Weekly Medical Update 178

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