146. Fluoroquinolone and Aortic disease, HPV Vaccine, Orthostatic Hypotension

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