130. Antibiotics, BIOTOK and Knee Osteoarthritis, and Bempedoic Acid

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!