com

Questioning Medicine Podcast

Athrosclerotic 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 Prevention
Treatment
- 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 treatment
  - Increase statin dose to max tolerated then add Ezetimibe
- Third line treatment
  - PCSK9 inhibitor

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

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Podcast

Gregory 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):e212713

Study 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 dose

a 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 THERE

China 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 worse

The 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 there

Or dont just do something let your patients do something

Scarinci 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 question

Does 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 there

Clinical question

What 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)

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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!

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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!

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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

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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).

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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

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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

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

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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

Semaglutide works while you take it but then it goes away. This would be great for weight loss if you can use it as a bridge to get people jump started into healthier lifestyles and more activity and if it were free or pennies on the dollar but it is not and likely will be cash pay as not FDA approved for weight loss yet and in my opinion still requires a serious shared decision making conversation.

A Pragmatic, Randomized Clinical Trial of Gestational Diabetes Screening | NEJM

pragmatic, randomized trial comparing 24,000 pregnant women,

researchers compared a one-step, 75-g glucose load with a two-step, 50-g (followed by 100-g if positive) glucose load for gestational diabetes screening.

The primary outcomes were a diagnosis of gestational diabetes, large-for-gestational-age infants, a perinatal composite outcome (stillbirth, neonatal death, shoulder dystocia, bone fracture, or any arm or hand nerve palsy related to birth injury), gestational hypertension or preeclampsia, and primary cesarean section.

Researchers found higher rates of gestational diabetes diagnosis with the one-step screen!!

maternal and neonatal outcomes (including hypertensive disorders of pregnancy, primary cesarean section, large-for-gestational age infants, shoulder dystocia, stillbirth) were not different between the two groups.

if you’re identifying more cases of gestational diabetes without changing related disease outcomes, this is bad.

identifying more disease, the burden of disease diagnosis is significant with multiple daily glucose checks for the remainder of pregnancy as well as the mental and emotional toll diagnosis can have on a pregnant woman.

Besides who cares if you find more of a number- that is just a LOOs if you are not finding more POOs.

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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
About 70% of the individuals in either relugolix group reached the primary endpoint compared with about 20 in the placebo group

This is great!! We stop bleeding—but this is a straw man argument that tells us nothing!!
They compared it to placebo.
That is not real life- to get into the trial you had have a diagnosis of fibroids with heavy menstrual bleeding--- you needed to be losing 160ml in one cycle or 80ml in two consectutive cycles… who is going to get that history and do nothing
PARTICIPANTS
Premenopausal women 18 to 50 years of age who had a diagnosis of fibroids as confirmed on ultrasonography and who had heavy menstrual bleeding, 9 Heavy menstrual bleeding was defined as a volume of menstrual blood loss of 80 ml or more per cycle for two cycles or a volume of 160 ml or more during one cycle.

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Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study (bmj.com)

A large linked database linked to Korea Immunization Registry Information System

This study is so cool because they did a cohort analysis and self-controlled risk interval analysis
382 020 girls aged 11-14 years who had been vaccinated against HPV and compared them to 59 379 had not been vaccinated against HPV. This is what we all know as a cohort analaysis. You look at a bunch of data at one point in time, preferable with the outcome you are looking at specified before looking at the data and you see if the data confirms your hypothesis. It is observational, its not the best form of data but it could be worse and sometimes it is the only way to find what you are looking for, such as serious adverse events from a vaccine.

BUT they also did a self-controlled risk interval analysis. Let me propose to you what if there is a difference between those who get vaccines and those who don’t?! What if a kid get a tetnus vaccine then 6months later develop migraines or narcolepsy. Do you blame it on the tetnus vaccine or the hpv vaccine??

So a self-controlled risk interval analysis – use each individual self as a controlled risk analysis. All girls who received the HPV vaccine had to also have received the Japanese encephalitis vaccine and tetanus, diphtheria, pertussis vaccine. This combination of other vaccines in the same girl served as a comparator for safety profiles compared to the hpv vaccine.

So the hpv vaccine is compared to girls who have never got a vaccine and then also compared to other vaccines in the same individual!

The ultimate safety test to measure it against yourself and against others!

They wanted to be extra extra safe!
They looked at 33 OUTCOMES!!! Remember p 0.05!

Graves’ disease, Hashimoto’s thyroiditis, hyperthyroidism, hypothyroidism, type 1 diabetes, Crohn’s disease, ulcerative colitis, peptic ulcer, pancreatitis, Raynaud’s disease, venous thromboembolism, vasculitis, hypotension, ankylosing spondylitis, Behcet’s syndrome, juvenile arthritis, rheumatoid arthritis, systemic lupus erythematosus, idiopathic thrombocytopenic purpura, Henoch-Schönlein’s purpura, erythema nodosum psoriasis, Bell’s palsy, epilepsy, narcolepsy, paralysis, migraine, Guillain-Barré syndrome, optical neuritis, neuralgia and neuritis, intracerebral haemorrhage, extrapyramidal and movement disorders, and last but not least tuberculosis.

results
“In this nationwide cohort study, with more than 500000 doses of HPV vaccines, no evidence was found to support an association between HPV vaccination and serious adverse events”

Association Between Indoor Tanning Frequency and Other Potentially Addictive Behaviors | PracticeUpdate

Type a person or a type b person—but the key to life might be how to be an AB person and I am not talking about my initials

Association between indoor tanning frequency during early life and other potentially addictive behaviors among US women- ClinicalKey

In this cross-sectional analysis of the nurses health study II –as a reminder a Cross-sectional analysis looks at data collected at a single point in time,

the authors investigated the relationship between the frequency of indoor tanning and other addictive behaviors,
including smoking,
alcohol intake,
and caffeine consumption.

Individuals who used an indoor tanner (>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.

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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

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A two part podcast on the top published articles of 2020

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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

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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.

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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)
BUT this article was great because it said what is the long term effect of this VTE caused by COC--- are their long term effects?

At 3‐year follow‐up, all women with COC‐associated distal DVTs were alive, and none had bled during anticoagulant treatment or had experienced a DVT or PE recurrence after stopping anticoagulants.

At 3‐year follow‐up, all women with COC‐associated PE were alive and none had bled during anticoagulant treatment or had experienced a DVT or PE recurrence after stopping anticoagulants.

At 3‐year follow‐up, all women with COC‐associated proximal DVT had a recurrence rate of 1.7% per patient‐year and there were no deaths or major bleeds

The take home is that DVTs and PE with COC are basically just as common in women . taking and not taking COC as long as they are not pregnant and not postpartum women less than 50yrs old without active cancer AND most importantly, The long term outcome or side effects are basically the same, just remember to stop the COC if they are on it and then treat with 3 months of anticoagulation..

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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?

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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.

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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

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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

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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
Then you smile real big and say, “Luckily this paper even did a secondary analysis looking at those with vit D levels >30 and
“no consistent evidence of different effects in subgroup analyses based upon potentially influential baseline variables including baseline 25OHD or study design characteristics, nor of different effects in trials of high-dose vitamin D or trials with higher achieved 25OHD concentrations.”

So said differently IT DOESN’T MATTER WHAT YOUR MADE UP NUMBER IS!

They will say, “we always treat under 30”

I have been fighting against the stream for 7 years now and the more I do the more I have realized that Upton Sinclair "It is difficult to get a man to understand something when his salary depends upon his not understanding it."

Sadly, as I have said on the podcast before, the belief of vitamin d is far greater than the evidence.

What I have learned is adult education can only be desired and can’t be taught. You can go to the best residency program in the world but when you get out you either keep reading and questioning or you just follow what someone else says like a blind dog. There is nothing wrong with either style and both want to do what they feel is best for the patient but no matter how hard you try, most of the time you can never make a blind dog see.

Best of luck.

COVID 19 vaccine
Dr. dodge and Dr. Layer appreciate you listening—and both have asked me variable questions about me getting the vaccine

Obviously the problem is we dont have long term data on this vaccine or even this type of vaccine. Those individuals who say o yes get the vaccine it is super safe are lying or at least not saying the whole truth. It is safe for now for the few months of data we have on it. I think in order to say yes this is safe we need long term data and its ok to say we just dont know at this time.

Luckily for me I have already had it

But then then you have people who have had and they are so concerned about immunity---says IGG titers go away after 6 to 8 months

When doctors say this I just shake my head

It is such simplistic thinking…..its almost like these doctors went to residency training with ob gyn and they forgot how to use their brain….. Sorry sorry I promise that will be one of the disses on the college of ob gyn
I refuse to believe this completely
The body is not that dumb
This is not cinderalla and the glass titers

When I was doing a deep dive on the flu vaccine one of the most interesting findings for me was that for the elderly individuals the flu vaccine one year was actually not that beneficial – its true go to Cochrane and look it up.

BUT BUT BUT if you were someone who got the flu shot every year then it was beneficial as you got older

How could this be

EXPERT OPINION ZONE

You have memory cells over time from all the vaccines!!!

https://science.sciencemag.org/content/early/2021/01/06/science.abf4063
·
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection.

Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset.
Notably, memory B cells specific for the Spike protein or RBD were detected in almost all COVID-19 cases, with no apparent half-life at 5 to 8 months post-infection. Other studies of RBD memory B cells are reporting similar findings (50, 60). B cell memory to some other infections has been observed to be long-lived, including 60+ years after smallpox vaccination (61), or 90+ years after infection with influenza

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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
Now rates of abortion after 20 weeks is much less.
So in this a morbidity and mortality weekly they estimate that risk of stillbirth was
5 per 458 which is about 1.6 per 160 covid births
And when you look at the CDC data on this they average the risk of stillbirth in the US is
Around 1/160
https://www.cdc.gov/mmwr/volumes/69/wr/mm6938e1.htm
BUT BUT BUT when you break that down by those women who had symptoms at initial presentation and those that did not have symptoms it tells a much different story
Remember the baseline risk of still birth is around 0.6%
If you came in with symptoms of COVID at time of admission your risk of still birth was 2.8%
4x greater risk of still birth if you came in with symptoms of covid19
Now if you didn’t have symptoms what was your rate of stillbirth? And the answer is 0.3%
Yes HALF the rate of still birth from the general if you didn’t come in with symptoms. You could make the hypothesis that those women who have covid but are asymptomatic are protected from having a still birth…
Which begs the questions of why do some have symptoms and why are some are asymptomatic---and what we seem to know from pure observation data is those individuals with co-morbid conditions or said differently those individuals who are already not living a healthy lifestyle are at great risk of getting a virus and dying from a virus. For many the thought that being unhealthy could lead to death or leave you prone to severe infection is a very new and foreign concept!

https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/aogs.13901
https://www.acog.org/en/clinical/clinical-guidance/practice-advisory/articles/2020/12/vaccinating-Pregnant-and-Lactating-Patients-Against-COVID-19

For those of you wondering the CDC has said – “Health care personnel who are pregnant may choose to be vaccinated.”
Which is what they should say because what they are really saying is “we are not going to stop you from doing it but we are certainly not going to promote you getting it”

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What you see is what you get- no more clearly seen then in
This paper titled

Nutritional Analysis of Foods and Beverages Depicted in Top-Grossing US Movies, 1994-2018

In JAMA internal medicine which looked at the nutritional quality of foods and beverages depicted in
the 250 top-grossing US movies from 1994 to 2018
these 250 movies sold 10 billion box office tickets and grossed $164 billion in theaters
worldwide. These are popular movies we all watch or are aware of
and what they put on the screen as a societal “norm”
in this study-
Two trained researchers viewed movies in their entirety and listed all
foods and beverages depicted in each scene.
they used the Nutrient Profile Index (NPI) to classify foods and beverages as healthy or not
penalizes components that should be limited like
sugar, sodium, and saturated fat and rewards fiber, protein, and fruit and vegetable
Now I understand this is not a one size fits all and the authors admit there is not portion control
on this so if the movie had a thimble full of high sugar intense soda and a whole garden of
lettuce the were considered “equal”
The results showed that-
nutrition ratings showed that 72.7% received a less healthy food nutrition score and 90.2%
received a less healthy beverage nutrition score.
But did it get better with time, I mean people use to smoke and now they don’t-
“We found no evidence of improvement over time in sugar, saturated fat, total fat, or sodium
content of foods or in sugar content of beverages”
part of the reason I bring up this article is because There were many disturbing findings like
G-rated movies, nearly 1 in 5 beverages (23 of 127 [18.1%]) were alcoholic beverage and 50%
of the time it was an alcoholic beverage in rated R movies!
the beverage sugar content was higher in movies targeting younger audiences --- on
average movies depicted 121 g (95% CI, 116-125 g) of total sugar per 2000 kcal, which is
higher than the total sugar content in 3 cans of Coca-Cola.
in summary- what you see is what you get and if you see your favorite actors eating junk food it
makes it ok to also eat junk food. . we already live in an obese society and any opportunity we
can to prvent or promote healthy eating should be done, even if that means during a movie
while you stuff your face with a 120oz coke and 620ounces of buttery popcorn.

But speakig of movies what do yu think of when you think of tom cruise or maybe I should say if
someone says the move “Jerry maguire” what do you think of?

I think “show me the money” which is a perfect segway to this paper in annals of IM titlted

https://www.acpjournals.org/doi/10.7326/M20-5665
Are Financial Payments From the
Pharmaceutical Industry Associated With
Physician Prescribing?
A Systematic Review
This was a systematic review to look to see if
payments from the drug industry is associated with physician prescribing practices.
The results were obvious, if you got money then you prescribed the drug companies drug more
often, and this was also associated with increase prescribing cost… the total cost and rates of
prescribing varied BUT NONE
And I repeat NONE OF THE identified studies had all null findings.
The easy answer is Receiving payments from a drug company may lead a physician to
prescribe more of that company's drug in the future.
Or you can sit back and question medicine and look at it from a different perspective--
prescribing may cause payments:
Drug companies may target payments to physicians who are already high prescribers of their
drugs. Both mechanisms are plausible.
The studies the look at temporal prescribing found substantial increases in prescribing immediately
after receipt of each industry payment.
Industry spending on drug promotion disproportionately targets drugs that are less effective or
offer little therapeutic advancement BECAUSE physicians want to use effective drugs
REGARDLESS OF THE PROMOTION!!! whereas marginally effective drugs require more
intensive promotion to increase prescribing!!
ASA after a stroke- we know it works, you odnt need to sell it to me
Statins after and MI- we know it works
Metformin for type 2 diabetes- we know it works

No need to show up at my door. I think the pharmacuetical industry is like the necessary evil, we
need them, they do great things and have the money to do fantastic trials because they have
the money to chase people down to get the outcome data we need but taking money from them
tugs on our need to prescribe their medications EVEN when our patients may benefit from
another or different or cheaper drug and if you think well this doesn’t apply to mean I want to
repeat what I said earlier
NONE OF THE identified studies had all null findings.
So unless you think you are magically different than every other provider that has ever been
studied then yes, even you are affected by drug money money and meals. Money talks so if you
cant stand the heat get out of the kitchen and speaking of heat
This next article titled
Associations between high temperatures in pregnancy and risk of preterm birth, low birth weight, and
stillbirths: systematic review and meta-analysis
Found a small but very real and consistent association between exposure to high enviromental
temperatures and pregnancy outcomes,
odds of a preterm birth rose 1.05-fold (95% confidence interval 1.03 to 1.07) per 1°C increase in
temperature and 1.16-fold (1.10 to 1.23) during heatwaves which were defined as two or more
days with temperatures above a predefined threshold.

This gives me two pieces of informtion which is those individuals who workout a lot should
probably avoid the hot yoga during pregnancy, stick to the regular yoga for 9 months and those
individuals with low economic status and no access to air conditioning will suffer and on a grand
scale will see higher rates of preterm delivery. This is sad and if a real finding it is one we will
never see on microscopic data remember it is only a 5% increase risk with the 95% confidence
interval going all the way down to 1.03% we are not good enough to pick up such small
differences in our day to day clinical practice but with macroscopic data. It becomes clear, I am
eager for more information on this in the future.

Remember when I said last year that according to me and now according to ACOG for almost
10 plus years we should let women get birth control over the counter!! When I told you that this
is insane that we has providers think we are so special they must come to us to get
contraception?? Well we are one step closer in this paper titled
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31785-
2/fulltext?utm_source=The+Scope&utm_campaign=f2254e45a6-
Weekly_Scope_Jan_12_2018_COPY_01&utm_medium=email&utm_term=0_809ad7d22b-
f2254e45a6-180869057

“Use of effective contraception following provision of the progestogen-only pill for women
presenting to community pharmacies for emergency contraception (Bridge-It): a pragmatic
cluster-randomised crossover trial”

pragmatic cluster-randomised crossover trial of almost 600 women receiving emergency
contraception in a pharmacy were randomized to either an intervention group or a control group.
In intervention group, women received a 3-month supply of the progestogen-only pill (75 μg
desogestrel) plus a rapid access card to a participating sexual and reproductive health clinic. In
the control group, pharmacists advised women to attend their usual contraceptive provider
The primary outcome was the use of effective contraception (hormonal or intrauterine) at 4
months.

Although there was a significant amount of people lost to follow up, almost 40% which was
higher than the expected 25% lost to follow up expected by the authors, however at 4 months
The proportion of women using effective contraception was 20·1% greater in the intervention
group, than in the control group. (mean 40·5%, 29·7–51·3 [adjusted for recruitment period,
treatment group, and centre]; p=0·011).

But taking birthcontrol or on BC is a surrogate outcomes so lets look at the secondary outcome-

Secondary outcomes were incidence of abortion in the 12 months following recruitment and an
economic evaluation of the intervention.
Sadly this study would have needed about 2000 patients to clearly tell a difference in
unexpected pregancy or abortion.
I guess the summary is that if you want women to be on birth control you have to make it easier
for them to acccess it and whatever format that is then fine, let them access it. Their risk of
children far exceeds your need for another easy RVU patient.

https://www.nejm.org/doi/full/10.1056/NEJMc2031173?utm_source=The+Scope&utm_campaign
=f2254e45a6-
Weekly_Scope_Jan_12_2018_COPY_01&utm_medium=email&utm_term=0_809ad7d22b-
f2254e45a6-180869057

https://www.nejm.org/doi/suppl/10.1056/NEJMc2031173/suppl_file/nejmc2031173_appendix.pdf

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020.283
4?guestAccessKey=4474ae2b-f5ad-45c1-a5b9-
4735927592c1&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-

But the next article is breath-taking

Titled- Managing Asthma in Adolescents and Adults2020 Asthma Guideline Update From the National
Asthma Education and Prevention Program

The important thing to know is
Those with mild persistent asthma should use either regular daily ICS with an as-needed
inhaled (SABA), or to use both ICS and SABA on an as-needed basis.
Those with moderate persistent asthma should use ICS and formoterol daily with additional
doses of the ICS/formoterol as needed
Some will say this is different than the gina guidelines which say ICS/formoterol right from the
start. I will say you are right this is different than the global initiative for asthma guidelines. And
you may be asking, well then what is the right thing to do and my answer is---
The only correct answer is not what you should be doing but what you should not be doing and
that means those individuals coming in with mild persistent asthma, the newly diagnosed
asthma patient really should no longer be on just prn albuterol. Those days are done, the data
and the guidelines agree. ----

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Get the best evidence because you want to know what they are looking at and occasionally people send me articles I was not aware of. Plus I ate spending my time sending them all the information then people say well ya but you are looking at the wrong evidence just right off the bat say “I will explain but tell me the evidence you are looking at”
So he sent me 5 articles and I going to break them down in hopefully a rapid fire dissection
And before we get started there is a very important piece of information that we all need to be clear on, low vitamin d DOES not mean that replacing the vitamin d then fixes the problem. We knew for a while that high HDL seem to have a protective cardiovascular effect but when we looked at the data it didn’t appear raising the HDL with a drug called niacin had an effect on cardiovascular events. This is the ultimate association and correlation connection. Sure it appears more popsicles consumed are associated with higher rates of drowning but getting rid of popsicles will not get rid of drowning. It appears more car accidents happen within 5 miles of your house and even more car accidents happen within 100 miles from your house but if you get rid of driving within 5 or 100 miles of your house you do not get rid of car accidents so it takes me to the

First article-
https://www.mdpi.com/2072-6643/12/9/2757/htm
In journal of Nutrients titled

Vitamin D Deficiency and Outcome of COVID-19 Patients

This is observational data looking at the associations of vitamin D (VitD) status with disease severity and survival and

Quick take away- Our study demonstrates an association between VitD deficiency and severity/mortality of COVID-19, highlighting the need for interventional studies on VitD supplementation in SARS-CoV-2 infected individuals.

Yes I agree with everything they just said but does replacing the vitamin level with supplements then mean you have a better outcome. This article doesn’t touch on that

Second article-
Also in journal of nutrients titled-

Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths
This is a review article. Review articles are never ever to be used as evidence because the authors have a story they want to tell and they set out to write a paper that tells their story. When you write a review article you never set out with a hypothesis and then you the scientific method to accept or reject the null. You start with a goal in mind and look for papers to confirm your goal. Review articles are the ultimate in confirmation bias. Anytime anyone ever gives you a review article as evidence you should automatically question medicine and politely hand it back to them and say, “thank you but I would prefer something higher than “expert opinion”.

Articles 3- next article was from scientific reports, titled-
https://www.nature.com/articles/s41598-020-77093-z
Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers
This was a continuous prospective observational study that look to analyze the vitamin D level in COVID-19 patients and its impact on the disease severity.
Basically they looked at patients vitamin d level during the course of follow up and then used statistical analysis to see if there was an association between vit d levels and severity of illness.
The results found that “vitamin D deficiency (as suggested by serum 25 (OH)D concentration So what they are saying is if you are in the ICU you are more likely to die. They are also saying that those individuals who are sick and in the ICU are more likely to have vit d. deficiency. Wait, you mean I am saying that if you are in the hospital then you have a lower laboratory value that is associated with being outside???? Ya, shocking statement to think of!! This is completely a duh statement, and being admitted to the ICU is also associated with higher rates of intubation. The authors are not saying replacing vit d levels with supplements PREVENTS ICU admission or death.

Next article- https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770157
In JAMA titled-
Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results
This is a cohort study that looked to see if vitamin D status was associated with test results for coronavirus disease 2019 (COVID-19)
Remember a cohort study is observational data, they look at people at one point in time and then again at another point in time. They don’t intervene, they don’t treat, they don’t do anything. They look at a point in time called ‘x’ and follow up at a future point in time ‘x’ and see what happens.
This study looked at 500 people who had a vit. D level within the previous year prior to being testing for covid-19 and found that if you had a low vitamin d level you were at 1.8 times greater risk for testing positive for covid-19
This study does not say that if we replaced the vitamin d levels with vit d supplements that then they would have tested neg for covid-19
It really just says if you have a lab value which is already associated with decreased activity and decrease going outside that you are more likely than to test positive for a virus in the next year. Wait, did I just say that if you don’t have a great lifestyle you are more likely to test positive for a virus or get sick from a virus?? Yes that is exactly what I said and I know I am sure this is another shocking finding.

Last article- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456194/
In journal of steroid biochemistry and molecular biology
Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study”
On the surface this seems like a potentially good study, it even says randomized in the titled, But then you go on to read that this was a randomized open label, double-masked clinical trial.
You think to yourself, wow double masked, that seems like a good thing. The key is who is masked? Because you also know open label is a bad thing because open label means that someone knows exactly what the drug is so that leads to a little bit of bias, if you really want something to work, you will alter your treatment towards that patient based on your own believe. The key is who is masked
This is a problem because the authors wanted this treatment to work and believed this treatment would work and you know how I know this, because they randomized participants in a 2 to 1 fashion. Normally you should enroll people 1:1 it is the most efficient method of randomization from a statistical perspective and requires the fewest number of patients. Enrolling in a 2:1 fashion usually requires about 12% more people to achieve the same level of statistical power.

Now, The reason you make it 2:1 is because you either think that it is easier to enroll patient-subjects in a trial if they believe they are more likely to receive the new/active treatment, or at least that is a reason stated by many authors and experts but this is really only valid when there is clearly one far superior drug from a non-superior drug. There is not enough evidence to say vit d is better than placebo or nothing thus is not valid UNLESS YOU IN YOUR HEART OF HEARTS BELIEF vit d is so much better based on faith and belief and no on evidence.
Another reason to randomize patients 2:1 is a budget issue and one arm of the trial is significantly cheaper BUT that is not the case in this trial because you either got an active drug or nothing. Not an active drug or placebo, it was an active drug or nothing and nothing is free.
Now if you are going to make unequal randomization then you should state why you did it that way. The authors did not. So we will never know the reason they did it.

But I will say the authors believed in vit dand this is easy to see if you know methods of a trial or you can just read the trail and the authors say. “The working hypothesis of this pilot trial was that calcifediol treatment would decrease the need for ICU admissions and the potential risk of death associated with these admissions.”
Said differently “we the authors of this trial have a belief that vitamin d will decrease the need for icu admission and potential risk of death.”

The primary outcomes was rate of ICU admission and deaths
Remember I said this was a “double-masked clinical trial”. The question is, who is masked.”
It is not clear who is masked but it appears the treatment list was “accessible only to non masked specialists in the study”. So some providers in the study had access to who was being treated with vit d. This obviously brings in observation bias and confirmation bias.

So in this study the outcome that showed such a huge benefit was the decrease risk of transfer to the ICU. This is a made up and bs endpoint because it is subjective!! In the paper it says

“A multidisciplinary Selection Committee was created, made up of intensivists, pulmonologists, internists and members of the ethics committee who decided on admission to the ICU.”

So what they are really saying is we have an endpoint for which human error is involved and the individuals who are involved in this outcome or endpoint have access to the information on which group the patient was randomized. So if you know the patient is getting the placebo, you may be a little more likely to transfer them to the ICU than you are if the patient is on vit d. Are you maybe a little more likely to try and treat them on the floor if you know the patient is already getting vit d and you want a positive trial so you can get a publication?? Ya I think so.

Plus they don’t give us the information on the patients transferred vs not transferred to the ICU. Why were they transferred? Did they need intubation? Was it maybe from a low sodium, maybe it wasn’t even covid related. FINALLY—the didn’t factor weight into their final analysis. They didn’t factor in BMI into the rates of severe covid! We know those that have larger bodies are more likely to have a poor outcome in covid and they didn’t include it because they say “ given the isolation characteristics of the patients, we did not collect the BMI,” which is total b.s. in most hospitals you can take a weight on the bed scale. The nurse already has to go into the room to deliver the meds and she or he can't hit one button on the bed to get the results of a bmi.

This paper while may look good just on the service is far far far far far from a slam dunk and between the combination of being open label, randomizing people 2:1, and outcome that is subjective by individuals who may know arm of the trial the patient is in and not including bmi in your analysis there are too many red flags to say this is even useable evidence.

And really this should only be used by attendings to teach students and others how to appraise the medical lit.

In summary- no vitamin d should not be used to prevent or treat covid19 or at least not with the current data I am aware of or have been presented.

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2020 Update to The Top Articles of 2019

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Alzheimers disease—doesn’t say what you think it says

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020.6432?guestAccessKey=807ca0d3-63aa-48f9-8a1d-16df0d828d42&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=olf&utm_term=113020

Conclusions and Relevance Alzheimer disease and related dementias were associated with adverse financial events years prior to clinical diagnosis that become more prevalent after diagnosis

I listen to a podcast and read articles and it seems omg this is great!! Maybe we look to see if people are missing payments or making poor financial decisions and screen them for alzheimers. Currently screening for alzheimers is difficult because we don’t have good treatment to slow or prevent the progression of the disease.

Remember a few basic principles of screening are

The condition should be an important health problem.
There should be a treatment for the condition that can change the outcome.
Total cost of finding a case should be economically balanced in relation to medical expenditure as a whole.
As I say those I cant think can we apply those to covid screening?? (say it again)

retrospective secondary data analysis of consumer credit report outcomes from 1999 to 2018 linked to Medicare claims data of 81 364 individuals

and they were looking for Missed payments on credit accounts (30 or more days late) and subprime credit scores.

Does an individual with Alzheimer disease and related dementias miss more financial payments than those individuals without alzheimers and they found

“Alzheimer disease and related dementias were associated with adverse financial events years prior to clinical diagnosis that become more prevalent after diagnosis”

But lets look at some of the results—

Overall, 54 062 pts without the diagnoses of ADRD were included and 27 302 who had the diagnosis of ADRD were included.
Those Medicare beneficiaries diagnosed with ADRD were more likely to miss payments on credit accounts at a rate of 7.7% compared to only 7.3% of missed payments in those individuals without a diagnosis of ADRD (7.7% vs 7.3%; absolute difference, 0.4 percentage points [pp]; 95% CI, 0.07-0.70:). You might say wait a second a 0.4 percent absolute difference is statistically significant?? Yes, remember the more people you have in a study the more likely even a very very very small difference is statistically significant.

This study also looked at those individuals who develop subprime credit scores 2.5 years prior to diagnosis – for those individuals with ADRD this occurred 8.5% of the time compared to only 8.1% of the time in those individuals without the diagnosis of ADRD. This was an absolute difference, 0.38 pp; 95% CI, 0.04-0.72

Once again this is statistically significnat because so many people were enrolled. HOWEVER here is the problem and somehitng to notice. The authors gave you percent here, not the actual number which is what you are a question medicine individual needs to know! The reason being is because it drastically changes the outcome and results

Lets look at the first outcome of miss payments on credit account, this occurred 7.7% of those with ADRD compared to only 7.3% of missed payments in those individuals without a diagnosis of ADRD. BUT REMEMBER the people that were enrolled in this study- 54 062 pts without the diagnoses of ADRD were included and 27 302 who had the diagnosis of ADRD were included

This mean you have to take 7.7% of 27000 patients with a dx of ADRD
And 7.3% of 54000 patients without a dx of ADRD

This works out to a total of 6000 patients but it breaks down to 2000 individuals diagnosed with ADRD missed a credit card payment and 4000 individuals without a diagnosis of ADRD missed a credit card payment. So 2/3 of individuals who missed a credit card report did not have a diagnosis of ADRD!!

When you look at the second outcome of a subprime credit score you find almost the same thing! Remember the results were 8.5% vs 8.1% WHICH CLEARLY shows that those individuals with alheimers dementia diagnosis are more like to develop a subprime credit score but when you look at 8.5% of 27000 and 8.1% of 54000 it is clear at 8.1% of 54000 is a much bigger number so the actual numbers work out to almost 2/3 of those indivudials with a subprime credit score DO NOT have diagnosed dementia.

The authors say in the discussion that the findings “suggest that ADRD is associated with adverse financial outcomes even in the prediagnosis stage”

Yes they are right it is associated with adverse outcomes, but so is breathing!! So it brushing your teeth, more people without ADRD had or made poor financial decisions than those with ADRD.

The outcomes of this paper would change drastically if they ssaid we looked at the numbers and out of almost 80,000 patients it turns out that of those individuals who missed a credit card payment or a had subprime credit score 1/3 of the time these individuals had ADRD and 2/3 of the time they did not have.

This is a drastically different conclusion than what the authors said which was

“ Alzheimer disease and related dementias were associated with adverse financial events years prior to clinical diagnosis”

I think the take home is we still don’t have good screening for alzheimer disease and looking at adverse financial events is still not the magic bullet of alzheimers screening. AND don’t be confused if the authors don’t give you the exact numbers.. if they give you percent or ratios then you need to calculate the numbers yourself because likely they are trying to hide something or spin the results

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https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2771041#:~:text=Conclusions%20and%20Relevance%20Initiation%20of,effective%20as%20brand%2Dname%20levothyroxine.

Comparative Effectiveness of Generic vs Brand-Name Levothyroxine in Achieving Normal Thyrotropin Levels
JAMA Netw Open. 2020;3(9):e2017645. doi:10.1001/jamanetworkopen.2020.17645

Quick history lesson- levothyroxine was cleared and approved for generic use in 2004 – until then Synthroid had enjoyed a huge market share. The only market share. They were it and there is soooo much money when you are the only drug on the market and the most prescribed drug on the market—in 2002 the revenue was estimated at 1 billion dollars.

I was alive in 2002 and I can tell you back then 1 billion dollars was a lot of money.

But then 2004 there is now competition, a generic drug.! What does the drug company do? Use some of their small fortune to trash the drug, pay of some doctors to write a paper and later in 2004 there was a paper released by The Endocrine Society released the paper citing concern for the generic drug and the bioavailability.
https://www.endocrine.org/advocacy/position-statements/bioequivalence-of-sodium-levothyroxine

as recent as 2014 the
American Thyroid Association guideline specifically recommends
“Switches between levothyroxine products could
potentially result in variations in the administered dose and
should generally be avoided for that reason”

Meaning don’t have them on brand name synthroid and then switch them to generic. Stay constant!

But todays study wanted to look at the comparative effectiveness of generic vs brand-name levothyroxine in patients initiating therapy for hypothyroidism

4570 patients initiating therapy with thyrotropin levels ranging from 4.5 to 19.9 mIU/L were 1:1 propensity–matched

One group was started on generic levothyroxine and the other group was started on brand-name levothyroxine also known as Synthroid.

As an outcome they looked at three different things
the numbers of individuals who attained a normal thyrotropin level within 3 months,
the clinically meaningful abnormal thyrotropin level within 3 months
the number of people with stable thyrotropin level(s) 3 months AFTER having a normal thyrotropin level

Among 4570 propensity score–matched patients those that received generic levothyroxine had a normal TSH 75.4% of the time and those that got brand-name levothyroxine had a normal TSH 76.9%
And in both groups about 4% of the individuals had a markedly abnormal TSH level (94 [4.1%; 95% CI, 3.4%-5.0%] vs 88 [3.9%; 95% CI, 3.1%-4.7%]; P = .65).

They then took the individuals who had a normal TSH at 3 months and propensity matched those individuals to 3 MORE months and the proportion maintaining normal TSH levels during the next 3 months was similar regardless if you received generic or brand name levothyroxine, 82% vs 83% respectively. (427 [82.6%] vs 433 [83.8%]; P = .62).

Here is the kick in the pants-
Per good RX

Levothyroxine is $4 on good RX
Synthroid is $45

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www.bmj.com/content/368/bmj.m149

No one wants to get pregnant two minutes after having a baby. And also agrees that an IUD is most effective form of conception. However placing IUD after delivering a child seems to be a point of debate as the risk of expulsion seems to be significantly higher immediately post pregnancy
In this study titled
Averbach SH, Ermias Y, Jeng G, et al. Expulsion of intrauterine devices after postpartum placement by timing of placement, delivery type, and intrauterine device type: a systematic review and meta-analysis. Am J Obstet Gynecol 2020;223:177-188.

They looked at the different rates of IUD expulsion postpartum. As you can imagine the rates vary based on if the IUD was placed within 3 minutes of child delivery or 3 weeks after child delivery. There also seemed to be a difference between hormonal IUD (LNG-IUD) compared with a copper T-shaped IUD. Finally there was a difference whether she had a C-section or a vaginal delivery as you can imagine the vaginal delivery was associated with significant less rates of expulsion which is the numbers we are going to talk about going forward as the rates of expulsion following C-section were significantly lower around 0-2%.
Brand progesterone IUD are called Skyla, Liletta, Mirena -- but in this study they only included those papers which she used MIRANA.
Copper IUD goes by paragard
Ultimately the authors looked at 3 different timeframes for placement of the IUD. 1-immediate placement within 10 minutes postpartum, or IUD placement anywhere from 10 minutes postpartum to 72 hours postpartum or early outpatient placement somewhere between 72 hours to 4 weeks postpartum
So let’s break them down by timeframe-
Those individuals who had an IUD placed immediately following delivery had a 27% exposure rate with Mirena and a 12% exposure rate with ParaGard
Those individuals who had an IUD placed not immediately but within the first 72 hours the exposure rate was 37% with the hormonal IUD and 7% for the copper IUD
And finally for those women who had an IUD placed in the outpatient setting at some point between 72 hours in 4 weeks there was no expulsion that occurred for either the hormonal or copper IUD.

I think the final answer here is for a woman who has a vaginal delivery and would like to have IUD placement following delivery there is almost no way we can justify placing hormonal IUDs within the first 72 hours as the expulsion rate of 30ish percent is way too high to justify. The ideal situation would be IUD placement in the outpatient setting at sometime point between 72 hours in 4 weeks however if you’re patient is insisting on IUD placement while still in the hospital then it appears the best option would be a copper IUD and this likely should be placed as close to discharge as possible because even those individuals who had a copper IUD placed prior to 72 hours still had a 7% exposure rate which seems a little high. If you’re going to use this paper and practice I think important thing to remember is that it was for woman with vaginal deliveries and not for women with C-sections as those individuals had near 0% expulsion rates.

The next our article talks about one of the most irritating conditions to treat and of course that is irritable bowel syndrome. In this randomized double-blind placebo controlled trial titled
Hamatani T, Fukudo S, Nakada Y, Inada H, Kazumori K, Miwa H. Randomised clinical trial: minesapride vs placebo for irritable bowel syndrome with predominant constipation. Aliment Pharmacol Ther 2020;52(3):430-441.

Author still just over 400 patients with a history of severe irritable bowel syndrome predominant constipation who were having less than 3 spontaneous bowel movements per week and randomized them to placebo or minesapride 10 mg, 20 mg, or 40 mg daily for 3 months.

The primary endpoint—an increase in one or more complete spontaneous bowel movements and in the end it didn’t matter what dose of minesapride you got because it was no better than placebo. All groups had about a 40% improvement in their rates of spontaneous bowel movement.
Irritable bowel is irritating to treat because pooping and bowel movement are so mental. Anxiety and stress and tension can back you up like a hoover damn and then a magical pill even if it is placebo can put you at ease and open the flood gates…running a trial is hard because you need to beat placebo and speaking of things that didn’t beat placebo

This paper titled

Boesen AP, Boesen MI, Hansen R, et al. Effect of platelet-rich plasma on nonsurgically treated acute achilles tendon ruptures: a randomized, double-blinded prospective study. Am J Sports Med 2020;48(9):2268-2276.

Looked to see if platelet rich plasma could be placebo in the treatment of acute Achilles tendon rupture.

In this randomized double-blind placebo controlled trial of 40 patient’s with acute Achilles rupture confirmed on ultrasound-
All patients were treated with a continuously worn ankle casts that kept the foot plantar flexed for 8 weeks. Every 2 weeks, the researchers lessened the degree of plantarflexion. After 9 weeks, all patients began an ankle rehabilitation program
But half were randomized to placebo or and half platelet rich plasma injections.
The patient’s were injected every 2 weeks starting within 4 days of the injury they then evaluated patient function via the Achilles tendon total rupture score at the time of removing the cast and then again at 3, 4-1/2, 6, 9, and 12 months after injury. In the end there was no difference between whether patient was randomized to receive platelet rich plasma injections or saline injections. Granted this study was only 40 patient’s and too small to determine differences such as the re-rupture rate but this was a really well done study that I think is hard to refute, they did a lot of things exactly how you want to see them done.
For example,
None of the patient’s nor providers nor the statistician’s nor the outcome assessors were aware of
Whether the patient had received saline or platelet rich plasma. There is only one person who did the injections which was an experience sports medicine physician and injected all patients under ultrasound but this provider had no other influence on the patient’s outcome or care and was also blinded to saline or platelet rich plasma injections as a sheeth was placed over the syringe and the help of the needle. This in all actuality was a very well done trial and methadone neurologically was one of the most sound trials I have read in a long time, if he ever want to read how a method section should be written then he should read this paper. The methods were given in such extreme detail right down to the exact gauge of the needle and to the to the brand of ultrasound machine was used.
If you doubt this trial then there is more than enough information in the method section you could easily repeat it in your office tomorrow without any questions.
But otherwise said placebo was not nothing placebo is hard to be especially if you’re trying to be treated with platelet rich plasma for an Achilles tendon rupture

The man noticed that I said they did a method section really well and if he doesn’t agree with the outcome then you can repeat the study yourself in your clinic. I notice when he comes a cold literature as well as vitamin D literature and other such literature which is borderline terrible those individuals who believe in something so powerful such as mask refuses to believe the outcome of the well done trial regardless of how well the trial was done. However the most important part of the paper size for the results is the method section. If you know exactly what gauge needle, what size syringe, what lab assay, what number years of experience the provider giving the intervention has you can almost do an exact simulation in your office and see if you, with the exact results because sometimes the results very just based on something he would never think of like the laboratory which is no more clearly seen in this article titled

Potter JM, Hickman PE, Oakman C, Woods C, Nolan CJ. Strict preanalytical oral glucose tolerance test blood sample handling is essential for diagnosing gestational diabetes mellitus. Diabetes Care 2020;43(7):1438-1441.

Which looked at the effect of processing and oral glucose tolerance test with either delayed or early centrifuge protocol.
There is a total of just over 12,000 women in this study approximately 7000 women received delayed centrifuge protocol and approximately 5000 women received in early centrifuge protocol.
The lumen that had the delayed centrifuge protocol Heather blood collected but then it was sent off to a central laboratory for blood glucose analysis those when that had a early centrifuge protocol underwent the same oral glucose tolerance testing but when they had their blood drawn for analysis but glucose testing was performed immediately.
All things being equal they’re really shouldn’t be much of a difference here the results showed that those individuals who had immediate glucose testing rales twice as likely to be diagnosed with gestational diabetes than those individuals with delayed glucose testing

Fasting- with fasting there was a difference of 4 mg/dl
1-hour samples 6.1 mg/dL and the two hour measurement was a difference of - 2.8 mg/dL (0.16 mmol/L; 2.3%).. this may sound very small change in the overall glucose but remember the fasting blood glucose concentration is less than 95 so a difference of 4 just based on higher lab processes the blood draw is almost a 5% error in the test.. Likely in the United States for many oral glucose tolerance test we use Accu-Chek monitors however the same question in the same importance and relevant supplies to the calibration and accuracy of the monitor being used.
We have a chance grab 2 different brand monitors and check the same person at the exact same time just with different fingers and all certainly you’ll come up with a slight difference in their blood sugar. I’m not surprised by these findings which is a constant reminder that will be due in medicine is small. Nothing is a parachute. Nothing is absolute. I recently heard someone compare a certain intervention to Russian Roulette which implies a 1-6 chance of dying, this is follow-up taking that gives us an over his zealous and heightened sense of our work almost nothing that we do as a number needed to treat of 6 and especially not for death. We have to keep this in mind make sure that our patients are also aware of the inconsistencies in our practice of medicine which is also clearly seen in this paper titled

McCormack JP, Holmes DT. Your results may vary: the imprecision of medical measurements. BMJ 2020;368:m149. doi: 10.1136/bmj.m149

Which looked at the variation or error that surrounds laboratory testing. This paper found much of what I mentioned previously on questioning medicine about laboratory findings such as a single HbA1c test result of 6.3% (45 mmol/L) could actually be as low as 5.5% (39 mmol/mol) or as high as 7.1% (51 mmol/mol).
The lab findings are thrown off by variability in the analytic or lab process (4.3%), as well as biologic variability meaning the variation in the same person over the course of days caused by physiologic changes.
Combined, these challenges to precision can make a single iron, bilirubin, or triglyceride level be inaccurate by as much as 50%.
That means you would require at least a 50% change in the levels to be considered valid true actual change and not just a stastical variability.

I have put a link to the office calculator as the very first piece of information in this podcast and think everyone should save it to their favorites to either bring up with the patient sitting in clinic or to discuss with your colleagues at the next zoom conference

Let’s recap the articles discussed today before this ship set sale in the sea of evidence

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Questioning medicine daily

https://www.acpjournals.org/doi/10.7326/M20-7448

https://www.acpjournals.org/doi/10.7326/M20-6817

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers
FREE
A Randomized Controlled Trial

Masks!!!! Do they prevent COVID19 transmission by preventing spread from infected people to others OR do they work by protecting wearers OR is it both.
We now have an answer to the second question, Do the mask work by protecting the wearers and in short the answer is no.
Fresh out november 18.
The DANMASK-19 trial

It a trial designed to examine the masks' protective effect.

Spring 2020 in Denmark, Social distancing recommendations were in effect, but masks were not recommended, they were rarely worn outside of hospitals, and the infection rate was modest around 2% per month which is pretty close to what we were seeing because remember we were around 1-3% here in american depending on where you lived with some places much much higher like New york but many places down to almost 0% like the fly over states and even places like salt lake city.
The endpoint was infection in the mask wearer!!! NOT infection in their contacts or the overall community infection rate.

This study enrolled 6024 adults who spent at least 3 hours outside their homes per day, had occupations that did not require masks, and did not have a previous known diagnosis of SARS-CoV-2 infection.
All participants were told to follow social distancing measures but randomized to wear or not wear a mask when outside the home.

The primary outcome was SARS-CoV-2 infection, defined as a positive COVID nasal swab OR development of a positive COVID antibody test OR a hospital-based diagnosis of COVID-19.
They powered it to find a 50% reduction in infection risk
After 1 month of follow-up, 1.8% (42 of 2392) of participants in the mask group and 2.1% (53 of 2470) in the control group developed COVID19 infection (risk difference, −0.3 percentage point [95% CI, −1.2 to 0.4 percentage point] [P = 0.38]; odds ratio, 0.82 [CI, 0.54 to 1.23] [P = 0.33]).
THERE WAS NO DIFFERENCE!!

BOOM FIRST RCT we have on wearing mask during COVID19 pandemic and it says that wearing a mask does not protect you from getting COVID19.
As with all trials which dont show what you want them to show there are people already knocking this well done trial. This is a common event and happens often in the cardiology or vit d literature. The study doesnt show what they want to they use very simplistic thinking to knock it down. Don’t get me wrong it has it’s flaws but use your brain to think deep and dont use the easy answer because they are not correct, in my opinion
Here are some of the things I have heard people say
1- “Well the study only looked at the effect of recommending mask use, not the effect of actually wearing them.”-In the study people were recommended to wear a mask not required to wear one-- yes, but that goes for every study—we recommend you to take a pill not the effect of actually taking them since we have no way of knowing they actually took them…This is every trial and either you believe in science and trials or you dont and you cant now all of a sudden not believe in medicine because the trial didnt show what you wanted.
2- How do we know people are wearing mask accurately??? Well in the trial 46% wore the mask as recommended and 47% wore it "predominantly as recommended," for a total of 93%. That is probably better than america, go to the grocery store and just walk around you might need more noses than heads of lettuce.
3- Some people say well this was done in denmark, we live in america so you cant use this evidence in america. This arguement works for some conditions and some treatments but I have no idea how this arguements works for wearing and not wearing mask. Unless there is a cultural difference in Denmark I am not aware of.
AND FINALLY---
4- Some say it is irresponsible to publish these results because this will give antimask people ammo--- I couldn't disagree any more-- More irresponsible would be to not publish the results of carefully designed research because the findings were not as favorable or definitive as some may have hoped. Science is not to be cherry picked

Here are one of the issues that are deeper thinking
Remember-
1) They powered it to find a 50% reduction in infection risk-- remember when you power your study you power it to find an outcome that you think is worth finding. Sure maybe they could find maybe a 1% reduction and it would be a positive study but people would say wait these stupid mask only give me a 1% reduction?? Also the smaller the benefit you want to find the more people you have to enroll. If you only wanted to find a true 1% difference you have to enroll over a million people depending on your standard deviation. That is just not feasible.
2) either you believe in science or you dont and if you want randomized control trials for the medications that you prescribe then you need have to be ok with them for mask that you tell your patient to wear. You dont get to change your belief on RCT because it didnt show what you wanted.
And finally
3) This trial does not tell us that mask dont work. We dont know if mask work to prevent us from spreading covid19 to other individuals. That trial could be done and should be done. You would have to randomized cities or areas to mask and no mask and see what happens. It would have to be done in other countries or small town america
My final thoughts are
Lots of people want to knock this study because it didnt show what they wanted- People wanted this to show how great mask are. People want to believe mask are a holy grail of wonderfulness. They want to shame people and post memes on social media shaming those individuals for not wearing a mask. in the end this study is a well done study that gives us good information. Unfortunately mask have become such a strong belief. It is like antivaccine people, their belief of evidence is much stronger than the actual evidence. Mask have sadly become political not science. I am not saying dont wear a mask and Im not saying always wear a mask. Do your best to try to wear them but if you dont have one on or you forget one, its OK!!! Mask are not parachutes. They are far from it. With all things being equal the NNT of masks is likely in the millions, especially for events we care about. Remember we don't care about catching a virus, people catch viruses all the time!! EVERY SINGLE DAY! Keep in mind we care if you have any morbidity and mortality from the virus. The event rate is still just a fraction of a fraction of a percent.

And with that!

Thanks for listening, thanks for your time and until next time keep the quest in questioning medicine

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https://www.clinicalkey.com/#!/content/journal/1-s2.0-S0140673620322339?scrollTo=%23hl0000424

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32233-9/fulltext

do statins work in old people?? This study in the lancet says-

“In a contemporary primary prevention cohort, people aged 70–100 years with elevated LDL cholesterol had the highest absolute risk of myocardial infarction and atherosclerotic cardiovascular disease and the lowest estimated NNT in 5 years to prevent one event.’

researchers calculated that 80 adults aged 80–100 years — would need to receive a moderate-intensity statin for 5 years to prevent one MI.
and145 adults aged 70–79 years — would need to receive a moderate-intensity statin for 5 years to prevent one MI.
and to prevent just one ASCVD event, the numbers needed to treat were 42 and 88, respectively.

But anytime you read the results you have to say “how did you come up with that number” what were your methods?

In this study they took a sample of people from a large Danish database and these were low risk individuals not on statin therapy. They calculated the number of reduced events by calculating the event rate they expected and dividing it by the number of events during the follow up.

But remember youi have to ask how did you come up with your calculation???

“For these calculations, we assumed 30% and 22% relative risk reduction of myocardial infarction and atherosclerotic cardiovascular disease, respectively, per 1·0 mmol/L reduction in LDL cholesterol in individuals free of atherosclerotic cardiovascular disease, as observed in the Cholesterol Trialist Collaboration meta-analyses.”

THIS IS FRUSTRATING because if you have read the cholesterol trialist you collaboration you know that the individuals in the studies were HONDA they were not low risk individuals. The higher the risk you are the more likely a drug is to work. Think about it like this a statin is more likely to work on someone who is really high risk because they are way more likely to have a MACE. Just like breast cancer chemo therapy is more likely to work on someone who has breast cancer and is even more likely to work if the person is a women.

So in this study they estimated the event rate based on really sick people and then said based on that we can say the likelihood for benefit in these more healthy patients would have a benefit or NNT of 42 or 80 to prevent just one MACE.

NOOOOO you cant take the odds of sick people or people with breast cancer and then say well look how it worked in them so it must work the same way in this population over here.

Do the trial of statins in the elderly or don’t publish the paper

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https://www.acpjournals.org/doi/10.7326/M20-2470

Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association's Standards of Medical Care in Diabetes Clinical Guideline
FREE
Which is as the artciel suggest in a sypnopsis of the 2020 ADA guidelines

metformin is still universal fist line but now the guideline says

The choice of agent to add to metformin therapy should be individualized on the basis of patient characteristics, preferences, and drug-specific effects.

The big rec from this paper is
Among patients with type 2 diabetes who have established ASCVD or established kidney disease, or heart failure, a sodium–glucose cotransporter-2 (SGLT2) inhibitor or glucagon-like peptide-1 receptor agonist (GLP-1 RA) with demonstrated cardiovascular disease benefit is recommended (Grade A recommendation).

they go on to say maybe one of the key lines--------The addition of these medications should be considered independent from HbA1c level in this patient population.

You might remember dapaggliflozin – the article last year that I said was one of the top articles of the year because it changed how we practice for both diabetes and heart failure!! Well now---I give you--- https://www.nejm.org/doi/10.1056/NEJMoa2022190

Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure in the NEJM

EMPEROR-Reduced trial recently out which looked to see if empagliclozin could join dapagliflozin for risk reduction in heart failure!!
This was a double-blind, randomized, placebo-controlled, using empagliflozin (10 mg daily)

At a mean follow-up of 16 months, patients receiving empagliflozin had a lower risk for the primary endpoint of cardiovascular death or hospitalization for worsening HF than placebo recipients with a shocking NNT of 20 although this was mainly driven by heart failure hospitalizations these numbers are similar to dapagliflozin -- (19.4% vs. 24.7%). –AND THIS was INDEPENDENT OF DIABETIC DIAGNOSIS!! AND when you looked at the change in A1C at the end of the trial—there was no difference, just maybe these SGLT2 inhibitors really are people drugs, not diabetic drugs which has to make everyone question the relevance of the surrogate marker we use for diabetes, A1C.

not to go on too much of a rant but if we look at A1C and say this is the standard by which all drugs should be measured and some drugs DO NOT CHANGE THE A1C or at least not with any clinical significance but they do prevent death, MI and hospisitliations while other drugs dont change any of the hard outcomes but they change the A1C we have to say maybe just maybe A1C is not the marker we should care about.
and as excited as I am abou the rush of evidence around SGLT2 inhibitors.
Sadly the best medication is likely still prevention, with healthy lifestyle- these drugs are still around $500 a month so we are talking at least 6grand a year for a drug that 95 out of 100 people will never benefit from. Which means we are talking roughly 120,000$ per event saved! So I grant you this is a really impressive article and empagliflozin is now joining dapagliflozin to prevent heart failure hospitalistizations, and I still think the SGLT-2 inhibitors are quickly becoming king of the castle for diabetes treatment—I also think they will never truly take the thrown till they are $4 a month like metformin.

And while talking guidelines

Synopsis of the 2020 U.S. Department of Veterans Affairs/U.S. Department of Defense Clinical Practice Guideline: The Diagnosis and Management of Hypertension in the Primary Care Setting
FREE

Also in annals of internal medicine but had a couple interesting or new recommendations like

we suggest using attended or unattended, fully automated blood pressure measurement. A fully automated BP programmed to wait 5 minutes and recod the average of threee measurements separated by at least 30 seconds
there goal bp is unless you are 60yrs old and older then but If you are 60yrs and older AND DM then
with any of the main medication- ACE, ARB, CC, thiazide and if they are on 3 or more of these medications then it is resistant and give spironolactone

nothing too shocking in this paper but just a good refresher and something to keep in mind, and speaking of keeping in mind!!

Seminowicz DA, Burrowes SA, Kearson A, et al. Enhanced mindfulness-based stress reduction in episodic migraine: a randomized clinical trial with magnetic resonance imaging outcomes. Pain 2020;161(8):1837-1846.

this RCT of almost 100 people recruited mostly white women who had on average about 8 headaches a month and 85% were not on prophylaxis medications
pts were enrolled in either mindfulness-based stress reduction classes or stress management for headaches classes. The classes met weekly for 8 weeks, then biweekly for another 8 weeks.
Those in the mindfulness classes went from 8 headaches a month down to 5 and those in the stress management classes went down to 7. So there was a much bigger difference in the group randomized to mindfulness classes. You might be saying this is a really small reduction in headaches to only go from 8 to 5 and at 1 year of follow up there was no difference, which is likely because the people stopped doing mindfulness. However I will remind you the treatment we have for headaches is some of the worst in medicine. We pass and prescribe drugs all the time that reduce your month headache burdon by 1 or 2 and part of what makes treating headaches so difficult is the mental aspect which is why placebo does so well in most trials.
a paper
Verhagen AP, Damen L, Berger MY, Passchier J, Koes BW. Lack of benefit for prophylactic drugs of tension-type headache in adults: a systematic review. Fam Pract 2010;27(2):151-165.
which was a systematic review looking at prophylaxis treatment of tension headaches. They looked at antidepressants, muscle relaxants, benzodiazepines, or vasodilators
and found There is no evidence -- or only poor quality -- that any of these prophylactic agents are effective for tension-type headaches

so keep in mind while a mindfulness course might night sound like a good headache treatment plan, it might be the best thing we have…..

effective as prophylaxis for patients with frequent tension headaches?

and while this podcast might be torture to your eardrums this last article should fall under torture and stupid-

Fitzgerald RC, di Pietro M, O'Donovan M, et al. Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial. Lancet 2020;396(10247):333-344.

which was a nonblinded trial that looked to see if swallowing a special sponge to sample esophageal epithelial cells for biomarker testing identify patients with Barrett's esophagus in primary care settings?
basically is it possible to diagnose BE in the outpatient primary care setting. the authors enrolled patients at least 50 years old who had received H2 receptor antagonists or proton pump inhibitors for at least 6 months in the previous year. The researchers randomized the patients to receive usual care which was continue acid surpression and maybe an EGD if the provider felt like it OR they would undergo this toture office-based screening. In total around 1500 patients underwent this torture procedure. before I tell you what the procedure was I will say that 89% of the patients felt the procedure was tolerable but while getting a foley cath is technically tolerable I would want one and while getting a rectal tube is tolerable, no….no thank you. soo

the intervention consisted of swallowing a capsule containing a sponge attached to a thread. After the patient swallows the capsule, the nurse yanks on the thread and pulls out the sponge and sends it for analysis looking at a couple markers found in the gut to tell us if the patient had barrients esophogus.
YOU SWALLOWED A PILL THEN JUST A NURSE PULL IT BACK OUT OF YOUR FROM WITH A STRING---THIS IS A PILL ON A STRING!!!!!

The results did show that who that had this string torture procedure were diagnosed more often, twice as often. The usual care was diagnosed with BE around 1% and the tampon string pill people were diagnosed with it a whopping 2% of the time. You were 2x as likely to be diagnosed with BE!!!
2 TIME AS LIKELY!!!
BUT we always have to ask whats the outcome… BE means nothing without cancer. afib means nothing without a stroke.
well the rate of BE turning to cancer is RARE- a cohort study titled
Hvid-Jensen F, Pedersen L, Drewes AM, Sørensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Engl J Med 2011;365(15):1375-1383.
estimated an annual incidence of esophageal cancer to be LOW, real LOW they say--
Barrett's esophagus is a strong risk factor for esophageal adenocarcinoma, but the absolute annual risk, 0.12%, is much lower than the assumed risk of 0.5%, which is the basis for current surveillance guidelines. Data from the current study call into question the rationale for ongoing surveillance in patients who have Barrett's esophagus without dysplasia.

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https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771093

meta-analysis of 78 original studies, looking to find the accuracy of ECG interpretation. In this analysis they looked at studies with med students, physiciansm even cardiologist and found on average we got the right diagnosis only 55% of the time.

Obviously education goes up with more education

42.0% for medical students,
55.8% for residents,
68.5% for practicing physicians,
and 74.9%) for cardiologists.

in the end it I think it says a couple things
We all have room for improvement at reading EKGs
When you don’t know what the EKG says the cardiologist only know the right answer an extra 6% of the time
I am not shocked by the results. Lots of these studies had you look at 10 ekgs and say what it is. I think most people can get the easy EKGS, it is the really hard ekgs that look like a four year old drawing that are challenging to name. I think a better question would have been if the providers knew what to do. Did the providers know to start cpr or now if given a vignette, or if they should shock or push epi…like a concerning mass found on imaging, sometimes you don’t need to know the diagnosis you just need to know what to do….

https://www.acpjournals.org/doi/10.7326/M20-4187

acute sciatica—not a lot of good options for this… what about PT??

that is titled

Physical Therapy Referral From Primary Care for Acute Back Pain With Sciatica
A Randomized Controlled Trial

single-blind, parallel-group randomized trial that took place in 2 Utah hospitals and randomized 220 to either receive early physical therapy (EPT) or UC.

all participants were given a copy of The Back Book (23), a patient education booklet with evidence-based messages about the favorable prognosis of LBP and the importance of remaining active and avoiding bed rest

The EPT protocol recommended 2 weekly sessions during the first 2 weeks and 1 to 2 sessions in weeks 3 and 4.

The primary outcome was score on the Oswestry Disability Index (OSW) score after 6 months., Oswestry Disability Index (OSW) is a 10-item measure of LBP-related disability. OSW Scores range from 0 to 100, with higher scores indicating greater disability.

our results found that EPT referral after an initial primary care visit for recent-onset LBP and sciatica resulted in greater improvement in disability

Participants in the EPT group had greater improvement from baseline to 6 months for the primary outcome (relative difference, −5.4 points [95% CI, −9.4 to −1.3 points]; P = 0.009).

But as they say in the paper---

Minimum important difference is 6 to 8 points for acute LBP and sciatica

So the results should have said “our results found that EPT referral after an initial primary care visit for recent-onset LBP and sciatica resulted in greater stastical improvement in disability but is arguable if these changes are clinically important”

The lesson is when you are using a scale to measure something in the study, also know or look for the minimally CLINICALLY important difference that is needed

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2772373

Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 YearsA Systematic Review and Meta-analysis

in children younger than 2 years what is better for short-term treatment of fever or pain do you choose ibuprofen or do you choose acetaminophen??

The anwer is it depends where you live and which guidelines you follow

For example the maximum daily dose of acetaminophen beyond the neonatal period varies from 60 mg/kg/d in New Zealand to 90 mg/kg/d in the United Kingdom and United States.5 Recommendations for ibuprofen also vary based on where you live -- The New Zealand Formulary for Children recommends ibuprofen at 5 mg/kg/dose 3 to 4 times daily starting at age 1 month with a MAX of 30mg/kg/d. The United States, ibuprofen max daily dose is 40 mg/kg/d and starting at 6months of age.

So this anytime there is more then one answer it means that likely neither are evidence based.

This systematic review and meta-analysis loked at19 studies that compare acetaminophen with ibuprofen for the short-term treatment of fever or pain in children younger than 2 years.
796 participants were included in the final pain analysis.

The primary outcomes were fever or pain within 4 hours of treatment onset.

and even after looking though 19 studies ONLY 796 participants were included in the final pain analysis. which point out that pediatric litature is terrible!!!! no one wants to enroll their kid in anything

and if you read the authors conclusions you will see that "Moderate-quality evidence from randomized studies showed that compared with acetaminophen, ibuprofen was associated with reduced temperature within 4 hours”

But I fyou go to figure two forest plot you will see the difference between ibuprofen and acetaminophen had a confidence interval that ALWAYS extended over the midline BUT that key is the point estimate for the odds ratio was ALWAYS on the side favoring motrin. Sure we can say each trial individually was not clinically significant but when combined they were stastically significant AND there was not a trial that even had a point estimate in favor of acetaminophen.

So we give ibuprofen to everyone right!!!????

Well not so fast- the authors did do a secondary analysis to see how young did a child need to be to get ibuprofen and still be considered safe and SADLY Only 2 randomized studies in the review had inclusion criteria which included those infants younger than 6 months and this was not enough information to draw any real conclusions.

So I guess at this point it is tylenol till age 6 then ibuprofen is probably ok.

The authors do mention that ibuprfen has been used for closure of patent ductus arteriosus in preterm infants and no notable harms in the short term BUT trials are needed so if you are a hospital with a nicu or just a hospital. Do the trial! From this trial those over the age of six get more benefit from ibuprofen is there something special at 6 months compared to 5 months??? My guess is no but we need the trial

Bottom line—acetaminaphen 0-6mths then ibuprofen is ok

From my childhood I can say my mother only told me two things growing up, don’t eat your boogers and you are what you eat and this is clearly seen in this article titled
https://www.nejm.org/doi/full/10.1056/NEJMoa2007448?query=pfwRS&jwd=000020154104&jspc=HOS

Weight Loss in Underserved Patients — A Cluster-Randomized Trial

In NEJM

Which looked do see the effectiveness of treatment for obesity delivered in primary care settings in underserved populations is lacking.

803 adults with obesity were enrolled randomly assigned to intensive lifestyle intervention or usual care—

The intensive lifestyle intervention focused on reduced caloric intake and increased physical activity, they had health coached and had The program consisted of weekly sessions for the first 6 months, followed by monthly sessions for the remaining 18 months. Patients received personalized food-intake and calorie-intake targets, were instructed to weigh themselves daily on digitally connected scales, and adjusted their eating and activity patterns, in consultation with coaches, to meet their weight-loss goals.

The primary outcome was the percent change from baseline in body weight at 24 months.

The mean BMI at start of the trial was 101kg or 222lbs—and maybe you are thinking well these people must have been really talll—there bmi was 37! When you weigh 222lbs you are either obese or really tall and these people were obese.

The percent weight loss at 24 months was significantly greater in the intensive-lifestyle group (change in body weight, −4.99%; 95% confidence interval [CI], −6.02 to −3.96) than in the usual-care group (−0.48%; 95% CI, −1.57 to 0.61), with a mean between-group difference of −4.51 percentage points (95% CI, −5.93 to −3.10) (P
4.5% of 222lbs is around 10lbs.

This tells me one thing—1) these people were in a study had weekly meetings with health coaches and over the course of 2 years could only lose 10 pounds. Weight loss is really hard. Even when you are trying really hard and you have weight loss coaches and personalized food intake plans and calorie consumption targets individualized for you, weight loss is really hard and although my mother was not totally correct because else I would have turned into a cookie by now, it remains clear that twinkies will turn you into a sponge cake.

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https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771670

trials are not real life. We know that. Realistically if your drug just barely hits 0.05 in a clinical trial then in the imperfect setting of the clinic of every day life the drug likely wont work. In this next study, in jama internal medicine titled
Concordance Between Blood Pressure in the Systolic Blood Pressure Intervention Trial and in Routine Clinical Practice

The authors used a prognostic study and took 3074 patients and wanted to see the difference between BPs obtained in routine clinical practice and the bp obtained during a clinical trial. Which trial you ask?? The sprint trial!!

This is brilliant they basically took 3000 patients who were in the SPRINT trial, and as a reminder the sprint trial is the land mark trial of
2015 that showed- In patients at high risk for CVD but who do not have a history of stroke or diabetes, intensive BP control (target SBP And compared the blood pressure that was taken for measurement and calculation during the trial and compared it with the bp that was calculated during the normal office pcp visit outside of the trial setting. Ideally these should be the same! Right?? If you are going to the study center and getting your bp taken or you are going to your normal doctor and getting your bp taken the results should be the same. You are taking the same meds you should get the same results?!??

But they found those in the intensive arm had a SBP that was 7mm hg higher in the doctors office compared to the SBP measured in the SPRINT trial.
those in the standard of care arm had a SBP that was 5mm hg higher in the doctors office compared to the SBP measured in the SPRINT trial.
What does this mean?? It means in the doctos office we don’t measure bp the same way they do in trials. I am not sure it means more MACE but if we extrapolate from other date we can say likely an error in bp reading of 6mm hg does make a difference.
Moral of the story. Studies are far from perfect. And often we overlook the methods and jump straight to the results but if you are going ot use a trial in practice the methods is maybe one of the most important parts of the paper if you want to get the same results else you can expect you clinical results to vary from the study results just like was shown in this paper.

topically applied corticosteroids and emollients are the mainstay of therapy for atopic dermatitis or that is at least the opening line on uptodate

but what if we question medicine as done in this paper titled

The Effects of Common Over-the-Counter Moisturizers on Skin Barrier Function: A Randomized, Observer-Blind, Within-Patient, Controlled Study

https://journals.lww.com/dermatitis/Fulltext/2020/09000/The_Effects_of_Common_Over_the_Counter.7.aspx

which look sough to look a little deeper into this standard of care for atopic dermatitis.

They took 20 points and randomized them to 1 of 4 moisturizers (Cetaphil Cream, Aveeno Eczema Therapy Moisturizing Cream, CeraVe Moisturizing Cream, Vaseline) on one arm but then NO moisturizers on the other arm. The patients were acting as their control. The right arm gets treatment the left arm gets no treatment. They did this for 4 weeks and then they accessed for Transepidermal water loss (TEWL), capacitance, pH, via tape stripping of stratum corneum.

The results showed that after 4 weeks of treatment there was no significant change in pH or in Transepidermal water loss. But the treated side did show an improvement in capacitance.. so basically the arm you put moisturizer on was more ‘hydrated’…shocking.

The authors conclude “The effects of moisturizers on nonlesional AD skin were small and need to be addressed when powering future studies.” Which really means that we give moisturizers for atopic dermiatitis with almost no evidence they do anything and it is about time we run some trials to see if what we have been doing for years is actually effective. AND since really the only outcome we can change is skin hydration then your best bet for atopic dermatitis is to use something really thick and heavy like bacon fat….or Vaseline.

https://www.bmj.com/content/371/bmj.m3576

there is an old saying that goes you can lead a horse to water but you cant make them drink… but what if you could make them drink. It turns it they would do just as well or so says this article in the BMJ titled Targeting rehabilitation to improve outcomes after total knee arthroplasty in patients at risk of poor outcomes: randomised controlled trial. That took 334 patietns who had just underwent total knee arthoplasty for kneee osteoarthritis and randomized them to either six weeks of outpatient physical therapy or to a home exercise based regimen. A Self directed PT!! You meet with the PT at the start of the 6 weeks then they give you a pat on the back and say, ok, good luck scooter.
Primary outcome was Oxford knee score at 52 weeks,

You needed at least a 4 point difference to be clinically significant and in this trial there was only a 2 point difference in the oxford knee score at 52 weeks, meaning there was no clincially meaningful difference in pain and function when you looked at outpt vs in your house physical therapy. I am a big pelaton fan because I can workout from home, maybe physical therapy from home should be the next app invention—you don’t need to lead a horse to water, you can lead to them to their house all you have to do is get them to drink or in this case do physical therapy after a total knee arthroplasty.
bottom line

Filion KB et al. Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: Multi-database retrospective cohort study. BMJ 2020 Sep 23; 370:m3342. (https://doi.org/10.1136/bmj.m3342)

Findings from a large observational study are consistent with results of randomized trials.
In several randomized, controlled trials, sodium–glucose cotransporter-2 (SGLT-2) inhibitors lower major adverse cardiovascular events compared with placebo; but what about sglt2 inhibitors next to things like an active arm!!!??

in this database obsersvational study from canada and the UK they identify 200,000 pairs of adult patients — each pair contained one who started an SGLT-2 inhibitor (i.e., empagliflozin, canagliflozin, or dapagliflozin) and the other who started or continued a dipeptidyl peptidase-4 (DPP-4) inhibitor. (DPP-4 inhibitors have no known association with adverse cardiovascular outcomes.)
During mean follow-up of 9 months, major adverse cardiovascular events occurred significantly less frequently in SGLT-2 inhibitor users than in the DPP-4 inhibitor users NNT of 200.. which doesnt sound like a lot but over only 9 months that is pretty good.
Results were similar regardless of age, sex, and specific SGLT-2 inhibitor used.
This study, although limited by its observational design, was conducted with active comparators in real-world settings and adds to the evidence that the three SGLT-2 inhibitors evaluated in this study have cardioprotective effects beyond those that derive simply from improved glycemic control.

Rangan A et al. Management of adults with primary frozen shoulder in secondary care (UK FROST): A multicentre, pragmatic, three-arm, superiority randomised clinical trial. Lancet 2020 Oct 3; 396:977
Frozen shoulder is the diagnosis but what is the treatment? You can do manipulation under anesthesia or arthroscopic capsular release or you can send them to PT.
Some of you might say wait andrew you forgot about hydrodilatation—I did not- the authors of this study prior to starting the trial did a search for the treatments of frozen shoulder and they say and I quote
The evidence of the effectiveness of hydrodilatation was deemed to be inconclusive based on poor study design and limited evidence and the evidence of effectiveness to be inconclusive….
What is the best answer?? Well prior to this the largest study on frozen shoulder was
in this U.K. that randomized 500 adults to receive manipulation under anaesthesia or arthroscopic capsular release (each followed by as many as 12 sessions of PT),, or an intra-articular steroid injection followed by early structured 12 physiotherapy sessions during 12 weeks.
The primary outcome was the Oxford Shoulder Score (OSS; 0–48) at 12 months - minimum clinically important difference of 5 points in OSS when comparing early structured physiotherapy with either surgical treatment
In the end the oxford shoulder score is a 48 point scale and all groups started around 20 at baseline which is by all accounts when someone is defined as having moderate to severe shoulder arthritis and should consider seeing an orthopeadic surgeon. but upon completion they were all around 38 which is looked at upon as a place that “May indicate satisfactory joint function. May not require any formal treatment.” …. So went from bad to not really bad at all—and No clincal difference between the three arms
Take home message--- if you have a frozen shoulder walk into your office, consider steroid injection and refer to a physical therapist you trust to get them in ASAP
Blinding of participants and clinicians to treatment allocation was not possible or desirable in this pragmatic trial. Therefore, participants and clinicians were informed about treatment allocation immediately after randomization which can only help bias the intervention group… we know people that have injections or surgery think that they do better even when they get a sham surgery..placebo is real because the mind is real and powerful
The surgeries were done on a day case by case basis within 18weeks, so maybe in the 3-4 months from time to randomization you got much worse frozen shoulder which made you was worse at baseline than those in started immediately with PT.
Finally this was a pragmatic trial which is an ideal way to run this trial. Often trials comparing two arms are run as explanatory trial.. explanatory trials are great for ideal situations, this basically says ‘could this work in ideal conditions’. Where pragmatic trials are great if you want to know how trials work in real world. Pragmatic trials have less exclusion criteria so more people can be enrolled. Pragmatic trials are great at asking could this intervention work if rolled out into the real world under the conditions that are the normal in our daily lives. Drug companies often don’t like pragmatic trials but this is a great example of one and certainly something I wish we saw more often.

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https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771095
SO HOW DO YOU LOSE WEIGHT!!

FASTING DOESN’T WORK or so says this study titled- Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and ObesityThe TREAT Randomized Clinical Trial
100 overweight or obese adults were randomized to regular eating or to a restricted eating pattern where you could not eat between 8pm and 12 noon and the result were no statistical difference between the group that at three meals a day and the group that could only eat between 12 and 8.

Here is the problem-
People could eat anything
You basically are only restricting breakfast. What grown adult eats a ton for breakfast. I mean sure there aer some but the majority of people I know maybe have a hard boiled egg or a piece of toast but never a huge meal. How many EXTRA calories are these people really getting??
I think a better way to do this trial would have been 12 hours of fast but make the hours 5am to 5pm or some random time frame in which you limit the person to not eating for TWO meals, breakfast and lunch. DON’T say hey you can only eat between 12 and 8 because that means that they can eat lunch and dinner.
This is a poorly done study and I wouldn’t be so fast to throw out time restriction eating I think there is still plenty of data saying it can and does work but one should be aware this study is out there.

A good magic trick makes you think one thing when something else is going on and I often wonder how often that happens in medicine, like I seen in this article

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771506?guestAccessKey=5cac67ed-13a3-4b78-b201-61c95f31bec9&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=olf&utm_term=100520

Early Noninvasive Cardiac Testing After Emergency Department Evaluation for Suspected Acute Coronary Syndrome

Which was a retrospective study using data from kaiser permanente looking to find if noninvasive cardiac testing (NIT) after an emergency department (ED) evaluation for acute coronary syndrome lowered the 30 day risk of death or acute myocardial infarction???
Sure a patient comes in for chest pain and the recommendations are for noninvasive cardiac testing within 72 hours but what is the evidence for this?? Do follow up stress ECG, stress echocardiogram, stress myocardial perfusion, or a coronary CT angiogram actually make a difference???

The result they give is like magic—they found noninvasive testing lead to improvements at 30days with The number needed to treat was 250 to avoid 1 death or MI, 500 to avoid 1 death, 333 to avoid 1 MI, and 200 to avoid 1 major adverse cardiovascular event within 30 days.

BUT was it the test that made a difference?? because this is where the magic happens.

There was no difference in the rates of revascularization procedures. So people have more test but they are not then having subsequent revascularization procedure.
LIKELY something else is going on?? Like what you ask?? A good PCP and medical optimization – those that had the noninvasive extra test had stastically higher rates of antihyperlipidemics (16.1% vs 9.7%; P

And speaking of magic—what about a pill you can take that would take away your peanut allergy. That sounds like magic!! Or at least that is what the drug reps will want you to believe about the newest drug Palforzia also known as peanut allergen powder

This is an oral immunotherapy for those with peanut allergy
It is for kids 4 – 17 yrs old and if taken correctly about 2/3 of kids will be able to tolerate exposure to about 2 peanutes.. wait did I just say they can tolerate 2 peanuts??

Yes that because once you start palforzia you take this medication FOR LIFE and you must maintain a peanut free diet – this is a not a peanut free party where you can jump in both feet into a payday candy bar.
The drug cost about 900$ a month AND Palforzia is linked to more epinephrine use than peanut avoidance alone… this sounds great in theory—TREAT PEANUT ALLERGIES. BUT to have access to only 1-2 peanutes it seems like 900$ is a lot of money for half a bite of a peanut butter and jelly sandwhich… I likely wont presribe this drug and just continue to encourage peanut avoidance but for the select few that get a peanut anaphalaxis just but walking past the peanut butter cookies then just maybe palforzia is for you.

2020 is not great for many people but those people are not SGLT2 inhibitors an article in NEJM titled
https://www.nejm.org/doi/full/10.1056/NEJMoa2024816
“Dapagliflozin in Patients with Chronic Kidney Disease”

4000 adults with CKD, mean gfr of 43 were randomized to 10 mg of dapagliflozin or placebo daily. after follow-up of 2.4 years, the primary composite outcome was — decline of at least 50% in estimated GFR, end-stage kidney disease, or renal or cardiovascular death — occurred was less often in the dapagliflozin group 14.5% vs the placebo 9.2%. which makes a NNT of 20 to prevent renal decline and death.

The flozins seems to be people drugs, not diabetic drugs and next time on rounds speak proudly when you say

dapagliflozin can lower the risk for kidney disease progression and death in patients with chronic kidney disease (CKD) — even when they don’t have diabetes.

And then don’t speak so loud and proud when you tell your patient that for a 30 day supply it cost $500 per good RX. Which mean for a NNT of 20 people to take the medication for follow up of 28months it would cost $280,000….

https://www.fda.gov/safety/medical-product-safety-information/invokana-invokamet-invokamet-xr-canagliflozin-medwatch-safety-alert-boxed-warning-about-risk-leg-and

https://www.bmj.com/content/370/bmj.m2812

The FDA says the boxed warning about the risk for leg and foot amputations can be removed from canagliflozin's label.
Based on FDA's review of new data from three clinical trials,
warning was added to the sodium-glucose cotransporter-2 (SGLT2) inhibitor in 2017 after several studies found an increased risk for lower-limb amputation. The FDA says that recent studies have found a lower amputation risk than previous studies — especially when patients were monitored — although the risk is still elevated.
recent study in The BMJ titled Risk of amputation with canagliflozin across categories of age and cardiovascular risk in three US nationwide databases: cohort study – in which Patients newly prescribed canagliflozin were propensity score matched 1:1 with patients newly prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist
the study showed
estimates that one lower-limb amputation would occur for every 556 patients treated with canagliflozin instead of a glucagon-like peptide-1 (GLP-1) agonist over 6 months.
that is, 18 more amputations per 10 000 people who received canagliflozin).

Sglt2 inhibitors prevent chf. They reverse CKD they are a magic drug, or at least work for outcomes we have rarely ever seen.

Start the drug, start low dose, the benefit seems to occur at lower doses with harm at higher doses but do foot exams!

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Doc my heart is racing—

Stop drinking—or so says this article in NEJM that found when they took 140 pts who severed from paroxysmal afib and who drank 17 drinks a week that when randomized to complete alcohol abstinence for 6 months there was significant reduction in afib recurrence.. how much of a difference?? 20% ABSOLUTE DIFFERENCE….. I have a rule of thumb that anytime someone says the improvement is any percent over 10% I almost always assume they are talking relative risk reduction, but this was 20% ABSOLUTE risk reduction. That is a NNT of 5. So when your patient says my heart goes piter pat pitter piter pat pat pat pitter what should I do, the answer is to stop drinking. Now let me grab a sip of bourbon and onto the next article.

DOC there is a puddle on the floor..
https://journals.lww.com/optvissci/Fulltext/2020/07000/Validation_of_a_More_Reliable_Method_of_Eye_Drop.7.aspx

Tell them to close their eyes or so say this article in optometry and vision science that had 30 pts and on one visit, eye drop were placed by a trained clinician, and on the other, patient placed eye drops. The Intraocular pressure was measured before drop instillation and 2 hours after drop instillation.

I know this doenst sound like a big deal but the clinician eye drop test was exactly as it sounds- open your eye and let me drop in the eye drop. The patient drop was different and awesome

for patient self-administration of an eye drop, one in which the lids of the eye that is receiving the drop are closed at the time of administration.

An eye drop placed anywhere over the medial area of a gently closed eyelid with the theory being that the eye drop will fall into the naturally occurring anatomical funnel and right into the eye. Basically the most midline part of the the eye, the part right next to the nose has a little opening and the eye drop should just funnel right in there or at least that was the theory

THE RESULTS

An average reduction in intraocular pressure was 3.75 ± 2.36 mmHg was found with clinician administration, and an average reduction of 3.32 ± 2.31 mmHg for closed eyed patient administration.

THERE WAS NO DIFFERENCE intraocular pressure!!! AMAZING!!

THIS IS BRILLIANT—larger trials are needed but for me this is all the evidence I NEED. I hate hate hate hate trying to put I drop in my eye. I feel like I waste the whole bottle
In a recent report, a glaucoma specialist reviewed videotapes of 300 patients trying to self-administer eye drops using the traditionally taught method. It was concluded that patients released an average of seven drops before they felt confident that one had hit the eye

So when your pt says there is a puddle on the floor, its from their eye drops, just have them close their eyes

Doc I have pain---

Take turmeric. Or at least says this trial annals of internal medicine that took 70 adults with painful knee OA and randomized them to turmeric 1000mg daily or placebo for 12 weeks. The primary outcomes was change in knee pain on a 100 point visual analog scale. Those randomized to turmeric saw a 24 point reduction while those in the placebo saw a 15 point reduction. The difference between a 24point reduction on a 100 point scale and a 15 point reduction on a 100 point scale is statistically significant. And if you listen to questioning medicine at all you might expect me to say this is not clinically significant and the real difference between the active arm and the control arm is the difference between 24-15= 9.

BUT this is game changing or at least I think it should be because the harms of 500mg of turmeric twice a day is almost nothing that I think it is worth prescribing for a 2 and a half point change on a 10 point scale. If you can get a pt with a pain score of 7 down to 4.5 just by prescribing turmeric that is a win and while it is not much better than placebo, sadly we am not allowed to write for placebo and have an pharmacist fill the script so until that happen. Turmeric 500mg bid for knee OA pain.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770959

Incidence, Characteristics, and Outcomes of Interval Breast Cancers Compared With Screening-Detected Breast Cancers

Invasive breast cancer is associated with a higher mortality rate than cancer detected during a routine screening mammogram—

70,000 women in Canadian health registries

Roughly 700 breast cancers were detected on screening, 200 were detected in the 2-year interval after a normal screening mammogram. Which means 500 were detected outside the screening program.

The bad high grade cancers were way way more likely to be an interval cancer odds ratio of 6.33!! that is huge!!! And terrible!! Right??

Of course it is bad—because when you looked at 7 yr follow up for breast cancer specific death you were also more likely to die with hazard ratio of 3.55

Authors say, "Improvement of breast cancer deaths and overall population mortality requires strategies above and beyond conventional screening mammography."

Rabbits, turtles, birds are all in a cage….its a small cage on 10 foot by 10 foot but no roof…..(go on to explain)

We want to catch the rabbits

If it is an interval cancer that means it is growing so fast it is a bird. It is flying away! Of course that is a worst outcome

It is often joked that size matters and clearly seen in this article

Waist Circumference Change During Intensive Lifestyle Intervention and Cardiovascular Morbidity and Mortality in the Look AHEAD Trial
https://onlinelibrary.wiley.com/doi/full/10.1002/oby.22942?af=R

this secondary analaysis of the look AHEAD trial sough to find the association between change in weight and waist circumference (WC) and CVD outcomes. They found that size matters and particularly waist size.
They found that “participants with increased WC had increased risk of cardiovascular outcomes, regardless of weight loss (hazard ratio: 1.55 [95% CI: 1.11‐2.17]) or weight gain (hazard ratio: 1.76 [95% CI: 1.07‐2.89]),”
In the analysis of 4590 individuals, 2840 had reductions in both weight and waist, 782 individuals had increases in weight and waist, but that only accounts for 79% of the sample. Which means 21% or one-fifth of participants had discordant responses in weight/waist. Lost weight but gained waist or gained weight but lost waist but the individuals who gained waist were in the big trouble regardless of the what scale said. So I guess its true, size matters, your waist size

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Rapid fire articles- no deep dive. Just good a lot of questioning, questioning medicine. If you want any of the articles for your own review or have any questions you can always reach me at andrewbuelt@gmail.com

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We stuck purely to the evidence. There was no evidence panel or committee to vote on the evidence like is often done by the American college of rheumatology and no expert opinion statements where their only citation is themselves like can be seen with the ACC. This was purely 100% evidence recommendations.

So lets start try to make it quick because guidelines on a podcast a boring, I want to hit the high points and get out of here

This guideline does not cover 1) adults
2) patients with ejection fraction
3) pts with life expectancy less than 5 years

4) Patients with genetic dyslipidemia conditions were also excluded

Now to the recomendations

. test a serum Cholesterol level every ten years!! Yes 10yrs. If you are testing more frequently than that you are likely seeing variability in the test and not a true change. Cholesterol levels are stable! If you see a change it is because you are seeing a change in the point estimate—remember it might say ldl 100 but there are CI around that 100 so you might check it again and it says 115 or 120 and those stastically are the exact same number AND there is intra-varibility. If you test on me Tuesday I might be 100 and test me on Wednesday I might be 130. I am the same person I am not at all of a sudden greater risk one day later it is just the intra-variability that exist within people

BUT just because you are checking a cholesterol once every 10yrs doesn’t mean you shouldn’t do a risk screen more frequent. recommended every 2 years when risk is 6-12% and every 5 years when risk is less than 6%. This risk assessment can use cholesterol levels obtained in the previous 10 years

And you might say well what can I use to help me predict the future, meaning we know some patients that are at 8% risk or really any percent risk will have a cardiovascular event. The ideal situation would be to predict the future and for those individiuals that are going to have an event we make sure that we treat them and we do not treat the individiuals who are never going to have an event. If you are never going to have an event but prematurely placed on therapy that is over diagnosis and that is very bad so we only want to treat the inidivudals that are going ot have an event, in the perfect world.

We we lookg for extra test and

Risk stratification is not improved by additional test including!! NONE! not coronary artery calcium, not high-sensitivity C-reactive protein, and not ankle-brachial index. There is no magic test to help you predict the future.

And speaking of forget about--- Omega-3 fatty acid supplementation forget about it. Other supplements like Fiber, ginger, green tea and red yeast rice forget about it!!! Or at least forget about it if your goal is cardiovascular risk reduction.. the evidence does not support this.

OOO fibrates and Niacin, please never again- not for primary prevention not for secondary prevention, evidence also does not support their use, just purge those drugs from your memory bank

And anytime I say the word purge it makes me thing binge and purge of diet and exercise so lets move onto that---

For a diet- Mediterranean diet decreases rates of cardiovascular events, stroke, type 2 diabetes, and all-cause mortality

For exercise- we recommend aerobic exercise of any shape and size. That’s right we don’t discriminate. We think all exercise is beautiful. Sure we would love for you do to 30 minutes a day but sometimes that is not feasible or reasonable so we say just do something. The largest benefit came in individuals that were sedentary then did something!! So 5 minutes is better than no minutes because ANYTHING is better than no minutes.

Woooo ok ok enough of the rant lets get to the treatment and get out of here

So that means for primary prevention we really ONLY have one drug. ONE drug and that is a moderate dose statin! Don’t do a high dose statin because for primary preention there is no benefit over a moderate dose statin. Moderate dose only.

That is easy to remember but for SECONDARY PREVENTION-

In secondary prevention, we recommend moderate-dose statins as the main treatment to be consistent with trial evidence, and remember if you write for a high dose statin even in secondary prevention you don’t improve fatal events ONLY NON FATAL EVENTS compared to moderate dose statin. And if you patient want to further reduce their CV risk. Then we suggest switching to high-dose statins or adding ezetimibe to moderate dose statin which seem to have pretty similar effects in reduction of nonfatal cardiovascular events. AND if they real high risk and still want to risk reduction we suggest PCSK9 inhibitors. However with pcsk9 inhibitors it is key to remember they were mainly studied in high risk populations, FOR EXMAPLE those with acute or recent MI. AND WE HAVE NO LONG TERM DATA. And they cost more than my house so your pt. needs good insurance. BUT if your pt fits all those criteria then you can go agead and disucss starting PCSK9 inhibitors.

So what do you do—uspstf or the AHA ACC or the VA LIPID

I am bias

Well article on Medscape

The Lipid Guideline I Follow in Primary Care written by Kenny lin a fp physician at georgetown

Until the USPSTF updates its 2016 recommendation statement, I advise mostly relying on the VA/DoD's guidance, particularly for primary prevention. By performing a more comprehensive systematic review of the key clinical questions and not making any recommendations that go beyond the supporting evidence, the VA/DoD ensured that its guideline is the most likely to improve patient outcomes and minimize harms.

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athlete heart covid
https://www.the-scientist.com/news-opinion/college-athletes-experienced-heart-damage-after-covid-19-study-67929
titiles like- “Images of the players’ hearts showed signs of inflammation consistent with myocarditis, a rare but potentially fatal condition.”
“two dozen of Ohio State University players using cardiac magnetic resonance (CMR), they found evidence of myocarditis in 15 percent, while a further 30 percent had cellular damage or swelling “

The Ny york times said-

https://www.nytimes.com/2020/09/16/well/move/is-coronavirus-affecting-the-hearts-of-college-athletes.html

Is Coronavirus Affecting the Hearts of College Athletes?

“In a new study of 26 college athletes who tested positive for coronavirus, four later showed signs of inflammation in their heart muscles.”

and my favorite-- CNN says
https://www.cnn.com/2020/09/14/health/covid-heart-inflammation-athletes-study/index.html
Covid-19 study suggests to screen recovering athletes for heart inflammation before they return to play

“As athletes recover from Covid-19, taking images of their hearts to screen for inflammation may help doctors determine when it could be safe to get back in the game, new research suggests.”

Now lets look at this paper and see if this paper says what you think it says or at least does it say what the Big Ten thinks it says!!

In the press release for the big ten return to football they say

“The Big Ten Council of Presidents and Chancellors (COP/C) adopted significant medical protocols including daily antigen testing, enhanced cardiac screening and an enhanced data-driven approach when making decisions about practice/competition. “
they go on to say
“All COVID-19 positive student-athletes will have to undergo comprehensive cardiac testing to include labs and biomarkers, ECG, Echocardiogram and a Cardiac MRI.”
The thing I find funny is they say things like ‘data-driven approach but then say things like ‘a positive athlete can not return for a minimum of 21 days’ and athletes must get a cardiac MRI along with a bunch of other non evidence based and non data driven recommendations. BUT this podcast is about the cardiac MRI in athletes so let's look at that paper and why it is dead fricken wrong!! This is a perfect example of why school presidents should play doctor and realistically speaking, I as a doctor don’t want to be a school president.

https://jamanetwork.com/journals/jamacardiology/fullarticle/2770645?guestAccessKey=ad3c4563-167f-452a-917f-7bfe15663b06&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=091120

The paper that has created this cardiac MRI craze is titled -
Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection
it was in jama cardiology on sept 11 and
they researchers at ohio state did CMR imaging in 26 competitive college athletes who previously had been diagnosed with COVID19.
and they found
“Four athletes (15%; all male individuals) had CMR findings consistent with myocarditis and Pericardial effusion was present in 2 athletes with CMR evidence of myocarditis.”

the authors conclusions,

this sounds terrible!!! I will give you a second to grab a drink and sit down because I think in the
next several minutes you will be both relieved and frustrated about what this article really says.

music

this was first released by anish koka on twitter but she was spot on and this sort of information
needs widespread dissemination.

As I said there were 26 athletes but out of those 12 had mild symptoms DURING the infection
and 14 were asymptomatic during the infection.
None of these pts had chest pain or required hospitalization not even a slightly elevated troponin from
demand ischemia during their infection was reported and
per the paper, “There were no diagnostic ST/T wave changes on electrocardiogram, and
ventricular volumes and function were within the normal range”
now the current return to play protocol is all expert opinion but in the article is cited as 2-week not activity and if asymptomatic then no diagnostic cardiac testing but if symptomatic then an electrocardiogram and transthoracic echocardiogram.

The authors want you to look at this and say hey we might need to add CMRI

lots look at their logic

“Cardiac magnetic resonance imaging has the potential to identify a high-risk cohort for adverse outcomes and may, importantly, risk stratify athletes for safe participation because CMR mapping techniques have a high negative predictive value to rule out myocarditis.4”
https://www.sciencedirect.com/science/article/pii/S0735109718388430?via%3Dihub
and they site
Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations
which the opening line says
“This Journal of American College Cardiology Scientific Expert Panel provides
consensus recommendations for an update of the cardiovascular magnetic
resonance (CMR) diagnostic criteria for myocardial inflammation in patients with
suspected acute or active myocardial inflammation”

This is the first fault--remember these were healthy athlets THAT DID NOT HAVE SUSPECTED ACUTE OR ACTIVE MYOCARDIAL INFLMMATION!! you cant say well this test does really good at detecting a specific illness in this population so it must do a could job at detecting it in every population. That it like say well antibiotics work well to make people feel better when they have bacterial infections so they must work to make patients with cancer feel better. NO NO NO

next they said,

“Cardiac magnetic resonance imaging evidence of myocardial inflammation has been associated with poor outcomes, including myocardial dysfunction and mortality.6 “

and this comes from a paper titled “Prognostic value of cardiac magnetic resonance tissue characterization in risk stratifying patients with suspected myocarditis.”

WITH SUSPECTED MYOCARDITIS!! this study was 670 patients who had CLINICALLY SUSPECTED myocarditis who then got a CMRI.
just to get in to that study you had to have one of the following
1) acute chest pain syndromes with symptom onset OR
2) signs of left ventricular (LV) dysfunction;
OR
3) subacute (onset ≥2 weeks) presentation of ventricular arrhythmias syncopal spells or abnormal ECG.

These athletes dont have chest pain, no increase trop., no signs of myocarditis, no change in EKG!!!!!

ONCE again you can’t use the results of a test in one population with a specific disease or condition and translate it to another population and expect it to do just as well!!

The pregnancy test seems to work well in women to let us know if they are pregnant or not. You can't take the accuracy of the pregnancy test in women and translate it to men!
In the studies that are cited for ‘badness’ patients have a bad clinical picture, it looks, talks, walks like myocarditis and CMRI is used to help validate these findings. In this current study used by the big ten the authors are taking athlete MRI findings INDEPENDENT of the symptoms and saying wait a second this looks like myocarditis even though it doesn't walk and talk like myocarditis. You can’t do this and you shouldn't do this….. imaging findings without a clinical picture is just an image.

let me give you my final thoughts before this ship sets sail into the ocean of evidence

still not sure what to think??

well on sept 15 the society of cardiac magnetic resonance release published an open letter and in
it the society said and I quote

“SCMR agrees that routine clinical use of cardiac MRI in asymptomatic patients with recent or prior
COVID19 infections is currently not justified based on recent preliminary scientific publications, and it
should not be recommended.”

with that I will leave you as I always leave you- with a reminder to question medicine so lets wait for the music

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the thing about RCT is they are random and everything is equal. its why in table one of an RCT you should never see a pvalue because they are random and should be equal but in observational studies you see pvalues because it is not equal, it can’t be, its not random. In observational studies you try to account for all the confounders but you just cant ever make it equal to an RCT but lets look a look at observational data using a real world example.

I will start with a question—is there an association between fluoroquinolone use and aortic aneurysm and aortic dissection (AA/AD).?

You might say well in dec 2018 the FDA issued a warning recommending avoiding fluoroquinolone use in patients with AA/AD or who are at risk for these conditions

But that was not the question I asked – I said “is there an association between c use and aortic aneurysm and aortic dissection (AA/AD).?”

The answer is ‘it depends’—clearly seen in recent issue of JAMA Internal Medicine

one paper – we willl call study number 1 titled

“Association of Infections and Use of Fluoroquinolones With the Risk of Aortic Aneurysm or Aortic Dissection”

found “Fluoroquinolones were not associated with an increased AA/AD risk when compared with combined amoxicillin-clavulanate or combined ampicillin-sulbactam (OR, 1.01; 95% CI, 0.82-1.24) or with extended-spectrum cephalosporins (OR, 0.88; 95% CI, 0.70-1.11) among patients with indicated infections”

And another study in the same journal we will call study number 2 titled

“Association of Fluoroquinolones With the Risk of Aortic Aneurysm or Aortic Dissection”

found a small, risk for AA/AD when comparing fluoroquinolones with azithromycin for pneumonia, but no association when comparing fluoroquinolones with TMP/sulfa for urinary tract infection.

AHHH SO WHAT DOES THIS ALL MEAN you ask!!!!!

Well in the second study when they did a secondary analysis and limited the analysis to patients who had imaging studies the risk of AA/AD disappeared. Suggesting there was surveillance bias. Surveillance bias refers to the idea that “the more you look, the more you find.” When you get more test you find more things. For example hospital number 1 uses 1000 covid test a day and hospital two uses 1 covid test a day. Both hospitals see the same number of patients. Can you say that hospital one has more cases of covid?? Of course not, they just have a surviellance bias..

Similarly
Also sicker patients who happen to get a flouroquinolone are also more likely to get a CT of their abd/pelvis which reveals aortic disease. An incidental findings that only comes about when you are sick and also happen to be placed on antibiotics.

But lets go back to study number 1- the one that found no increaes risk of aortic disease when comparing flouroquinelones to other antibiotics—likely it is because they included only patients with what they termed indicated infections. This would suggest that likely it is not the antibiotic causing the AA/AD it is the illness! It is the confounders that cant be accounted for in any oberservational data set, AA/AD are not more common with flouroquinolones but unfortuneately sicker patients are both more likely to be prescribed fluoroquinolones and severe illness just also happens to be a risk for AA/AD

So I ask you again, “is there an association between fluoroquinolone use and aortic aneurysm and aortic dissection (AA/AD).?”

The full answer is it depends on the secenaro, it depeds on the bias, it depends on the cofounders. It just depends

https://jamanetwork.com/journals/jamadermatology/fullarticle/2769109
Advisory Committee on Immunization Practices (ACIP) has issued an update on recommendations regarding HPV vaccination.
Approx.. 33700 HPV caused cancers annually in the US
One big problem with the data is only 8% of the studied participants are male—we basically are doing this in female and then translating the information to men which is not always the best, for example statins do not work in women to prevent heart attacks when you look at some group analysis, they help prevent strokes but not heart attacks, the numbers don’t always translate when you are crossing the gender barrier

Few important points to this new update
Catch-up vaccination is now recommended for all persons through age 26 years. Did get it as a kid, you can get it now, call me mustard cause when it comes to vaccines it is time to katchup

ACIP recommends routine vaccination at age 11 or 12 years (or as early as age 9 years) for all persons.—
regardless of prior or current HPV infection status.!!!
ACIP continues to recommend age-based dosing schedules, with 2 doses for persons beginning HPV vaccination at ages 9 through 14 years and 3 doses for persons beginning after age 14 years or persons who are immunocompromised.

https://www.acpjournals.org/doi/10.7326/M20-4298

what if I told you that intensive blood pressure control is not associated with incrase risk of orthostatic hypotension

Effects of Intensive Blood Pressure Treatment on Orthostatic Hypotension
A Systematic Review and Individual Participant–based Meta-analysis

Annals of internal medicine

Researchers examined five trials, with a total of 18466 participants and 127,000 follow up visits to examine the effects of intensive BP-lowering treatment on OH in hypertensive adults. As with all meta analysis the inclusion criteria of the studies did differ on what they call intensive therapy.
But in the end intensive bp treatment lowered yes it actually LOWERed the risk for OH (OR .93 with 95% CI 0.86-0.99)

I read this and I though no way does Intensive BP-lowering treatment decreases risk for OH. And the authors say ‘well long term or chronic hypertension can throw off many of your regulatory mechanisms, and so there for you throw off these mechanism with poor blood pressure and that is what causes the OH not the actual lower number, it is the uncontrolled bp’ and maybe they are right, that is for the ivory towers to decide
I could not wrap my mind around this but then I stumbled upon it—OH does NOT mean falls. OH does not mean syncopal episodes. In this study OH only means a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing.
This is again a surrogate marker- I don’t care if you number changes briefly if you feel fine
The paper even says that the Data on falls and syncope was not available. The patient oriented outcome I care about was not available!! This is a headline paper that likely doesn’t say what you think that it says.
THIS IS A LAB VALUE that grabs the headline and makes you think well intensive control actually leads to less falls or less syncopal episodes when in actually this paper just say intensive control just mean less changing of a bp number! WHICH makes sense— if you start at a lower number you have a lot less ability to change! Think about this for one second --One person in intensive control has a bp of 120 and they stand to a bp of 110 while the other person in the not intensive control arm has a bp of 130 and they stand up and the bp falls to 110--- both of those people standing have a bp of 110, the exact same bp!!!!! but one droped 20 points and is diagnosed with OH and the other is told they are normal.

This next article falls into the quickest summary I have every given on a paper and it is in The Lancet Rheumatology. Titled

How How long does a shoulder replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 10 years of follow-up

---which comes from the same authors that last year gave us

How long does a hip replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-up
https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30226-5/fulltext

And the famous

How long does a knee replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-up

Now use their same massive database to try and answer the question how long does a shoulder replacement last and the answer is at least 10 years for most everyone. It didn’t matter if you were having humeral hemiarthroplasties, osteoarthritis with reverse total shoulder replacement, or a rotator cuff arthropathy with reverse total shoulder replacement it appears at 10 yrs approximately 90% of shoulder replacements were doing well with sustained clinical benefit.

If your patients needs a new shoulder—tell them the good news is it will likely last at least 10 yrs

And that was a fast summary but lets do one more---

https://jamanetwork.com/journals/jama/fullarticle/2769724?guestAccessKey=75076244-d788-4a4f-ba64-2eee4284fd70&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=etoc&utm_term=082520

Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D LevelsThe VDKA Randomized Clinical Trial

192 children with persistent asthma and low vitamin D level ----if you gave them vit d did you improve the time to next severe asthma exacerbation
, In this randomized double-blind, clinical trial were put on either placebo or vitamin D3, 4000 IU/d
The most simple answer is…..no. there was no difference between placebo and vit d

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Finance ethics committee, big pharma with deep pockets, mafia like arrangements, and a patient with a 40% increase risk of ischemia myocardial events have in common?

I will say todays podcast was inspired by a tweet, yes a tweet from Dr. john Mandrola and he said
“I am embarrassed to have not (really) known the details of the rosiglitazone affair. Teaching this to learners has to be 10x more valuable than the krebs cycle. My gosh – talk about lessons to learn. We have to promote more skeptical priors’

He attached a link to a paper titled

The rise and fall of rosiglitazone

European Heart Journal, Volume 31, Issue 7, April 2010, Pages 773–776
https://academic.oup.com/eurheartj/article/31/7/773/433556
I also will say I did not know the details of the rosiglitazone affair but after spending the last 3 days digging through this paper and the sources to this paper and the sources to those papers and by the end you will know exactly what
Finance ethics committee, big pharma with deep pockets, mafia like arrangements, and a patient with a 40% increase risk of ischemia myocardial events all have in common.

This was a wonderful summary about rosiglitazone and the scandal of the mafia like drug company hiding and covering up the evidence in related to cardiac events….

For those of you that don’t know or are not medical roseglitizone is a diabetic drug, it part of the glipizide family and although rarely seen on medication this day in are it is a tragic and sickening story for a drug that was once the largest selling diabetes drug in the world.
In 2006 sales of the drug reached over $3 billion.
So when study came out in 2007 in the New England Journal of Medicine titled “effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes” which was a meta-analysis that sought to find if cardiovascular morbidity and mortality were decreased by rosiglitazone. Ultimately the results showed that those in the rosiglitazone group compared to those in the control group were 43% more likely to suffer a myocardial infarction ((((odds ratio for myocardial infarction was 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03), ))) and a trend towards increase rates of death from cardiovascular causes ((((1.64 (95% CI, 0.98 to 2.74; P=0.06)
THAT IS A SHOW STOPPER—the top drug on the market for diabetes bringing in over 3 billion dollars actually causes heart attacks and death
Of course GlaxoSmithKline, the maker of the drug came out and said, NO NO NO it is one trial and our drug is just as safe as any other diabetic drug.
Hindsight we can all look back and say, “OMG are you kidding me, how did the FDA not step in right away’ and THAT is where the story begins.

But in order to get to the beginning of the story to go back to 1998 when troglitazone was the only TZD glitazone on the market. Unfortunately, troglitazone was associated with rare but potentially fatal hepatotoxicity. This is obviously bad publicity in the FDA as well as all diabetics and physicians wanted better option.

Insteps rosiglitazone= dysuria over drug was approved by the FDA after 5 trials consisting of just under 3000 patient’s. - https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21071_Avandia_medr.pdf
2 of the studies were placebo controlled that only lasted 26 weeks
1 study was a double blind comparing RSG with glyburide to just glyburide lasted 52 weeks
1 study was a 26week study looking at the effects of either RSG or placebo added to metformin
And the last
A 26 week double blind study comparing metformin monotherapy vs RSG monotherapy vs RSG + metformin

There you have it- the 5 trials that got RSG FDA approval. Just under 3000 patients and a grand total of 3 yrs TOTAL of data.
One of the problems is a duration of these trials. A million one week trials is not equal to one trial that is a million weeks long. The hard outcomes need time to develop. It is like a good play action pass, it takes time to develop the play. Death and heart attacks take time to develop and short trials often miss these outcomes PLUS the trials were looking for……..A1C and FBS
There are many problems with the A1C and FBS but the main one is the lack of association with A1C and hard end points. High A1C is bad, that seems pretty clear but as long as it is some what controlled the macrovascular risk does not appear to change very much. TO ApprovE diabetes drugs based on glycemic effects is not smart. Who cares if a drug lowers your blood suger but makes you 50% more likely to have a heart attack. Yet, we are obsessed with the number and the patient outcome. ((((((((((((The current SGLT2 inhibitors that are showing cardiovascular benefits change the A1C very little. A1C seems to be a surrogate marker we put way to much strength in when there is likely something else going on since it is clear A1C does not tell the whole picture but lets get back to RSG)))))))

Of these 5 trials you will find that when you dig a little deeper into the numbers In 3-5 trials LDL cholesterol was increased by an average of almost 20%
PLUS- There is also significant amount of weight gain with rosiglitazone in the 6 months trials those randomized to rosiglitazone gained almost 10 pounds more than those in the control group. Saying that differently, 20% of the patients randomized to rosiglitazone had gained 5-10% of the body weight at 6 months compared to only 2% of the patient’s placebo group and 1% of patients in the metformin group.
BUT MAYBE the biggest problem was ----
And when you combine all 5 trials the rates of ischemic cardiovascular events were almost twice as likely in individuals receiving rosiglitazone compared to those randomized to the control arm.

BUT good news, remember how I said, troglitazone was associated with fulminent hepatitis? Well it looks like RSG did not share this trait, there were no cases report! This is great news and remember FDA, patients and doctors want another option, they want a better option.
And when you scroll down to page 40-41 of the medical officers review of a new drug for RSG you will read
“Heart disease due to atherosclerosis is a major cause of morbidity and mortality in patients with type 2 diabetes, and it cannot be assumed that treatment with rosiglitazone will decrease the risk” the go on to say “my concern about deleterious long-term effects on the heart should be addressed by requiring a sponsor to provide adequate information in the label about changes in weight and lipids. A post marketing study to address these issues needs to be a condition of approval.”
TWO big things happened right around this time—
May 1999, FDA approval rosiglitazone
Dr John Buse a diabetic special at UNC was speaking at an American Diabetes Association symposium where he called into question the cardiovascular safety of rosiglitazone

Both of these things in and of themselves are not bad things. Sure the FDA hindsight should have required more data but their backs were against the wall so although I do point blame I don’t point a ton of blame. Dr. John Buse he is allowed to question medicine he is allowed to say hey I don’t think this is correct.
But for every action there is an equal and oppisite reaction for the action of FDA approval of RGS the reaction was a ton of prescribing of RSG-
Drug reps were in the office showing you how great this new drug is that does not cause liver failure and how it lowers your A1C blood test which we have all artificially made as the gold standard compared to any hard outcome. The drug reps would talk about how RSG lowered the CRAP marker….. wait did I just say crap marker?? Oooo sorry, I mean to say it lowered the CRP blood marker, but given the value of CRP I was probably right the first time. Sadly, we as physicians ate from their hands and prescribed a bunch of it. TONS of it. Over 3billion dollars of it.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2099503/
https://www.finance.senate.gov/imo/media/doc/prb111507a.pdf
But remember I said for every reaction is equal and opposite well when Dr. John Buse spoke out against rosiglitazone is certainly triggered a reaction from glaxosmithkline… what kind of reaction you ask?
Well they went after Dr. Buse with a team of lawyers and per paperwork given to the United states senate committee on finance it was clear that Dr. Buse was bullied into signing in agreement stating that he was no longer worried about cardiovascular risks associated with RGS. And he was barred from probably expressing concerns about safety of the drug in the future. The company was threatening to sue him for damages from his comments which glaxosmithkline was claiming cost them over 4billion dollars because of a stock price drop.

Yes- this is 1999 and glaxosmithkline is acting like the mafia. They don’t care about the patients. They care about their 4billion in loss revenue.
What is even more discussing is glaxosmithkline used this forced retraction letter to gain a foothold with financial investors.
Some of the testimony and documents that were revealed in the senate finance committee will make you never want to prescribe another glaxosmithkline drug every again. Truly sickening.
https://www.finance.senate.gov/imo/media/doc/prb111507a.pdf

so we have this drug company, glaxosmithkline that knows they have a “bad drug’ or at least a drug that requires further investigation and evaluation but is doing everything they can to cover up or hide what leadership knows to be true.

Likely for the world and patient’s everywhere in 2004 glaxosmithkline was sued over their drug paroxtine by the state of NY claiming they had not released or published the results of their unfavorable or negative trials on paroxtine.

And I will get back to RGZ but stop me if you have heard this one before
GSK runs 2 trial of paroxtine in adolescence, Study 329 conducted from 1993-1996 and at the itme was the largest trial to date for the use of SSRI in the pediatric population. In this study paroxetine didn’t beat placebo. The other study, Study 377, placebo was actually more effective than the antidepressant.
However, instead of releasing these results there was an email that was later accidently leaked from within the corporation stated that because the results were “insufficiently robust“ the company needs to “effectively manage the dissemination of these data in order to minimize any potential negative commercial impact”
The data was hidden or covered up and in 2003 paroxetine was a 4.9 billion dollar drug
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC343848/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC437671/
Luckily for us, when GSK settled this case, they wrote a check for 3 billion dollars, or roughly 9months of income from just the sales of paroxtine in 2003 and they agree to make a clinical registery that has all their data after dec 27 200.

Are you asking how is this a good thing when a company that is bringing in deca-billions is hit with a measly 3 billion dollar fine?? Well then you don’t know how it ends,

Now that the data was out there in a clinical registry you can do a study of
And it turns out that is exactly what happened, a meta-analysis of 42 studies, 35 of which were unpublished. The authors poor over the data and submitted their paper for pubication to the all wonderful and incredibly high impact journal most of you have heard of called the NEJM. \
Now when you submit an article to a journal it has to undergo peer review process. Basically this is when other experts in the field or individuals with knowledge of the subject at hand review the paper to make sure all the T are crossed and I are dotted.
When you peer Review of paper it is supposed to be secretive. He’ll share the document with anyone. Not even your best friend. Unfortunately one of the individuals that reviewed the paper, Dr. Steven Haffner at University of Texas in San Antonio, sent the analysis to GKS. Remember you don’t share this with your best friend let alone the DRUG COMPANY! This is a breach of ethics and every journal has rules on this and it certainly violates those.
Why would someone do this??? Oooo maybe because Dr. Steven Haffner was getting paid by GKS, almost a $100,000 in total payment up to that point.
This is the mafia, the mafia we see in movies, they cover up information and have every cop or ‘good guy’ in the city on their payroll.
This NEJM of medicine article is the same one I mentioned at the beginning of this podcast, the article
titled “effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes” which was a meta-analysis that sought to find if cardiovascular morbidity and mortality were decreased by rosiglitazone. And Ultimately the results showed that those in the rosiglitazone group compared to those in the control group were 43% more likely to suffer a myocardial infarction ((((odds ratio for myocardial infarction was 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03), ))) with a trend towards increase rates of death from cardiovascular causes ((((1.64 (95% CI, 0.98 to 2.74; P=0.06)
THIS PAPER that was a show stopper for GSK they had in their hands 2 weeks prior to publication and they did their own statistical analysis and concluded that the numbers were spot on. They were not surprised by the findings.

You may be asking why within not surprised by the findings? Well it’s because in 2006 GSK had already done their own analysis which found a 30-43% increase in ischemic events and this data was shared with the FDA who then did their own analysis and found a similar 40% increase in ischemic events..

However near the FDA nor GSK ever announced this information or released it to the medical community.. why would this happen you ask?? My guess is money but I couldn’t prove this to be true.
“Music”
How does this story end????
Eventually, 5 months after the meta-analysis published in the New England Journal of Medicine and almost an entire year after the FDA made there own similar conclusions about rosiglitazone they finally added a black box warning for increased risk of ischemic myocardial events.
And remember when the drug was bring approved by the FDA and they said in the final analysis “. A post marketing study to address these issues needs to be a condition of approval.”
Well it comes at no surprise the GSK knew this would be bad news for them so No well-designed cardiovascular outcome trials were conducted. The RECORD trial was the only cardiovascular outcome trial which look to compare cardiovascular outcomes and it was a seriously underpowered open label study with low adherence to medications, and not completed until 10 years following launch.
HOWEVER the FDA mandated the study in 2007 after the release of internal documents and the adversory committee and the metaanalysis showing a 40% increase in ischemic cardiac events. It is no surprise this was big news and the trial struggled with slow enrolled because anyone who watched tv or read the news paper knew this was a bad drug and no provider wants to enroll a pt. on a drug that is knowingly harmful!
https://www.nejm.org/doi/full/10.1056/NEJMoa066224

Ultimately the trial was halted in 2010 and I think for good reason, When you are a patient going into a trial hopefully you get a miracle cure drug and at worse you get placebo. In this trial you at best would get a placebo and at worst a harmful drug.
Dr. Buse, the physician who made the initial statement and warning in 1999 and was shut up by the drug company?? Well,
At a 2007 FDA safety panel meeting on RGS, FDA scientists presented data showing RGS was estimated to have caused approximately 83,000 excess heart attacks since coming on the market. If a scientist was able to speak freely and question medicine it is almost certain SOME of those heart attacks would have been prevented.
https://www.finance.senate.gov/imo/media/doc/prb111507a.pdf

Luckily, not all bad came from this story – it led a bunch of people to question medicine which I will forever be a fan of, I agree with Dr. John Mandrola we need to promote more skeptical learners.
Also because of this in December 2008, the FDA issued a new guidance for development of drugs to treat diabetes, requiring cardiovascular outcomes trials. This is the reason we now have the SGLT2 inhibitors that seem to be working to prevent cardiovascular events. They didn’t know the outcome was going to be a decrease in events they were just hoping there was not an increase in cardiovascular events.

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In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions,

this was a freak out statement if I have ever heard of one
I mean Covid is doing something directly to the heart? and this thing it is doing to the heart is independent of preexisting conditions??

this study was viewed over 500K times and on 196 news outlets with 12,000 tweets

this is in and of itself one of the main reasons that the BIG TEN shut down football.

of course we will never know for sure but it has been cited in many of the articles as one of the biggest concerns for player safety and potential damage to the heart!!

Nevermind the fact that this mean age in the study was almost 50 and the mean age of a college football player is around 20. That is just a small detail and we need to shut down sports for the safety of the athletes because we the big ten have a HEART and dont want to ruin theirs.

BUT turns out that was not the only problem and twitter erupted with more errors- and you might say, wait twitter!? yep

the authors even say--

We were made aware of the errors in our original report as they were discussed on Twitter through a journalist, who was covering the publication of the article. We immediately studied the Twitter discussion, which made note of 2 problems: the use of inaccurate metrics for the data analysis as well as inconsistencies between the reported data in the legend of Figure 1 and the data points provided for the patients with COVID-19 in Figure 2. As a result, we have reviewed the data and repeated the analysis.

https://jamanetwork.com/journals/jamacardiology/fullarticle/2770026?fbclid=IwAR1ke0Afd5vLUhGMeGDggExbzvy8xy8j81OEMXnqg9aK5PNaq5RujkUnLqI

part of the problem was the authors misuse of mean and median and standard deviation and (interquartile ranges)

median is the middle number and mean is the average. the SD and the IQR

The standard deviation takes into account all the values of a dataset, including any outliers. It is dependent on the mean, because the value is used to tell how much the data deviates from the mean of a dataset.

the interquartile range (IQR), also called the midspread, middle 50%, --The Interquartile Range tells us how spread the data is. The larger this value is, the more spread out the data is, and the smaller the value, the less spread the data is.

in the original paper

The EF of the Covid 19 patients is shown as 56 (54-58) -- what weird is when the calculations were done on this 54-58 was not
Not IQRs
Not ± SD
Not ± SE (standard error)
Not ± 1.96 SD
Not ± 1.96 SE
Not ± 2 SD
Not ± 2 SE
but lets pretend it was an IQR-
This means that half of the EF values lie between 54 and 58. So with a 100 people in the Covid arm that means that 50 people or 50% had an EF between 54-58. Obviously this is so insane its impossible or certainly so close to impossible it should make you says hold the phone

another problem was blood pressures originally reported at median 129 with a range of (125-133)-- again was is the 125-133?? no way 50% of the people had a bp pressure in this rand so almost certainly not IQR and almost no way the standard deviation was only 8 blood pressure points. it was this mystery number range that still doesn't have a clear answer to it and has not been answered by the authors --

What about in age- the original paper had an age of 49 with IQR 45-53. that is 8 yr difference to account for 50% of the population. That is insane unless you are trying to account for a certain age.

in the Original Investigation, “Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19),”1 published in JAMA Cardiology on July 27, 2020.

We have recalculated all data according to data type. Now, we correctly report means (SDs) or medians (interquartile ranges).

During the correction and recalculation process, we were able to provide some missing data from the original CMR scans as well as correct some data entry errors.

-- but the authors dont say how they were able to provide this missing data and why was it missing in the first place- and where did the calculated numbers originally come from. but they go one to say. I have read an interview with the authors and they basically say -- ya it was a mistake-- I commend them on saying it was a mistake but sad that it hapened and got past the editors and checks and balances that are suppose to have checks and balances-- they go on to say

We are pleased to confirm that reanalysis of the data has not led to a change in the main conclusions of the study.
which as a reminder was--
"CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions,"

NOW this is a problem because this statement would have you believe that if you got Covid you had a 78% chance of having cardiac involvement and if you dont get Covid then your odds of myocardial inflammation is 0%.

almost that Covid acts as a light switch and 78% of the time you are at risk of cardiac problems and there are no other factors in the world the could possibly give you these findings.

Its almost like they are ignoring that fact that those individuals with baseline CAD, htn, hlp, obesity, noncompliance, DM could ever have an abnormal finding. Like those individuals are of perfect health without any cardiac abnormalities EVER.

this is absurd and
what we really really want to know is in the individuals who have Covid how many MORE TIMES are their hearts affected compared to a risk factor matched control group.

well if you look at the CRP and the high sensitivity trop which are two blood test you would expect to be elevated with acute myocarditis you will see that whether you had Covid or not once you matched up the risk factors the CRP and Hstrp were basically the same and wnl.

wnl is the important factor-- so sure maybe you can have an MRI that shows 'signs concerning for myocarditis, correlate clinically' but when you correlate clinically with someone who has normal Hstrp and normal CRP then the diagnosis is not myocarditis.

and what about what you look at the data for T1 abnormalities
73 individuals out of 100 with Covid
compared to the risk adjusted match that had 33 of 57 which happens to be 58%

well when you look at the numbers for the new data!

73% of 100 Coviders had the abnormal T1 imaging

58% of 57 non-Coviders (with similar risk factors) had abnormal t1 imaging.

Drum roll please ....

Difference 15 %
95% CI-0.1902% to 30.0537%
Chi-squared3.703
DF 1Significance level
P = 0.0543

Covid survivors DO have abnormalities in their T1.
But it is JUST AS COMMON or not statically different in people with similar risk factors who have NOT had Covid.

it is the risk factors that make it so people are at risk of having badness with their heart so if you look at this study you shouldn't say hey look at this we should stop sports you should say hey look at this we all need to take a multivitamin and by take a multivitamin I of course mean you leave a vitamin at the store and you walk 5 miles to the store every day to take the medication but that is the only way a multivitamin will work and the best way to prevent a problem in imaging....

exercise more, sit less
it really is the best
to decrease cardiac magnetic resonance
and I can say that without any hesitance

finally in the interview I read with the authors the authors basically say

Q. Would you stop such patients doing sport?

A. After a bad infection, I would encourage them to only gradually ease themselves back into heavy activity.

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https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2768888
Serial Bone Density Measurement and Incident Fracture Risk Discrimination in Postmenopausal Women
Carolyn J. Crandall, MD, MS1; Joseph Larson, MS2; Nicole C. Wright, PhD3; et al

OBJECTIVE
To assess whether a second BMD measurement approximately 3 years after the initial assessment is associated with improved ability to estimate fracture risk beyond the baseline BMD measurement alone.
In this prospective observational study 7419 women from The Women’s Health Initiative with a mean (SD) follow-up of 12.1 (3.4) years

Incident major osteoporotic fracture (ie, hip, clinical spine, forearm, or shoulder fracture), hip fracture, baseline BMD, and absolute change in BMD were assessed
a second bone mineral density (BMD) assessment approximately 3 years after the initial measurement was not associated with improved risk discrimination, beyond the initial BMD assessment, between women who did and did not experience hip fracture or major osteoporotic fracture.
.
I hate this because it add nothing!!
The uspstf came out in 2018 and said in their guidelines titled
Screening for Osteoporosis to Prevent FracturesUS Preventive Services Task Force Recommendation Statement

THEY SAID AND I QOUTE!!
However, limited evidence from 2 good-quality studies found no benefit in predicting fractures from repeating bone measurement testing 4 to 8 years after initial screening.

Do the trial we all want to see with follow up for 10 or 12 or 15 yrs or don’t do the trial you are just wasting time and money on what we already know!

Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates

Nejm

196,129 women 50 years of age or older who were receiving bisphosphonates and who were enrolled in the Kaiser Permanente Southern California health care system; women were followed from January 1, 2007, to November 30, 2017

primary outcome was atypical femur fracture- usually defined as fractures in the subtrochanteric region and along the femoral diaphysis

277 atypical femur fractures occurred

hazard ratio went from 8.86 at 3-5 yrs (95% confidence interval [CI], 2.79 to 28.20) up to 43.51 (95% CI, 13.70 to 138.15) for 8 years or more. (likely why guidelines say stop at 5 yrs or at least take a drug holiday)

when you look at the data it appears to be exponential that longer you on a biphosphonate the more likely you are to have an atypical fracture.

But the thing I like most about this study is a huge data set that tells us on average since there was 196,129 women, and 277 atypical femur fractures occurred then baseline normal is (1.74 fractures per 10,000 patient-years)

They also used a computer model to try and figure out how many fractures were prevented and depending on your race at 5 years there were anywhere from 500-800 fracture prevented

We don’t have information like what was the baseline dexa, how were these people started on bisphosphonate but we can say they do prevent fractures and if you are concerned about atypical fractures the data would say it happens about 1 in every 5000 women.

https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21628
“All participants (GDG members, ACS staff, expert advisors) were required to disclose financial and nonfinancial (personal, intellectual, practice‐related) relationships and activities related to cervical cancer and screening that might be perceived as posing a conflict of interest.”
The American Cancer Society (ACS) now says average-risk individuals should begin cervical cancer screening at age 25 — rather than at age 21, as recommended in 2012. The group's guideline update appears in CA: A Cancer Journal for Clinicians.
The other major change from 2012: The preferred screening approach is primary human papillomavirus (HPV) testing (i.e., stand-alone testing for high-risk HPV types) every 5 years through age 65. If FDA-approved primary HPV testing is not available, then HPV-cytology cotesting every 5 years or cytology alone every 3 years is acceptable.
Of note, there are currently two approved primary HPV tests, and access to them may be limited. The ACS says that cotesting or cytology alone "should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers."
The guidance applies to all average-risk, asymptomatic people with a cervix, including transgender men who still have a cervix. Such individuals should be screened regardless of their HPV vaccination status or sexual history.

Randomized, double-blind, placebo-controlled trial of intraarticular trans-capsaicin for pain associated with osteoarthritis of the knee. Stevens RM, Ervin J, Nezzer J, et al. Arthritis Rheumatol. 2019;71(9):1524-1533. doi: 10.1002/art.40894.

double-blind, randomized, placebo-controlled trial of adult patients (45 to 80 years of age) with X-rays showing chronic OA, pain for at least two months, and mean pain score of 5 to 9 on a 0 to 10 scale.
randomized to one of three groups
group 1- 0.5 mg of capsaicin intraarticular
group 2- 1 mg of capsaicin intraarticular (CNTX-4975)
group 3- placebo control group.
primary endpoint was area under the curve (AUC) for the change from baseline through week 12 in daily WOMAC (Western Ontario and McMaster Universities Arthritis Scale) pain with walking scores. -- FIRST RED FLAG- you can normally report your results as outcome at the end of the study (EOS) -- the pain was this, gave this drug and this was the pain at the END OF THE STUDY or you can report it as area under the curve. NOW area under the curve (AUC) is a summary measure that integrates serial assessments of a patient's endpoint over the duration of the study- so pain was this and gave medication then at 6 weeks pain was this then 12 weeks pain was this and 24 weeks pain was this- some will argue that this format means AUC better reflects the clinical course of the disease. they will say well looking at it in a single point in time doesnt tell me anything about the rest of the time and they are correct but when you look at multiple time periods it becomes very risky that you will maybe skew the data and say well we are going to look at results at week 12 but then once you get the results you say - ‘’ well look at these shiny results with improved awesome amazing results at week 24, who cares about week 12 we are not going to report on week 24”
enough of that rant- back to the study- music
as I mention the primary outcome was AUC at 12 weeks and not your typical pain scales, the authors results were
“In this study, capsaicin provided dose-dependent improvement in knee OA-associated pain. capsaicin 1.0 mg produced a significant decrease in OA knee pain through 24 weeks; capsaicin 0.5 mg significantly improved pain at 12 weeks, but the effect was not evident at 24 weeks.”

this is exactly what I am talking about! Your primary outcome was 12 weeks but you read the results and they brag about the results at 24weeks.
it smells like- drug money and you are correct! Centrexion Therapeutics was the sponsor of the study, controlled the study and my guess is they manipulated the numbers because when you go to clinical trials.gov they dont say they are going to use area under the curve they just say the difference in pain score. They dont say they are going to use least square mean they just do it. this trial is a scam I suspect - after all they were only looking for a 0.45 effect size-- you have a ten point scale and you power the study to find a 0.45 difference-- the cool thing and annoying thing about powering your study is you have to power it for a change that you think is clinically important, there is no rules on how big your study has to be it just has to be big enough to rule in or rule out the effect you are looking for. THEY THOUGHT A 0.45 difference was a good outcome! and this is clear because when you look at the benefit there is a p value of 0.00001 which makes you think WOW this is so great till you realize the individuals that got placebo had a 2 point improvement in their pain scales and those that got the capsaicin injection had roughly a 2.7 improvement in their pain scale.
for me this is a no go and I can promise you drug reps will be in your office pushing this, you will hear about it at conferences or maybe even your colleagues will say this is the hot new thing, and I will say it is hot, so hot I actually dropped this article in the trash right next to the 0.5mg and 1mg capasaicn injection.

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Sometime I wonder how the world will change post covid- or how the board questions will change?

And that is clearly seen in this article titled-

Yip L et al. Serious adverse health events, including death, associated with ingesting alcohol-based hand sanitizers containing methanol — Arizona and New Mexico, May–June 2020. MMWR Morb Mortal Wkly Rep 2020 Aug 14; 69:1070.

hand sanitizing gels and foams containing ≥60% alcohol (either ethanol or isopropyl alcohol) has been proven to be effective -- Methanol is not an acceptable substitute
in this paper they looked at 15 cases of methanol poisoning due to ingestion of methanol-containing hand sanitizers From May through June 2020

All patients had a history of ingesting alcohol-based hand sanitizer
presentation included visual disturbance, seizures, gastrointestinal involvement, altered mental status, and anion-gap acidosis with blood pH varying from 6.70 to 7.23.
in the end Four patients died and three others were discharged with new visual impairment.

I can see it now- beth comes into the office and has visual changes and slightly altered mentation – she is known to be a prepper and vary scared of covid and he husband said she recently read that if you swallow hand sanitizer it will kill covid19 just like it does when it is on your hands—what is the most likely diagnosis for this pt. and the answer will be methanol poisoning!

Next artciel

Are antibiotics as good as surgery for pediatric appendicitis? The answer depends on who is asking the question
In this trial
Association of Nonoperative Management Using Antibiotic Therapy vs Laparoscopic Appendectomy With Treatment Success and Disability Days in Children With Uncomplicated Appendicitis
nonrandomized study of nonoperative treatment of 1068 pediatric patients with uncomplicated appendicitis.
Roughly 65% chose to undergo urgent laparoscopic appendectomy, while 35% chose nonoperative management with IV antibiotics in the hospital followed by oral antibiotics at home
The primary outcome was defined as not requiring appendectomy within 1 year of study enrollment. And in the end Two thirds of youth who received antibiotics to treat uncomplicated appendicitis avoided surgery, and
Nonoperative management was associated with a 67% success rate for avoiding surgery in the subsequent year
But the important thing here is how you power your study- you power it to find the minimal clinically important difference (MCID)—the MCID is a a mystery- you wont a number that is reasonable difference in practice for the reader but attainable for the study so we don’t have a million neg. trials and what this difference is completely determined by the authors. Sure they can look at other studies and see what they used but ultimately this is up to the authors—if in this trial they say I think the clinical meaningful difference is to avoid 25% of surgeries then they set that as the standard and BOOM in this trial about 65% of surgeries were avoided in those in the antibiotic arm. This trial would have been a smashing hit! But instead the authors chose a much hard outcome of 70% based on surgeons they work with! And when you asked parents they said ‘well I think 50% would have been good enough’--- HOWEVER since 70% of pts had to avoid going to surgery- this means it was a negative trial.
I think this is a great article that points to the shared decision making conversation because no article or paper is 100% if you do this then this will happen, bit if you say well if you do this then about 2/3 of the time you will prevent having to go to surgery that is a much different conversation than well if you do this then you wont have to go to surgery because the truth is they still do around 33% of the time which is good enough odds for me and my child or at least any child I would be babysitting since I don’t have children.
So I ask again is it ok to spare 2 out of every 3 children a surgery and invasive procedure, I guess it just depends who you are asking

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2769373?guestAccessKey=7518012e-17e8-48cd-8278-c3b68652db52&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=olf&utm_term=081720

Is an article that will leave you breathless- in jama internal medicine

Effect of Sustained-Release Morphine for Refractory Breathlessness in Chronic Obstructive Pulmonary Disease on Health StatusA Randomized Clinical Trial

They asked the question- Does regular, low-dose, oral sustained-release morphine improve disease-specific health status or cause respiratory adverse effects in patients with moderate to very severe chronic breathlessness due to advanced chronic obstructive pulmonary disease?

and the results were = ---
In this randomized clinical trial of 111 patients with chronic obstructive pulmonary disease, morphine 10 mg twice daily for 4 weeks significantly improved CAT SCORES or the Chronic Obstructive Pulmonary Disease Assessment Test scores
. compared to placebo

This is good we think!! Except when you read the study you see in the sample size they say-

To detect a mean (SD) change in CAT of 3.8 (6.1) “62 participants per group needed to be included.

remember thiswas only 111 pts so no matter how you cut it they didnt achieve adequete power of their study.

The CAT questionnaire consists of eight questions, assessing the symptoms on a scale from 0 to 5. The total score ranges from 0 to 40, with higher scores representing worse health status.

And remember they wanted a difference of 3.8 but in the end there was only a 2.18 difference ---And the authors say but our finding of a 2.18 difference is important because there is previous data saying that the minimal clinical important difference (MCID) for the CAT is 2·0 to 3·0 points. YOU CANT DO THAT!! Its like saying I am going to do a triple back flip then after doing a double back flip saying well that is still really good and worth a blue ribbon!! NO NO NO not everyone gets a blue ribbon- sometimes negative trials are important or just as important as the positive trial!!

the authors are saying we understand we powered and ran our study to find a 3.8 difference in the cat scale and we understand that we barely found half of that but because of cherry picking study we found from 3 yrs ago we still think our trial is ‘positive’ and we will think that there should be “a larger and longer trial is warrented”

and I would say – it is not warrented---and incase you were wondering—yes this is absolutely another study where the authors were tainted by drug company conflicts of interest but am sure you already assumed that

Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood ScoresA Randomized Clinical Trial Long-term vitamin D
https://jamanetwork.com/journals/jama/article-abstract/2768978
Roughly 18,000 adults (aged 50 and up for men, 55 and up for women) free of depression at baseline, including 1700 at risk for recurrence of depression but without treatment over the preceding 2 years, were randomized to receive either vitamin D3 (2000 IU per day of cholecalciferol) or placebo. After a median treatment duration of 5 years, rates of depression were similar between groups at about 13 per 1000 person-years. Mood scores were also similar.
The authors write: "The findings do not support a role for supplemental vitamin D3 in depression prevention among adults." Read Dr. Peter Roy-Byrne's take on this study in NEJM Journal Watch Psychiatry in the coming days.
Any benefit is seen in observational data!!! Confounders!!
We all want it to be but the evidence just doesn’t support vitamin d or at least not when we look at the evidence for the RCT

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henry ford once said “failure is simply the opportunity to begin again, this time more intelligently”
Designed to Fail? the Future of Primary Care
Journal of General Internal Medicine (2020)
Access to primary care has been shown to improve patient outcomes and lower cost although outcomes are debated the cost is not-
its because we can be the jack of all or the referral of all.
neither is wrong
the authors in this paper analyzed the 2019 “in-basket” activity of our clinical faculty at the University of Michigan to determine the average weekly activity by category of EMR tasks.
A full-time primary care faculty member had a total of 390 in-basket tasks per week or 17,542 in-basket tasks per year.
they surveyed 56 clinicians, and asked how much time, to the nearest minute, they spent on in-basket tasks: and a median time of 1199 min (~ 20 h) per week on these tasks
many task require further steps- like addressing lab work, or ordering follow up imaging, or doing a prior authorization ALL of which are unpaid. essentially PCP see patients full time then have another part time job they do for free in answering inbox messages and we wonder why pcp is a dying speciality that no one wants to go into. a change is needed

onto the next article

I have said many times that I love an article that answers a simple question

The Journal of Sexual Medicine
Are We Overstating the Risk of Priapism With Oral Phosphodiesterase Type 5 Inhibitors?
J Sex Med 2020 Jul 01;[EPub Ahead of Print], ME Rezaee, MS Gross

Viagra and cialis have the famous saying on their commericial to consult a dr. if you have an erection lasting longer than 4 hours. Well in this study they looked to answer the question how often does this actually occur!

They evaluated all cases of priapism reported to the FDA since 1998 which happens to be when viagra hit the market and they were able to identify a total of 411 cases due to Phosphodiesterase Type 5 Inhibitors

Now it is hard to get exact or precise numbers on number of viagra and cialis prescriptions out there but In the first year and a half of marketing in the United States, more than 15.6 million prescriptions of Viagra had been filled.

So even if there was not another single script of Viagra written for and we just went based on the first year and a half and we assumed each prescription was for only 3 pills then the rate of priapism would be 411/46.8million which in % terms comes out to 0.0008%-- basically nothing!! And that is just the first year scripts, obviously the numbers are much larger and we are over exaggerating the evidence.

Although PDE5i-induced priapism does occur, it appears less common than once suspected. When counseling patients, this should be considered.

Dean martin once said “Everybody loves somebody sometime” well it appread in medicine Everyone wants to treat subclinical hypothyroidism sometime –

Clearly seen in this paper -- https://jamanetwork.com/journals/jama/fullarticle/2768464?guestAccessKey=cafa97b4-33a8-49f3-9c5c-df1ebf349f84&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=etoc&utm_term=072120

Effect of Levothyroxine on Left Ventricular Ejection Fraction in Patients With Subclinical Hypothyroidism and Acute Myocardial InfarctionA Randomized Clinical Trial

Where they sought to find if levothyroxine treatment improved left ventricular function in patients with subclinical hypothyroidism presenting with acute myocardial infarction?

A double-blind, randomized clinical trial took 95 participants with subclinical hypothyroidism and acute myocardial infarction, treatment with levothyroxine, compared with placebo
Levothyroxine treatment (n = 46) started at 25 µg titrated to aim for a TSH levels between 0.4 and 2.5 mU/L

And after 52 weeks-the authors nailed it when they say- “treatment with levothyroxine, compared with placebo, did not significantly improve left ventricular ejection fraction after 52 weeks."

Don't trust the person who has broken faith once.” – William Shakespeare. But I think what he meant to say was don’t trust a medical journal abstract--- clearly seen in

https://www.acpjournals.org/doi/10.7326/M20-0289
Sodium–Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis
A Multicenter Cohort Study

In the abstract they say
Conclusion:
SGLT-2 inhibitors were associated with an almost 3-fold increased risk for DKA, with molecule-specific analyses suggesting a class effect

They looked at Electronic health care databases from 7 Canadian provinces and the United Kingdom and found a total of over 400,000 pateints on either a ddp4 or sglt2- mean follow up was almost one year. And during this time out of all those people there were only 521 cases of DKA.
And if you just go by the numbers then risk for DKA was 2 per thousand for the SGLT2 inhibitors and was 0.75 per 1000 person-years for the DDP4 inhibitors.

A three fold increase is scary! But the fact that no DDP4 has ever shown to be beneficial ofr the outcomes I care about like MACE and chronic kidney disease I think I and all my patients will take their chances.

Mr jones I can give you a medication that will put you in the hospital once every 500 yrs but out of every 20-50 people that take it we will prevent a heartattack or a death or a renal failure or a stroke

Or I can give you a drug that will only put you in the hospital for dka once every 1000 years but have never been shown to do anything. What would you like to do??
This is a strawman argue and a terrible comparible arm and a gentle and continued reminder to always question medicine and don’t trust the abstract

Reference
US Preventive Services Task Force. Screening for hepatitis C virus infection in adolescents and adults. US Preventive Services Task Force recommendation statement. JAMA 2020;323(10):970-975.
These recommendations replace the previous 2013 USPSTF recommendation of screening adults born between 1945 and 1965

In this updated 2020 review, the U.S. Preventive Services Task Force (USPSTF) found adequate evidence that hepatitis C virus (HCV) screening accurately detects HCV infection. Although there is no direct evidence on the benefit of screening for HCV infection on patient-oriented outcomes, there is convincing evidence that treatment results in a high proportion (95.5% - 98.9%) of adults who maintain a sustained virologic response (SVR), with a strong association between SVR and improved health outcomes. The task force also recommends screening for HCV in all pregnant women.

now is time when we have annual exam worth something hep c screening and hiv screening for everyone

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https://twitter.com/NarducciDusty/status/1290044202852614145?s=20

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Characteristics and Strength of Evidence
of COVID-19 Studies Registered
on ClinicalTrials.gov

Looked at ClinicalTrials.gov

identified 1551 studies registered fromMarch 1, 2011, to May 19, 2020,
Lets look at the gold standard RCT
Of the 664 RCT (76.1%) were single center. PROBLEM! Weather analysis!
Only half of the rct looked at clinical course with only 8% of the rct looking at mortality and this is a problem because blinding was only reported for half of the trials so half of the time your outcome is clinical course and half the time you are not blinding them to the treatment do you think the people you knowingly got the treatment drug will ‘get better’ faster. And maybe they got better because they knew they were getting the good stuff or maybe they got better because eh provider knew they were getting the active. Both can be bias when they know if the patient is getting placebo or active arm.
The authors state it best “evidence, the large proportion of studies with
an expected low level of evidence is concerning. Rapid dis-
semination of studies with low-quality evidence studies can
influence public opinion, government actions, and clinical prac-
tice in potentially harmful ways,3

And I couldnt agree more so lets talk about something else that has no evidence-- MASK

Lets be clear about mask—we have no evidence that they work for what we think they work for—we have evidence they says they help decrease the spread of droplets when you speak but we don’t have evidence that then says that this decrease in droplets leads to a decrease in coronavirus cases and rememeber we don’t care about cases we care about deaths and does that lead to a decreaes in deaths. We don’t have evidence on this so ANYONE that has an opinon on mask is purely giving you their opinion—zero fact!

Well my hospital sent out an email saying hey look at this study https://jamanetwork.com/journals/jama/fullarticle/2768533
In the journal of the american medical association PROOVES that mask actually work!!!!

A research letter- https://jamanetwork.com/journals/jama/fullarticle/2768533
Association Between Universal Masking in a Health Care System and SARS-CoV-2 Positivity Among Health Care Workers

The study assessed the association of hospital masking policies with the SARS-CoV-2 infection rate among HCWs.

12 hospitals and more than 75 000 employees in Mass General

They looked at HCWs who tested + for SARS-CoV-2 between March 1 and April 30, 2020

This was broken down into 3 time periods
before implementation of universal masking of HCWs (March 1-24, 2020)
intervention period with universal mask (April 11-30, 2020).
out of the 75000 employees – only 10k got test and only 1271 had a positive result-

During the preintervention period, March 1-24, 2020, the SARS-CoV-2 positivity rate increased exponentially from 0% to 21.32%!!

During the intervention period requiring mask from April 11-30, 2020 the positivity rate decreased linearly from 14.65% to 11.46%
THUS
Universal masking at mass general was associated with a significantly lower rate of SARS-CoV-2 positivity among HCWs.
This association may be related to a decrease in transmission between patients and HCWs and among HCWs.
MAY BE or may not!! Always be careful!
The decrease in HCW infections could be confounded by other interventions inside and outside of the health care system (Figure), such as restrictions on elective procedures, social distancing measures, and increased masking in public spaces, which are limitations of this study.

this study doesnt say that mask prevent infection because what we were doing during the rest of the time was drastically different!!
how we handled covid on march 1 was drastically different than april1! they are not even close to the same, we shut down bards and restauranted by april 1 and we didnt do that by march 1 so if you want to say look at the huge benefit mask made then you have to say look at t a huge benefit mask, and social distance and limits to group gatherings and economic shut down had on the cases of covid19 for of health care workers--- this is just another article that spins the numbers come up with a covid conclusion that is not accurate or tell the whole story.
As far as the answer on mask, the answers will vary wide and far – they are kind of like butts, everyone got one and none of them are evidence based

or something like that

But the next article has also hit the press and a popular title saying ‘kids don’t spread covid’
Which comes from this article

Posfay-Barbe KM et al. COVID-19 in children and the dynamics of infection in families. Pediatrics 2020 May 26; 146:e20201576. (https://doi.org/10.1542/peds.2020-1576)

What is a child’s role in transmission of COVID-19? This study looked at 39 patients RESULTS:
Of the 39 children, 18% required hospitalization, and none required intensive care unit admission.
Cough was the most common symptom (82%), followed by fever (67%) and nasal discharge (64%)
HERE IS THE KICK IN THE PANTS
In 79% of cases, at least one adult in the household had COVID-19 symptoms before the child.
They use this to say look 4 out of 5 times the adults in the house has symptosm before the kids so this “confirms that children are infected mainly inside familial clusters” – no it does not it just confirms child don’t have symptoms or don’t report their symptoms prior to the adults.
“Interestingly, 85% (75/88) of adult household contacts developed symptoms at some point, compared with 43% (10/23) of pediatric”
The article uses this to say – look the kids are not developing symptoms or they are developing them at a rate half that of adults so obviously this means kids don’t get covid right???? wellThe mean age was around 11. How many 11 yr old are going to mention to their parents ‘hey I have a runny nose today’ OF COURSE NOT, wipe it on your sleeve and keep playing ball with your friends or video games or whatever kids do these days. Or please name me the number of 11yr olds that are going ot say ‘um I cant smell’ or ‘my taste isnt the same’ – OF COURSE NOT in my house if you said this “taste kind of funny” or “this taste terrible” or this doesn’t taste right you would get sent to bed with an extra bowl of broccoli! Kids are not going to speak up about these odd and weird symptoms! So maybe it is not that kids don’t develop symptoms half the rate of adults they just don’t complain about them at the same rate as adults
And
The the weirdest part of all which we have seen over and over is this line “Surprisingly, in 33% of households, symptomatic HHCs tested negative despite belonging to a familial cluster with confirmed SARS-CoV-2 cases”

Why is this happening? You could say it was a bad sample- but it is a single center so really it should be the same swabbers for everyone. Why are we seeing so many people test positive then 1/3 to half the time the household contacts even spouses are not testing positive??

Which takes me to my next article
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2768377?guestAccessKey=ff853102-6da2-4db9-bf72-1ce8904ecd57&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=olf&utm_term=071420
Outcomes of Universal COVID-19 Testing Following Detection of Incident Cases in 11 Long-term Care Facilities
We know or we think we know that Residents in long-term care facilities are at particularly high risk of infection and poor outcomes associated with coronavirus disease 2019 (COVID-19).
Some of this may be because residents in long term care facilities are at particularly high risk of infection and poor outcomes associated with EVERYTHING! A bad fart can derail some of these ships.
We performed universal testing of untested residents across 11 Maryland long-term care facilities that ) had known positive cases and had recently undergone targeted testing based on individual residents’ symptoms and (2) had known positive cases.
Of the almost 1200 residents of the 11 long term care facilities just doing target testing resulted in 153 cases
Among the remaining 893 residents who were universally tested, 354 (39.6%) tested positive for SARS-CoV-2 RNA.
so many questions- why no symptoms in almost 40% of the individuals. that tested positive. In total there were 56% of the individuals testing positive? why not the other 44%, what is special about them?
If this had not been a study with universal testing we would have missed 40% of the people that tested positive for covid19, we are likely drastically underestimating how many people have had this illness already and by these numbers we are underestimating it by 40%.

I wonder if this would also work for people that have no symptoms--- like football player.
Self-collected swabs research in JAMA Network Open (Free)
Self-collected Midnasal vs Clinician-Collected Nasopharyngeal Swabs to Detect SARS-CoV-2 Infection
Self-collected midnasal swabs: Midnasal swab specimens self-collected at home may be comparable to clinician-collected nasopharyngeal swab specimens for detecting SARS-CoV-2 in symptomatic patients,
Nearly 200 symptomatic patients — 85% of whom were health care workers — contributed both types of specimens for analysis.
with the clinician-collected swabs as the reference, home swabs had a sensitivity of 80% and specificity of 98%.
The authors acknowledge study limitations but write, "This approach is safe and scalable in the pandemic setting, permitting widespread testing of symptomatic participants early in illness and the potential for prompt self-isolation and [contact] tracing."

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Initiating Pharmacologic Treatment in Tobacco-Dependent Adults. An Official American Thoracic Society Clinical Practice Guideline
https://www.atsjournals.org/doi/full/10.1164/rccm.202005-1982ST

ultimate take home- varenicline is first line!!
For Tobacco-Dependent Adults in Whom Treatment Is Being InitiatedShould Treatment Be Started with Varenicline or a Nicotine Patch?
40 more per 1,000 patients; Compared with a nicotine patch, varenicline increased long-term abstinence, measured at 6-month follow-up (RR, 1.20; 95% CI, 1.09 to 1.32; ARR, 40 more per 1,000 patients;)
For Tobacco-Dependent Adults in Whom Treatment Is Being Initiated Should Treatment Be Started With Varenicline or Bupropion?
77 more per 1,000 patients taking Varenicline increased tobacco abstinence at 6-month follow-up compared with bupropion (RR, 1.30; 95% CI, 1.19 to 1.42; ARR, 77 more per 1,000 patients;)
who andrew so just varenicline by itself?? thats it??
should Treatment Be Started with Varenicline plus Nicotine-Replacement Therapy or Varenicline Alone?
105 more per 1,000 patients; taking Varenicline plus a nicotine patch significantly increased abstinence compared with varenicline alone, (RR, 1.36; 95% CI, 1.07 to 1.72; ARR, 105 more per 1,000 patients; 95% CI, 21 more to 211 more; high certainty in the estimated effects)

they mention ecigs vs varenicline and admit we dont have direct evidence but indirect evidence says varenicline is better but they admit because we dont have good evidence and all we have is indirect evidence then base on that go with varenicline but it is given a conditional rec with very low certainty of evidence.

In Tobacco-Dependent Adults Who Are Not Ready to Discontinue Tobacco Use, Should Clinicians Begin Treatment with the Optimal Controller or Wait Until They Are Ready to Stop Tobacco Use?
to me this was huge maybe one of the biggest recommendation because I always wait till the person is ready to stop but in studies where people could stop or were not interested in stopping those started on varenicline were more like to stop smoking. my mind was blown!! and the evidence on this gives a strong recommendation, with moderate certainty in the estimated effects.
infact 173 more per 1,000 smokers were able to stop smoking at 6 months after starting varenicline despite the provider not waiting for affirmation of readiness (RR, 2.00; 95% CI, 1.70 to 2.35; ARR, 173 more per 1,000 patients; 95% CI, 121 more to 234 more; high certainty in the estimated effects).

Tobacco-Dependent Adults with Comorbid Psychiatric Conditions, Including Substance-Use Disorder, Depression, Anxiety, Schizophrenia, and/or Bipolar Disorder, for Whom Treatment Is Being Initiated, Should Clinicians Start with the Optimal Controller Identified for Patients without Psychiatric Conditions or Use a Nicotine Patch?
“boxed warning regarding possible neuropsychiatric adverse events for both varenicline and bupropion. These concerns stemmed from case reports and postmarketing surveillance, as no RCTs found evidence for these events and early observations suggested no significant increase in neuropsychiatric adverse events with pharmacotherapy compared with placebo, even among patients with preexisting mental illness.”
to summarize --with moderate certainty
compared with nicotine patches, varenicline 1) may result in a large benefit for nicotine abstinence and 2) compared with nicotine patches, varenicline would likely result in little to no difference in SAEs

and last but not least- if you are given the choice to write a script for an Extended-Duration (>12 wk) or Standard-Duration (6–12 wk) then with a strong recommendation and moderate certainty in the estimated effects you should always chose the longer- go with 12 weeks!

Guntupalli SR et al. Safety and efficacy of apixaban vs enoxaparin for preventing postoperative venous thromboembolism in women undergoing surgery for gynecologic malignant neoplasm: A randomized clinical trial. JAMA Netw Open 2020 Jun 1; 3:e207410.

Following surgery for gynecologic malignancies, The American Society of Clinical Oncology has developed guidelines for postoperative VTE prophylaxis and they recommend almost 1 month of subcutaneous low-molecular-weight heparin is recommended to prevent venous thromboembolism (VTE); however, patients' hate this!! giving shots!
randomized trial of 28 days of subcutaneous enoxaparin (40 mg daily) versus oral apixaban (2.5 mg twice daily) in 400 women (median age, 58) undergoing open or minimally invasive surgery for gynecologic cancer.
primary end point of this study was the incidence of major bleeding events occurring during the treatment phase and in the 30 days after treatment.
Major bleeding was defined as fatal bleeding and/or symptomatic bleeding in a critical area or organ or bleeding requiring the transfusion of 2 units of packed red blood cells.
Major bleeding was limited to one participant in each group, incidence of clinically relevant nonmajor bleeding (hematoma, bruising, epistaxis, and vaginal bleeding) was similar between groups (12 [apixaban] and 19 [enoxaparin]), and VTE occurred in 2 and 3 patients, respectively.
In the apixaban group, satisfaction was greater regarding ease of use (99% vs. 59%; Phaters will say --This study was underpowered because incidence of VTE and bleeding events was soooo much lower than anticipated, They are not wrong- they wanted to be able to tell a difference of 6% between the two groups but over all there were only 31 cases of bleeding in both groups which is only 7% of the whole population!! so very low rates of the primary outcome which likely can be attributed to the 90% compliance rate seen in this trial. over all I think we are seeing that the bans and trans work for anticoag in those with or without cancer

Carbone PS et al. Primary care autism screening and later autism diagnosis. Pediatrics 2020 Jul 6; [e-pub]. (https://doi.org/10.1542/peds.2019-2314)

screening instruments for autism spectrum disorder (ASD), such as the Modified Checklist for Autism in Toddlers (MCHAT), are ideal- we screen for autism and we catch these children with autism at 6-12-18 months!! what a great tool we an get them early treatment and therapy!! right
researchers examined electronic medical record (EMR) for 36,000 children who had 18- or 24-month well-child visits from 2013 to 2016.
same toddlers' charts were subsequently reviewed for autism diagnosis codes in 2019, was they were almost 5 yrs old. 67% of children with Autism had screened negative at 18- and/or 24-month visits-- which means the Modified Checklist for Autism in Toddlers (MCHAT), has a sensitivity, 33%), and the positive-predictive value was only 18%.
and that is a terrible screening test- but this is important to know because parents mght get a false sense of security. having a child with autism is by no means the end of the world but having a child with autism after they test negative for what you may think as the autism screening test would be shocking and something we should prepare parents for.

Link JO et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature 2020 Jul 1; [e-pub]. (https://doi.orLink JO et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature 2020 Jul 1; [e-pub]. (https://doi.org/10.1038/s41586-020-24038

We have many antiretroviral medications, but they require daily dosing, this is a problem.
what if we had a long acting hiv med???? GS-6207, now named lenacapavir, might be the answer is and entering phase 2/3 studies, it is dosed every 6 months.
In a study of healthy participants, a single subcutaneous injection produced GS-6207 levels that exceeded the concentration needed to inhibit HIV for >24 weeks. In a separate study, involving people with HIV, a single 450-mg subcutaneous injection of GS-6207 led to a decline in HIV RNA levels of 2.2 log10 copies/mL.

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https://www.youtube.com/watch?v=EBhEjYhVoZk

Goggin K et al. Reductions in parent interest in receiving antibiotics following a 90-second video intervention in outpatient pediatric clinics. J Pediatr 2020 Jun 15; [e-pub]. (https://doi.org/10.1016/j.jpeds.2020.06.027)

acute respiratory tract illnesses (ARTIs; cough, congestion, sore throat, and earache) is a PROBLEM with a capital P. or maybe I should say its a pain in the A with a capital A and that A of course is referring to antibiotics-- parents want antibiotics, sometimes demand antibiotics and no matter what you say, its hard to say no time and time and time again and eventually EVERYONE and yes I mean everyone will eventually give an antibiotic when they in their heart of heart knows it is likely not indicated. BUT what if we could educate our pts before we walked in the room.

In this study they surveyed 1051 parents about their knowledge of and interest in receiving antibiotics for their children. Surveys were conducted before and after parents watched a professionally created 90-second cartoon-- I dont have access to the cartoon but I didnt find a two minute cartoon on youtube and it is the in the show notes-- just go to details of this podcast! how do you get to the details??
if you are listening to this podcast on apple you click the little dots in the lower right hand corner, click go to show, then it goes to this show and click on details and BAM its magic all the information about this show. and ths me there is a listener named paul and I wont give the last name but you emailed me about an article and for the life of me I can’t find that article back so please re email me andrewbuelt@gmail.com
back to the study
in this survey
Parents rated their interest in receiving an antibiotic using a visual analogue scale ranging from 0-100, with 0 being “I definitely do not want an antibiotic,” 50 “Neutral,” and 100 “I absolutely want an antibiotic.”

at baseline average score was 57 and it reduced down to 47 BUT if you were one of the parents that scored much higher say a mean around 83 which is geting close to the 100 “I absolutely want an antibiotic.” your score dropped down to 63 which is much closer to neutral!! This gives you a chance to not write antibiotics if not needed- i dont take care of kids 1-5 but if I did EVERY parent would be watching this video or it would be on repeat for the education videos.

last episode I talked about breast cancer screening and the age old saying is when it rains it pours which is clearly seen in this paper

Le Blanc JM et al. Association of Medicaid expansion under the Affordable Care Act with breast cancer stage at diagnosis. JAMA Surg 2020 Jul 1; [e-pub]. (https://doi.org/10.1001/jamasurg.2020.1495)

Affordable Care Act (ACA) went into full effect in early 2014.
luckily for us as of 2018, 37 states, including the District of Columbia had adopted Medicaid expansion and 14 had not.
this is prime time to look to see what happens when all of a sudden these women have insurance and can get mammograms! Ideally we should see a burst of new early cancers that then prevent all these really aggressive late cancers!! riiiiiight??
in this retrospective cohort analysis they looked at Stage at diagnosis was compared between patients who were uninsured, had Medicaid or Medicare, or were privately covered during the preexpansion years (2012-2013) and postexpansion years (2015-2016)
Stage at diagnosis (early [stage 0 or 1] vs. late [stage 3 or 4]) was assessed by state and insurance status for pre-expansion years (2012–2013) compared with postexpansion years (2015–2016).

“Between 2007 and 2012, the percentage of late-stage cancer was around 12% for those that were insurance or had medicaid”- this makes sense if you have insurance all things being equal all states should have pretty equal rates of breast cancer
BUT
Patients with late-stage cancer who were uninsured in nonexpansion states exhibited a 1 percentage–point non significant decline from 24.2% to 23.5% (P = .14), whereas patients with late-stage cancer who were uninsured or had Medicaid in the expansion states saw a significant decrease from 21.8% to 19.3% (P
What they are trying to say is look at this if you are in a state that has insurance expansion then you yes you are more likely to see a decrease in late or advance breast cancer BUT the devel is in the detail. First they gave you a decrease in percentage points which is always a red flag, do you not think I as an educated individual reading your paper can tell the difference between hard numbers?? If you go to the actually hard core numbers it tells a different story!
If you look at the hard numbers you will find that all of a sudden the numbers are not so clear- infact those states that expanded medicaid and took on the ACA actually had a 7% decrease in their rates of advance cancer while those who did not expand medicaid or take on medicaid had almost a 15% decrease in their rates of advance breast cancer. maybe the final results should be -- if you want to lower your rates of advance breast cancer then dont advance medicaid and give mammograms for everyone cause it didnt do the job-- or at least that would be the finals results if I was writing the paper---

Yamamoto JM et al. Thyroid function testing and management during and after pregnancy among women without thyroid disease before pregnancy. CMAJ 2020 Jun 1; 192:E596. (https://doi.org/10.1503/cmaj.191664)
retrospective cohort study of 111 522 (59.2%) women who had at least 1 TSH measurement
in total 4% or 4417 women had “subclinical hypothyroid which was defined as a range between 4.01 and 9.99 mIU/L. about half were started on treatment synthroid and half were not. of the almost 2000 with subclinical hypothryoid that were not started on therapy and got another TSH test- 68% had a repeat TSH wnl. and if you thought o good the tsh went back to normal, that women is fine, you would be wrong because despite the numbers going back to normal for 68% of the women, roughly 40% of the women WERE STILL STARTED ON synthroid or thyroid medication!! The frustration with TSH exceeds my words and the logic is exactly the opposite, purely illogical.

At baseline almost 1400k women had normal TSH and were still started on treatment- with a normal TSH!
AND of the women with TSH value of 10.00 mIU/L or higher, the women that you would think need to be started on TSH or at least may benefit from being on thyroid hormone therapy only had initiated during only 300 (17.6%) of the pregnancies. LESS than 1 in 5 women were started on thyroid therapy with TSH > 10 and roughly 1 in 10 were started on thyroid therapy with TSH in normal range. Sometimes I really get worried

how do you know that hip pain is osteoarthritis and not a strangulated inguinal hernia

Does this patient have hip osteoarthritis?: The rational clinical examination systematic review Metcalfe D, Perry DC, Claireaux HA, et al. JAMA. 2019;322(23):2323-2333. doi: 10.1001/jama.2019.19413.
Let’s say your patient has hip or groin pain. How do you know if it’s osteoarthritis (OA)?

results
in the end Six studies with 1,110 patients; 509 (38%) had radiographic hip OA.
The following features were found to be useful:
Squat causing posterior pain (likelihood ratio [LR] +6.1)
Groin pain on passive adduction or abduction (LR +5.7)
to rule out OA is normal passive hip adduction (LR –0.25)
while these are not high LR ratios over 10 that we would hope for, if you combine a couple of them together they can work synergistically to give you a higher likelihood ratio and more secure diagnosis.

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Orkaby AR et al. Association of statin use with all-cause and cardiovascular mortality in US veterans 75 years and older. JAMA 2020 Jul 7; 324:68. (https://doi.org/10.1001/jama.2020.7848)

retrospective cohort study of about 327,000 patients (age, ≥75; mean age, 81; mostly white men) without prior statin use, without a prior cardiovascular event;
in total 326K vets that were 75yr old and older and had never had a cardiovascular event those started on statin therapy did better!!!
all-cause mortality was 78.7 per 1000 person years in those started on a statin and 98.2 per 1000 person-years in those not a on a statin.
BUT devel in the details-- they say they looked at 7.2 million vets- then once you took out the people that had prior statin exposure, and removed the people with missing data, and then excluded those with a prior cardiovascular event, and threw out those individuals who died in the first 150 days -- you then get the 326K. and of those about 57k got a statin prescription and 269K never got a statin prescription. BUT those individuals who started a statin were more like to have the diagnoses codes of hyperlipidemia, diabetes, and hypertension AND less likely to have dementia.
so the patients that benefit from a statin are over the age of 75, have CV risk factors and dont have dementia.. well isnt it shocking that those individuals benefited from statin therapy!
out of the initial 7.2 million people you cut it down to the 7% or 57k that got a statin and you say “look they did better” than the people that had fewer risk factors and were demented that didnt get a statin. OR the statin had nothing to do with it -- we will never know cause you can match up the confounding variables in retrospective data, no matter how hard to yu try!! NEVER.
At this point statins are safe, we dont know if they work in the elderly because the data and studies often exclude them BUT we dont need any more observational studies, especially not ones that looks at 7.2 million charts then cuts it down to 326K. That is cherry picking the data and the cofounders will never be equal, at this point it is RCT or nothing, do the trial we all want or dont do the trial.

Family med- jack of all and master of many—because you can do so many things- I am bias-

Wallhed Finn S et al. Treatment of alcohol dependence in primary care compared with outpatient specialist treatment: Twelve-month follow-up of a randomized controlled trial, with trajectories of change. J Stud Alcohol Drugs 2020 May; 81:300. (https://doi.org/10.15288/jsad.2020.81.300)

moderate levels of alcohol dependence are more likely to seek care in primary care than a specialist
randomized controlled noninferiority trial
researchers in Sweden randomized 288 fulfilling ICD-10 criteria for alcohol dependence to comprehensive treatment by a team of experienced specialists at a single center or brief interventions provided by general practitioners who had received 8 hours of training.
primary outcome was change in weekly alcohol consumption measured in grams of alcohol before inclusion compared with 12 months after start of treatment
to give you and idea the averahe baseline alcohol consumption of these individuals was around 350G a week which equals about a 25 drinks a week
the results were that no matter which group you were in – at 12 months you were drinking less – you wer down to about 12.5 drinks a week if you went to a specialist and about 13.5 drinks a week
I guess this study fit my confirmation bias and specialist are not needed for anything ever-

I am kidding of course
BUt I am not kidding when I say I think screening for cancer is often a waste of time, at baseline people are healthy so it is very hard to screen for something when the person is healthy! conveying this message to patients can be very challenging.

It is hard to explain risk and benefits. When talking to my patients I try to lay the numbers out – make like dr. sues and say
“Today you are you! That is truer than true! There is no one alive who is you-er than you! And when it comes to screening it is not clear on what you should do”

but sadly not every screening website follows my advice-

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2763813

Assessment of Lung Cancer Screening Program Websites”
it looked at How do lung cancer screening program websites portray benefits and harms, and what next steps do they recommend for individuals considering screening?
looked at 162 lung cancer screening program websites

websites presented benefit far more than they presented harm (98% presented any benefit vs 48% presented any harm).
Apparently only 44% actually quantified benefit,= approximately 3 fewer deaths per 1000 people at high risk screened over 7 years).
about 1 in 5 reported the harms of false positives, radiation exposure, incidental findings, or the possibility of overdiagnosis.

This is consistnet to what we have seen in the past
people tend to overestimate benefit and underestimate harm.3

Shared decision-making can only be as good as the quality of the information being conveyed. At a minimum, any communication about lung cancer screening must cover some basic ground. google it!

Benefit (and harms) should be presented in absolute terms. For example, 18 in 1000 people died of lung cancer in the low-dose computed tomography group compared with 21 in 1000 people in the chest x-ray group, which represents 3 fewer lung cancer deaths per 1000 people screened (Figure
however in the 1000 people that are scanned there will be 350 false alarms and of thsoe about 20 people will get an invasive procedure or biopsy and have the risk for a collapse lung, infection, bleeding from the lung.
the evidence is not so clear cut as we wish and if they are against getting screening that is OK because thats wasnt the most important part of the visit---
Be clear that avoiding tobacco will have a larger and broader health effect (ie, reduce cardiovascular and lung disease risk as well as a variety of other cancers) than screening.

but while we are talking about screening the chest lets talk about my next favorite screening test in this paper titled-
Burton R and Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the State of Victoria, Australia. JAMA Netw Open 2020 Jun 1; 3:e208249. (https://doi.org/10.1001/jamanetworkopen.2020.8249)

In the perfect world- breast cancer screening should identify women with early breast cancer (Stage I and II) while reducing incidence of advanced malignancies (Stage III and IV).

These Australian investigators analyzed associations between crude breast cancer mortality trends and uptake of adjuvant therapy and downstaging by mammographic screening.

Diagnosis of early breast cancer (EBC) in women by mammographic screening and postsurgical adjuvant endocrine therapy and chemotherapy (termed adjuvant therapy) began simultaneously in many countries in the 1990s.

So was it the screening that saved lives or was it the better treatment that saved lives- maybe the stage at which we caught it didn’t matter because the drugs were that much better?

Just as a reminder the argument for breast cancer is!
this is the argument- we catch cancer early so look at all the lives that we save!

In total from 1982 through 2013 there were 76,630 women with invasive breast cancer registered in Victoria Australia
When looking at death certificates the rates of mortality of women in the registry was 31.6 per 100 000 women in 1982 BUT IT FELL 23.9 per 100 000 women in 2013’

You might be saying well this make sense- in 1982 we don’t have much going on in the world of breast cancer, I would expect you to die more often than the same individual with the same diagnosis in 2013

PLUS in 1991 a program called breastscreeened was developed where women aged 50 to 69 years invited biennially for breast cancer screening. Prior to this program breast screening was 5-10% now it was around 55%.

So just maybe screening does save lives
Remember the death rate went from 31.6 per 100 000 women in 1982 BUT IT FELL 23.9 per 100 000 women in 2013’ and we have all this new screening

BUT BUT BUT from 1986 to 2013, incidence of advanced breast cancer rose from 12 per 100,000 women to 24 per 100,000.

Wait andrew are you telling me that from 1986 to 2013 the mortality with breast cancer decreased but despite a 1000 fold increase in mammogram screening during this time period we were actually were seeing double the rates of advance cancer?!?! Yes that is what I am saying and you are saying OMG how can that be-

TREATMENT
By 1999, 74% of women with early breast cancer were receiving adjuvant endocrine therapy (tamoxifen).
The treatment is better so we can find it later and its ok we still don’t have a problem.

I think the authors say it perfectly in their conclusion- “This study found that mammographic screening did not downstage breast cancer in Victoria from advanced to early, so population mortality benefit is lacking. Adjuvant therapy uptake was associated with all of the decline in Victorian breast cancer mortality since 1994.”

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Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report

(RECOVERY) trial is a randomized, controlled, open-label,

comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone.
2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care.

The primary outcome was 28-day mortality

(21.6%) patients allocated dexamethasone vs (24.6%) patients in usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P
No oxygen then dexamethasone did not reduce mortality at 28 17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14).
patients receiving oxygen without invasive mechanical ventilation dexamethasone did reduce mortality at 28days (21.5% vs. 25.0%,-- a number needed to treat around 30.
And if you were intubated then dex 6mg for for to 10 days really was a show stopper with a nnt of 9 for mortality at 28days.

Last case bias.
but things I dont like about this
open label- obviously not ideal but I do believe doctors are better than open label
enrolled if confirmed or clinically expected covid-- not quite the same thing
-the good news is almost every vented pt. had criteria for acute resp destress syndrome or ARDS and would have met criteria for every ARDS trial performed to date. and this is similar to numbers we saw with what is now standard of care- like the 8% benefit we saw low title volume and 16% benefit we saw with proning. It is totally possible these results are real. and if they arent then who cares!!
examethasone has little mineralocorticoid activity, which is potentially beneficial for a few reasons. Mineralocorticoid stimulation may promote fluid retention and hypernatremia (which are especially undesirable in patients with ARDS).

6mg oral or IV once a day!

now

Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension

JAMA Intern Med. 2020;180(4):542-551. doi:10.1001/jamainternmed.2019.7454

To compare the effectiveness and safety of chlorthalidone and hydrochlorothiazide for first time antihypertensive drug users

730 225 individuals retrospective, observational, comparative cohort design- 2001-2018 large cohort and had to have taken the medication for a year prior to having any event occur.

The primary outcomes were acute myocardial infarction, hospitalization for heart failure, ischemic or hemorrhagic stroke, and a composite cardiovascular disease outcome including the first 3 outcomes and sudden cardiac death. Fifty-one safety outcomes were measured.

That’s a total of 55 outcomes

“To address multiplicity concerns, we indicate which estimates remain statistically significant after a Bonferroni correction for 55 hypotheses”
“
IN THE END
No significant difference was found in the associated risk of myocardial infarction, hospitalized heart failure, or stroke

Chlorthalidone was associated with a significantly higher risk of hypokalemia (hazard ratio [HR], 2.72; 95% CI, 2.38-3.12), hyponatremia (HR, 1.31; 95% CI, 1.16-1.47), acute renal failure (HR, 1.37; 95% CI, 1.15-1.63), chronic kidney disease (HR, 1.24; 95% CI, 1.09-1.42), and type 2 diabetes mellitus (HR, 1.21; 95% CI, 1.12-1.30).

No difference in cardiovascular diseaes- but these are first time hypertesnive patients. They are not honda—did we expect sick???

chlorthalidone was associated with an increased risk of hypomagnesemia, hyperkalemia, vomiting, syncope, gout, impotence, and anaphylactoid reaction and associated with a decreased risk of anemia, depression, dementia, and anxiety. BUT
many of these did not pass the bonferroni threshold

Bonferroni

If multiple hypotheses are tested, the chance of observing a rare event increases, and therefore, the likelihood of incorrectly rejecting a null hypothesis (i.e., making a Type I error) increases.--- example
If you test one negative person for covid your of that one test being positive are low but if you test 55 negative people for covid for odds of having one test turn positive is much higher. The Bonferroni correction accounts for this and says well you are running all these test so you now need to see a statistical number that looks like XYZ in order for it to be significant.

So even after calculation and the Bonferroni chlorthalidone

And many will say well yes but chlorthalidone is STRONGER than hctz it is more potent so clearly you cant compare apples to apples or at least not the same bushel basket of apples to the same bushel basket.

The subgroup receiving 12.5 mg of chlorthalidone vs 25 mg of hydrochlorothiazide had an uncalibrated HR for hypokalemia of 1.71 (95% CI, 1.37-2.11) and calibrated HR of 1.57 (95% CI, 1.25-2.01), passing the Bonferroni threshold (eTables 1-2 in the Supplement). No other outcomes passed the threshold.

I think in the end the real thing we call care about are cardiovascular events- and many of us care about the surrogate marker of blood pressure. In the end just control the blood pressure, use one drug and your more than one drug but if you have the choice you should like choose drugs with fewer sides effets as a standard rule of thumb and I think we can say HCTZ for sure has fewer side effects than chlorthalidone so it is probably what you should be writing for.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792273/
Does Rewording MRI Reports Improve Patient Understanding and Emotional Response to a Clinical Report?
Remember few weeks ago when I talked about 50% of people knew that broken bone and fracture were the same thing or that 1 in 5 pts couldn’t describe nonweight baring? Well this study looked o see what would happen if we changed the language in MRI reports
100pts-
list of all shoulder, elbow, wrist, and hand MR images ordered in 2011 was obtained from the radiology service-- The original reports were reworded to the recommended reading level for effective health education below the eighth-grade level
words such as “tear” were replaced by more descriptive and accurate words such as hole, signal change, or defect. They also used analogies (eg, gray hair, bald spot)
looked at bunch of outcomes but thing I care about was understanding—did the pt understand it and they used a 10 point scale- basically asked th pts. On 1-10 scale how did you understand that report-
The understanding score (mean ± SD) of all the original reports was lower (4.2 ± 2.3) compared with the reworded report (8.1 ± 2.6, p

https://www.bmj.com/content/368/bmj.m7
Objective To assess whether an association exists between financial links to the indoor tanning industry and conclusions of indoor tanning literature.
Results 691 articles were included in analysis, including empiric articles (eg, original articles or systematic reviews) (357/691; 51.7%) and non-empiric articles letters (eg, commentaries, letters, or editorials) (334/691; 48.3%). Overall, 7.2% (50/691) of articles had financial links to the indoor tanning industry; 10.7% (74/691) articles favored indoor tanning, 3.9% (27/691) were neutral, and 85.4% (590/691) were critical of indoor tanning. Among the articles without industry funding, 4.4% (27/620) favored indoor tanning, 3.5% (22/620) were neutral, and 92.1% (571/620) were critical of indoor tanning. Among the articles with financial links to the indoor tanning industry, 78% (39/50) favored indoor tanning, 10% (5/50) were neutral, and 12% (6/50) were critical of indoor tanning. Support from the indoor tanning industry was significantly associated with favoring indoor tanning (risk ratio 14.3, 95% confidence interval 10.0 to 20.4).

Listen to an interview with authors that basically point out the tanning industry is doing what the smoking industry was doing for years- trying to hide and bury and throw money at it

https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-proair-hfa
generic pro-air—problem is the drug and the delivery system!
give credit to the FDA
Under the Generic Drug User Fee Amendments (GDUFA), individual companies can meet with the FDA as part of its pre-Abbreviated New Drug Application (ANDA) program to support the development of such complex generic drug products. The FDA also publishes guidance documents describing the steps the FDA recommends companies take to submit complete applications for generic drug products.

In 2016, the FDA issued a revised draft product-specific guidance for proposed generic albuterol. the draft guidance provides bioequivalence recommendations.

And the article that has me the most stumped is this article titled
https://www.ncbi.nlm.nih.gov/pubmed/31976865
You see most of the time randomized trials of anticoagulation for atrial fibrillation exclude hemodialysis patients. However this analysis of observational studies including almost 72,000 dialysis patients sought to seek the risk and benefits of anticoagulation for those individuals with atrial fibrillation on dialysis. To me this would be no-brainer. Patient has a fibrillation makes you more prominent clot dialysis makes you more prone to clotting. Easily getting anticoagulation has to improve the rates of thrombotic events. However of the 16 studies only abixan 5 mg was associated with lower ALL CAUSE MORTALITY. Compared with placebo or no anticoagulation -warfarin and apixaban were not associated with fever embolic events. Warfarin was associated with higher risk for major bleeding then no anticoagulation

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2766471

Effectiveness of Adenotonsillectomy vs Watchful Waiting in Young Children With Mild to Moderate Obstructive Sleep ApneaA Randomized Clinical Trial

Look to find if ‘Is adenotonsillectomy (ATE) more effective than watchful waiting for treating otherwise healthy children, between 2 and 4 years of age, with mild to moderate obstructive sleep apnea (OSA)?'

A total of 60 children, 2 to 4 years of age, with an obstructive apnea–hypopnea index (OAHI) score of 2 or greater and less than 10, were randomized to Adenotonsillectomy ATE (n = 29) or watchful waiting (n = 31).
The primary outcome was the difference between the groups in mean obstructive apnea–hypopnea index OAHI score change

THE SAY
“Both groups had a decrease in mean obstructive apnea–hypopnea index OAHI score, and the difference in mean obstructive apnea–hypopnea index OAHI score change between the groups was small (−1.0; 95% CI, −2.4 to 0.5), in favor of AdenotonsillectomyATE”

A difference of 2 in obstructive apnea–hypopnea indexOAHI score change was used as a minimally clinically important difference between the groups, with a standard deviation of 2.5.

The AdenotonsillectomyATE group had a mean obstructive apnea–hypopnea index OAHI score decrease of −2.9 (95% CI, −4.0 to −1.9; Cohen d = −1.14), the watchful waiting group had a mean decrease of −1.9 (95% CI, −3.0 to −0.9; Cohen d = −0.71), and the difference between the groups in mean change was small, −1.0 (95% CI, −2.4 to 0.5; Cohen d = −0.37)

“Both groups had a decrease in mean obstructive apnea–hypopnea index OAHI score, and the difference in mean obstructive apnea–hypopnea index OAHI score change between the groups was small (−1.0; 95% CI, −2.4 to 0.5), in favor of ATE”

– which is interesting because it didn’t reach stastical signifance or your end point so why you would say smal but favor of ATE was my first red flag and then

The authors go on to say

there were large differences between the groups in favor of ATE regarding the Obstructive Sleep Apnea–18 (OSA–18) questionnaire, OSA–18 questionnaire (eg, total OSA–18 score: −17; 95% CI, −24 to −10).

basically saying when questioned those that got surgery were happier-- those that had an invasive surgery FELT like they were doing better but we know that that there was no difference in those individuals

again not blinded THIS IS THE PROBLEM- blinding the pt. prevents you from bias prior to randomization and during the study.. blinding the provider prevents you from bias during and after randomization

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Covid info
https://melwy.com/blog/lancet-paper-on-chloroquine-is-overhyped-real-world-data-should-not-be-a-black-box

So I couldn’t miss the largest observational study published to date on the effects of (hydroxy-)chloroquine, in 96 032 hospitalised Covid-19 patients, from an international registry comprising 671 hospitals in six continents:
Surgisphere is the company that put it all together is in the end it showed not only no benefit with hydroxychloriquine but also possible harm!

No transparency- they dont really say how they got their data and wont release how they got there data and no review. Lancet being this all great academic journal wont mention or say who did peer review on this article. WHAT! one of the beliefs is Lancet editor-in-chief Richard Horton. Let it slip through the cracks cause he doesnt like trump. This is well known he doesnt like trump but then to intentionally release a bad or falsified study that disagrees with a drug that president trump has openly supported is just crazy!

https://www.bmj.com/content/369/bmj.m1435

Nalaxone is used to treat opiod overdose.
Nalaxone can save lives- we all know that but you have to give it early because and it has to be easy to use
What if we made it over the counter!!?? That would be awesome!!
But in order to be available over the counter you have to have easy instructions like with motrin 1-2 pills every 6 hours not to exceed 10 pills in 24hrs. but how to do you write instructions for the common man for naltrexone—I had never thought of this will they did it in this study

FDA Initiative for Drug Facts Label for Over-the-Counter Naloxone

They asked 710 particpants what the instructions meant and
Primary end points in our study corresponded to participant understanding of the key steps in naloxone administration as depicted on the label.
The label was very easy for a medical professional, thinks like check to see if they respond. Give medication, call 911 immediately, stay with patient till EMS arrives. and mainly eveyrone got all the details correct and would only mess up because when tested on it they would say call 911 and not call 911 immediately.

“Overall, the FDA found that the model label was adequate for use in the development of a naloxone product intended for over-the-counter sales.”

I think this is great news cause the medication should be over the counter it is easy as not everyone who does opiods gets it from a provider but they should have easy access to the reversal medication just incase the street pill is stronger than they thought.
https://www.nejm.org/doi/full/10.1056/NEJMsa1912403?query=primarycare-hospitalist

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2765248
some people need reminders- not me! You can ask my wife, I always so everything the first time I am asked and never leave my shoes in the middle of the room but that is not the case for everyone and this is no more clearly seen than in this study

Effect of Patient Portal Reminders Sent by a Health Care System on Influenza Vaccination RatesA Randomized Clinical Trial

randomized clinical trial of 164 205 patients served by 52 primary care practices look to see if reminders sent through a patient portal increase influenza vaccination rates

Patients were randomized within primary care practices to 1 of 4 study groups (no reminder [n = 41 070] vs 1 reminder [n = 41 055], 2 reminders [n = 41 046], or 3 reminders [n = 41 034]).
The primary outcome was receipt of 1 or more influenza vaccines as documented in the electronic health record,
37.5% for those receiving no reminders,
38.0% for those receiving 1 reminder (P = .008 vs no reminder),
38.2% for those receiving 2 reminders (P = .03 vs no reminder),
38.2% for those receiving 3 reminders (P = .02 vs no reminder).

It appears you don’t get a lot of bang or your back with the extra reminders and just like those annoying postal cards from bath and body that I get in the mail most of these notifications are ignored and trashed

SO even though the gain was very minimal .07% overall which was the difference from 37.5% to 38.2% this did reach stastical significance and the rate of arm is almost nonexistent so I am all for it especially as this can be automatically implemented into the EMR and doesn’t require any human work on the part of the pts.

I am too poor to buy this twice- the same cant be said about ablation

Mansour M et al. Persistent atrial fibrillation ablation with contact force sensing catheter: The prospective multicenter PRECEPT Trial. JACC Clin Electrophysiol 2020 May 8; [e-pub].

381 patients with persistent AF;

Efficacy, defined as freedom from any documented 30-second AF episode, was 62% at 15 months; (so basically 40% still had AF at 15months BUT
freedom from AF symptoms was 80% at 15 months. Meaning that even though 40% still had afib 20% of those individuals said, I know I am still having afib but I don’t have any symptoms. The annoying part is this is not randomized the pt. knows they get a very invasive procedure just pure placebo their symptoms will resolve especially when the symptoms are subjective things like ‘palpitations’- my other problem is when you look at the characteristics the avg chadsvasc was 2!!!! 65yr old and 2!!! That is like you are a 65 yr old male with htn and no diabetes, no previous stroke, no heart failure.. This is not my pt. population. AND
Repeat ablations were performed in 14%. – remember still 20% of individuals were in afib and had symptoms. So why isn’t this number 20% of people had repeats?

The adverse event rate within 1 week was 3.8%, which included cardiac tamponade in 1.5%, stroke or transient ischemic attack in 0.6%, diaphragmatic paralysis in 0.3%, and vascular complications in 0.9%.

If you are having a lot of symptoms of if you have severe heart failure with afib then I think there is likely benefit to ablation else you are undergoing an invasive procedure with risk so tred lightly – especially when it only works on semi health chadsvasc score of 2 individuals just over half the time. The old saying is correct “if you go to an ablation once you go to an ablation twice”

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Prostate Cancer Incidence 5 Years After US Preventive Services Task Force Recommendations Against Screening
JNCI: Journal of the National Cancer Institute, djaa068,——Published: 20 May 2020

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2762575?guestAccessKey=1c75486d-f2a4-4e1b-ac99-25ca247be690&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=etoc&utm_term=050420
Sex Differences in Salaries of Department Chairs at Public Medical Schools

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Fox MT et al. Comparative effectiveness of antibiotic treatment duration in children with pyelonephritis. JAMA Netw

vOpen 2020 May 1; 3:e203951. (https://doi.org/10.1001/jamanetworkopen.2020.3951)

Rates of treatment failure did not differ significantly between the short and prolonged courses (11.2% and 9.4%).

https://jamanetwork.com/journals/jama/fullarticle/2765729?guestAccessKey=2169ba8b-43fc-4360-bed7-acf7a31b1c9d&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=etoc&utm_term=051220

Effect of Biomechanical Footwear on Knee Pain in People With Knee Osteoarthritis: The BIOTOK Randomized Clinical Trial

In jama may 12 – look to see if special biomechanical footwear could help osteoarthirits knee pain-

At 24 weeks of follow-up, the mean standardized WOMAC pain subscore improved from 4.3 to 1.3 in the biomechanical footwear group and from 4.0 to 2.6 in the control footwear group (between-group difference in scores at 24 weeks of follow-up, −1.3 [95% CI, −1.8 to −0.9]; P
however the listers likely know I am going ot say the difference of one on a 10 point scale may not be clinically significant. in fact I dont think there is significance cause I find it hard to tell between 1 and 2 or 6 and 7 on a ten point scale—to me it is six one way and half a dozen another.

https://jamanetwork.com/journals/jama/fullarticle/2765728?guestAccessKey=9a7f39b3-11e8-46c7-a4b8-c160cd779135&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=etoc&utm_term=051220

Effect of Surgery vs Functional Bracing on Functional Outcome Among Patients With Closed Displaced Humeral Shaft Fractures: The FISH Randomized Clinical Trial

This study wanted to find if you have a displaced, closed, humerus shaft fracture can you just put it in a brace or do you need to go in and open it up, do you need a surgeon or just someone who knows how to make a good cast. The answer was “Among patients with closed humeral shaft fracture, internal fixation surgery, compared with nonoperative functional bracing, did not significantly improve functional outcomes at 12 months."

Hum SW, Shaikh KJ, Musa SS, Shaikh N. Adverse events of antibiotics used to treat acute otitis media in children: a systematic meta-analysis. J Pediatr 2019;215:139-143.e7.

How often do children experience adverse effects from the antibiotics used to treat otitis media?

diarrhea was the most common adverse event, but it ranged from 2.2% (azithromycin) to 18.9% (amoxicillin/clavulanate). The placebo caused diarrhea in approximately 7% of children, perhaps a reflection of underlying viral infections. BUT WE KNOW BOTH STUDIES AND FAMILIES WILL UNDERREPORT-- In the 3 studies that used diaries, the rate of diarrhea was higher (range = 14.6% - 21.1%). Diaper rash occurred in 4.6% of children and varied up to 14.8% in children treated with amoxicillin/clavulanate.

The FDA has approved bempedoic acid (marketed as Nexletol) --- which cost around 333$ a month per good RX-- to help lower LDL cholesterol in adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease for whom statins are deemed insufficient.

But to be fair they weren’t really looking for a change because the follow up was 12 months. And there were low event rates aka the patients were healthy at baseline.

IN FACT!!!

Evidence suggests a possibility of harm with bempedoic acid, with a non-significant trend toward higher CV (0.4% versus 0.1%) and all-cause mortality (0.9% versus 0.3%) in the treatment group compared to the placebo group. – yes I know evidence doesn’t work that way but when you have such small events it would be nice to not see a 3 and 4 fold difference in the events that do occur.

For me – when you cant prove real benefit and in the phase three study the best you can show is a 18% change in an outcome I don’t care about with an although not statistically significant but 3-4 fold increase in CV and all-cause mortality compared to placebo--- I would say no thanks!

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https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2762699

Association Between Renin-Angiotensin System Blockade Discontinuation and All-Cause Mortality Among Persons With Low Estimated Glomerular Filtration Rate

The answer was no; In a 5-year follow-up, ACE-I/ARB discontinuation was associated with an increased risk of both mortality (hazard ratio, 1.39; 95% CI, 1.20-1.60) and major adverse cardiovascular events (hazard ratio, 1.37; 95% CI, 1.20-1.56).

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2762509

Lobbying Expenditures and Campaign Contributions by the Pharmaceutical and Health Product Industry in the United States, 1999-2018

pharma makes a lot of money—how do they spend it

https://www.ncbi.nlm.nih.gov/pubmed/31801739
With the best way to treat gout according to his article in annals rheumatology disease titled the contact trial-“comparing naproxen and low-dose colchicine for treatment of gout flares in primary care “

“electric scooter injuries and hospital admissions in the United States, 2014-2018” - https://www.ncbi.nlm.nih.gov/pubmed/31913417

“What is the risk of missing legionaires disease relying on urinary antigen testing solely? A retrospective Belgian multicenter study.
“https://www.ncbi.nlm.nih.gov/pubmed/31838606

The association between low-density lipoprotein cholesterol and incident atherosclerotic cardiovascular disease in older adults: Results from the National Institutes of Health pooled cohorts.” Which looked at the degree between ldl cholesterol levels and risk of first cardiovascular event in 2700 healhty adults age >75yrs old. And in the end both unadjusted and adjusted analyses, researchers found no significant association between LDL cholesterol levels and 5-year incidence of adverse CV events

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https://science.sciencemag.org/content/early/2020/04/24/science.abb5793
read an interesting paper title- Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science 14 Apr 2020.

First, some basics but still things that I learned:
• The two corona virus currently in cirulation are HKU1 and OC43 and they are seasonal- mainly the winter months with peaks around oct, nov, dec. ;
• HCoV-OC43 and HCoV-HKU1 infections, are the common circulating coronavirus and may be asymptomatic or are associated with mild to moderate upper respiratory tract illness” -- rarely do these kill you while obviously SARS-CoV-2 has been shown to be deadly even though the fast majority of people have been shown to be asymptomatic or with mild symptoms that can be controlled at home
• Immunity to HKU1 and OC43 wanes fairly rapidly, over the course of about a year;
https://www.ncbi.nlm.nih.gov/pubmed/2170159?dopt=Abstract

Epidemiol Infect. 1990 Oct;105(2):435-46.
“the time course of immune response to experimental coronavirus infection of man”
followed in 15 volunteers inoculated with coronavirus 229E on 10 people got infected. It then looked at the IgG and IgA antibodies at point zero, 3wks, 12wks and 52wks. remember at point zero you have baseline antibodies and you would no matter what which is a log of around 3.0 and . At 3 wks in the subjects had antibodies up around 4.0 but then at 12 weeks that number was around 3.6 and at one year they were down to around 3.3. remember at baseline is was 3.0!!!They don’t give us the actual numbers cause this is old school EBM so I just had to guess based on the graphs but they mention how this change from beginning to end of the study is statistically significant, BUT remember the 5 people who tried to get inoculated but the virus didn’t take?? Well their baseline was around 3.5 so maybe 3.3 is enough that you wouldn’t get inoculated again. In in order to know we would have to inoculate all these subjects again

At one year they re-challenged 9 patients of the 10 patients that had been previously infected the first go around and this time 6/9 became re-infected. The good news is during initial challenge, the patients were shedding virus for 5-6 days and during the re-challenge period this was only 2 days.
So the take home—if you believe antibodies prevent infection then maybe just maybe it works at 12weeks but we don’t really know since they didn’t re-test at 12 weeks and we know for certain it didn’t prevent infection or virus shedding at 52 weeks- thus if our current corona virus act anything like other coronavirus we are in a world of hurt.

s I said early we currently have no effective therapies for covid19- even though people are desperate for one infact I recent read a paper in jama IM titled
Internet Searches for Unproven COVID-19 Therapies in the United States
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2765361?guestAccessKey=8b161394-e122-412b-a3fe-812451a9396d&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=olf&utm_term=042920

in which they looked at the google searches using the words buy, order, Amazon, eBay, or Walmart in combination with chloroquine or hydroxychloroquine
per 10million searches on google that combination on feb 1 was searched 1000 times but on March 16- 3800 estimated searches, March 22 -- 170006estimated searches, and March 29 - 5000 estimated searches
which proves that people are not being scienctist they are taking what the news says and running with it- sadly they are taking what our president and the owner of tesla tweet as the spike for google searches went up over 1300% in direct relation to their endorsements – its sad, and I think that this just shows that people will believe or do anything if it comes from the right source which was a lesson I was hoping we learned to not do after WW2.

https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaa152/5814216

Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure
They bring up something that I think we should all talk about around the water cooler because although it is not the most popular idea, maybe it should be.

That acknowledge that getting a vaccine will take 12-18months. However a majority of this time is spent in phase 3 clinical trial—

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https://covid19treatmentguidelines.nih.gov/
A National Institutes of Health panel has released new guidelines
against use of hydroxychloroquine plus azithromycin outside of clinical trials

https://www.ncbi.nlm.nih.gov/pubmed/32001253
Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis

Epinephrine is the cornerstone of anaphylaxis management but continues to be underutilized

ANTIBODY—

https://jamanetwork.com/journals/jama/fullarticle/2764954

“Yet, according to Theel, several companies are marketing lateral flow assays as rapid point-of-care tests to identify active COVID-19, something the FDA announced it will take action against. “We do not really know how well these assays work at this point,” Theel said in a follow-up email.”

https://www.sccgov.org/sites/covid19/Pages/press-release-04-21-20-early.aspx
They say the Santa Clara Medical Examiner identified two individuals who died at home on February 6, 2020 and February 17, 2020. And the autopsy came with……..positive for SARS-CoV-2.

https://www.cdc.gov/mmwr/index.html
Titled – Assessment of SARS-CoV-2 Infection Prevalence in Homeless Shelters — Four U.S. Cities, March 27–April 15, 2020
They used PCR to test resident and staff members at 19 homeless shelters- almost 1500 people in total and it was impressive that in those locations for which there was already at least two previous COVID19 test found the rate of positive cases was extremely high

— 17% of residents and staff members in Seattle; roughly 35% of those tested in Boston; and 66% of the residents in san Francisco. This tells us what we already know, this disease spreads like wild fire, of those that it spreads not

https://annals.org/aim/fullarticle/2764585/utility-appropriateness-content-electronic-consultations-across-medical-subspecialties-cohort-study
Utility, Appropriateness, and Content of Electronic Consultations Across Medical Subspecialties: A Cohort Study
Objective of this retrospective cohort study was to assess novel metrics of electronic consult appropriateness and utilityTo assess novel metrics of e-consult appropriateness and To assess novel metrics of e-consult appropriateness and To assess novel metrics of e-consult appropriateness and To assess novel metrics of e-consult appropriateness and To assess novel metrics of e-consult appropriateness.
Most consultations were answered within one day and approximately 70% of the consultations that all 4 criteria for appropriateness indicating about 70% of time the patient could be spared a visit to a specialist and have a better conditions managed by the primary care provider with just subtle guidance from the specialistMost consultations were answered within 1 day, with variation across specialties (73.1% for psychiatry to 87.8% for infectious disease). Overall, 70.2% of e-consults met all 4 criteria for appropriateness; the frequency of unmet criteria varied among specialties.

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More cover 19 information based on antibody testing, pregnancy and pre-symptomatic spread

https://www.medrxiv.org/content/10.1101/2020.03.30.20047365v1.full.pdf

https://www.nejm.org/doi/full/10.1056/NEJMc2009316?utm_source=The+Scope&utm_campaign=86f20fbd35-Weekly_Scope_Jan_12_2018_COPY_01&utm_medium=email&utm_term=0_809ad7d22b-86f20fbd35-180869057

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Remdesivir for compassionate use?? Recently published in the New England Journal of Medicine- Is this the COVID19 treatment we have all be hoping for.

https://www.nejm.org/doi/full/10.1056/NEJMoa2007016

https://jamanetwork.com/journals/jama/fullarticle/2764727?guestAccessKey=72e8a5f3-3754-4bf8-bb17-8c2f1cf358b0&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=041320

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Treatment that works-- MASK!

https://annals.org/aim/fullarticle/2764367/effectiveness-surgical-cotton-masks-blocking-sars-cov-2-controlled-comparison

High Velocity Nasal Insufflation (HVNI) Therapy Application in Management of
COVID-19 Have patients wear a surgical mask—in this computer study it showed that mask do help but not necessarily mask on you but mask on the pt.

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Id be happy to send you links to any of the articles talked about in this podcast but I cover the new test on the corona virus that claims to be great but the devil in the details as well as talk about more hear-say medicine and the ever popular ACE inhibitor debate

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https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v1.full.pdf

https://www.sciencedirect.com/science/article/pii/S0399077X20300858

https://first10em.com/chloroquine-for-covid-no-good-evidence-yet/

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https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-000890-25/FR

https://www.sciencedirect.com/science/article/pii/S0924857920300996?via%3Dihub

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Question Everything-- EBM not hear-say medicine

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A listener wrote in with a question about a drug, this is my response. Let me know your thoughts? Would you prescribe this drug? Andrewbuelt@gmail.com

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1705848

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There was a paper to start the year that got a lot of hype saying that just maybe we should target an LDL but that is not what the study actually showed and I will tell you why I think it is wrong.

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https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2757311?widget=personalizedcontent&previousarticle=2757307

Prior authorization requirements increased from 8% to approximately 24% of covered drugs on Medicare Part D plans between 2007 and 2019.

Solutions-
First, focus prior authorization on its intended purpose. Health plans should eliminate prior authorization requirements for medications that have very low final denial rates… this should only be for people that are outliers
protect continuity of patient care. For patients who are stable with chronic treatment, insurers should offer protections to minimize disruptions and inefficiencies—get a drug forever shouldn’t need to go off the drug or switch insurance than try a new drug on their formulary when you have already failed it on the other insurance
Third, promote transparency, efficiency, and fairness. Technology exists to enable prescribers to view the formulary status, prior authorization requirements, and cost sharing for medications and alternatives in electronic health records (EHRs

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2757311?widget=personalizedcontent&previousarticle=2757307

FDA updated its gadolinium warning in 2010, specifying that 3 agents (gadopentetate dimeglumine, gadodiamide, and gadoversetamide)- the FDA stated that other GBCAs could be used cautiously under certain circumstances
We needed a solution so BOOM newer agents, termed group II agents (gadobenate dimeglumine, gadobutrol, gadoteridol, and gadoterate meglumine),
In this study – almost 5k pts. stage 4 and 5 CKD receiving group II GBCAs, including patients undergoing dialysis. They report a 0% pooled incidence of unconfounded NSF

https://www.bmj.com/content/368/bmj.l6669

Sticking to a healthy lifestyle including not smoking, not being overweight, and exercising regularly, is associated with a longer life expectancy at age 50 free of major diseases such as cancer, cardiovascular diseases, and diabetes,
The number of extra disease-free years is around 7.6 for men and 10 for women, compared with participants with no low risk lifestyle factors.

https://jamanetwork.com/journals/jama/article-abstract/2758598

prostate cancer and diet
Time to progression did not differ significantly between the groups (unadjusted hazard ratio, 0.96 [95 percent confidence interval, 0.75 to 1.24]; adjusted hazard ratio, 0.97 [95 percent confidence interval, 0.76 to 1.25]). For the intervention and control groups, the 24-month Kaplan-Meier progression-free percentages were 43.5 and 41.4 percent, respectively (difference, 2.1 percent; 95 percent confidence interval, −8.1 to 12.2 percent).

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2759737?guestAccessKey=dc41fd4e-5c0c-46bb-9353-ceca16f96b25&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=olf&utm_term=020320

just read the summary- These findings suggest that, among US adults, higher intake of processed meat, unprocessed red meat, or poultry, but not fish, was significantly associated with a small increased risk of incident CVD, whereas higher intake of processed meat or unprocessed red meat, but not poultry or fish, was significantly associated with a small increased risk of all-cause mortality.

SUMMARY
This study revealed approximately 3% to 7% higher relative risks and less than 2% higher absolute risks of incident CVD and all-cause mortality over the 30 years of follow-up. People who consume more servings per week would have greater risks.
Why they are wrong and the big problem
Furthermore, risks of CVD and mortality are determined by a range of factors, including but not limited to genetic predisposition, demographic factors, socioeconomic status, weight, lifestyle factors (eg, smoking, sleep, physical activity, and diet), and the built environment
Overall looked at 6 studies total- large heterogeneity- people could eat all sorts or amounts of meat
Food preparation methods were not consistently and universally assessed across the cohorts in this study. Therefore, separating fried chicken from poultry intake was not possible
They used questionnaires- we know people lie to be healthier on questionnaires
Only baseline diet data was analyzed from the 6 studies in this cohort. – 19 years of follow up but only used one questionnaire for each study!!!!!!!!!!!!!!!!!!!!!! only 1 dietary measurement was used—

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https://annals.org/aim/fullarticle/2760034/disclosure-form-work-submitted-medical-journals-proposal-from-international-committee. disclose everything for the papers that you keep..or write

Patient comprehension of common orthopedic terminology Cosic F, Kimmel L, Edwards E. Heal Lit Res Pract. 2019;3(3):e187-e193.
patients don't understand all that we say

https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.32700

one article is good to go for HPV (maybe)

https://jamanetwork.com/journals/jama/fullarticle/2759002

sunscreen gets into the blood but so what

and uptodate says use Tamiflu past 48hrs but look at the study and what do we find???

https://www.ncbi.nlm.nih.gov/pubmed/31839279

clinical trials regisitery told it all

https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004471-23/results

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Try not to read these all at once!!

https://www.ncbi.nlm.nih.gov/pubmed/30715088

https://www.bmj.com/content/365/bmj.l2006

https://www.ncbi.nlm.nih.gov/pubmed/30359476

https://www.ncbi.nlm.nih.gov/pubmed/30964526

https://www.ncbi.nlm.nih.gov/pubmed/30415629

https://www.ncbi.nlm.nih.gov/pubmed/31454046

https://jamanetwork.com/journals/jamapediatrics/article-abstract/2723523

https://ginasthma.org/

https://www.acc.org/~/media/Non-Clinical/Files-PDFs-Excel-MS-Word-etc/Guidelines/2019/2019-Afib-Guidelines-Made-Simple-Tool.pdf

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32531-5/fulltext

https://www.ncbi.nlm.nih.gov/pubmed/30782340

https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/human-immunodeficiency-virus-hiv-infection-screening1

https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prevention-of-human-immunodeficiency-virus-hiv-infection-pre-exposure-prophylaxis

https://journals.lww.com/greenjournal/Fulltext/2019/10000/Over_the_Counter_Access_to_Hormonal_Contraception_.41.aspx

https://www.nejm.org/doi/full/10.1056/NEJMoa1811744

https://www.nejm.org/doi/full/10.1056/NEJMoa1911303

https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz754/5602478

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No summary YET! I promise it is coming, but here are a few more articles I think were pretty impressive from 2019.

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It is that time of year again-- Top articles of 2019 part 1. This is my opinion, but I think it is a pretty good opinion.

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https://jamanetwork.com/journals/jama/fullarticle/2751726 uspstf now grade B for asymptomatic urine in preggo
https://pediatrics.aappublications.org/content/144/6/e20192739kids do shoot their eye out!
https://www.nejm.org/doi/full/10.1056/NEJMoa1908142Metoprolol does not treat COPD
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2754809?guestAccessKey=d3ef4800-287b-43aa-9d58-fd3c1e8359c2&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=olf&utm_term=111819
HIV and social media!!

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https://www.nejm.org/doi/full/10.1056/NEJMoa1806515

-- IVC filter after a severe injury = it is ok to wait 7 days

https://www.nejm.org/doi/full/10.1056/NEJMoa1904143

antithrombotic therapy with afib after a pci and 1 year == just the DOAC

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31791-X/fulltext

polypill for primary prevention just might work but likely need more research

https://www.bmj.com/content/366/bmj.l4570

the more you exercise the more you live-- seems like a basic concept and it is easy to understand but sadly hard to follow for many

https://www.ncbi.nlm.nih.gov/pubmed/31189511

dulaglutide can save non-fatal strokes and for just 20million dollars you can help the industry make a killing in this very flawed study

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https://www.ncbi.nlm.nih.gov/pubmed/31550435 mono and athletes -- stick with 21 days

https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32738

Hair Dye does not cause breast cancer

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2753986?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=110619

mailing the HPV kit is better because it increases screening rates

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https://jamanetwork.com/journals/jama/article-abstract/2753909?guestAccessKey=03d877eb-6d48-476f-9487-aa6fbbd8a8d5&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=103019

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2754091

https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz754/5602478

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https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2753986?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=110619
mailing hpv gets more people screened! Shocking!
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32135-X/fulltext?rss%3Dyes
patiromer might work but 70% of people don't need it cause they don't get hyperkalemia!

https://www.acc.org/latest-in-cardiology/journal-scans/2019/09/04/14/45/sleep-duration-and-myocardial-infarction
sleep 6-9 hours-- its good for your heart!

https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(19)30366-9/fulltext

sertraline does not work for depression but it works for anxiety-- likely best to just hold off on the meds for most PCP depression
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2753318
cutting medications makes people happy
https://annals.org/aim/article-abstract/2751453/blood-culture-results-before-after-antimicrobial-administration-patients-severe-manifestations

if you delay blood cultures then O NOOOO cause antibiotics are really good and work really fast
https://www.ncbi.nlm.nih.gov/pubmed/31265456?dopt=Abstract
maybe just maybe long gone are the days of letting any pregnancy get to 41 or 42 weeks!!!

https://www.ncbi.nlm.nih.gov/pubmed/31265456?dopt=Abstract

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https://insights.ovid.com/crossref?an=00006396-900000000-98602

https://jamanetwork.com/journals/jama/article-abstract/2751887?guestAccessKey=8fa2f772-1ba4-40ff-9015-4fcb46d6829e&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=091819

https://www.ncbi.nlm.nih.gov/pubmed/14604741

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2749268?widget=personalizedcontent&previousarticle=0

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2749265

https://www.jwatch.org/na44775/2017/08/10/nonsteroidal-anti-inflammatory-drugs-back-pain-and

https://www.ncbi.nlm.nih.gov/pubmed/28153830

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https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2748452 -- come one come all unless you are a kidney

https://www.ncbi.nlm.nih.gov/pubmed/31054907 SURPRISE!! Women prefer to do self swab rather than clinician swab

https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/hepatitis-c-screening1 If the pt. is breathing then you test for Hep C

https://jamanetwork.com/journals/jama/article-abstract/2748796 high dose vit d. might be harmful

https://www.nejm.org/doi/full/10.1056/NEJMoa1811744 Canagliflozin is here and so are the SGLT2 inhibitors--IMPRESSIVE

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https://www.ncbi.nlm.nih.gov/pubmed/30347032 Terbinafine adverse effects are rare

https://www.ncbi.nlm.nih.gov/pubmed/31189511 Dulaglutide prevents MACE but at a high price tag

https://www.ncbi.nlm.nih.gov/pubmed/30853124 If you punch your buddy then get some buddy tape

https://www.ncbi.nlm.nih.gov/pubmed/31076416 prediabetes gibes me a headache

https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Gynecologic-Practice/Access-to-Hormonal-Contraception Over the counter birthcontrol!!

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Let's look at the numbers behind CAC! The best evidence is found here https://jamanetwork.com/journals/jama/fullarticle/2687224 but the largest study is found here https://www.sciencedirect.com/science/article/pii/S0735109715072253?via%3Dihub but in the end they use this https://en.wikipedia.org/wiki/Net_reclassification_improvement which might trick many people but I know it won't trick the smart people that listen to questioning medicine

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https://www.ncbi.nlm.nih.gov/pubmed/30874755 - ACC/AHA and ESC are still not evidence based

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.939.1670&rep=rep1&type=pdf -- only need to check every ten years-- it is the other risk factors that matter!

https://www.ncbi.nlm.nih.gov/pubmed/26680162 Signal to noise is around 1 in 10 yrs

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https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2739056 not all guidelines are equal, think for yourself. Some guidelines even do harm when you actually look at the evidence.

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2740207 doacs and surgery what do you do-- low risk surgery stop one day prior and start one day after surgery. with high risk surgery you stop two days prior and start two days after

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2747871?guestAccessKey=90abe76b-3a15-4b95-9b42-4f751c5fbe64&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=etoc&utm_term=081919 Pt in the hospital for a non-cardiac condition and they have a high bp== don't worry about it- no evidence for what one week of high bp will do but we do have evidence that starting medications while in an acute state will cause harm. just let it be!!

https://ginasthma.org/wp-content/uploads/2019/04/GINA-2019-main-Pocket-Guide-wms.pdf
GINA guidelines- budesonide formoterol prn OR SABA plus ICS prn for stage 1 or for stage two still budesonide formoterol prn OR scheduled ICS twice daily with prn SABA

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https://www.nejm.org/doi/full/10.1056/NEJMoa1813959 even when we dont know where the stroke is coming from- aspirin is still king all these years later

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30840-2/fulltext Aspirin is such a king that is doesn't matter if you have a spontaneous brain bleed or intracerebral hemorrhage it does appear safe to restart aspirin after a 2-3 month break

https://jamanetwork.com/journals/jama/article-abstract/2736564 smart-choice trial looked 3 months compared to 12 months of DAPT and

https://jamanetwork.com/journals/jama/article-abstract/2736563 STOPDAPT-2 trial looked at 1 months followed by monotherapy clopidogrel compaed to 12 months of DAPT and BOOM 1 month is winner winner chicken dinner

https://www.ncbi.nlm.nih.gov/pubmed/31063082 all of medicine has variation- some pcp will give an antibiotic for otitis media. some will not. Some radiologist will say follow up is needed and some will not

https://ginasthma.org/pocket-guide-for-asthma-management-and-prevention/ new asthma guidelines from the global initiative for asthma says NO MORE EVER solo albuterol it is now soooooooo simple you get budesonide/fomotorol PRN

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https://www.cdc.gov/mmwr/volumes/68/wr/mm6825a2.htm we are not testing people for HIV even though guidelines https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/human-immunodeficiency-virus-hiv-infection-screening1 since 2006 have recommended that everyone be tested! 13yrs later!! Time to do it!!

https://www.ncbi.nlm.nih.gov/pubmed/30658933 The self swab is as good if not better than provider or clinician testing- it is time to educate the population and move to at home cancer screening- save the office visits for important things- like what to do in the 7% of women that are hpv positive.

https://www.fda.gov/drugs/medication-health-fraud/public-notification-big-penis-contains-hidden-drug-ingredient?utm_campaign=CDER%20New%2007%2F17%2F2019&utm_medium=email&utm_source=Eloqua&elqTrackId=6371f8c053574a478fea3a734e8041ed&elq=1631be58825d49e3803c4b92a2cb8553&elqaid=8776&elqat=1&elqCampaignId=7246 Big Penis is a drug that has the drug Viagra in it- over the counter medications are not regulated and this is a perfect example of you really have no idea what you are taking even if you think it is 'all natural'

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737752 everyone thinks they will live forever, including those on dialysis but in reality 60% will die within 5yrs-- have the end of life conversation sooner than later

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2737844 want to live longer and longer without disability then be happy

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https://www.ncbi.nlm.nih.gov/pubmed/30608562 A1C level low is not good and high is not good cause both seem to wind up have you the pt. in the hospital for hypoglycemia- the low point of the U curve is around 7-8% which ironically seems to fit perfectly with recent guidelines

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2735985 pts don't take the medications and if they have hypertension at least in this candania study 1/3 were magically curred of their hypertension one they were monitored

https://www.ncbi.nlm.nih.gov/pubmed/31147311 PPI are still a drug with real side effects and should not be given out like candy but if your patient needs them they lets make no mistake about it they do work really really well

http://cancerpreventionresearch.aacrjournals.org/content/12/5/305 smoking puts you at 2-3 times risk of bladder cancer-- peeing blood is not for me so I choose not to smoke

https://www.ncbi.nlm.nih.gov/pubmed/31112386 no more PRN albuterol -- instead when you want to write for albuterol inhaler you will instead right for daily ICS or PRN ICS/LABA --- GAME CHANGING!! Lets have a moment of silence for prn albuterol in mild asthma-----

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https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31942-1/fulltext If you are over 70 or 75 and primary prevention then likely no benefit in statins and secondary benefit is very small

https://www.nejm.org/doi/full/10.1056/NEJMoa1806802 Get the glucose down! After you max out other risk factors as intensive control doesn't have a legacy effect

https://www.nejm.org/doi/full/10.1056/NEJMoa1809944 vit d doesnt beat placebo for anything- ever. Except for the vit d lab number

https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-hypoactive-sexual-desire-disorder-premenopausal-women Vyleesi (bremelanotide) will make you have more sexual desire on a sexual desire scale but not more sex-

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https://www.ahajournals.org/doi/10.1161/JAHA.118.011318 energy drinks prolong the QT just ever so slightly in healthy 22yr olds so if you are thinking of telling grandma to slam 32ounces of energy drink and she is on QT prolonging medication then you probably shouldnt

https://www.nejm.org/doi/full/10.1056/NEJMoa1808082 zolendranae is not a magic drug that cures osteopenia they just have magic trial makers the rigged the trial to show benefit

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2734709 in a study that looked at 7 days of step for 70 plus year old women it seemed that over 2000 seem to have a cardiac benefit and the benefit significantly leveled off around 4000 steps

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2734798 if going to the dentist and you have a fake heart or fake heart valve or previous endocarditis then you need antibiotics else you dont
https://jamanetwork.com/journals/jama/fullarticle/2717474 give a ppi with anticoag to prevent GI bleed hospitaliazation by about 33%
--

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vitamin d- if you cant give up on it then give up on checking the lab value- fire and forget.

https://www.nejm.org/doi/full/10.1056/NEJMoa1800566 induction at 39 weeks is okay with me

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2698631 cardio test and all test have varibility

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31131-0/fulltext our evaluation of you prior to surgery is basically worthless based on current evaluation or stress test

https://annals.org/aim/article-abstract/2708163/kidney-damage-biomarkers-incident-chronic-kidney-disease-during-blood-pressure kidney disease from lower bp doesnt seem to be actual damage just hemodynaic effect

https://www.ncbi.nlm.nih.gov/pubmed/30688979 lower that bp and doesnt seem to have an effect on dement and might even be protective

https://www.gastrojournal.org/article/S0016-5085(18)35193-X/fulltext pt going for elective colonoscopy- keep the clopidogril

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afib- new guidelines!
https://www.google.com/search?q=2019+American+Heart+Association%2C+American+College+of+Cardiology+and+the+American+Rhythm+Society+focused+update+from+their+2014+guidelines+for+the+management+of+patients+with+atrial+fibrillation&rlz=1C1CHFX_enUS708US708&oq=2019+American+Heart+Association%2C+American+College+of+Cardiology+and+the+American+Rhythm+Society+focused+update+from+their+2014+guidelines+for+the+management+of+patients+with+atrial+fibrillation&aqs=chrome..69i57.1079j0j7&sourceid=chrome&ie=UTF-8

FIT test has high sensitivity and specificity for crc and it gets more people to do colon cancer screening and lets be honest it is only a good test or a good drug if people actually do it

https://www.ncbi.nlm.nih.gov/pubmed/30802902

afib can wait to be converted and over 50% of the time will convert on its own
https://www.nejm.org/doi/full/10.1056/NEJMoa1900353

good news for you lazy people listening to this on the couch you can still inprove your all cause mortality with increase exercise in your midlife crisis.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2727269

if a person has an arterial blood clot they dont always have cancer but most likely they have cancer and we have not found it... yet

http://www.bloodjournal.org/content/133/8/781?sso-checked=true

UTI and foley cath- probably dont need to replace the foley cath give the correct antibiotic

https://www.ncbi.nlm.nih.gov/pubmed/30094820

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https://www.bmj.com/content/364/bmj.l42 skip breakfast- it doesn't help you 'lose weight'

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2723074 Automated BP cuffs are the new rage and for good reason they are about equal to awake ambulatory blood pressure

https://www.ncbi.nlm.nih.gov/pubmed/30653040 if you have a pt. going to surgery for their knee because of osteoarthritis-- let it be and DONT do an injection.

https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30191-1/fulltext if you have a choice-- give apixaban

https://jamanetwork.com/journals/jama/article-abstract/2719307 you can not pay physicians for readmission but then they will try and game the system and in the pt. misses out and dies more often-- oops

https://jamanetwork.com/journals/jama/article-abstract/2727448 tramadol increase mortality! WOW shocker-- maybe this isn't real but it is really is worthing making us stop to think.

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shared decision making for lung cancer rarely happens in the community and when it does happen 2/5 said no thanks to cancer screening
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2720126

vit d. - does not work on a bus it doesn't work with white women or black women anyone
https://www.ncbi.nlm.nih.gov/pubmed/29905969

achilles tendon rupture- if you go to surgery NNT for rerupture of 1 and 66 but risk of infection 1/33
https://www.bmj.com/content/364/bmj.k5120

Topical pain creams dont work for chronic pain- BUT low risk of side effects and still getting almost 2 point decrease on 10 point scale-- I will take it!
https://annals.org/aim/article-abstract/2724041/compounded-topical-pain-creams-treat-localized-chronic-pain-randomized-controlled

Alirocumab is still way too expensive
https://www.ncbi.nlm.nih.gov/pubmed/30597485

concussion in an athlete-- get them to the sub-symptom heart rate
https://jamanetwork.com/journals/jamapediatrics/article-abstract/2723523

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https://www.emrap.org/episode/rightonprime/introduction RIGHT ON PRIME IF YOU NEED CME

10% likely isn't high risk but it certainly deserves more than 0.6% of people on statins so don't forget your statins
https://annals.org/aim/article-abstract/2725144/characteristics-high-cardiovascular-risk-1-7-million-chinese-adults

Oxycodone "the best high of all" https://link.springer.com/article/10.1007/s11916-019-0751-7

Smart phones are actually being smart
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32993-3/fulltext

You lose weight and want to keep it off you better keep moving
https://onlinelibrary.wiley.com/doi/full/10.1002/oby.22373

Dont be that guy that gives 1.2million extra days of antibiotics
https://www.bmj.com/content/364/bmj.l440

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https://www.emrap.org/episode/rightonprime/introduction RIGHT ON PRIME IF YOU NEED CME

https://www.bmj.com/content/364/bmj.l240 hpv is still boss

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2724778 push up to push good health

https://www.bmj.com/content/364/bmj.k4681 prepping for HIV education
https://www.ncbi.nlm.nih.gov/pubmed/27149090?dopt=Abstract very effective if used
Still effective in san fran https://www.ncbi.nlm.nih.gov/pubmed/26334052?dopt=Abstract

https://www.ncbi.nlm.nih.gov/pubmed/30596290
the made up time that are expiration dates

https://www.nejm.org/doi/full/10.1056/NEJMoa1808779 ecigs are great but meds are better when you look at the med trials as well
https://www.ncbi.nlm.nih.gov/pubmed/12171809
https://www.ncbi.nlm.nih.gov/pubmed/10053177

Questioning Medicine: Recent Episodes

Questioning Medicine

FDA tells the companies but the companies don't tell the public! (thread) #MedTwitter This should be a #publichealth issue.

But taking birthcontrol or on BC is a surrogate outcomes so lets look at the secondary outcome-

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2737844 want to live longer and longer without disability then be happy