Miscellaneous
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 nothingPARTICIPANTSPremenopausal 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. ... [Message clipped] View entire message 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 analysis382 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) were2.5 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.pdfhttps://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 MedicineLevonorgestrel vs. Copper Intrauterine Devices for Emergency ContraceptionN. 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 SandersIn 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 outcomesMI = NNT- 81ischemia-driven coronary revascularization= NNT 65 (which makes sense, cheating way to add more numbers to your outcome)cardiovascular death- no differenceischemic 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 BADWe 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.