143. Dexa Scans, Atypical Fractures, Cervical CA Screening, Capsaicin intraarticular

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.
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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!


Next article

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.