20 Episode results for "ace inhibitor"
COVID-19 A DIRE MESSAGE TO OUR ELDERLY
"What is it that you know? Those that are over the age of sixty five in that. What should we know about this? And specifically to that really small group experience a much higher you know rate of of an acute reaction. These are great questions so age is interesting and If you look at the average age of death and and this current pandemic as we track it Northern Italy is six to eight years older than southern Italy and so a and it's one of the oldest countries in the world its average as is around forty nine years of age the United States and China about thirty six years of age. So we're thirteen years younger as population. And so when you see the United States having the highest death toll from this thing anywhere else in the world now you need ask what is going on with the United States. Why is the United States? Apparently older biologically. Then it is chronologically. Why is China At the same age average age or know many European countries As similar aged to you know our country why are we dying more and the answer is pretty obvious when you when you rank in chronic disease or health outcomes everything from neonatal death all the way to end to end of life things. The United States ranks thirty fifth in the world by the most friendly measurements from the government watchdog organizations that we might renege closer to to forty six or something in the world. But we're somewhere between thirty fifth and forty ninth in the world where the tail end of all modern societies autumn of list. So if you look the top economies and industrialized nations. We're dead last of health outcomes and so why is the United States dying? Why are we have so many examples of younger people dying? It's because we are sicker than any other nation and so specific to this cove and it turns out that we know that the corona virus both the common cold as well as these know more severe versions of it in and SARS Moore's and Cova binds to a receptor in the lung. That's called that's called ace to in so this as two receptor is expressed naturally on our lung surfaces as we age ace two can go especially if there's respiratory disease. Copd for example has very high ace two expression along the surface we have lots of channels in and COPD is one of the only lung conditions that that puts yet increased. Risk of death from this. The all the rest of our Right it's cardiovascular renal disease coronary disease and cerebrovascular disease these N. diabetes. And like if you look at those co morbidity is that people are dying from and their relationship to this as two receptor gets pretty interesting because as goes up Napoli in in lung tissue from from damaged from Emphysema type things with COPD but not in cardiovascular disease until you add to drugs and so when you add a statin drug suddenly the whole system up regulates receptors. When you add an ace inhibitor. Which is our leading number one recommendation. From all medical societies if you have diabetes heart disease or chronic kidney disease the first drug. You're supposed to be on and you can. You can get sued for Malpractice. If you don't have a patient on one of these drugs is an ace inhibitor. If they don't tolerate. Nay Senator the most common side effect ace numbers is cough because up regulated. The aced yours in in in their lungs. And now they're reacting to their environment abnormally. So if they develop an ace inhibitor. Cough which means change the balance of their reactivity to their environment. Then you need to put them on an AARP which is an androgen receptor blocker which again up regulates a stewart receptors and so- ace inhibitors and. Aarp's are now seem to be a major risk factor. For Death Ron Cogan why because it up regulates the days two receptor and so the United States is the most medical is systems so yes we have high in chronic disease rates and in response to those chronic disease that we put on medications. That are we know are putting you at risk of dying from Khurana Myers. So if we had a true public health organization that was really concerned about the next few months of death from grunt of that just got discovered over in Wuhan Providence. The very first thing we should have done is announced doctors. You need a transition all your patients who are ace inhibitors. Calcium channel blocker or some other form of blood pressure control. Or Hey may put him on a healthy diet but regardless off the ace inhibitor. If we had done that we would have saved thousands of lives take them off the staten. There's no in the absolute risk of dying from a heart attack by taking somebody stat and is near zero for three months. Six month period. So take them off of their stat and put him on on a healthy plant based diet so their classroom doesn't go up and then take them off their ace inhibitor. If we had done that we would have completely changed the death toll in the United States. We knew that these drugs increase to 'em we knew based on SARS and the common cold corona that binds the two receptor. If we had done that we would have saved thousands of lives all over the country not to mention all over the world and then we should have stopped influenza vaccination because an extraordinary study came out in twenty seventeen showing that if we vaccinated for flu your risk of getting thrown of falling your goes up and this is not just corona but six other common respiratory viruses that risk goes up and this is commonly seen. This is a this is a well describe scientific phenomenon that if you get exposed to the real influenza you develop at. What's what's called kind of this transverse immunity where you get immune to bugs that aren't even represented in influenza. You get this this immune system intelligence and you'll were now become resistant to other bugs if you don't get flu and you're you're exposed to an abnormal protein within that flu virus and so you have to mount a Weird Antibi- that you can't get your normal heard type or kind of immune system response to the environment. Then you get increased risk of this so what we should have done is if we really believed that. This thing was ten times more deadly than flu if we well actually said at the beginning of one hundred times more deadly than if they really believed that then in December they should have frozen all influenza vaccines at no more influenza. Vaccines come off your neighbor and your Arab and your statin drug. Don't get influenza vaccine. We're going to cruise through the season because we have a new strain. We didn't do any of those things we know that science and I h knows at science. Cdc knows that science we did not make public. Health moves to protect the community from Corona virus. Why I think we kind of knew. Well I knew right away just gets. I have a calculator anybody with a calculator. As soon as the first cruise ship stopped in Oakland. We knew everything we needed to know about. This had that nobody died on that ship for fourteen days. They were quarantined on that ship. It has a five day Lynn infectious period. You will develop symptoms in five days if you're going to develop symptoms at all and so we should have seen high amounts of blue people and in and you know liver failure and all that on that ship because it was the worst population you could possibly ice. Because they had an average age over seventy on that ship and and there were children running around. So you've got children. Which are the best microbiome swampers outside of dogs? Dogs are are definitely our best but kids from this awesome gift that they're so get at microbial communication and you got kids running around the ship. You've got old people. They're sequestered and they didn't and they didn't sequester they they didn't quarantine those patients away from each other and those initial couple weeks and so it should have been massive death toll ownership and yet. Nobody was even critically. I think one or two people came off critically ill. The rest of the three thousand seven hundred people weren't even there was only one hundred dollars so that was showing the ended. Fourteen days. A few people weeks later died and we said they died of Groenemeyer crossovers definitely in their in their experience. It was present may have contributed in some way unmasking toxicity of their STATIN drugs in their ace inhibitors and their flu vaccine the Yod but ultimately we know that the death toll on that ship was low enough that if we extrapolate over the United States we would see somewhere around a death toll of point one percent maybe point three percent at worst and we know that flu. Can you know in two thousand seventeen was causing a seven percent mortality rate? We knew at the beginning that this was not going to be some massively fatal thing and last we managed it wrong and we did if you like that clip and be sure to check out our live broadcasts of the high wire every Thursday morning at eleven. Am Pacific Time. You can watch it on facebook youtube tunes and twitter. We'll see you there.
A Nephrologists Take on Renal Function Testing
"Mayoclinic toxic curated weekly podcast for physicians and and healthcare providers. I'm your host daryl. Chapter general internists dat mayo clinic in rochester minnesota. How many times have we had had a patient. We presumed was doing well and we found the serum creatine into be slightly elevated or a urinalysis where there were a few red blood cells dell's present common problems we encounter and most often they don't represent anything serious but they could helping to sort out these common common problems is dr suzanne norby an internist and nephrologist at mayo clinic. Welcome suzanne thank you daryl. Let's start by talking about the creation and what we've used it for measuring mental function but what exactly is it and where does it come from. That's a great question russian so creatine breakdown product of muscle that everyone's body produces and it's eliminated by the kidneys when we see the blood level of create need increasing thing. We know that the kidneys not doing its job is the creatine in a reasonably good test in assessing renal function. It's actually not very sensitive because you can lose a lot of kidney function before the creatine increases significantly in what situations would that take place often. It's in patients with is lower muscle mass so they don't have as much muscle that would produce the creatine waste product. That's why we have the concept of the estimated g._f._r. That most labs calculate okay okay so patient may be very thin frail female elderly patient <hes> it may not be accurate and that may be the age group that you really want to assess renal function shen exactly so in that case the create need could really underestimate the degree of renal insufficiency right and so that's why the estimated g._f._r. Far was developed. There are formulas that take into account a patient's sex age and race either african american or not african american in in order to determine what the estimated g._f._r. Is because you will see a change in that before you will see a change in creatine or you'll see a more significant change in the estimated g._f._r. Before the croat knee might raise alarm bells okay all right. We've also used the blood urea nitrogen or be u._n. How does that compare with the creatine the b. u. N. is more of protein waste product than that can be influenced by other things besides kidney function for example. <hes> steroids can cause an increase in be u._n. Or g._i. Bleeding can cause an increase in be when not necessarily related to the kidney function. There's another marker called staticy. Have you heard of that one when i have met her to so statin c is a protein that's produced by all of the cells in the body and it's not affected by race gender age protein intake or muscle mass and so that's another the marker we can check and using the estimating g._f._r. Formulas to give us a non creating based way to look at kidney function. Is this test easily available. Do most a <hes> labs have the capability of running that test i think most labs would or it can be sent to a reference lab. Okay all right so let's see we have. I have a patient and we get their labs back and they have a somewhat unexpected rise in serum creatine and what steps do we take to evaluate that i think the first thing might be to repeat the crowd and he make sure there wasn't a lab error and then take a good history from the patient to see if they have had any changes in medications indications or other factors that might cause the creatine to increase if you find that this is something that is persistent and real than you'd want to evaluate wait further with a urinalysis considerate renal imaging such as an ultrasound a one problem that i see often in terms of resulting in a slightly elevated the creation and is the fact that we tell our patients to avoid eating and drinking after their evening meal and if they were a little bit low and fluids at day and they haven't had anything to drink come in a little bit on the dry side and that can elevate their craton in first thing i do is i have them recheck well hydrated state and very often it comes back down to normal normal right and there are certain medications that can predispose patients to having that increasing creating when they get a little dry such as non steroidal anti inflammatory medications ends ace inhibitors receptor blockers. Those all can do that. What else should we look for that can indicate a patient having kidney disease z's the urinalysis is really important to look for any evidence of protein urea or abnormal cells in the urine micro. Albumin urea is another marker of kidney disease and also real imaging is important. If you find somebody with an elevated <unk> needs to look at the kidneys make sure there isn't any evidence of obstruction or structural oh abnormalities. Some patients have a solitary kidney. You never know it. Some people can have polycystic kidney disease which is a very common genetic disorder that affects the kidneys though such things. We don't pick up unless we actually go looking okay now. We use a lot of ace inhibitors for treating essential hypertension. Is it necessary to check assume create an after we start the ace inhibitor if they're in his normal prior to starting it. I generally recommend that because the keratin often will i'll go up when you start the ace inhibitor because of the way it affects the filtration pressure across across the globe mary-louise and in that case you can get a new baseline with starting the drug drug and that way when you go back and look if the crowds increases in the future you'll know when it was associated with the drug and what could be indifferent also some patients who may have renal the vascular disease can have a disproportionate increase in the evening and that might make you want to back off and look for further causes of why the creating increased more so basically just one recheck that's adequate and then maybe just assess annually as in the past right so i would check one <hes> create an potassium about seven to fourteen days after starting nacer nacer arab and then go from there if everything is stable again with ace inhibitor or a._a._r._p.'s are they safe to use in patients who have cla some degree of renal insufficiency. They're actually the preferred medication to use for hypertension in patients with kidney disease because of the beneficial effects they have on slowing slowing progression of kidney disease particularly in patients with diabetes or protein area okay. Let's talk about medications that we should be concerned about in in patients that have some degree of renal insufficiency. Which ones should we be alert to. I think the big one are non steroidal anti inflammatory medications those <hes> and reduce also the g._f._r. And can have <hes> bad effects on the kidneys can cause hyper kalia fluid retention worsening hypertension so we advised our patients to stay away from those some other medications that you need to adjust for the level of <hes> jaffar are things like metformin that that can be used safely down to a g._i._f. Are thirty <hes> gabba penton and other medications that <hes> can have effects on the neurologic system and are eliminated eliminated by the kidney can really result in some problems patients can become somnolent have asterix's muscle issues when they are taking too much for their level of kidney function also proton pump inhibitors have been associated with. I'm declines in kidney function. Although it's not clear whether they're entirely causative. There's a strong association and so that's another thing to look at whether your patients really need to be on a p._p._i. <hes> so common medications that we often use in the elderly population right. Are you an n._p._r. P._a. looking to fulfill your two thousand thousand nineteen c._m._e. And pharmacology credit requirements we have designed our online inpatient medicine for n._p.'s and as course just for you learn about treatment pathways from admission to discharge in an interactive case based format visit c. e. dot mayo dot e._d._u. To get started on your credits. Now join us weekly here at mayo clinic talks we discuss best practices and burning questions subscribed today using itunes or your favorite podcasting app. I've i heard i don't know if this is true or not that the anti hypertensive effect from hydrochlorothiazide is lost or decreases as one gained some real insufficiency is that is true. That's true they end up not being very effective once you get below jaffar of say thirty or so good to know and that's because they need to be filtered at the guerrillas in order to get to the transporters where they work and jia fargo is down they become less effective <hes> so what degree arenal insufficiency should we determine this patient that needs to rally just that's another great question so i think it deter it depends on <hes> what else is going on with the patient so patients who might have stage one or two chronic kidney disease or fairly normal kidney function but they may have <hes> blood in the urine protein in the urine family history of kidney disease or maybe even a rapid decline in their kidney function would want to be seen by nephrologist just to try to figure out what is the problem and go from there patients who have a longstanding history of diabetes or high blood pressure who have <hes> advancing chronic kidney disease stage two three four chronic kidney disease should be seen by nephrologist probably around stage three or four to develop a plan for for <hes> renewal replacement therapy should that be happening in the near future to get education about kidney disease to learn about ways to slow the progression and the complications nations also that can occur at that level of kidney functions such as anemia and bone mineral disease associated with chronic kidney disease patients one of the most common types of patients. We see he's a diabetic with renal impairment. <hes> we realized that this is getting progressively worse. Is it wise to have those patients seen early in algae or is there not much you can do until they get more into the advanced stages. I think it's good to have them seen early and by that i mean somewhere in stage three if you're convinced there's nothing else going on besides diabetes and hypertension just to make sure that there is no other cause for their chronic kidney disease for example simple could have a super imposable mary disease. Could they have interstitial nephritis. Could they have some other problem that we would manage differently and if we don't find that you can be reassured that managing their risk factors such as diabetes and high blood pressure is the best thing to do also with the complications of anemia and bone mineral disorders. It's good to hugh address those and get on a plan really to manage those to avoid further complications okay well. Let's talk about urinalysis. Now we commonly order order these they're inexpensive. Give us a fair amount of information but sometimes they come up with abnormalities and we're not exactly sure what to do with them. Struck about micro micro humid area. When should we evaluate patients with a small number of red blood cells in the urine so according to recent guidelines micro materials should be evaluated when you see more than three red blood cells per high power field and so if your lab does a dip stickier analysis where you would see blood or hemoglobin on the urinalysis you'd want to get a urine microscopy to see if there are red cells present if there aren't red cells president could be from a number of factors such as <hes> urine and maya globe in and hemoglobin can also <hes> 'cause the dip stick to be positive or certain bacterial reactions and infections can cause that to be positive so you'd want to confirm mm-hmm with red blood cells under microscopy if you see more than three per high power field than you'd want to proceed with an evaluation for microsoft materia and is one urinalysis this is adequate or do. We need more than one to begin this annella. The review apparently one year analysis is off even in a patient on anti coagulation unless issue suspect something different such as menstruation or <hes> trauma. Something of that nature that you think is transient. So how should we evaluate these <music>. What do they need their uh so white cells on the urinalysis. You'd want to get a urine culture to see if there's an infection <hes> checking to see if if there's any degree of chronic kidney disease or acute rising create need and then also checking the patient's blood pressure because that's a very important indicator of kidney health as as well so once you do those tests and try to <hes> stratified whether there is an urgent reason to <hes> have the patient evaluated or whether under this can wait origin indications might be if the blood pressure is high say one eighty systolic over one twenty that would be a high blood pressure that would warrant urgent evaluation perhaps in the emergency department and then if there was fever and flank pain that could indicate potentially an obstruction due to a stone or some other factor that would want to be evaluated by urology. Oh jeez sooner. If you don't have those things <hes> make sure to check a physical exam. The abdominal exam pelvic genitalia prostate all those issues can occur and cause structural causes of bleeding. The preferred evaluation is a. c. t. eurogramme with stocks copy so that you can see the kidneys kidneys the whole urinary tract and also inside the bladder if you have a patient with stage four or five chronic kidney disease and don't want to use contrast than non contrast c._t. Not at a p with retrograde would be the way to go does an ultrasound have any role in the evaluation of micro huma cheerier currently. It's not considered a first line test but sometimes with the c._a._t. Scan you may see a mass in the kidney that they can't quite tell with see whether it's cystic or solid and then in that case the ultrasound how can help you determine that but it wouldn't be something that you would get. I would have some of the common things we find. When we look for micro material oftentimes you'll see patients agents who have <hes> bladder cancers if they have some microwave materia kidney stones are also very common and in nephrology we will see a lot of patients who have he material and protein area because of a process but stones and malignancies are the things that you'd kind of want to worry about something that you would would treat if you come up with a negative structural evaluation and a patient doesn't have protein area it would be good to repeat the air analysis annually and then two to three years later are considered whether the structural evaluations should be repeated. I've had some patients where we find michael. He maturity on the urinalysis and they can't remain in town long enough to get the evaluation done and they send me the evaluation to get home and they often have a seat to your grand but it stops there <hes> but it really is important to do escapee to look at interior the bladder as well correct absolutely all right. How 'bout urine cytology does that. Is that helpful urine cytology really isn't very sensitive and so i think a lot of europhilia malignancies can be at missed if you're just using urine cytology not getting the full structural evaluation or if you're getting the full structural evaluation the urine cytology does not add much in patients who have a known euro theol- malignancy <unk> are urologists will monitor your cytology from time to time but it's not considered a first line test any longer more optional okay is the urinalysis analysis is inexpensive in i have found a few kidney cancers bladder cancers from evaluating patients with microsoft. Is it a good screening test for <hes> renal or bladder cancer now. It's actually pretty insensitive. You know so you can have a especially reno. Malignancies may not cause materia area and you can have have those are incidentally discovered on imaging or for evaluations from pain patients. You've never had any microwave materia all right. We've been talking about abnormal renal function and micro humid with dr suzanne norby a physician in the nephrology and hypertension division at at mayo clinic in rochester. Thank you for sharing your expertise with suzanne. Thank you great to be here. If you've enjoyed mayo clinic talks podcast. Please subscribe stay healthy and and see you next week.
S5 Ep20 What is the new normal? What and why did this happen?
"Everybody house It'd be awesome Then Dr On here. Host of Dr Rodney unfiltered uncensored our twentieth episode of this season and probably going on three months of the corona virus. It's been a long long time. I guess we're all tired of it. But thank you for tuning in his Dr Ron. And we're going to have a few little news episodes for you today and we'll see how it goes. Generally I know exactly what I'm going to be doing. I know exactly what my guests are going to do. But today we're GONNA SORTA wing it a little bit and before we get going after. Tell you that this program contains general medical information. Medical Information heard on this program is not advice. It should not be treated as such your income. You're encouraged confirm any information obtained from this program with other sources and review all information regarding any medical condition or treatment with your physician. And I welcome you with an attitude of gratitude has some ready to. Hey how about our hands? Look at your hands. Look look what they do. We should be great for having those hands. Let's try to appreciate beauty. That's right try to find the best in others to leave the world a bit better whether by healthy jar childlike garden. Patch a redeems condition to know. Even one life has breathe easier. Because you have live. That's the that is what Ralph Waldo Emerson said. You need to succeed and don't educate your children to be rich. Educate them to be happy. When they grow up they will know the value of things and not just their price. Eight-year food as your medicines. Otherwise you have to eat madison as your food you are loved when you are born you will be loved when you die in between only you are in charge of your life. Think about it so it looks like the seven best. Doctors are God sunlight rest exercise diet self confidence and friends that we can't forget the friends and social gatherings of this Kobe. Social distancing really really hard on a lot of people so ladies and Gentlemen I wanNA give a shoutout to all. Our first responders are nurses or doctors firemen or police officers or he went out there trying to keep us safe and keep themselves and their family safe. I hope we all remember our veterans yesterday on Memorial Day people that gave their life for our roar. We have today. I WanNa thank Dr Wrong for last week I know went on a little long a little confusing but you know all our shows are archived. You can listen to them again and you can listen to Dr Wong's Youtube show would number three seventy and I was him. Giving us the supplements we need to do case. Forcedly vaccinated and we'll get into that later and was basically were activated. Liquids Zeolite okay. Liquid Core Fil Eyeso- printing I as a P. R. I N. O. S. I n. A eyeso- print zine Ivermectin. Iv E. R. M. E. C. T. I N. Believe it or not using in animals but early. It works really well along with doc cycling. Which is the old fiber mice for this Cove it isn't that something. Dr Slightly making a comeback and he also mentions zinc and quinine zinc at about two hundred twenty milligrams a day and Quinine. Well we're Queen I. You can get quinine. The hawks hydroxy quickly though. But you also can get it in tonic water and if you take zinc zincs I trade. You'll you'll prevent this covid virus from mutating and getting into ourselves. So what's going on? What what what is happening in this world of ours one thing happening in my field is physicians are not being allowed to practice their profession. They're being told what to do. They have a drug alcohol. Hydroxy quinto but out since nineteen fifty five and not allowed to prescribe in Kobe patients. You know wasn't thinking of starting with this. Maybe a will because hydroxy quit them. You know if you take a bunch of people falling out of an airplane okay and some of them are infected with Cova it just falling and they have this virus in them well. Wouldn't it be nice if they had a parachute because right now the high risk people are going to be hitting hitting hitting the ground putting on a ventilator and dying? The tests are are horrible where we talked about that last week. So with this an allergy. It'd be good to have a parachute and this parachute you know. You should soon as you start falling out of airplanes. You should start take taking this drug will be your parachute hydroxy. Quinlan with gaily zinc and vitamin D three and vitamin C. They slow this virus from duplicating itself and Slowest Lhasa down. So you can't open a pirate if you're falling on an airplane you can't open the too soon right. What was your near the ground to leap so hydroxy. Grennell the plus zing when or after any of your tested positive. Maybe too late is might be good to start as a prophylaxis. But it's only a bucket day you know it's not thousand dollars a day. The one she wants everybody to take the this never been proven to work anyway. And if you're on ace inhibitors or AARP's and you're testing well the AARP's like about certain Divan you know you're gonNA fall really for more rapidly so you. WanNa maybe if you're in a area and you have to get out you might wanna start thinking about this. I actually work but some doctors should being persecuted for using it. And if you take too late it's not gonNA work. And that's why some studies show that this drug does not work late even if you take it with that. Zithromax Z pack. We don't have socialized medicine but independent physicians are of being forced to rely on fallacies faulty testing. And it's a. It's a shame. So what's the risk of opening? That parents should shoot too early. Taking a low dose hydroxy chloroquine two hundred milligrams per week or less after a small loading does. This drug has a half life of twenty two days to two hundred milligrams per week. You may might need less so low. Dose Hydroxy Clerk Win has little dangerous side effects and there's even safe in pregnancy because it's been using malaria patients that are pregnant. Always want to consult your physician and there. There's a chance that you know we're going to have a second wave because we don't have heard immunity because everybody's been inside and his Co. Vig Nineteen virus. I think is had twenty five mutations already. So ask your physician. If you're in a high risk category maybe you WANNA take two hundred milligrams once a month to prepare for these further mutations and don't forget your multi vitamins and vitamin C. Vitamin D three. I remember the half life of Hydroxy Corcoran is twenty. Two days longtime all right. So let's Let's talk about a few things first thing. Let's let's talk about the all the projections that The CDC and south she made and you let me know. Whether would you think of there are people that have writing that this lockdown should be rescinded immediately and that found? She has to investigated to find out why he pushed this catastrophic measure. There's if there's fell out there called Matt Margolis he's over a PJ media he's reporting that the CDC estimates. That the case tally rate I remember that the CFO or maybe only zero point. Four tenths of a percent zero point for now. That's the case fatality rate. They were much lower than without. You told us or doctor's scarf the scarf lady they said it'd be two three or four percent. And that's what got us into this lockdown this case fatality rate is those cases in which someone was symptoms how they test confirming they were infected and some that were not confirmed. Just symptomatic there's another race. Call the infection fatality rate which is the rate among the totality of those infected. Only so you can die with Kobe but argued dying from of it. That's the difference so the infection fatality rate the I. R. represents the odds every random person contracts the virus as as dying on the other hand that that cf mentioned okay. The case mentality rate. Isn't it really of interest to us right? It's just Is it just like a normal person trying to understand how the consequences everybody everybody had died? Not Those with from cove it you go to the CDC's website and they estimate that only sixty five percent of those who contracts virus actually wind up with any symptoms at all that means that the infection fatality rate. Those that are that have. Kobe definitely is sixty five per it. Gets a little confusing? Since ninety five percent of the case fatality rate. Anyway the numbers come down to about zero point two six percent and and we just really haven't tested everybody so it's GonNa be less than that remember when we were told it was going to be three point four percent which is about and a half times higher than it is now. Fasi was wrong. Why we don't know yet we have to find out it's interesting fast. Came on and gave us all these bad numbers and then he goes and writes an article for the New England Journal of Medicine stating that. It's a little worse than the common flu. Why did he report to his peers? In an article New England Journal of Medicine. One thing and tell us something else again. I don't know the answer unless he lie but we have to find that out. He pushed us into economic shutdown. And have you anybody seen the amount of suicides incredibly a lot? Nobody's talking about them. We'll talk about them a little later so Dr Fallacy has been not been right one hardly anything. He's talked about hardly anything. And how about the vaccine and he's pushing you know him engaged or pushing this Maderna's that scene. We talked a little bit about it last week. It's the RNA. Vaccine champion by algae financed by gates is using an experimental our NATO technology. Value was confident. he's well. We don't even eat animal studies as associate. Well here's another mistake. He made they had fifteen human guinea pigs. Guinea pigs humans that suffered serious serious adverse effect within forty three days. Receiving this this vaccine a vaccine with those kind of reaction race could cause grave injuries to one point. Five billion humans if it was giving everybody on earth and that's what gates issued happen otherwise you can't travel. He wants to. He wants a tattoo. You're like the Nazis Tattoos. Jews he wants to give you a ID number by the way you know some people say well. How did they come up with that name? The C is for certificate the Oh is for of certificate of vaccination. Id Cove it certificate of vaccination. I Day that you don't hear many places but here and the challenges for the vaccine are still ahead has attempts for for Kovin. Vaccines have always faltered. They gave you get the animals. I think they were using ferrets. In the other study I read about. They get great anybody response when they're exposed to the virus now. The you know we have a lot of anybody's you're supposed to be immune to the virus. But then when they gave the they expose these I the wild virus they got sick and then died Robert. F Kennedy Jr. had good article on that. So where are we? Well we've been talking a lot of We've been lied to an abused. Ladies and gentlemen got us all wearing masks. Well the best definition of mass. I've come across. Is that you know you don't put up a cyclone fences. Flies mask induces a hypothesis state? You don't get enough oxygen and so what happens. Your immunity goes down. It increases your sympathetic drive. What's that mean it means you? It makes you nervous. You have more cortisol. Your immunity goes down. There's more carbon dioxide in that mask you have an increase with fire rate. So when you're you know you have a lot of carbon dioxide and low oxygen. Can that be good? And how many people get irritated on their face and now they're touching their face. Baras are so small they get through these masks. And then you touch the money outside then you touch your face. The front. He's mass or or are laden with bacteria and viruses. You're supposed to wash your hands before you take the mask off with your hands. You see anybody doing that. So there's lots of studies about mass. I mean one after the other About the damage they do. Okay and then. There's a study going out now. This has been period viewed. But it's it's it's not. It's it's not that greatest study it's a review of previous studies prevents the evidence fairly but is quite limited with no evidence that worry them in crowded places helps at all and no evidence at all that it's related to the nineteen and the bottom line is they're pushing this lady around. It's not even been peer reviewed but aligns itself with the findings of a similar review of research studies by the World Health Organization that was published in October last year which concluded there was no evidence that face mask or effective in reducing the transmission of the flu. So they want us all. Wear face masks just crazy stuff happening ladies and gentlemen this really crazy. Okay so this. Kobe is a historic toxic. Hypoc injury in other words. You're just lacking oxygen. Almost like you have a carbon monoxide poisoning. And no one's talking about it. No one's talking about viruses. We have tens of thirty one. Ten thirty one is. That's at ten with thirty one zero zero after a lot of Zeros. That's a lot of viruses. You know our gut. Our Body has three hundred eighty trillion viruses in it. Three hundred eighty trillion. So do you think people that that that foul cheese and the doctor scarf lady really serious about this thing you know in twenty seventeen the mortality rate from the flu. You have any idea because I know you're not seeing on television. It was seven percent and now we have a covert Corona Virus. That is zero point. Four zero point two percent and we're locked down. Nobody's talking to you about air pollution. Well it's getting better. Thank God to the lockdown. 'cause that's a good thing maybe we we. We won't be using many anybody anywhere. Any idea any antibiotics reuse here. Four point five billion pounds. That's be with a billion with a B. crazy crazy crazy and you hear about people turning blue with this. Covid happened before happened with SARS. The two thousand one thousand two same thing patients. Turn Blue Long filler fluid. They they knew then. It was more from lack of oxygen than respond Tori failure and we went into this already. So I'm not GonNa Redo review this but I will tell you that the cyanide levels in our errors arising and the higher they are the death rate. We'll go out so maybe this virus which Israel don't get me wrong is real. Virus it can penetrate the cells. What if you're predisposed to having further injury in other words if you've had a lot if you have gotten a lot of flu vaccines if you're on an ace inhibitor. If you're on a any art to if you're on a staten you're more prone to get the side effects of this virus. And how do you think your your body's going to react? If you wear a mask you don't have enough oxygen and and you know what airplanes do affect. How virus is transmitted from one area to the other. It would've gotten there anyway. A couple more days it would be airborne and get to travel around the world so when we think about what what do we have to look forward to an in. The new normal probably will be a lower travel already when you know what that might be. A good thing goes our carbon monoxide particular matter in the air probably down. I might be good. Maybe he'll get better used dealing with each other on a social basis. Maybe we'll go. We'll go from the most. Medical is DH population in the world. Here in the United States. Maybe you know not so medical is maybe we'll let doctors go ahead and treat people rather just treat tests the sad part about this and and our virologist no this. I FOUL KNOWS CORONA VIRUSES. Have a two year life history so here mark my words. They're gonNA come out with with the via with a vaccine probably in a year or so you're fifteen Mazda's still too soon usually takes five years your vaccines and see all the immediate side effects. They have no idea the long term side effects. And we'll get into that another time but you know so this vaccine out there virus is going to go away two years anyway knows it all went away because the vaccine mark my words we have to take care of her. Elderly we have to be like Marines. Never leave a soldier. Leave our soldiers behind so we have to take care of the elderly. We have to take care of this tyranny of fear. This is just killing us. We get so much information five times more now than we ever did on. Television computers hit has stagnated. We don't know what to do but nine point. Eight percent of people recover. They don't tell you that they just tell you how many people die and bill gauges funding all that Mapping at the John Hopkins. So sure they're gonNA show you millions and millions of cases. Well the more they test more of the quarter fine but a lot of people had no symptoms at all they just had it and or developing immunity and go on with their life so we are biological body and we're a spiritual being. We don't want to get trapped. You WanNA celebrate life we WANNA stop fearing death. Maybe it takes. We have to work at not being afraid to die. And how do you get rid of your fears how they get by them? While you have to learn to love more you have to see our humanity. See The people around US Love Each Other. That's going to be the new normal appreciate your days. That's that's my take on this if we come out of this and and and we don't drive as much and we just maybe walk more and enjoy life more. This may not be so bad because a particular matter in the air is increasing and certain areas Like Italy you know with the airports and the Gripe is seen and all the vaccines. You could almost Correlate that with the covert and amazing gentleman United States. We spend so much money but on the list of healthy countries were down at the bottom and as I said we take the most medicine of any country in the world. We are sick. Nation thirty fifth in the world in Ellison debt. Thirty fifth. You'd think we'd be first or second right so if the founder of the world. We're serious about this this this Corona virus. They should tell everybody that's on a statin drug to stop it. Everybody on the nascent or to stop it. You know what the side effect of Hebron is if you take it every day as a cough it would tell everybody on. Aarp's get off them get on a calcium channel blocker and. Don't take a flu shot because the flu shot has corona and retroviruses it. You didn't hear that from anybody you heard it here. You'll hear from some other physicians that are on Youtube. That's what we need to do and mental illness from this. This virus is incredible. You know the tenth leading cause the United States now is suicide increase of thirty one percent with this virus. Well people staying inside losing their jobs. No place to go no interaction with other people. We are socialized social people and in the past economic conditions correlated with the number suicide attempts right and we got to keep that in mind and suicide very rarely ladies and gentlemen is reasonable of just having free will usually thought out. It's a conscious conscious decision. Irrational decision not always psychiatric so there are people during the at pandemic struggling with mental. We really have to find a way to take care of them and get them treated. Okay so where are we? Well we we definitely WANNA turn. Our wife is off at night. We WanNA take the vitamins. We talked about the Zeolite. The probiotics You're GonNa have either met on hand. Get that at a feed store. One C. C. Four hundred thousand emphases safer fifty pounds above that you take it orally mix it with anything Scotch. Beer wine cranberry juice. Whatever okay and you want zinc he to either zinc lozenges or or Dr Wong's zinc which is zinc psychiatry. You want you want to take zinc re day really important during this time and you want to say educated you want to be the CEO of your own body. You want to learn more about these ornate vaccine's they go in your body and they become party you. They may produce antibodies. But do they protect you against the virus? And that's the sixty four thousand dollar question so far. The answer is no so far. The answer is no so. What do you think's GonNa Happen? You think they're gonNA come in and have the army take come in and put us all down and give us a shot. I don't know I think just too many people with guns. I don't think that's going to happen. How do you how do you vaccinate seven to eight billion people anyway but they might make it hard? They may want to have everybody have this vaccine with his idea and so they can track us for the rest of our life. You know you see all these actual contact tracing what do you think therefore so it makes people paranoid they make us turn on one another you come in contact with somebody that had covid nineteen. Now you're in this tracing nap and you had to be vaccinated because you are quote unquote. You have to protect the public. They may even have your boss You know if you're not vaccinated you can't work you don't know what kind of what kind of pressure they can put him under. The cultural part of it is probably going to be pretty strong in the future. Companies to say we prolly. You're giving free shots. Well these shots you know. They're they're so safe where people dying from them and be. Why can't you have sex and children after these shots? What are they afraid of? Our we were guinea pigs you know and and every time there's a flare up more shots maybe you can't get on airlines who is You don't have that. Tattoo I keep comparing it to the Nazi Germany. So we're going to be forced to forced into this one way or another culturally collectively Maybe militarily is probably be a full-time job for some people trace contacts get vaccinated. Then we'll have bill gates on a Tedtalk tell us how great it is and yet. His kids aren't vaccinated. So I'm told incrementally gates wants us all vaccinated and idead covert certificate of vaccination ide- don't forget that you heard it here? Dr Ron unfiltered on censored. We know about the mass worth hydro clerk when Probably something you WanNa think about. If you're in a high risk group May WanNa keep someone hand you might. WanNa listen to last week's program. Dr was about what to do. In case you are forced forcibly vaccinated. There's a doctor there's that be. There's even this study with Ouchi. In New York. It was not allowed to prescribe cove and he had to go to a private hospital to do it. And that crazy and and like I actually a couple years ago. I guess the figured out what the Joey Adams has been here. He could make more money now now. He doesn't like it only been around for sixty years. So heck you know. How are we letting people get away with this? You should read about Dr. Stephen Smith was trained by faust. He's the guy told you about. And he's he's really enthusiastic about this. Malaria Drug Graduate Yale. That pretty good credentials right. Well he say cooed. I don't have words to describe how frustrating this always there. There's just a craziness out there and I don't know how to correct it. The truth doesn't matter anymore from Dr Smith Unquote. He to use drugs Corcoran. They won't let them use it quote. Either I've gone nuts or they have well we can't both be saying unquote he said in New Jersey and he himself has been taking hydroxy quirk when since March before even began treating patients with it in April. He said a poll of sixty two hundred physicians in thirty countries found Hydroxy Corporation to be the best drug available to treat cove in nineteen the nineteen. We're that called from first. Letter of the alphabet is eight. One the ninth letter is I artificial intelligence a all code he calls. I dropped Sikora when a game changer. And he's not allowed to use it and that crazy. Well I could go on and on but look. We're GONNA start talking about things that we can control next week. We're going to start talking about our immune system talking about teaming our shower. Hey clean how many people off their shower head? You know if you have a dirty shower head and have the water goes on your head. You know you can get pneumonia. Maybe we should be a little more conscious back. Do we take a shower. Clean off that shower showerheads Huh. So Ladies and gentlemen I don't WanNa ripper over. Where were you know? We welcome our humanity and realized we are human okay and spiritual beings and treat each other with respect kindness and gratitude. We can come out of this thing. Maybe a little more respect for the environment okay. That's not a bad thing Decreasing the amount of carbon we put in the air so we don't have some particulate matter and so much carbon monoxide. You know so If we all stay together and stay on track we might be able to come out of this thing and please do not fall into the trap if you have antibiotics home and don't feel feel good for any reason so we'll just take some z pack. Been saving. Don't do that because we can't forget about the Super Bowl. We used to talk about all the time. Remember that causes the C diff right two point eight million a year thirty five thousand deaths in this country every year according to for the drug resistant superbugs like see thirty five thousand year in year out. The don't invite that enemy into your house. Okay antibiotics don't kill viruses when they're unions with Ivermectin hydroxy alone. I dropped Sequeira Quinn. Yeah I mean there's they do treat the secondary infection but please don't be say well. I got a headache. I got us through it. I wanted to take an antibiotic at your last last option. So we're going to get out of our houses and we're going to have her surgeries and checkups and everything else. Please don't do it up. On antibiotics there is zero proved. Come protect you from getting infected with the corona virus or catching covid nineteen prophylactically. Okay there's we talked about drastic Quinlan hydroxy core Quinn different different Drug altogether okay. So I'm not gonNA TAKE ANY QUESTIONS TODAY. My seat all the callers here but just know that we're going to get back to a more normal schedule next week Talking about things that matter for your health for your longevity and start bringing back our special guests and we'll have Our friend Freddy. Who's been writing songs for me. Route Great Song for our daughter's birthday or disgrace on pop died and now he just starting to fool around with raiding closing song for our podcast. So we do appreciate. We have an attitude of gratitude for Fred. Man was a professional musician. Whole life toured with bb King Guy. So He's a gentleman. This is Dr Ron this episode. Twenty the new normal. It's we're going to have to work at it why this happened. I would ask you to If you're interested in why it happened is beyond my pay grade but it would ask you to to look up a video very Dr Sheba s HIV and it has to do with the money. The big guys were having too much time Too much trouble. I ain't ten percent interest rate to the Fed back in the last quarter of last year. They wanted to make sure the interest rate came down. That's just theory and they did it by locking us all down decreased demand for everything. Oil PRICES FELL. Interest rates fell to zero now. They went from ten percent and the last quarter of last year two zero. So we're SORTA PALMS BUT WE DO Hopefully we can get together and get a one page with this thing and they have great rest of the week. It's been good talking to you. Tell your friends about Dr Ronald filtered uncensored? We're here live every for every Tuesday and We are on Alexa. We are on Google. We're on spotify or every place you go. Just just say Dr Ronald filtered uncensored. You will get our podcast. It's been great talking with you. I thank you and have a good one here. Everybody's got run today. Wisdom all about good A tune in next win is a win. This is When the DON is how Is How digest Net know by the happen. Call if you have stray call. Death were a winless is oh is.
#98 - Peter Attia, M.D. and Paul Grewal, M.D.: Coronavirus (COVID-19) FAQ
"Lou everyone welcome to the Dr Podcast. I'm your host. Peter Attiyah this podcast. My website and my weekly newsletter. All focus on the goal of translating the science of longevity into something accessible for everyone goal is to provide the best content in health and wellness full stop and we've assembled a great team of analysts to make this happen if you enjoy this podcast. We created a membership program. That brings you far more in depth content. If you WANNA take your knowledge of the space to the next level at the end of this episode. I'll explain what those benefits are. Four if you WANNA learn more now head over to Peter Attiyah. Md DOT COM forward slash. Subscribe now without further delay. Here's Today's episode Special Bonus episode. I guess at the drive further focusing our attention on Kovic nineteen in addition to the episode. We just released with Dr Peter. Hotels wanted to follow up where we kind of had a chance to dig a little bit deeper into various topics that we've been learning about over the past weeks as I mentioned in his podcast. Our team both clinically and on the research side has been pretty much nonstop working on this for two weeks. And if you've been following you on twitter or instagram under the handle purity. Md You probably noticed a number of updates in both those platforms mostly videos on instagram. I'm joined in this episode by Dr Paul Gray. Well who has been on the PODCAST? Previously in his context is also a colleague of mine who works with us in the practice. Paul and I spend about an hour. I think doing a pretty effective job going back and forth on. We've learned in the past week and also putting it in the context of what we've been paying attention to for the past four to six weeks and where we've become more optimistic. Maybe we become a little more pessimistic and I think we probably touch on as many topics as most people would ask us about in this episode. Don't consider these things sort of standalone episodes. We try not to really emphasize or cover material. That's covered in the episode with Dr Hotels. And of course these things are going to continue to evolve so I would invite everybody if you're interested in this and I hope at this point you are. I hope everyone's attention has been grabbed to to sort of not. Just listen to these episodes but sort of stay up to date with us for updates. Podcast will probably be coming out sort of irregular intervals until we have similar continuity of of information and as I mentioned before the podcast with Peter Hotels for all things related to corona virus. There will be nothing behind a paywall so whatever we have in the way of shouts including a lot of the content that we've been sharing with our patients. Were going to just make available for everyone so without further delay. Please enjoy our discussion today cove. Nineteen everyone welcome to a special edition of the drive. This is kind of an informal version of the podcast. I'm speaking with one of my colleagues Paul Gray while Paul is Previous guests on the podcast. A lot has happened. Actually since Paul was a guest on the podcast lease at the time of that recording since then Paul has actually joined our practice so he is now one the clinical members of our team and of course the other and more relevant thing. That's happened since that interview. Is that corona virus? Outbreak has kind of taken hold over many of us so with that said Paul and I thought an efficient way that we might be able to communicate what we've been doing for the past couple of weeks is to actually sort of sit down and have a discussion. Allah the type of discussion. We're kind of having five times a day between ourselves but also with our clinical team and our research team so Paul. Welcome back good to be here. It's it's funny. I mean I think we just have to set the stage for everybody. 'cause I'm now I'm sitting in my parents basement with three other thirty something men who are my my brothers. And we're all living in like a thousand square feet right now so. Forgive any background noise. That might be a knocking about in the distance. But yeah I mean this has been a a wild ride for the last couple of weeks. I think emotionally for me. It's been a roller coaster because we kind of had our eye on this a few of our more in the know patients started asking US questions probably about three almost four weeks ago and so we've had a bit of a bead on this and and to be honest. It's a bit like it's been watching a slow-motion car crashed because the numbers around all of this and the disease progression and the epidemiology there as kind of abstract is they. Are they do model out. Pretty when you're talking about exponential growth. They model out. Whether you have an exponent of one point two or one point five. You're going to have some pretty explosive reality on the ground. So we've just gone from. Okay what is the most likely scenario? What IS THE BEST CASE SCENARIO? What is the worst case scenario? Where do you think we are actually in terms of what we were thinking a week ago versus where we are now while I was gonNA actually back a little bit before that? I mean I think it was sort of mid January win. Actually some of our more astute patients began asking questions mostly at the time as it pertained to travel to Asia at that time I sort of appointed you and then shortly thereafter teddy one of our analysts as our in house SARS slash as the time I think we were just referring to it. As a corona virus. We weren't necessarily referring it to Covy to the name it now carries because I don't think that designation existed but so I sort of put you in charge with fielding all those questions and then teddy on the back end in charge of looking at things that required some sort of a research topic so for me. It all changed in mid February about three weeks ago. I don't remember exactly what the wake-up was but I think I realized this was absolutely not going to be contained was absolutely coming to the United States and what I was reading an I guess believing was that we were not going to be very well prepared for even at the time what I thought would be a slowing disease. I'd say for me. The next big thing that was a wakeup call was last Friday. So that would be just from the time. We're recording this seven days ago. That's when I got somewhat pessimistic. I think independently you got kind of pessimistic on that day as well and you were. I think much more optimistic than me in the weeks leading up to that. I mean I can explain what changed for me. But what in your mind concern you a week ago? Well it was really. I think the fact that testing had not been rolled out and the fact that we had even a small handful of cases meant that the ball was completely dropped. And that containment was no longer going to be an option. And if we look at the I know you were talking With Dr Houghton a few hours ago about the the are not and the the replication rate of this virus. But you know I think we've understood that it's probably on par with or more than the flu and based on those numbers alone and the numbers of cases that we actually saw. We knew that there had to be hundreds or thousands of cases. That were as yet undiagnosed so that was when I knew that in the US at least that we were going to get blindsided by this thing which we are and you know what the I actually just got a message from one of our colleagues in the in one of the Ers in New York. Who is he's like? We saw this thing coming three weeks ago and we just had our president patting themselves on the back for their response but three weeks ago we could have seen this thing coming and didn't but I guess that's what happens when you say you want a government. You can the size of which you can drown in a bathtub and now we're kind of drowning in a bathtub so you actually emailed me earlier today. A back of the envelope calculation that said in the state of New York if we have four hundred twenty one confirmed cases. Twenty percent of whom require hospitalization. That's eighty four people requiring hospitalization if we at full capacity have three thousand ICU. Beds I assume that means no one else needs an ICU. Bed who's not a corona virus patient which is a pretty generous assumption. You then would take the log rhythm of three thousand by eighty four contracting with the growth rate and if we stay with the growth rate of one point three which is actually pretty aggressive. Hopefully we're closer to one point one or one point two but I've no reason to believe that we've certainly been higher than one point three on daily reps that puts you at two weeks to filling all the ICU beds if that sounds extreme has. Italy taught us anything about that. Yeah I mean that actually is the point that we were talking about last Friday. Which is that. It wasn't actually the mortality rate. That was scaring us. So we kind of pegged the mortality rate at somewhere south of one percent it looked like in South Korea with a very young population and they were very on it in terms of their response. The number was about point. Six eight in terms of the mortality and it was about one percent reported in places outside of so when China had time to prepare. It was about one percent. Italy was reporting as high as six percent and so I think the discrepancy there is not the mortality rate per se but the morbidity rate which is the percentage of patients who experience a very serious illness that requires hospitalization and then from there the number of those patients or the percentage of those patients who will require an elevated level of care which from the first cohort of patients out of Wuhan. Which was I think? One hundred and thirty eight patients. It was about forty five to fifty percent of the people who were hospitalized required either noninvasive or invasive ventilation and I think it was half of those so about twenty five percent or twenty percent of people who were hospitalized that required mechanical ventilation and intimation. So you're talking about five percent of people who get the illness will require intensive care and so our capacity as a nation is somewhat limited. We actually have I think. Some of the fewest number of hospital beds per capita and then in terms of ICU. Beds just looking up what we are seeing we again we have. We have like three thousand issue beds in New York. I think there's about ninety five thousand in the country as a whole and again those needs to be staffed and so the number is when if this thing grows at the daily multiplier that we were seeing out of some of the countries that didn't handle it as astringently as South Korea Singapore and China after the first month of the virus then the easy calculation is that we would be overrun in terms of system capacity pretty quickly so even if you make that I think when I was sent you that calculation that was based on twenty percent even if we put that number at five percent of people got only gets us to lake three weeks essentially so we would be effectively overrun within three weeks in terms of our ICU CAPACITY. Now again as to physicians speaking to the public. We need to be very careful about what that means. And how do we address kind of panic around it? And and so there's things we should probably talk about. Number one is the natural history and pathology of this disease which were starting to piece together. And there's still some uncertainty about and then two is the kind of the idea of flattening the curve or slowing the number of cases that require intensive care over a period of several months rather than several weeks. So Peter I know we put together a bunch of stuff but what's your kind of current sense of. Let's walk through maybe the story of a how you come in contact with the virus and then be what are the downstream steps from biological level that are occurring that lead up to that respiratory failure at seven to ten days. Yeah I mean I think as we learned starting Saturday morning. I think that's when you and I basically started hopping on nonstop calls with anyone who could spare the time to speak and amazingly people were so gracious to sort of hit pause on their work and sort of hop on thirty fifty. Sometimes if a ninety minute calls with us my hand to a sewer from how much I was taking notes on those phone calls and I think we learned a lot. I think that's when we sort of got an understanding of how. The pathophysiology of this virus differed from that of influenza which is always something worth understanding and not just the sort of garden variety. Influenza that reeks traditional havoc each year killing about one thousand people that it infects but also the really scary influenza viruses such as the h one n one and of course the most frightening of them all the nineteen eighteen Spanish flu which was a pandemic that killed staggering sums of people all of those variants of influenza. Have something in common. Which is they really ravaged. The immune system maybe to be more specific the immune system itself react so violently to those pathogens that you actually get a hyperactive immune response in fact in the Spanish Influenza. The highest mortality was actually seen in two groups not just young people that presumably had the best immune system but also pregnant women who didn't necessarily have the healthiest immune system but had the most switch don immune system because of course when a woman is pregnant. Her Immune system is navigating a very delicate balance between rejecting and not rejecting fetus. Which is foreign so. How does that compare them to something like this? Well it turns out that of all the risk factors that we look at from the cohort today and I think as we stand here today we've seen again depending on the data probably about one hundred and forty to one hundred and fifty thousand confirmed cases over five thousand deaths. What we know is that the immune response doesn't seem to be the critical part here. The critical issue is the cell that is damaged by the virus and maybe it is worth spending a moment to explain what the Hell of viruses and why that happens. So I'll try to be quick about this because I don't think anybody really wants to hear long detailed microbiology but viruses are kind of these things that aren't truly living in the way of bacteria is they have genetic material in the case of the corona virus they carry are in a so not DNA but actually are in a which comes from DNA and ornate of course contains the instruction set to make protein. But they don't have the machinery to actually replicate and so in. That sense of virus is really a true parasite and a virus infects a host. That has all of the machinery necessary to help it. Replicate are more viruses than I could ever count and the good news is most viruses are actually not pathological we sort of exist in a state of symbiosis with them where we let them borrow our cellular machinery to replicate and they don't harm us in any way shape or form and therefore we spread them without being aware of it etc but every once in a while virus comes along and the viruses harmful so for example influenza virus infects cells of the respiratory tract and in the process of doing so it actually causes damage to those cells which is part of why you have some symptoms like a sore throat and things like that but as I said it's that immune response to it that ultimately goes from a hyperactive response to a paralysis response and therefore a lot of the damage is either from this immune response itself and the cytokine storm it generates or superimposed infections that come on to a weakened immune system well in this case this corona virus infects cells that carry these ace two receptors and there are lots of cells in the body that have them but the probably the most important sell that for the purpose of this discussion. At least right now our cells in the lung called Numa sites and in particular very version that called the type to Numa site so the viruses getting into that cell presumably because it gains access to that cell through receptor interactions. And it just from a purely evolutionary standpoint wants to reproduce and we're GONNA get teleological on it. It's not necessarily looking to harm us. But it's that's it's port of entry at wants to reproduce in wants to use the cellular machinery to replicate. It's a and therefore replicate itself but in the process had damages that cell. And that sal makes a very important thing called surfactant and maybe you can tell folks why damaging enough of the cells of the lung that makes her fact and becomes the the sharp edge of the wedge that leads to a very rapid demise potentially yes so the first reports out of Wuhan from mid February there describing a rds which is basically where you have normally in a in a pneumonia. We have what's called a focal consolidation? Right so you have some patchy area of the long that is filled with fluid inflammatory cells. Pus and that part of the long is not available for gas exchange. But you have you know. Seventy eighty percent of the remaining lung tissue that can participate in gas exchange. And keep you going. What happens in a rds or acute respiratory distress syndrome is you have basically a fluffy white out on x Ray which means that? The entire long is filled up with some amount of fluid or collapsed. And so the primary pathology here that they're seeing in these severe cases that there's diffuse Alveoli damage so Alvie Alveoli or the kind of small sacs that use a soapy material called surfactant to lower the surface tension and allow them to stay open like tiny little bubbles and participate in gas exchange and so the Numa sites that make this surfactant or it appears that they're being completely invaded and overloaded by the virus replicating and destroying them. And so. What's happening that there's direct damage of the virus to the cells. Rather than a hyper inflammatory injury. Now it's getting complicated because I mean that was when we were talking to the virologist and immunologist last week it seemed like that was something unique that we hadn't seen in some of the other viruses. But unfortunately we're also getting reports of the other standards types of things that we see in these respiratory viruses which is both superimposed bacterial pneumonias as well as site a kind storm so essentially the immune system with being tasked with something so novel is just going completely haywire and doing the damage itself. And what we're seeing actually clinically. Is that the people who end up even surviving when they're put on respirators. It looks like they're on respirators for mechanical ventilation for three to six weeks or longer. And so when you're talking about being ventilated for that long. We don't know what the long term injury is there. And you're just setting yourself up for a host of other complications. That are too scary. To even enumerate on the podcast. So we're dealing with a double whammy here and and what's particularly scary about this virus in particular is that it is affecting some number of people in their thirties forties fifties. We wouldn't normally associate or identify as having immune compromise or being susceptible to something like a seasonal flu. The Standard Risk factors apply but. It seems like hypertension and cardiovascular disease are actually higher than lung disease in terms of predicting how poorly you're going to do in response to this virus and circling back to that ace two receptor so as to is basically what helps recycle and turn off. Ngo tents into NGO tents into is what your body makes after cascade in order to increase blood pressure and so in people with hypertension the amount of Angie attention to is elevated in air. Go the amount of ace receptor would also be elevated as kind of a negative feedback or positive feedback loop and those ace receptors are not just in the long but as Dr Houghton has mentioned are in the intestine and are present in the cardiac muscle. Well so some of the other reports that we're seeing are that people are succumbing to Myocarditis or inflammation of the heart muscle. Whether that's big again. We're kind of playing armchair pathologists here but I have some suspicion. At least that that the ace receptor distribution in the cardiac muscle might be a playing role here and that dovetails into a really interesting conversation that we've been having over last week which is okay. Given a paucity of data and mechanistically high throughput screening of drugs that might have an effect based on the receptor lag- and interaction of the virus. We quickly zoomed in on ace inhibitors or NGO tencent receptor blockers. Which would stand to reason that if you're able to block the virus from entering through this a two receptor that you could either prevent or mitigate its damage when it tries to replicate and spread to the other Numa sites but it was only a couple of days later when we made a complete one eighty in our thinking on that because what we do see is that within about two weeks of being on an NGO tencent receptor blocker which are among the most commonly prescribed medicines for hypertension in the US and have some of the best safety profile right so we give these medications to literally millions of people. We have millions of patient days. Tens of millions of patient days of them being on these medications and they have an excellent safety profile but it might be the case that because the two receptor is up regulated by three or four times in the heart muscle or in the lung that could just set you up for being particularly susceptible to this virus and and so we went from Eureka. Wow what a beautiful kind of potential therapeutic too holy cow. We really don't know. So what do you think is going to be the next kind of data piece of data that we'd be looking for in order to be able to make a decision around that well? I wish I was GonNa ask you a question. Which is we're getting a lot of people asking. If they're taking engineer in receptor blockers or ace inhibitors which are two different classes of drugs that have comparable effects if everything you just expressed was confusion around weather. People who do not take them would benefit from them in the prophylactic sense I or the treatment sent second. We are now at the point where we would say no. We just don't have sufficient information to take that chance but of course it begs the question which is for the people who are already taking those medications. They continue to take them and presumably benefit from the blood pressure lowering effects and the protection of Kidney. Or do they stop them. Our current thinking of is that patients should stay on those medications. Were not advising people to stop that. But what I'm looking forward to your question is who I've tasked one of our analysts with which is every single day to be looking at pubmed and every other source out there for case reports because what we expect to see is daily updates from analyses coming in from countries that were leading us on this and I don't expect to see randomized data yet. What I do expect to see his case control studies where we look at again. We have five thousand plus mortality so far we should be able to extract from that at least signal versus noise with respect to how many of those patients were on ace inhibitors or Arb's when matched for people who had otherwise comparable hypertension. But we're on diuretics Beta blockers or things like that now again. That is so far from perfect and people have heard me forever rail on the Challenges of Epidemiology. But it's these things that would at least point two questions that could then be studied prospectively but I think if I were to put a bow on that I would say eight days ago was the first time I was reading a paper from two thousand five looking at the potential theoretical benefit of. Aarp's in this. And I thought it was a pretty exciting avenue to go down and I think in the last days. My excitement for that has gone down and we are continuing to look at. I guess probably seven or eight other drugs including chloroquine. So do we want to say something about chloroquine which is currently being used off label to treat a number of patients. What can we tell folks about that? I think some of what we're we're seeing in the news. Reports and case reports is really kind of inertia rather than data chloroquine had been used in. It was SARS or Murs. I'm blanking on which one it was used in the study there. They didn't show clinical end points but what they did show is that there was a rapid decrease in the viral load at relatively low concentrations and so it stands to there is a kind of high sequence. Kamala g between both SARS CORONA viruses SARS. Moore's and now Cova nineteen and so it stands to reason that mechanistically it might be susceptible to some of the same weaknesses that Clark win helps exploit which effectively again. I'm not my understanding of pharmacology. Here is incomplete but it changes LEISA SOMO PH and makes it a little bit easier for the immune system to destroy the virus and makes the environment a little bit less hospitable to it. So yeah so I mean it. Decreases the viral load pretty quickly in the previous krona viruses? So the doctors who Han rightly so said. Listen we've got people who are on that store? We need to at least try something. So they threw on the chloroquine the viral proteases which is what because the corona virus is an rn. A virus uses a protease that is similar to the protests that helps HIV replicate and so it also stood to reason that some of the HIV medications namely Retana Vir Lapenne. Aveer was tried. A few of them are currently in clinical trials and the return of lapenne. Aveer one of them really just prevents the from being degraded. So you're only getting the action of one of those but they've been using both chloroquine and the HIV antiviral together anecdotally. They've seen some result. They haven't seen any obvious harm from it. They seem to be using it. Mostly in the severe cases I do know I've seen the protocols now from a few hospitals both in China in the Lombardy region of Italy as well as in and it's now being used kind of as the standard protocol for anybody that's considered to have severe version of the virus. Yeah so electra. Being the trade name for that along with chloroquine is probably I think as of today what would be kind of first line adjunct beyond the obvious supportive care so there's another drug out there that seems very promising rim dissa veer which is a drug that's produced by Gilead. It was obviously someone's listening to this and saying Oh my God that's amazing already. Came up with a drug. No this is a drug that had been in the pipeline for a long period of time to treat Ebola but it's being re purposed and being used via compassionate exemption. I've seen reports. That Gilead is being incredibly generous with it and that it's very easy for physicians to access this through direct contact with Gilead but again this is not at all being used prophylactically. This is being used in treatment again. I I haven't seen anything in two days on it. Are you aware of any updates? In the last forty eight hours that are moving us either to a more bullish or more bearish view of that. Yeah I think everything is pointing to remedy severe having some clinical impact is it. Iv Only I think it might be. Maybe that's the reason that it hasn't been rolled out more widely at we'll have to fact. Check that for you guys after we record but I know at least the producers of Kalita are ramping up production pretty quickly so there hopefully won't be any type of run on the drug or shortage and certainly I don't think we are generally recommending that our patients who have mild to moderate illness necessarily take this drug right. So it's probably the case that if you know you're going to have a self limited illness you don't want to do much of anything because even the best drug is. GonNa maybe shorten the duration by a couple of days. The question is is it going to prevent you from converting to severe more severe form of the illness? And we don't know the answer to that so it's really hard to make a blanket recommendation that everybody who is either suspected of or test positive for the virus should begin taking so. We're still struggling with what we're telling our patients in particular. We've had at least a few calls this week from our patients and it's not always obvious that they should start the medication because a testing is not widely available so this is a cold than certainly. The only thing that could do is harm and it is then. We're kind of flying blind so this is nothing that med school really prepares you for in terms of answering the question on which medication to treat which that said. I think what would also be useful for US? To talk about is how our thinking has changed in terms of from a public health perspective from containment to to right. So what are we telling our patients to do? What are we doing ourselves? And what are we recommending? The public do in light of the current Government Response Right. So what constitutes a reasonable response if we locked everybody in their room for two weeks or three weeks? Would this virus disappear? I mean in theory? It would unless it has like a reservoir where it's not cleared by the immune system but that's going to cause obviously grievous economic harm as it already has so. I think my suspicion is that last week I thought you know. Maybe there's some slight possibility of containment that we're able to track down. The cases do a strict contact. Follow up for anybody who is suspected of having the disease watching that unfold and not seeing any guidance from from the CDC or the authorities. I think it's now what the UK is doing is essentially. They're just saying listen. We're aiming for her immunity so they say you're going to get this disease we're going to expect forty to seventy percent of the population get it over x period of time and hopefully with that. It's not going to be a continuous exponential increase. At some point there's a difference between an exponential curve epidemiologic one. So do you want to kind of dive into your thoughts around that public health management? Piece Peter Yeah I mean. I think it's important to explain why these things can't grow exponentially forever. And that's why simply doing line extrapolations with simple calculus equations is not the answer here because that's how biology works. Every time you do a calculation you make an assumption and if you go from the early replica to cycle of a virus. The assumption you're making is that each infected person is able to come in contact with a given number of uninfected individuals so when we talk about the are not or replicated number being again Peter. Hotels was quoting some of the most conservative numbers. I've heard which is about two and a half to three and a half others we've spoken with have all been more in the three to four and one person even suggested five as a replica of number so again but suffice it to say we don't know what it is but it's. I think at least in the threes meeting. Every person who gets the virus is able to infect on average three other people will at some point that math starts to become a bit difficult to maintain because there are enough people that are infected. And you're presumably knock going to reinfect somebody or infect somebody who's already infected which of course becomes a logical. So that's what really starts to slow these curves down a little bit. And that's kind of what we talk about when we go from exponential growth to exponential slowing and of course it's the latter that we wanna get to now. We're not there yet. Obviously and in fact the most recent data that I trust are two days old so our favorite databases for tracking this are starting to break and therefore I'm losing faith in the twice a day updates that we're generating off the primary sources so Patou days ago. I was seeing data that I found that I thought were actually quite reasonable. They were very disconcerting. So on the one hand you can look at China and you can see that on the back of Wuhan it had an exponential growth period through about February eleventh February twelfth before hitting an inflection. Point which is when it turns from being an upward shaping curve that could hold water to a downward shaping curve that would have water roloff. It's think of an upside down. Gulliver's is a right side. Opole if you look at the cases outside of China up until March eleventh there is absolutely no sign of abatement and it is a perfectly increasing exponential curve. Furthermore when you break it down by country you see that of all the countries that are not China for which we have reasonable figures. Only South Korea seems to have passed its inflection point the other countries with major foe sigh of infection which are Italy and Iran at. This point are still on the upward trend and then of course if you exclude. South Korea Italy Iran and China. You then get into this. Next Tranche of France Germany Spain Japan in the United States Switzerland etc. And all of us appear to be still wildly on that uptick where we are still in the exponential phase. Now you throughout some numbers earlier. I think Mark Lips. It has been the most vocal on those types of assumptions that go into the type of analysis they were hearing coming out of the UK. Which is that. Hey look is this is simply the new norm and in eighteen months or in two years. We should just expect that. Fifty percent of our population has been exposed to this virus and there's a mortality of somewhere between half and one percent. I haven't seen the full discussion but I saw the summary discussion that came out of UCSF two days ago and they were projecting somewhere between. I WANNA say one three two one five million lives lost. American lives lost within about eighteen months. And that's they say the story right like a million lives. Lost is a statistic a single life. Lost is a tragedy. Well it's important to put those statistics in perspective last year. Two Point Eight. Roughly million Americans died of every single possible. 'cause imaginable heart disease stroke cancer. Copd suicide accidents. You name it every single cause of death. We'RE TALKING TWO POINT. Eight million that gives you a sense of what a million lives lost in a year to an infection would look like it is truly something we have not seen in one hundred years in the United States and so that is a frightening statistic and again I don't know that that's a fait accompli. I don't know that that is something that is necessarily going to happen. Well it's important to know. I think that the are not or the replica of rate is not an intrinsic property of the virus. It actually is some of the viruses infective kind of capability and its ability to access new hosts so the are not when if human beings were not the social species we were and we were all kind of holed up in our rooms. The are not would be much lower and so from a public health perspective. What should we be doing to make an effectively lower or not? And how low do we need to make it in order to make this manageable because obviously at some point the government's going to have to decide what is the acceptable rate of infection. Here such that. We don't have a prolonged economic crisis and try to balance it with the other factors of running a functioning society. What do you think Peter? What is the best case? Scenario of government action or intervention or public health action and. What would you like that to accomplish over the next? Let's say three months. That would make you more or less confident about how we manage this as society. I mean truthfully I don't feel like I'm qualified enough to speak of that in the United States. Because it's so complicated. I mean I can tell you that if I were the czar and I had a magic wand and I could do anything I wanted in this country what I would do. And of course certain countries that have governments that function in a more streamlined. Manner might have that. But let's start at the very top and work backwards go from objective strategy tactics so the objective would be to reduce the amount of lives lost and the amount of suffering and the amount of economic damage. Okay that's the objective. What's the strategy while the strategy is very clear and you actually began to allude to a second ago a few days ago. I posted a video on instagram where I explained the are not or spread versus legality and a graph and I showed people in that video a drawing I had made where I placed the SARS covy to virus on this graph in relation to chicken pox H One n one Spanish flu ebola smallpox polio and measles and I said basically. We don't yet know where this disease is going to shake out but it's sitting at an awful junction right now. Awful in that. It has a relatively high rate of spread in a relatively highly valley. And that's for a deadly combination while that also points to the answer. The strategy is to reduce both of these. If you reduce the rate of spread from say three point five to one point one one point two all of a sudden every person that gets infected on average only infects one other person. That's a huge change from where we are now. Furthermore if the mortality of this disease goes from one to two percent which I think is still a very conservative estimate. And I've seen nothing to suggest that were significantly below that but if you could reduce it from say one point five percent two point five percent that would have a profound effect so again if I'm now thinking about this. Through the standpoint of this framework the objective is to obviously reduce. This strategy is to do everything from a scientific and policy perspective to reduce are not and to reduce the Saudi. So that begs the question. How would you do that? Well you've already talked about how you would reduce are not you could theoretically reduce are not two zero if we were all automatons if you decided that every person needed to live in an isolated bubble and they couldn't come in contact with anybody else within about two weeks are not would fall to zero but for obvious reasons. That's not practical. So then the question is what would a practical policy solution? Look like on that and it would have to be one. In which basically people are taking the maximum amount of distance and isolation that is feasible economically and sort of society. It also means that you have a functioning system by which you can triage people and that would obviously imply being able to test people with a test. That is both sensitive and specific. Now Paul I have task you guys including some of the analysts to be looking into this. I think Rachel is actually driving on this particular question. I haven't even looked at the data on the test when we look at the. Cdc approved test for which at the time of this recording there. Maybe a hundred thousand of these things kicking around the country. Do we know the sensitivity and specificity. I saw the number sixty eight somewhere but I can't be quoted on it which is not terribly good for sensitivity. That's abysmal that that means you're going to have a lot again if whether that's a sensitivity. Specificity tells me how it's either going to have a lot of false positives negatives and and in this case the false negatives are more dangerous so it's important to understand that a false positive here is is bad because someone who's not positive is going to be told they're positive and that causes distress and isolation but the much bigger catastrophe is to have a high false negative rate in other words. We need a test that never tell somebody that they have it that they don't fit. That person goes out there. That's to your point that's driving the are not. Let's turn our attention to the legality component. Rtp CR real time polymerase chain reactions are actually super accurate. But because we don't understand why would it be a number? That's so low but I think what's happening is that we don't know where the virus is in the body right so it definitely gets to the lungs at some point but we're doing nasal for NGO SWAB. So we're just taking a cue tip basically and sticking it in the back of your nose and hoping that some of the virus arena is sitting there somewhere that we can replicate it so the tests. I don't know if I have super high. Especially if this has the virus has unique properties that are tests will ever be super accurate although obviously it will get more accurate over time but there's a few different follow ups on that which is why am I isolating myself. Why are you isolating yourself? And does this play into the lethality. Who are we trying to protect so we want to protect ourselves? Obviously I'm I'm a bit Cavalier. About my own personal safety so. I'm not I've come to accept that at some point I will be exposed to the virus but we want to protect our elderly and immuno compromised loved ones and we want to protect society at large. So what is the socially responsible thing to do? And for how long and both those things will by reducing the kind of rate of spread the lethality will naturally come down a because fewer people are infected. Be Because I think what we've been gathering is that we may have some effective treatments and or a vaccine hopefully sooner than the standard amount of time right so I know you were talking with Dr Hotels about potentially using convalescent serum so the antibodies that have been purified from people who have recovered from the disease. When's the last time that's been done on a large clinical scale? I have to imagine it was like. Did they do it with the nineteen eighteen flu you did? I mean I think they've done since then. But it was the drawback of that is I think that that's truthfully harder than it. Sounds to me because they're still an enormous infrastructure required to obtain convalescent serum so you have to obviously identify the people for whom they've produced it but then to be able to open a pretty massive clinic for for recess and again if you're talking about treating people who actively have a severe form of the disease you're basically looking at one to one was my understanding from a discussion which means for every person who has recovered. They can donate enough serum to help one person. You would have a higher multiple when you're doing it from a prophylactic standpoint so it's a great tool to have in our tool kit but I think we need all the tools there are now if we're still eighteen months away from an approved vaccine. That's one thing. My personal view. Is that our best short term. Scalable OPTION TO REDUCE LEAF. -ality is twofold one is repurposing existing. Drugs one it doesn't have to be one drug so you could identify sort of seven drugs work in varying capacities. That in theory are much easier to scale than convalescent serum and or something brand new and to flattening the curve the flattening of the curve by itself reduces lethality. Because you're basically taking fewer shots on goal you're spreading out those shots so if you can make it such that. The healthcare system doesn't get overwhelmed and the people who deliver healthcare themselves aren't getting infected and then you couple that with repurposing available drugs maintaining the supply chain throughout the entire system. When I'm talking about supply I don't just mean the drugs to treat the condition. I mean oxygen. I mean swabs. I mean gowns. I mean when we're talking to people in the front lines. It is unbelievable the things that we are running out of masks sheets than a later tubing. I mean things that we would never assume could run out. But they're out. I've seen people be both older adults who are like. I've been through more in my time than you've seen in your short pathetic existence and I'm not afraid of some silly virus and then we've seen our New Yorkers who are like. We made it through nine eleven. Why are we afraid of this virus but really what you WANNA do as your civic duty in terms of the social isolation is really just by time for our system to build up capacity so if we look even at the simple I keep coming back so that number of the ICU beds? They've released some of the numbers out of Wuhan and they have scaled up their ICU. Bed Capacity by an order of magnitude over the last six weeks and they now just now and we're looking what eight ten weeks into the epidemic over there. There's finally a small amount of slack in the system. Where every single is you bet is not fully occupied one hundred percent of the time and so we need to use this kind of bending of the curve that we're doing as part of our civic duty of lockdown in social isolation and hurting ourselves socially and economically in that time the powers that be needed to be heavily investing in in scaling out the manufacturer rollout and staffing for these. Icu beds and then so I think both staffing capacity and then in terms of treatment people are working on obviously the vaccine. Antibodies convalescent serum some combination of existing antivirals and anti inflammatories. And just knowing the disease course in pathophysiology better so that we can predict who is going to need care and went. Yeah which also gets into another step in reducing lethality and reducing are not. Is the sooner. We can put a really fine tooth. Comb on the susceptibility factor. Because right now and we have a pretty decent idea but you know again this question. We talked about earlier. Which is okay. Say people high blood pressure risk. But if you're at high blood pressure and you're on an ace inhibitor or an A. R. B. R. u. At higher risk or lower risk than somebody. Who's on a Thia side? I mean to know those things allows you to start making harder decisions less hard which is should have given individual undergo the very difficult very traumatic form of quarantine even if the ray symptomatic as a means of protecting themselves so time is the single most important asset. We have because with time comes options and again. I think there's no magic bullet. That's going to fix this. It's a combination of a whole bunch of things that bring down are not that Brindley thallady so that the dot product of those things is hopefully much smaller impact than what otherwise really freaking. Smart people are out there saying could happen. Yeah so I got a few questions from my personal peanut gallery. What are we telling our parents to do? What are we telling our grandparents to do? How does that differ from what we're telling ourselves or friends or siblings? Let's say you know. We're in our thirties forties fifties. Well again I want to be really clear that what I'm saying is sort of me being probably a little bit airing on the side of someone who's more conservative and more willing to suffer short term consequences at the expense of long term consequences so I tend to be somebody who plays a very very long game live in started my parents as clear as day to stay away from everyone and to be as quarantined as possible and to avoid their own children their grandchildren any sort of meeting place. I've basically almost asked them to go into complete quarantine and have groceries delivered and look. That's a huge ask of them and I don't know how well they're following that instruction well. My Dad got on a plane to Seattle to visit his sister and he sent me a picture from the cabin which had about three people on it. So that's how much my advice is valued to my parents but actually brings up an important question which is okay. How does that play out? How long can you reasonably expect that to last even for a population like China? Let's say they've completely locked. This disease down the ours. The are not has gone down to a point where the disease is almost disappeared. When do they open up their borders again? What happens when the quarantine is stopped? And how much time are they forcing themselves to buy? Because at some point they're going to have to come back into the reintegrate with the outside world as each individual is going to have to and so what constitutes reasonable what needs to play out in order for us to back off on that recommendation. Well here's where again. I hope we don't make the same mistake twice. We will learn this from China. We will learn this from a handful of countries. Actually that are head of us on this so I think we will find out. Exactly how much glowing amber is sufficient to reignite a flame based on what we see happening in the other countries that have already reversed their growth. Trajectories have allowed their healthcare system to catch up have developed a testing infrastructure and then are now going to loosen restrictions. And we'RE GONNA find out. Maybe three little glowing embers is sufficient to keep the fire under control. Or maybe it's going to kick start another fire but I really hope that somebody a lot smarter than me is paying attention to that when it happens so that we can extrapolate to our experience in a sense. You're asking a rich Man's problem which is what are we gonNA do when we get this thing under control? I tend to be a little bit more focused on the current problem. Which is we? Don't have this thing under control. When are we going to get it under control? So what are we doing personally to kind of preserve our own individual vessels and make them as robust as possible such that we don't become one of those unfortunate statistics. Should we contract the virus? Well I mean I really wish I had something incredibly brighter inciteful to say I don't think I do. I mean I. I think this is one of those things where some modicum of common sense prevails. But it's the single most important thing I'm doing is avoiding the temptation to interact with anybody other than the people. I'm sort of quarantined around. Which at this point is mostly my family but but a few other people who have also agreed to be in the Corentin sleep to me is probably the single most obvious thing. I don't feel like sleeping truthfully. I mean I'm working away working away working away at ten thirty at night which you've probably heard me talk about. I'm normally a guy who goes to bed at nine and wakes up at five and before. I know it's eleven o'clock at night and I don't feel like going to bed because I haven't returned all my emails and I haven't done this. Well I think part of it is. I'm I'm forcing myself to spend eight hours in bed heavily relying on some of the supplements use including Fox with it'll Syrian. Which makes such a difference during this period of time because it is sort of calming down my cortisol storm around anxiety so fortunately I've been sleeping really well when I'm really. I'm really happy about that. I'm exercising every day. Kind of doing a pretty straightforward not overly onerous workout. Where I'm doing sort of some zone to in some lifting not killing myself on either sort of sticking to my time restricted feeding and try and eat pretty. Well probably not eating as well as I could be in theory. I must admit there's a few times I've my youngest guy is toilet training and he gets. Mlm's when he goes on the POTTY and I've literally snuck so many em in the last few days telling myself well. I mean U. N. P. on the potty. So you can get some EMINEM's too because as part of me that's like dude if you get corona virus than you bite it. You don't want to know that you didn't have that last. Eminem so I had leftover pizza. I couldn't even tell you the last time I ate pizza. I came to my mom's house and there was a leftover slice and I ate it cold and that was a pretty low point for me but you know what I've got my apocalypse beard growing nice bags under my eyes. I'm actually because some part of me was like if we act quickly enough we're going to contain this thing. Shut it down now. It's like okay. It's just a matter of when so I've almost an eerie sense of peace. About the whole thing. I don't know why I am a little more optimistic today. And yesterday I was a week ago last Saturday Sunday Monday Tuesday. My depression anxiety stress were probably not palpable to anybody outside of me because it was sort of in a bit of Morose Way and I don't know something in me I just I feel like people have woken up. We can sit here and talk about how late. The government has been to respond. And that's been that's true but the reality of it is. I think they are taking this more seriously. And I don't know maybe I'm a fool but I I'm somewhat optimistic but at the same time I just I know that all I want more time and I know that a week from now we're going to know so much more I mean we're probably a two thousand. Us cases confirmed right now which is obviously enormous underestimate. That's doubled in. I WANNA say about five days so it'll be really interesting in five days. Did we double the same are we? We were probably more than double just based on the fact of being able to test but again have we gone up by a log or have we doubled. That's really going to matter. If nothing else I guess I just. I'm looking forward to living being part of and watching this movie unfold. Doing all we can to make difference. I guess two weeks ago. We felt like Cassandra chicken little and I think now we're being. I do think people are finally paying attention. There's still turning people away at the Ers in New York who are not symptomatic enough to warrant test. So we're not going to really know these numbers for a while. That's it. I've got a video game backlog. You wouldn't believe so I'm GonNa be sitting pretty for the next couple of weeks for sure but yeah. I think anything else that we didn't touch on. I'm sure it's going to create a bunch more questions than we'd probably be happy to jump on again and answer them. I think we're going to sort of put the regular podcast at least on hold for another week or so and sort of try to focus on this done once we feel like we're saturating information and there's no point repeating what's being stated everywhere else then. I'm really happy to go back to sort of talking about other aspects of health but I do think in the meantime this is a high priority and I WANNA make sure that we're one of many voices that can provide valuable information so I think if people do have other questions I think social media is probably the best place to put them out there because it's easier for our team to track them. We will sit down and probably repeat this exercise in a week or so. Yeah and then. Last non sequitur. I wanted to get your opinion on Peter was. We saw that paper today. Out of I think it was from Wuhan about the mode of transmission of being aerosol versus droplet versus contact. I think a lot of people want to know like all this handwashing. All this social distancing. What do we actually know about where this virus lives? How long does it take to die? And somebody have to cough in my face or is this thing. GonNa be lingering in the air for hours and I just have to be walking by in order to get it. Yeah so you're referring to the paper that came out of the New England Journal Medicine. Today was that in the Journal. I just I think saw a pre release version so I didn't see with journal. It was in. Let me pull it up. So I've got New England. Journal of Medicine. Pre Release is the first time I've ever seen in N. E. J. M. Paper in this format like where it still has. The line designations and stuff. So I don't know if we're talking about the same paper but this paper is actually out of Princeton. Ucla the CDC and NIH. Oh Yeah Yeah Yeah. That's the one this is the phone might paper. It's looking at the survivability of the virus outside of the body on different surfaces so this is a really important question you actually found his paper this morning and I was super happy to look at it because at least it's sort of giving us some insight on what the paper did. Was it compared the SARS covy to with the SARS covy one so the virus that was responsible for the two thousand three SARS outbreak compared to the cove in nineteen current outbreak. In it looked at how much of the virus survived down to a certain threshold so below a certain threshold. We say below this is not clinically relevant in an looked at it on the surfaces of plastic steel copper and cardboard and actually. I think I mentioned this on the podcast with Peter. But if anyone hasn't listened to that I mean the longest shortest was on plastic. It was surviving out to about somewhere between seventy to ninety six hours on steel somewhere between about forty eight hours copper actually did seem to along with cardboard have the shortest survivability copper by twenty four hours you were sort of free and clear maybe even actually eight hours and then by cardboard looked like actually had a survival advantage out to forty eight hours. Where the SARS covy to survive longer than the covy one so. I don't think those numbers are actually. You don't want to take those to the bank what I think you WanNa take to the bank here. Is this thing survives outside the body for quite a while and if you contrast this with something like HIV where a person that has HIV sheds virus on surface for all the negative consequences of HIV. Fortunately it doesn't survive very well outside of the human body or at least out of body but this virus does so. I think what that says is. Can you get this by touching a table or a desk or something that has virus that was shed on it eight hours earlier? If you grab it and put it up into your mucus membranes. I think we have to assume the answer is probably and that also very likely contributes to the are not so it's all of these factors including the lack of symptoms on folks when they get it so and then what do you. WanNa say about the nature of it's airborne spread. Yeah so I think what we were initially postulating is that you kind of would need somebody directly coughing or sneezing in a few foot radius from you. So there's a difference between something that's technical difference between a droplet which is kind of a larger than five microns or so in diameter. It's a hydrophobic but it contains the particles or the viral particles. Which again this corona virus is envelope based virus? So it's got a lipid member essentially a lipid membrane which would make it more fragile in actuality so a droplet would basically something we worry about droplet transmissions things like tuberculosis. So you basically need to be in close contact with somebody for several hours in order for the odds of a droplet which is kind of like a liquid the same way we imagine it to make its way into your lungs are interior mucous membranes. An Aerosol is essentially something that can travel much longer distances because it weighs so little and is so small and it has it's the electrostatic. Properties are such that it doesn't sink immediately to the floor and it'll stay in the air much longer. So this paper did describe that it is possible for this virus to aerosolize and something that hospitals need to be very careful about is actually when you put people on by pop or noninvasive positive pressure ventilation that can create aerosols very quickly and so. It's almost certainly going to be a better idea. Just to intubate the person where you have a closed loop system in order to prevent infection within the hospital as well and that probably also provides some explanation for why we're seeing such a high mortality amongst otherwise young healthy healthcare workers. It might be that they're simply being exposed in a more aggressive way to the virus so on that bright note. Well okay so thanks for making time. Let's get back to work in. We'll pick this up when there's something to talk about speaks. Thank you for listening to this week's episode of the drive if you're interested in diving deeper into any topics we discuss. We've created a membership program that allows us to bring you more. Indepth exclusive content without relying on paid ads. It's our goal to ensure members. Get back much more than the price. The subscription at that end membership benefits include a bunch of things one totally kick ass comprehensive podcast. Show notes the detail every topic paper person thing. We discussed each episode. The word on the street is nobody's shown. Us rival these monthly ama episodes or asked me anything episodes hearings episodes completely access to our private podcast. 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13. HF part 2: Approach to GDMT with Dr. Randall Starling
"Worldwide cardiovascular disease affects the lives of hundreds of millions dedicated cardio nerds everywhere are working hard to fight this global epidemic. These are their stories. Welcome back Carter nerds eyemouth here. I'm very excited to learn more about guideline directed medical therapy today as part of our special heart failure awareness week series joining me. Today is my good friend and Co fellow Dr Kartik Telecom Law. Thanks Comet happy to join so carthy completed medical school the University of Miami. He decided that Miami rather was not up to par and so later moved to Philadelphia for Internal Medicine Residency Training at the University of Pennsylvania. Winter just kept getting colder and colder as he moved to Cleveland for a general cardiology fellowship. At the Cleveland Clinic. And I for us. Who will be staying here for advanced heart failure fellowship the following my co fellows. Carthage was Actually the first person I met and I think what we had. What three or four interviews together? It's it's been so great having Kartik as my fellow Love learning from him and really excited to dive into today's case Carthage. What are we doing? So thanks for the kind intro and equally excited to be here with you. We're going to be talking with Dr Starling today. As part of our heart failure wearing this week and we're going to be specifically talking to him about guideline directed medical therapy in heart failure. Amazing and friends before we dive in. Just remember this. Podcast is not meant to be used for medical advice. The views expressed here do not necessarily reflect the opinions or policies if our employers the goal is simply to enjoy learning about cardiology directly from expert. Cards take hardy innards our series for heart failure awareness week continues with a very special episode car thick and I are absolutely thrilled for our discussion. Dr Randall startling today about Gd nt or guideline directed medical therapy in heart failure. Carthy take it away. Thanks we feel so honored to have this time. Dr Starling. Actress Darling obtained his bachelor's degree and master's in public health at the University of Pittsburgh Medical Degree from Temple University. He went back to University of Pittsburgh for his internal medicine residency training and then went to Ohio State University for his cardiology fellowship. He stayed on as faculty at Ohio. State until nineteen ninety five. At which time he joined the Cleveland Clinic. It is difficult to mention all of Dr starlings accomplishments and contributions to this field in such a brief bio but simply put. He has done it. All he's the former section head of the division of heart failure and former vice chairman of the Cardiovascular Medicine Department Dr Starling has been the principal investigator on numerous clinical trials and most recently completed his tenure as president of the Heart Failure Society of America. Most importantly he has and continues to be the strongest advocate for his patients on a daily basis and serves as a tremendous role model for all of the fellows. We always learn so much rounding with Dr Startling and we're very excited for him to join us today. Thank you cardiac very happy to be here so Dr Starling as we start as the immediate past president of HFS say can you tell us a little bit more about Heart Failure Awareness Week? And what it's all about. Thank you very much for bringing that up and I should mention as historical footnote that my friend in esteem cardiologists who spent plenty of his career at Hopkins. Dr Arthur Feldman has recently reminded me that he is the one that really kicked off. Heart Failure Awareness Week. Initially I believe in the year. Two thousand two. Yeah so Dr Arthur Feldman who's now at my Alma Mater Temple. Hey reminded me 'cause he saw something. I said publicly and he combing I was incorrect. It goes back to. When he was president of the heart failure society they he actually went through some political avenues to make it official selves. Heart failure awareness. It has been around for awhile and we would like to think that this year the efforts that are made by the Heart Failure Society of America and the Cleveland Clinic many other fantastic medical centers around the country are GonNa be the best efforts ever. So what is it about? It's you can summarize. It very quickly is. The name. Says it's awareness so we want to get the word out to the public that heart failure is one of the largest major important medical conditions in the world and certainly in the United States. It's just not well recognized the number one cause of hospitalization in the US is heart failure. It's not recognized what the consequences of heart failure are. Perhaps most importantly it's not recognized that we have fantastic treatments for heart failure now so heart. Failure Society of America is doubling down if you will on our efforts And many of them are collaborating with some of our industry partners. That have been responsible to bring all these fantastic therapies to market. That are now available. So it's a team effort like most things. We do a fantastic and you know. We have the cardinals. Were very proud to join and be a part of this effort and also to be able to help Dr starling correct the record publicly for Dr Feldman and we all have to make sure that Dr Feldman has a chance to hear this podcast. Because I know he'll be very happy to hear A. We've set the record straight there so I wanNA talk a little bit more about those fantastic treatments. When we started residency life was simple and there were three main groups of life saving medications in heart failure with reduced ejection fraction with Beta blockers. Arbs and emory's plus the Hydraulic Zine. I soar by nitrate in the right context. How have things changed since those days and what is in our arsenal today for guideline directed medical therapy? Yes thank you and let me just put one more pitch in that When we say. Gd M. T. I think it's important that we think in terms of guideline directed management and therapy so the key there is medicine is part of the therapy but the other important parts of the GD. Mt Approach are managing the patient which starts with. Did you make the right diagnosis? Did you find an underlying condition? That was unrecognized. Did you deploy pacemaker and cardiac synchronisation so? It's really comprehensive. We spend most of our time talking about the medicines but we would like to convey the message that it's really guideline directed management in therapy. The the question that you've posed to me. I guess I have liberty to quote the guidelines but I also will be free with level evidence or expert opinion we've known for years and it can be the US or the Canadian or the European guidelines. Were all pretty much in sync. Or even the most of the Asian Society so betablockers. Let me talk about that. I I believe that Betablockers arguably the cornerstone one of the most important drugs that we use and at the same time. Beta blockers are the most commonly underused drug that I see and by that I mean rarely does a patient come into my office or to the hospital. That has been on maximal medical therapy with respect to target does and we'll talk about target doses. What we know about target diseases in a minute but why her betablockers so important that they're so important because of all the drugs that we have the ability to quote reverse remodel or facilitate improvement of ventricular structure? I think hands down is with Beta blockers. So we have Beta blockers. We have as inhibitors. Arb's and Arnie. Or INSULIN RECEPTOR NEVERTHELESS INHIBITORS. Just to be efficient about this. A I think it's clear that my bias now is to get most patients on security trove out. Certain with rare exception in this is we're talking about half wrath for reduced ejection fraction forty percent or less now so we have the data from the paradigm H F for chronic outpatient stable heart failure. We have the pioneer trial which has taught us. We can initiate the drug in the hospital. After the patient is stabilized we have an ongoing clinical trial through the heart failure. Network that to be determined. But we're looking at very severe heart failure and way. Ha Class Four. That's called the life study. And that's GONNA enroll four hundred patients with a six month and point in bear in mind that paradigm H F was mainly Class two and three the total number of patients with class four in that whole thousand plus study was less than one hundred saw. We really don't have much information on severe heart failure so my colleagues Doug Man from Washington University Dr. Brian Wall Dr Hernandez from Duke and Michael Adverts from Brigham and women's we've worked through the heart failure network to put the trial together which would be very important now in the meantime. Is there a patient or two at the Cleveland? Clinic has severe heart failure that we've put on Vowel certain and been encouraged absolutely so that's segment and then perhaps statistically the most underused drug are the Marez al-dostur antagonist the mineralogy Receptor antagonist and clearly. If you look at a typical registry you'll see in Europe about seventy percent of the patients on an Ra if you look in the US it's more like twenty five or thirty percent so the fraction Yep Americans tend to be a little bit more skittish and I recently. How discussion with Faez odd? When I was at a meeting actually in Dubai and his comment was he felt this doctors. In odd who led a lot of the apply renown Outcome studies that the whole hype over hyper? Kinley MEA is over exaggerated so yes. We are pretty adamant about pushing to get a patient on that modality of therapy. Also now diuretics are not on the list right so I say to. Patients often think about a loop diuretic as something light lasix. Most people were taking zero semester towards some and we're trying to figure out which one is better now through a study called transform. Hf which Rob Mansa and others are leading through a Corean So it's a large study. We don't know the answer but we all have our favourite diuretic but what I tell. Patients is the directs. Not GonNa make you live longer. We have to be cognizant of the fact that many times we need to downtown Detroit Many patients present in say. I feel really bad. And the reason why they've improved and they're being over. Diaries and they need to come off the diabetic. So Dia Radic's are something that are in the background. I described them. Moore's 'cause medic they're designed to make you look good and feel good but they have no mortality information about them and so Every Cardio nerd knows about car yet using ovation therapy and I have lived through from the first study. The Miracle Study which we participated in the Cleveland Cleaner. So back then. We didn't know whether and we were blinded and so we quickly learned that. Crt get were and it's important to emphasize that CRT comes on the background of optimized medical therapy so the cardio nourish should understand that if a patient walks in with a nice left. Bundle on it. You are s a one sixty and their medication nye. The temptation is to throw in a crt but guess what sometimes they do very very well on. Madison's allow and when you evaluate them later on that killer s may still be wide. It may be narrow but if the APP is forty. Five or fifty. They're not going to qualify for crt but CRT is clearly a game changer. I am a believer. In this entity of synchrony cardiomyopathy super responders have been well described by our center and others. So it's a fantastic there are. It's initiated on the background of Genie. Mt Medical Therapy and I also would advocate. If you have a patient it's a super responder. Most of the time they're gonNA stay on medical therapy in addition you're not gonNA remove that background therapy so much starling. I especially appreciate you broadening. Our conception of GMT gallon directed medical therapy to management and therapy to include all the device therapies and likely structural interventions that the dupleix such an important role for our patients. We have so many tools in our tool kit. For patients with reduced ejection fraction. What is your strategy for initiating these medications? Do you have a go to for which medicine you start first? Does it matter on the indication schemic or not and gentle? How are aggressive? Are you with up? Titrate them as an inpatient and outpatient. What's our practical approach here? So there is a paper that's been written on the very question that you're raising a the author on that paper is Javid Butler. Having said that I don't know that there's a specific cookbook on how to do this. So I'm going to give you my approach that has worked well for me over the years. So I that a hospitalized patient or an outpatient first off we would like them to be. You've only mic and I use the word. You've only Tongue in cheek because I could ask both of you to define you've Lamia but if you go to the bedside. I think it's hard to be confident and safe. This patient is you've lameck. It's like assigning. What is his patients dry weight? That's kind of a treacherous undertaking to make that assignment. Having said that you look for Dima neck veins a screen cow up all the usual things and if you think the patients in pretty good spot with volume you may be aggressive if they have plenty of blood pressure and start them on an ace inhibitor. Angie tension receptor locker or army right off the bat and a low dose of Beta blocker. If I'm worried about the patient's still having some degree of congestion I will tend to start the vase odile later. Hold off on the Beta blocker. Maybe give them the Ra the same time depending on the renal function potassium. So that's where it gets. Tricky depending on whether the patient has any degree of CK D. with their blood pressure is et CETERA. I think in the hospital we would tend again to be liberal with the diabetics and then move ahead with the vase odile later and probably the Beta blocker a little bit later. Of course there's nuances. There's patients with Raging hyperthyroidism or sometimes a young patient. Who's very tack Kartik with a non ischemic cardiomyopathy? Where you really? I really feel compelled to try to work to get their heart rate down. We may have a marginal blood pressure. It may be a very small dose and I'm more than content just to get the patient on a low dose of the visa. Die Waiter Especially anonymous schemic and then I will get aggressive about tight treating the Beta blocker now as far as how quickly we knew it in. What's the timing that the conventional teaching if you go way back to the? Us Corrado all trials and studies were done years ago now published in a New England Journal when it was in a clinical trial. We were taught every two weeks you uptight and pace and we were taught when a patient comes in the hospital. That's on a Beta blocker. You never ever stop the Beta blocker called. Unless the patients called an Encarta Jennings shock but you worry a little bit in the background about. Beta blocker rebound. But if you're worried about the patient you cut the Beta blocker in half and you win them off over the next couple of days. If that's what you think is racing to do as far as uptight trading in the hospital Unclearly more liberal about that now than I was twenty years ago so if I have somebody in the hospital I may change their Beta blocker dose every two to three days if I think they're very stable if they're very very tenuous. I'm very very cautious with a Beta blocker and as far as an outpatient. I don't think either review a work in my clinic but If I have a patient that I think has got the Common Sense and the ability. I will write out and Beta-blocker tight ration- for them to do at home to insect increase dose every week or two depending on how they're feeling and if their vital signs are okay the entrust stow or Artan as you know Again when we did the Paradigm H F study which we participated in that here at the Cleveland Clinic. Were doing titrate Now in the life. Study those titrate Tend to be no sooner than every one to two weeks where you do the usual assessment of the patient with Martin or any ace inhibitor. Angie tencent receptor blocker most of the time the limitation on titrate is Stolac blood pressure as we all know as far as far as you're concerned the source data on that very interesting so I'm GonNa tell you something that perhaps you are unaware of bet you may wonder why the rows study look at twenty five milligrams of spiral ACTA. So there's an obscure paper published in the American Journal of Cardiology where a small physiologic study was designed to look at. What does Brana lack? Tom was required to read sodium balance in patients with heart failure and the dose that was reported in that paper with somewhere around seventeen or eighteen milligrams of spiral lactone so when they design the row. Study Dr Pit and others. They said Okay Twenty. Five milligrams is the dose. That very interesting so with an MRI. I personally don't get super aggressive with titrate unless I'm dealing with a patient were. I'm worried about as escape. Or they're particularly refractory. Bit Most patients in my practice twelve and a half to twenty five milligrams of player known earns Byron Black Town. A small percentage lined up on a higher does and I do pretty much adhere to the guidelines. Which is an important point to emphasize the guidelines extremely conservative suggest that you check potassium seventy two hours after initiating an MRI. I try to keep that within three to seven day window. But we do do that most of the time and I think you have to be really cautious if you're moving with the RA as well as the rats and had been at the same time decker styling in general. And how well are we doing? A country getting people onto GMT car tech. This is a very important question. That is something I'm very passionate about. And when I gave a presentation in Philadelphia last December I made an announcement and the announcement that I made was that the heart failure society of America was recognizing that one of their focuses would be to facilitate the optimization of guideline directed medical therapy specifically medical therapy we targeted that based on a lot of work but I will mention the champ c. h. a. m. p. registry which there's now a series of papers that who've been published in Jack Jack Heart failure so the champ registry looked at upwards of three thousand patients that were at number of centers in the US. So what did we find that was particularly concerning so this registry told us two very important things one what were percentage of patients that were on these three major classes of drugs? Beta blocker am Ra or Arnie is a rb and what we found was sobering and disappointing that the percentages were far from one hundred percent and and many cases sixty to seventy percent for Beta blockers and ace inhibitors for Arnie. At the time of that register report as I recall the number was around. Eighteen or twenty percent and for 'em are a it was also A low number now. The second part of this is that the investigators looked at target doses. So what our target doses so that information is buried in the appendices of these studies. So what you find in. The appendices are doses of any drug. You can think of in heart failure. That were the mean doses in the clinical trials so for example merit H F which was source trial for Auto Sung sonate. The average dose in that study was one hundred fifty four milligrams of sucks innate okay are pretty high. That's pretty high. But that's why I pushed for one fifty two hundred milligram. Now we know so you can go back and read that paper and with Carve Adl. It was twenty five milligrams twice a day if you're less eighty five kilos and if you're over eighty five kilos fifty milligrams twice a day of Carve Adl as long as heart rate and blood pressure. Were adequate so in the champ registry. They took those numbers as far as doses. And they said we're GONNA give you a free pass and deem you as on target therapy if you're fifty percent or more of what was used in a clinical trial so very reasonable bar very reasonable very liberal. And what did they find again? Extremely disappointing that very few patients in the US are on target doses. As I recall from the powerpoint at sent us our colleagues in Europe in Asia earned a particularly better. Yes so I've looked at a number of studies in Europe and Asia and that's exactly correct So this is a global issue and it enables people like me and others to get up to the podium in speak into hypothesize that if did a better job of using the proven drugs at the recommended doses. Common Sense would say we would reduce many ways the burden of mortality and morbidity and heart failure. So that's why the Heart Failure Society of America is looking intensively into this issue. Now having said that as you can imagine this is a complicated multifaceted undertaking and I think our current president become boss Cart Baylor. She wrote a very nice editorial where she said. We have to think about patient related factors that limit us we have to think about provider related factors that limit us and we have to think about pair related factors that limit us. I don't let them aspects of treatment gap. Yes absolutely so. I don't WanNa throw any of our friends and colleagues under the bus. But we've all had a situation where we had a patient that we wanted on a specific therapy where it wasn't so easy depending on who their provider was to get approval or access for that therapy. Right as multidisciplinary communication is unsure so key in coordinating such a multimodality treatment algorithm for our patients right. That's very interesting to hear. And hopefully in the future we can do a better job with this so let me turn our direction to the inpatient setting. We've all taken care of patients who've been admitted with compensated heart. Failure and oftentimes were changing their medications. Around what is your threshold for stopping or reducing doses of these medications during these hospitalizations. Should we be doing that? Should we be leaving them where they are? Well a cartoon. I didn't expect you to ask me easy question. This is this. We have one coming up later. This is a case by case at the bedside decision. But I think there's there's perhaps one simple way to think about this announced to us So-called four quadrants approach that was described and popularized by Dr Lynn Stevenson. Who's had vanderbilt in her colleagues when she was at Ucla in Boston. So or you can think about the adhere registry in Dr. Greg Monroe currently chief of cardiology at UCLA. He published a very nice study in one hundred thousand hospitalized patients where he came up with a cart analysis so Lampley Fai that a little bit so the patient wind comes in and they're quote unquote warm and wet so their volume overloaded. They we think they're cardiac output his fine. You can probably do anything you want to that patient. Within reason you can choose whichever arm of the dose. Study you prefer. Give them away subscriber. Give them boas furious End Give them a visa die waiter and as the three of us know in our ICU. For example it's pretty comment. That will be giving something like sodium nitro process side or oral vase Waiters in a lace strap all at the same time right so. I think you have a lot of latitude and as I mentioned earlier if the patients already on a Beta blocker I'm probably not going to down titrate it unless I think the patient's in trouble Let me get to what I think in trouble is so if the patient comes in in their hypertensive and they're cool in their lactate is then it's a whole different ballgame right that's credit okay And then we have all those patients that are in between patients that have CK D. chronic kidney disease and I just rounded on a patient a short while ago that got started on an ace inhibitor capture parole in the hospital and my phenomenal Cleveland Clinic. I fear fellow. Alan King said Dr Starling. Do you think we should continue the capture pro in this patient and should why do you ask Alan and he said well? Crowning went from two point. Two two point five in the passing went from normal to five point. Four and I said let's look at the GFR's we did and they were all between eighteen. Nineteen so some will say if the Jaafar under thirty watch out some all even go as low as twenty Which is what we're doing in the life study you can have. Jeff are as low as twenty to qualify Hearten so that has to be taken into consideration. Obviously not telling anything novel that you don't know And the car analysis looks at some simple things like systolic blood pressure be UN creatine and without quoting this specific numbers depending on those three numbers you can see an inpatient mortality from as low as one of the two percent to his highs eighteen to twenty percent. I think the different streto right off the bat from the it here registry so my fellow probably had to put up with me ten or fifteen times today asking him systolic blood pressure serum sodium creating the UN. And I'll throw in terminal. Bnp end that mix now also because we have a lot of data that his emerge courtesy docker Jacuzzi and others and the guide. Hf clinical trial which was quote negative trial but the dated starting to appear now says if you can drive that BNP level down onto the prognosis better and that's one of the key factors behind security. Drove out certain issue. Now if you look at pioneer H F for example the primary endpoint was a change in in Terminal B in pay right. Yeah that's right so we think that that's a good surrogate of other important. Now comes at a high threshold to decrease or stop betablockers low threshold to start an increase data leaders not only four GDP but also to help diagnosis and using hard numbers. Data points to help stratified our patients to see who will respond to what the stick. Thanks for now brought up Arnie and one of the Terminal End Points about the program to say I have a patient. Who's on listen a pro or one of the other ace inhibitors or ARB's and I'm seeing them in clinic. And I want to switch them over to Arnie. How you go about doing that. So I think that's a pretty simple undertaking and there's two two choices basically one is you get thirty. Six hours off the inhibitor. And you start to Mont Secure Patrol vowel certain and there are algorithms that. Look at the dose of Ace to give you guidance as to which dose of You went to start with so there's three doses that we're all familiar with low medium and High Myer. Oh with them. Most of the time I start low if somebody is in clinic in their taken forty with senator pro and their blood pressure's one twenty. I'll probably start the mid range dose of Security Patrol Valves Arcton if I'm being real conservative. I'll check labs just to see where they are but the irony of it. Is that if you look at the published clinical trials including Paragon Pioneer and paradigm h F. Guess what when you look at worsening renal function when you look at creating compared to the ace Versus the army the army was fine and in Paragon the signal would even suggest that there may have been some beneficial effect of the army versus develop certain so I think that sometimes security about certain the hype about it trash the kidneys and leading to worsening renal function. I suggested people looking at the patient's volume status and what were the other factors play because I don't think we have any specific information that the drug is never tops. And in fact one of our former trainees who's very very renowned heart failure specialist in Europe. Now Wilford Mollins. He's starting to publish papers on the Reno Protective Effects Secure Patrol vow. Certain of. I think there's going to be a lot of important information coming out on that. And you know I would just heartfully rotation had such a great time learning from Dr Mountains Taylor and it was pretty cool to see Be Able to go down and diagnosis and one case. Just stop it all together with starting Armenian is there. Do you have a rule of thumb for what you do with your riddick does when you do switch over. So that's a very important point that you bring up. Doctor Goyal and I think that I learned a lot in the context of the life study we're now recommending in the context of that clinical trial that the investigator a priori consider like a thirty percent reduction in the die radic. It's good to know at the time of initiating the security twelve outside so how does that translate into the real world so if we used our mock patient that were using as an example blood pressure one twenty? That was on forty center pro. Let's say they're on twenty furor and I thought they were totally you In fact I just had the patient not too long ago that Zach. My clinic fellow and I were presented with. Who's from Qatar? That we had to finesse some things we just immediately started to down titrate but in that imaginary patient with High as good blood pressure I would probably say stop the furious somebody and keep that in the background kind of as needed if I could communicate that clearly to the patient how to use a prn diuretic which I should mention that. I really try to encourage training a patient. Just like you would. Train somebody to us Regular INSULIN PR. Depending on their glue. Commader I don't have a fluid auditor that that that I could check but if I did I I would advocate. Prn diuretics and try really hard not to over. Diaries a patient I really liked that a push because I think that by empowering them to help adjust when medications probably get more engaged in their own data and numbers and care one hundred percent and I would argue that some of the most engaged patients are the types that wind up with internal pressure. Sensors like the product that we're all familiar with the cardio mems device that before you know it. Patients WanNa know there are readings. All I think the key point that you just said is empowering the patient I think in heart failure. It's so important to educate the patient. It's not about here's bottle pills taking pills. They need to understand why so? Oftentimes patients Ame Why should I take him? I felt fun. Why should I switch from Lucinda? Pro Security drove out. Certain and I tried to call very cool. Calm and patient while I'm glad you're feeling well. But a the spiral actum and clinical trial reduce mortality by thirty percent security events Artan reduce mortality by almost twenty percent so that's led to some people saying perhaps the most to gain or the class to patients where they're looking at many years ahead versus vary severe patients time for the Kurdish. Here you're trying to buy them the survival advantage with better drug and Sukova trove out certain shortly after the paradigm study. We published a paper in circulation with Milton Packer. In many co authors it showed in the paradigm cohort. We looked at things like need for transplant. Need for Alvin. You're not surprised that that paper said the patients on security patrol while certain did not progress at the same rate is the patients over on in l. for as good a motivator anything one of the medications we haven't talked about during this podcast is of average. Can you give us a couple of your thoughts on that? Yeah so I I think. Of Aberdeen is an important drug. And Carl spent bird. Roy led the charge with a drug and for reasons that I don't fully understand of Aberdeen just has taken off in the. Us like it has outside of the US and four or five years ago. My calway Wilson. Tang in I. We proposed study within the heart failure network to use evaporating and at the end of the day We got some pushback and that that he was not prioritized and without mentioning any specific names. There was some hesitancy from some of the leadership that in general in the US. We didn't use Beta blockers appropriately and one of the criticisms that has come out of the Aberdeen trials which. I'm not sure that I buy as valid. Was that they never optimize betablockers appropriately. So in my own practice I have some patients now on evaporating so either review or my patient and I had you on the maximum dose of a Beta blocker and your heart rate was seventy five or eighty. I put you on evaporating So it turns out. It's a small number patients at least in my practice but I think toll. We should use grace so we have so much data to support the use of these medications. But what do we know about? How different populations respond differently and do the equivalent benefits women and minority groups. So again Roy. Good question and let me reflect on that a little bit from Paradigm Shop so paradigm H F. I was involved in and the US was looked at to see that we did a good job. In addressing the Afro American Cohort. So because not every country can recruit patients that are afro-americans. We were asked to recruit five hundred patients from the entire. Us We fell a little bit shorter that mark. And if you look at some of the editorials that had been written about paradigm. Hf One of the limitations. It is cited at times is the sample of Afro. Americans was not adequate now. Pioneer did a better job with increased enrollment of afro-americans. So all the data that I'm aware of would suggest that efficacy in afro-americans is equivalent and safety also because the concern was NGO Naroda There was the push that was put on us to get adequate. Numbers of diverse populations was for safety. Also so I don't. I'm not aware of any signals at this time There is a study and I don't recall the name of it but there is a clinical trial that I'm almost one hundred percent. Positive has been conducted in Asia to look specifically at Certain in the Asian patient population. I'm not aware of the results of that trial but one of my friends and colleagues professor. He wrote to Sui whose past present in the Japanese heart failure society has been leading that clinical trial testing here. And the number of Hispanics was not a significant number so we don't have a lot of data in that area. As far as women are concerned. You know rarely. Do we get a balanced trauma as far as males and females but a little bit off the path of our primary discussion here. But just. Because I think it's important to mention that Paragon H F which was heart failure with preserved ejection fraction or you five percent or greater val sutton versus Vitriol certain right so Dr Solomon published the primary data on that and the number of women in that trial was one of the highest percentages of any heart failure clinical trial and in some of the sub analyses. The signal showed that perhaps women with ejection. Fractions of fifty six percent or less had potentially the most robust response to that drug and there there will be more data that comes along an additional clinical trials looking at a security profile certain in patients that are hospitalized with ojection fractions greater than forty percent. Those clinical trials are just getting off the ground as we speak. Let me play devil's advocate here for a second. We have all these life saving drugs and my patient is taking the coreg twice a day. The army it's also twice a day the MRI and all of these medications are only helpful if one the providers prescribing them into the patient is taking them. How many is too many when we get to these medications for our patients or is there no limit so Dr Colvin contact? I thought you were going to throw out the Paulie Code word so somebody asked me that question do by two weeks ago about the pill so it's a very important question and you know an imperfect world. We would want a patient to take one poa day right so that is something that I worry about. And especially if a year from now we have another drug right in. Sglt two inhibitor. I think that's in the back of everyone's minds. That was a question that I personally asked Professor John macmurray at the heart failure meeting when he was kind enough to present data h F there. I said John. We can't get people to take three. Madison's what are we going to do? So this this is a big challenge. I don't have the answer attempts at the polly pill in the past by Salim. Yussef when you know grammar parole and other drugs came along at least in the US. Never Roy took off. But it's an important point that you raise which is that of compliance and it does bring another important point up that I'd like to make which is. How do I tell patients to take these drugs? And I've actually learned some very interesting things from our patients with pressure monitors in their bodies the Rothe to tell the patient is for six Cuba trove out. Certain don't take anything else either. Two hours before or two hours after the drug because very common situation is the patient that comes in clinic that says Gee I cut this drug in half or I'm not taking this drug. Why well I take my medicines and I feel Kinda unsteady on my feet for an hour or so and I say how do you take him? Well I take everything and put them in my hand. Pop down the hatch all so sometimes the simple thing like spreading out when they take medicines does the trick and again is we know. We've all given all these drugs to people with Swan. Ganz Catheters in right so. I've now got a collection of patients that trying to titrate. They're secure control valve. Certain and the nurses were telling me G. P. A. Pressures Arroyo allow and this and that and the other so I had to drill down and find out Wendy. Take the secure cardamoms Reading take place and patients with checking his ratings like twenty to thirty minutes after Sequoia Patrol while we were getting here at the peak of that rate of the drug. It's also very cool. You see that that correlation factors physiology plates is working so our last question for you today. Decker starling is what makes your heart flutter about heart failure. Well what makes my heart flutter about heart? Failure is a few different things and probably the biggest flyer is that I needed patient sick. They have low enough sometimes. They're in the hospital sometimes are not an end. We embark on journey which is optimized GMT. And you wait. You follow the patient. You titrate sometimes. Maybe they had some a fifth that you had to deal with your took care of that and then six months later a year later. They're in great anticipation. What happened to my heart. What's Mine Ojection? Fraction? What's going on. The greatest joy is the day that sometimes in clinic. I'll have two or three or three or four patients that day one. When I met him there Af was twenty and I'm sitting there in the office saying you're ejection. Fractions fifty five percent. You're Mitral regurgitation is gone and your heart has gone from seven centimeters to five centimeters. That's really cool and I'll tell you one other quick anecdote. We have a patient that I've been taken care of. He needs heart transplant. Okay and long story short. He wound up in our ICU on a balloon. Pump waiting to get a transfer sixty one days later. Last Friday I get the email I was actually in another city at a meeting but Mr so and so we have done her heart I was in Houston. That was probably run. Eight or nine o'clock so by ten o'clock I called in to the hospital. I said patch me through to heart. Failure Eye Patch me through to room six so I got to talk to my patient and say it's happening. That's just amazing. Yeah there's so many special moments sprinkled throughout medicine in patients but moments like this have to be among the top. Yeah it's and we're not here to convince all the cardio nerds to be hard coded one of the one of the Co things about being a heart. Failure doctor is a longitudinal aspects of care so that I have patients now. I've been taking care of twenty years. I saw lady upstairs today and she said thank you for taking care of my husband. Thank you for taking care of my son. Thank you for coming by to see me today. So it's not just a quick interface which could be life changer. In the case of with surgeons and interventional cardiologists do but I look at the heart failure. Dr As some of my colleagues would say you're egotistical. Were were the general contractor with the coach of the team where the conductor of the symphony. We need many instruments to play good music. We need help from everyone. But we have to know when to coordinate those efforts when to bring the right people in in our focus is on the end result with the patient. Of course that's That's just so beautiful starling in so inspiring. It can't thank you enough for your time today. I know you're busy serviced staffing. What thirty two thirty three patients just today? But this was so incredible we learned so much and I just I kind of wish. I had this when I started my fellowship. Thank you thank you that brings us to the end of our show. So it's time to make like an s to split. You can follow us on twitter at cardiac nurse and please share. What made your heart flutter this week send us a clip two Cardi inert gmail.com. Who enjoyed the show the narrative and spread the word?
The new eye implant giving diabetes patients hope
"When you have an experience the expansiveness yet. You haven't experienced the next generation of Samsung galaxy a cinematic Infinity display the practically blurs the lines between your screen and the world we're an ultrasonic fingerprint ID unlocks your world and the program cameras sees it like you do and in all day intelligent battery optimizes power to your needs the Samsung s ten s ten plus preorder by March seventh and get free. Galaxy buds limited time only terms apply. Our site is a gift one that serious diseases could compromise but yearly exams from an eye. Doctor can detect them before it's too late. Find an eye doctor today at think about your eyes dot com. Sponsored by the American up to metric association. Welcome to the Yahoo. Finance presents podcast. I'm Alexis Christopher's diabetes affects more than twenty three million Americans about one in three patients suffer some level of vision loss will there is a new treatment from a company called Alamara sciences that is helping to reverse vision loss for diabetics with an implant that is the size of a grain of rice. Joining me on today's podcast is the CEO of Alamara sciences. Rick is worth and Rick welcome to the podcast. I find this fascinating. I'd love to just start with you painting a picture for people hearing this as to what this implant is like and how it works. Great. The the implant is health is very unique. And we think it's novel technology to treat retina disease. It is it's actually one thirty second. This is of a granary. So it's much smaller than a grand rice. It's about three and a half millimeters long point three five millimeters in diameter, and it's engineered to deliver a consistent. Slow daily dose of corticosteroid over up to three years, right? And that's very important because retina disease fifteen years ago when we started development this drug Di diabetic macular deem, specifically was treated with laser photo relation. There were no pharmaceutical products approved. So we designed to move in early and was designed to deliver that consistent low dose and mitigate the waxing and waning and the drug. And so what alluding does as mitigates or reduces the recurrence of the disease provides more stability for the patient. So it was approved by the FDA three years ago. So there. Our people and tell us how many are actually using Levin now and have been on it for the past three years for sure. So there's there's there's about six hundred thousand patients in the United States that have what's considered clinically significant macular Dima, we believe about half of those or about three hundred thousand are being treated, so our market penetration. The US is only three and a half to four percent right now. It's pretty low. We think we're just scratching the surface because really we're trying to change the paradigm of the way physicians treating the disease offering a different way to treat the disease as opposed to the acute there because I was mentioning earlier is that because more doctors are finding out about it because it's being prescribed more. Why are you seeing that growth? Well, it's certainly being prescribed more. I think more doctors are becoming aware of it. And the doctors that have been using it or getting more and more comfortable with how to use it. And so therefore using it more frequently what kind of data have you been able to glean from the from the three years since these implants were put in patients is sure a couple of things. Well, one of the great things about alluvial is because it's dosed consider. Over time to get one insert for three years. It's very compliant. Right. You're not reliant on the patient to come back and be treated again. So unlike the acute therapies where in the clinical trials, there was a very specific dosing regimen. For example, he sent us is one of the drugs, and it was once every month for thirty six months in clinical practice that patients not coming back every month and being dosed every thirty six months, so the efficacy is less in the real world than what you saw in the clinical trials alluvia is exactly the opposite le'veon's efficacy in the real world is very consistent with what you saw on the clinical trials. So it holds up to clinical practice, and the other thing is corticosteroids do have side effects in the I just like they do elsewhere in the body. The two side effects are increases in interacting more pressure in some patients, which have uncontrolled can lead to glaucoma typically about forty percent of the patients. No matter what the steroid is have that side effect, but it's very very manageable. And we've seen that it's even more manageable in clinical practice. It's also predictable patients received another steroid the. The other side effect is cataract surgery. Most patients that receive a steroid ultimately going to develop cataracts and aft have their natural ends removed in an artificial ends put in however, most diabetics are predisposed that anyway, so not as big of a deal. So we're learning that it holds up compared to what it did. In the clinical trials, we developed more data and clinical practice in compared to the anti. Jess that are now standard of care. And we have shown that we do indeed significantly reduce the treatment burden for the patient. So after the three years is is up. Do they get another injection for that lasts another three years, presumably? Yeah. That's right. Presumably they would. I mean, the drug last up to thirty six months. It depends on the patient and depends on the severity disease. We've seen some patients that had to be reinfected before thirty six months or up. We've seen some patients that got to go beyond thirty six months before they got reinjected, but that's similar to any other chronic disease, hypertension. Some people get five milligrams of an ace inhibitor, some get ten somebody data diuretic, so. Is just like any other disease where it depends on the severity. All right. Let's let's talk cost and how are insurance companies covering this? If at all, sure sure, we've got great coverage the cost of Leuven, you know, sounds expensive. It's just under nine thousand dollars in the US in that price is pretty consistent across Europe. However, the acute therapies are anywhere from twelve hundred dollars per jecklin to eighteen hundred dollars per injection. So if you add those up over three years le'veon's, very very cost effective and over the course of three years within ninety days of launching the product back in two thousand fifteen we had positive coverage from ninety five percent of the commercial payers, and it's obviously covered by Medicare based on the FDA label. So very good coverage. Great what about what is this meant to to the company's bottom line, and in terms of revenue what kind of a revenue generator is this chirp for well as I said, we're sort of scratching the surface. We we pre released earnings for the full year a couple of weeks ago, and we'll do just over forty five million for the year. That is good growth. It's a little bit over twenty five percent. Growth record growth for the company is record grocer the company's record revenue record growth both in the US. And in Europe over his Alamara gosh elementary was founded back in two thousand and three. Okay. And the trials for this drug were started in two thousand and five. So it took us almost nine years to get through the trials and through the FDA because of a few challenges to their showroom. But the products been commercialized in the US since, you know, first quarter of two thousand fifteen what are projections like, and I understand alluvia NHS. The only product the company has at the moment. I I'd imagine you're looking to expand your also a new CEO, right? Just a few weeks old. I am I am. So I'm looking at ways to certainly changes the stories we move forward. I think there's still a lot of opportunity with the Levin. There's a lot of geographic expansion opportunity to for that. We are commercially available in the US and in seven countries in Europe right now, excuse me, six countries in Europe right now. But Spain is just coming online through a partnership, we expect to have the product commercially available in France later this year, and we just recently. Received pricing in the Middle East in the United Arab Emirates, and we expect expand their I mentioned the pipe essential for re-treatment or you did. And we see those patients coming back, and that that would be the first time we will see an opportunity for recurring scripts. We don't have that certainly is an opportunity for more growth there. And then outside of a LeVine, one of the strengths. We have as a company is we're one of the only companies in ophthalmology that has a retina commercial team both in the US in Europe. The only other one would be Allergan out there. Most of the rights to the retina pharmaceuticals are split up between larger companies and so separate teams. And so I'd like to leverage that and find some other retina products, we could put in the bag pharmaceuticals being the first choice, but open to the idea of retina diagnostics or retina devices because most of our physician customers are surgeons as well. And so they're using devices. So that's that's the initial goal. There is to try to build out in the retina platform over the next twelve to eighteen months, you touched on it earlier. But can you expand on how alluvial is different from other? That are already on the market. Sure. I think the biggest thing is that it's it's it's a chronic or persistent treatment for chronic or persistent disease, right? Everybody knows diabetes doesn't get solved. Nobody gets cured of diabetes and typically people are not cured of the side effects. You know, people that have better control their diabetes are going to be less subject to the ocular complications of it. But typically does not go away and the current standards of care out. There are as I said drugs that last one to two to three months right efficacy is is pretty good across the board for all these drugs. They all have approval, and they work. Well, but it's that consistency the patient needs. And that's the unique thing that'll leave brings to the table. Is there a candidate for this particular treatment that actually wouldn't is there a person who wouldn't be a candidate put it that way? Do they have a condition that would preclude them from being able to have this treatment? Yeah, we like to say everyone is a candidate for a living until they're not a candidate for leaving. And what we mean by that is, you know, the one issue that really causes doctors. The problem is a concern that they are going to call. Ause glaucoma. Right. Most of that increase is manageable. But if you tested a patient, and they were truly one of the small population of patients that are really high responded to a steroid you probably want to maintain those on an anti Vegf. Well, look, it's been fascinating learning about this particular treatment illusion. Good luck as you continue to expand and grow elenora sciences. Great. Thank you very much. Thanks for listening to the finance presents podcast. I'm Alexis Christopher be sure to rate review and share this podcast and remember to subscribe. So you never miss an episode. Meet the next generation Samsung galaxy to demonstrate how the new wireless power share works pay close attention on this side, the new galaxy on this side your friends phone by just putting both phones together. Your new galaxy starts moving energy from your phone to your friends phone extending the battery just like that the Samsung galaxy s ten s ten plus order by March seventh and get free. Galaxy buds limited time only terms apply.
S5 Ep20 What is the new normal? What and why did this happen?
"You. Everybody into. house. It'd be. Awesome. then. Dr On here host of Dr Rodney unfiltered uncensored, our twentieth episode of this season. And probably going on three months of the corona. Virus It's been a long long time. I guess. We're all tired of it. But. Thank you for tuning in his Dr Ron, and we're going to have a few little. News episodes for you today and we'll see how it goes generally I. Know exactly what I'm going to be doing. I know exactly what my guests are going to do. But today we're GONNA. SORTA wing it a little bit. And, before we get going. After tell you that. This program contains General Medical Information. Medical information heard on. This program is not advice. It should not be treated as such your income. You're encouraged. Confirm any information obtained from this program with other sources and review all information regarding any medical conditioner treatment with your physician, and I welcome you with an attitude of gratitude has some ready to hey. How about our hands look at your hands? Look look what they do. We should be great for having those hands. Let's try to appreciate beauty. That's right. Try to find the best in others to leave the world a bit better. Whether by healthy jar childlike garden patch. redeems condition. To know even one life has breathe easier because you have live, that's to be. That is what Ralph Waldo. Emerson said. You need to succeed. and. Don't educate your children to be rich. Educate them to be happy when they grow up, they will know the value of things and not just their price. eight-year food as your medicines otherwise, you have to eat madison as your food. You are loved when you were born. You will be loved when you die in between only you are in charge of your life. Think about it. So it looks like the seven best doctors are God sunlight, rest, exercise, diet, self, confidence, and friends that we can't forget the friends and social gatherings of this. Kobe. Social, distancing really really hard on a lot of people. So Ladies and Gentlemen I WANNA. Give a shoutout to all our first responders. Are Nurses or doctors, firemen or police officers, or he went out there trying to keep us safe and keep themselves and their family safe. I hope we all remember our veterans yesterday on Memorial Day. People that gave their life for our roar. We have today. I WANNA. Thank Dr Wrong for last week. I know went on a little long a little confusing, but you know all our shows are archived. You can listen to them again and you can listen to Dr Wong's Youtube show would number three seventy. And I was him giving us. The supplements we need to do case forcedly vaccinated, and we'll get into that later and was basically were activated Liquids Zeolite. Okay. Liquid core fill. Eyeso- printing I as a P. R. I n.. O. S. I N. A. Ice Oh print zine. Ivermectin IV E. R. M. E.. C. T. I n.. Believe, it or not using in animals, but early it works really well along with doc cycling, which is the old fiber Mason for this cove it. Isn't that something. Dr Slightly making a comeback. And he also mentions zinc. And quinine. Zinc at about two hundred twenty milligrams a day and Quinine well we're Queen I. You can get Quinine. Hawks hydroxy quickly though, but you also can get it in tonic water, and if you take zinc zincs I trade. You'll. You'll prevent this Kobe virus. From mutating and getting into ourselves. So what's going on? What what what is happening in this world of ours? One thing happening in my field is physicians are not being allowed to practice their profession. They're being told what to do. They have a drug alcohol, hydroxy Quinto, but out, since nineteen, fifty five and not allowed to prescribe in Kobe patients. You know. It wasn't thinking starting with this. Maybe a will because. Them. You know if you take a bunch of people falling out of an airplane. Okay, and some of them are infected with Cova it. Just falling. And they have this virus in them. Well wouldn't it be nice if they had a parachute? Because right now. The high risk people are going to be hitting hitting hitting the ground, putting on a ventilator and dying. The tests are are horrible where we talked about that last week. So with this analogy, it'd be good to have a parachute. And this parachute you know you should soon as you start falling out of airplanes, you should start. Take taking. This drug will be your parachute. Hydroxy Quinlan with gaily. Zinc and vitamin D three in vitamin C. They slow this virus from duplicating itself its lowest velocity down. So, you can't open a paragraph if you're falling on an airplane, you can't open the too soon, right? What was your near the ground to leap? So Hydroxy Grennell though plus zinc. When or after any of your tested positive maybe too late? Is might be good to start as a prophylaxis, but it's only a bucket day. You know. It's not thousand dollars a day. The one she wants everybody to take the this never been proven to work anyway. And if you're on ace inhibitors or AARP's. Well the AARP's like. About certain Divan. You know you're gonNA fall really for more rapidly, so you WANNA maybe if you're in a area and you have to get out, you might WanNa. Start Thinking about this I actually work, but some doctors should being persecuted for using it. And if you take too late, it's not gonNa work, and that's why some studies show that this drug does not work late. Even if you take it with that Zithromax. Z Pack. We don't have socialized medicine, but independent physicians. Are. Of being forced to rely on fallacies faulty testing. And it's. A It's a shame. So. What's the risk of opening that parents should shoot too early. Taking a low dose hydroxy chloroquine, two hundred milligrams per week or less. After a small loading does this drug has a half life of twenty two days? To two hundred milligrams per week. You may might need less. So Dose Hydroxy Clerk Win. Has Little dangerous side effects. And there's even safe in pregnancy because it's been using malaria patients that are pregnant. Always WanNA consult your physician. And there! There's a chance that you know we're going to have a second wave. because. We don't have heard immunity because everybody's been inside. And His Co. Vig Nineteen Virus I. Think is had twenty five mutations already. So. Ask Your physician. Risk Category. Maybe you WANNA take two hundred milligrams once a month. To prepare for these further mutations and don't forget your multi, vitamins and vitamin. C. Vitamin D three. I remember the half life of hydroxy. Corcoran is twenty two days longtime. All right, so let's Let's talk about a few things. First thing, let's let's talk about the All the projections that The CDC and south she made. And you let me know whether. Would you think? There are people that have writing that. This lockdown should be rescinded immediately. And that found. She has to investigated to find out why he pushed this catastrophic measure. Is If. There's fell out there called Matt Margolis. He's over a PJ media. He's reporting that the CDC now estimates that the case fatality rate I remember that the CFO or Maybe only zero point four tenths of a percent. Zero Point for now. That's the case fatality rate. They were much lower than without. You told us or doctor's scarf. The scarf lady. They said it'd be two three or four percent. And that's what got us into this lockdown. This case fatality rate. Is those cases? In which someone was symptoms had a test confirming they were infected. And some that were not confirmed just symptomatic. There's another. Race call the infection fatality rate. which is the rate among the totality of those infected only? So you can die with Kobe but argued dying from. That's the difference. So the infection fatality rate the I. R. Represents the odds. Every random person contracts the virus as as dying. On the other hand that that cf worry mentioned. Okay the case mentality rate. Isn't it really of interest to us right? It's just Is it just like a normal person trying to understand how? The consequences everybody everybody that died not those with from cove it. You go through the CDC's website and they estimate that only sixty five percent of those who contracts virus actually wind up with any symptoms at all. That means that the infection fatality rate those that are that have Kobe definitely. Is Sixty five per confusing since he five percent of the case fatality rate. Anyway, the numbers come down to about zero point two six percent. And and we just really haven't tested everybody, so it's GonNa. Be Less than that. Remember when we were told it was going to be three point four percent. which is about and a half times higher than it is now? Fasi was wrong. Why we don't know yet, we have to find out. It's interesting. Fast you came on and gave us all these bad numbers, and then he goes and writes an article for the New England Journal of Medicine, stating that it's a little worse than the common flu. Why did he report to his peers? In an article New England Journal of Medicine, one thing and tell us something else. Again I don't know the answer. Unless he lie, but we have to find that out. He pushed us into economic shutdown. And, have you anybody seen the amount of suicides incredibly a lot? Nobody's talking about them. We'll talk about them a little later. So! Dr Fallacy has been not been right one hardly anything he's talked about. Hardly anything. and. How about the vaccine did he's pushing? You know him engage pushing this Maderna's that scene. We talked a little bit about it last week. It's the RNA vaccine. Champion, by voucher financed by gates is using an experimental. Our NATO technology. Value was confident He's well. We don't even eat animal studies as associate well. Here's another mistake he made. They had fifteen human. Guinea Pigs Guinea pigs humans. That suffered serious serious. Adverse effect within forty three days receiving this this vaccine. A vaccine with those kind of reaction race. Could cause grave injuries to one point five billion humans if it was giving everybody on earth. and. That's what gates issued happen. Otherwise. You can't travel. He wants to. He wants a tattoo. You're like the Nazis Tattoos Jews. He wants to give you a ID number by the way you know. Some people say well. How did they come up with that name? The C is for certificate. The Oh is for of certificate of vaccination ID. Cove it the certificate of vaccination I day. that. You don't here many places but here. And the challenges the vaccine are still ahead. Has Attempts for for Kovin. Vaccines have always faltered. They gave you get the animals I think they were using ferrets in the other study. I read about they get great anybody response. When they're exposed to the virus. Now the you know, we have a lot of anybody's. You're supposed to be immune to the virus, but then when they gave the they expose these I the wild virus. You got sick and then died. Robert F Kennedy. Jr. had a good article on that. So where are we well? We've been talking a lot of We've been lied to an abused ladies and gentlemen. Got Us all wearing masks well, the best definition of mass that I've come across is that you know you don't put up a cyclone fence to keep out flies. A mask induces a hypothesis state. You don't get enough oxygen and so what happens your immunity goes down. It increases your sympathetic drive. What's that mean it means you. It makes you nervous. You have more cortisol. Your immunity goes down. There's more carbon dioxide in that mask. You have an increase with fire rate. So, when you're, you know you have a lot of carbon, dioxide and low oxygen. Can that be good? And how many people get irritations on their face? And now they're touching their face. Baras a small. Get through these masks. And then you touch the money outside, then you touch your face. The front, he's mass or or are. Laden with bacteria and viruses. You're supposed to. Wash your hands before you take the mask off with your hands, you see anybody doing that. So there's lots of studies about mass I mean. One after the other. about the damage they do. Okay And then there's a study going out. Now this has been period viewed, but it's it's. It's not it's. It's not that greatest study. It's a review of previous studies. Prevents the evidence. Fairly But it's quite limited. With no evidence that worry them in crowded places helps at all and no evidence at all that it's related to the nineteen. And the. Bottom line is. They're pushing this lady around. It's not even been peer reviewed, but aligns itself with the findings of a similar review of research studies by the World Health Organization that was published in October last year, which concluded there was no. Face mask or effective in reducing the transmission of the flu. So they want us all wear face masks. Just. Crazy stuff happening ladies and gentlemen. This really crazy. Okay so this Kobe is a historic toxic hypoc injury. In other words. You're just liking oxygen almost like you have a carbon monoxide, poisoning and no one's talking about it. No one's talking about. Viruses we have. Tens of thirty one ten thirty one is that's at ten with thirty one zero zero after. A lot of Zeros that's a lot of viruses. You know our gut. Our Body has three hundred eighty trillion viruses in it. Three hundred eighty trillion. So. Do you think people that that that foul cheese and the doctor scarf lady really serious about this thing? You know in twenty seventeen. The mortality rate from the flu. You have any idea because I. know you're not seeing on television. It was seven percent. And now we have A. Covert Corona virus. That is zero point four zero point, two percent and we're locked down. Nobody's talking to you about air pollution. Well, it's getting better. Thank God to the lockdown 'cause. That's a good thing. Maybe we. We won't be using many anybody. Anyway I have any idea any antibiotics reuser here. Four point five billion pounds. That's be with a billion with a B.. Crazy crazy, crazy. And you hear about people turning blue with this cove. What happened before happened with SARS the two thousand one thousand. Two same thing patients turn blue long with fluid. They they knew then it was more from lack of oxygen than respond Tori failure and we went into this already so I'm not gonNA. Redo. Review this. But I will tell you that. The cyanide levels in our errors arising. And the higher they are the death rate. We'll go out. So maybe this virus which Israel don't get me wrong is real virus. It can penetrate the cells. What if you're predisposed to having? Further injury in other words if you've had a lot. If you have gotten a lot of flu vaccines, if you're on an ace inhibitor if you're on a any art to if you're on a staten. You're more prone to get the side effects of this virus. and. How do you think your your body's going to react? If you wear a mask, you don't have enough oxygen. And and you know what airplanes do affect. How virus is transmitted from one area to the other? It would've gotten there anyway a couple more days. It would be airborne and get to travel around the world. So when we think about what what what do we have to look forward to an in the new normal, probably who will be a lower travel already been. You know what that might be a good thing. Goes our carbon monoxide levels in a particular matter in the air probably down. I might be good. Maybe will get better used dealing with. Each other on a social basis. Maybe. We'll go. We'll go from the most medical is DH. Population in the world here in the United States. Maybe you know not so medical is. Maybe, we'll let doctors. Go ahead and treat. People rather just treat tests. The sad part about this and and our virologist. No this. No, she knows corona viruses have a two year life history. So here, mark my words. They're gonNA. Come out with with the via with a vaccine. Probably in a year, or so, you're fifteen. Mazda's still too soon usually takes five years your vaccines and see all the immediate side effects. They have no idea the long term side effects and we'll get into that another time, but you know so this vaccine out. The virus is going to go away two years. Anyway knows it all went away because the vaccine mark my words. We have to take care of her elderly. We have to be like Marines. Never leave a soldier. Leave our soldiers behind, so we have to take care of the elderly. We have to take care of this tyranny of fear. This is just killing us. We get so much information five times more now than we ever did on television computers. Hit has. Stagnated! We don't know what to do. But Ninety. Nine point eight percent of people recover. They don't tell you that they just tell you how many people die. and Bill Gauges funding all that mapping at the John Hopkins. So sure they're gonNA. Show you millions and millions of cases well, the more they test. More of the quarter fine, but a lot of people had no symptoms at all. They just had it and developing immunity and go on with their life. So we are biological body. And we're a spiritual being. We don't want to get trapped. We WanNA celebrate life. We WanNA. Stop fearing death. Maybe it takes. We have to work at not being afraid to die. and. How do you? Rid of your fears how they get by them while you have to learn to love more. You have to see our humanity. See The people around us. Love each other. That's going to be the new normal. Appreciate your days. That's that's my take on this. If we come out of this, and and and we don't drive as much and we just maybe walk more and enjoy life more. This may not be so bad. Because a particular matter in the air is increasing and. Certain Areas like Italy. With the airports and the Gripe is seen and all the vaccines. You can you can. Correlate that with the covert. and. Amazing Gentleman United States. We spend so much money, but on the list of healthy countries were down at the bottom. And as I said, we take the most medicine of any country in the world. We are sick nation. Thirty fifth in the world. In Ellison debt thirty fifth. You'd think we'd be first or second right. So if the couches of the world, we're serious about this this this Corona virus. They should tell everybody that's on a statin drug to stop it. Everybody on the nascent hitter to stop it. You know what the side effect of Hebron is. If you take it every day as a cough. It would tell everybody on AARP's get off them. Get on a calcium channel blocker. Don't take a flu shot because the flu shot has corona and retroviruses it. You didn't hear that from anybody. You heard it here. You'll hear from some other physicians that are on Youtube. That's what we need to do. And mental illness from this this. Virus is incredible. You know the tenth leading cause the United States now is suicide increase of thirty one percent with this virus. Well, people staying inside. Losing their jobs, no place to go no interaction with other people. We are socialized social people. And in the past, economic conditions correlated with the number. Suicide attempts right. And we got to keep that in mind. And Suicide Very Rarely Ladies and gentlemen is reasonable of just having free will usually thought out. It's a conscious conscience decision irrational decision. Not always psychiatric. So there are people during this at pandemic, other struggling with mental. We really have to find a way to take care of them. And get them treat it. Okay so, where are we well, we we definitely WANNA. Turn her wife is off at night. We WanNa take the vitamins we talked about. The zeolite the probiotics You're GonNa have either met on hand. Get that at a feed store. One C. C.. Four hundred thousand emphases safer fifty pounds above that you take it orally mix it with anything scotch beer wine. cranberry juice whatever. Okay! And you want zinc. Want, to either zinc lozenges, or or Dr Wong's zinc, which is zinc psychiatry. You want you want to take zinc re day? Really, important during this time, and you want to say educated, you want to be the CEO of your own body. You want to learn more about these ornate vaccine's. They go in your body, and they become party you. They may produce antibodies, but. Do they protect you against the virus, and that's the sixty four thousand dollar question so far. The answer is no. So far the answer is no. So, what do you think's GonNa Happen. You think they're gonNA come in and have the army take come in and put us all down and give us a shot. I don't know I. Think just too many people with guns I. Don't think that's going to happen. How do you? How do you vaccinate seven to eight billion people anyway? But they might make it hard. They may want to have everybody. Have this vaccine with this idea and. So, they can track us for the rest of our life. You know you see all these actual contact tracing. What do you think therefore? So it makes people paranoid, they make us turn on one another. You come in contact with somebody that had covid nineteen. Now you're in this tracing APP and you had to be vaccinated. Because you are quote, unquote, you have to protect the public. They may even have your boss You know if you're not vaccinated, you can't work. You. Don't know what kind of what kind of pressure they can put him under. The cultural part of it is probably going to be. Pretty strong in the future. Companies to say we prolly you're giving free shots well. These shots you know they're. They're so safe where people dying from them. And Be. Why can't you have sex and how children after these shots? What are they afraid of? Our we were guinea pigs. You know and and every time there's a flare up more shots. Maybe you can't get on airlines. WHO IS You don't have that Tattoo. I keep. Comparing it to the Nazi Germany. So we're going to be forced to forced into this one way or another. Culturally collectively. maybe militarily. Is probably be a full-time job or some people trace contacts. Get vaccinated. then. We'll have bill gates on the tedtalk. Tell us how great it is and yet his kids aren't vaccinated. So I'm told. Incrementally Gates wants us all vaccinated and idead. Covert certificate of vaccination ide-. Don't forget that you heard it here Dr Ron, unfiltered on censored. We know about the mass worth hydro clerk. When probably something you WanNa think about. If you're in a high risk group May WanNa keep someone hand. You Might WanNA listen to last week's program. Dr Wong's about what to do. In case, you are forced forcibly vaccinated. You know there's a doctor. There's that be? There's even this study with Ouchi in New York, it was not allowed to prescribe cove and he had to go to a private hospital to do it. and that crazy and and. Like I actually A. Couple years ago. I guess the figured out what the? Joey Adams has minimum here. He could make more money. Now now he doesn't like it. Only been around for sixty years so. Heck. You know. How are we letting people get away with this. You should read about Dr. Stephen Smith was trained by faust. He's the guy told you about. And he's. He's really enthusiastic about this malaria drug. Graduate Yale. That pretty good credentials right? Well he say cooed I. Don't have words to describe how frustrating this always. there. There's just a craziness out there and I don't know how to correct it. Doesn't matter anymore from Dr Smith on quote. He to use drugs Corcoran. They won't let them use it. Quote either I've gone nuts or they have well. We can't both be saying unquote he that. In New Jersey. And he himself has been taking hydroxy quirk when since March. Before, even began treating patients with it. In April, he said a poll of sixty two hundred physicians in thirty countries found hydroxy. Corporation to be the best drug available to treat cove it nineteen. The nineteen we're that called from. First Letter of the alphabet is eight one. The ninth letter is. I artificial intelligence A. All Code. He calls I dropped. See Corkman a game changer and he's not allowed to use it and that crazy. Well I could go on and on but look. We're GONNA. Start talking about things that we can control next week. We're going to start talking about. Our immune system. Talking about teaming our shower, Hey, clean! How many people off their shower head you know if you have a dirty shower head and have the water goes on your head. You know you can get pneumonia. Maybe we should be. A little more. Conscious back. Do we take a shower clean off that showerheads Huh. So ladies and Gentlemen I. Don't WanNa ripper over. Where were you know we? Welcome our humanity and realized. We are human. Okay. And spiritual beings and treat each other with respect, kindness and gratitude. We can come out of this thing. Maybe a little more respect for the environment. Okay, that's not a bad thing. Decreasing the amount of carbon we put in the air, so we don't have some particulate matter and so much carbon monoxide, you know. So If we all stay together and stay on track. We might be able to come out of this thing and please do not. Fall into the trap if you have antibiotics home and don't feel. Feel good for any reason, so we'll just take some Z pack been saving. Don't do that. Because, we can't forget about the Super Bowl. We used to talk about all the time. Remember that causes the C diff. Right two point eight million a year, thirty five thousand deaths in this country every year, according to for the drug, resistant superbugs like see. THIRTY FIVE THOUSAND YEAR IN YEAR OUT The don't invite that enemy into your house, okay? Antibiotics don't kill viruses when they're unions with Ivermectin, hydroxy quintal alone. I dropped Sequeira Quinn. Yeah, I mean there's they do. Treat the secondary infection, but please don't be say well. I got a headache. I got us through it. I wanted to take an antibiotic. At your last last. Option. So we're going to get out of our houses. And we're going to have her surgeries and checkups and everything else. Please don't do it up on antibiotics. There is zero proved. Can protect you from getting infected with the corona virus or catching covid nineteen. prophylactically. We talked about drastic Quinlan hydroxy core Quinn different different Drug altogether. Okay! So I'M NOT GONNA. Take any questions. Today my seat all the callers here but. Just know that we're going to get back to a more normal schedule next week. talking about things that matter for your health for your longevity. And start bringing back our special guests. and. our friend Freddy. WHO's been writing songs for me? Route Great Song for. Our daughter's birthday or disgrace on pop died. And now he just starting to fool around with raiding closing song for our podcast, so we do appreciate. We have an attitude of gratitude for Fred. Man was a professional musician. Whole life toured with bb King. Guy. so He's a gentleman. This is Dr Ron this episode twenty, the new normal it's. We're going to have to work at it. Why this happened. I would ask you to if you're interested in why it happened. Is beyond my pay grade, but it would ask you to to look up a video, very. Dr Sheba S HIV. And it has to do with the money. The big guys were having too much time too much trouble. I ain't ten percent interest rate to the Fed, back in the last quarter of last year. They wanted to make sure the interest rate came down. That's just theory and they did it by locking us all down. Decreased demand for everything, oil prices fell interest rates fell. There's zero now. They went from ten percent and the last quarter of last year two zero. So we're SORTA palms but we do uh. Hopefully we can get together and get on one page with this thing. They have great rest of the week. It's been good talking to you. Tell your friends about Dr Ronald filtered uncensored. Where here live every for every Tuesday and We are on Alexa. We are on Google. We're on spotify or every place. You go just just say Dr. Ronald filtered uncensored. You will get our podcast. It's been great talking with you I. Thank you and have a good one. here, everybody. Finished today. Wisdom. All about good A tune in next. Win. Is. A Win this. Is. When the DON is. How? Le Is. How? Digest. No. By? The. Happen. Call. If you have a stray. Call. Man. And no one. A winless live. Is. Oh! Is.
36. Diuretics, ARNi, SGLT2/GLP1 therapies and iron for HFpEF with Dr. Robert Mentz
19. COVID-19 interactions with ACE-I and ARBS with Dr. Oscar Cingolani
"Worldwide cardiovascular disease affects the lives of hundreds of millions dedicated cardio nerds everywhere are working hard to fight this global epidemic these are their stories hi? Cardio nerds Corinne here in light of the current Cova nineteen pandemic Ahmed. Dan Heather and I have decided to take a break from our regularly scheduled broadcasting that includes heart failure awareness week and instead hope to shed some light on the cardiovascular implications of Corona virus. There is so much that is still unknown but that is part of the art of medicine. The need to constantly grow evolve as we gain more information in that spirit. We're organizing a series on cove in Nineteen. We sincerely believe that every cardio urge should pay keen attention for these three reasons. One patients with cardiovascular disease are at higher risk of infection with Cova nineteen and once infected develop more severe complications too as with other viruses. Cova nineteen appears to lead to cardiovascular complications and three given one into cardio nerds will be among the key providers in the trenches. And my friends. We Cardi promise you that we will be working hard to bring to you. The Best of what we know at the current time however the constant flow of information is honestly dizzying. In our knowledge base continues to evolve. This episode was recorded on March Sixteenth. Twenty twenty but by tomorrow we may very well know something new which is why this time period is both a very exciting time for science and a reason why everyone should endeavour to stay up to date with professional organizations like the. Who NCDC as well as local and federal government officials and guys for our first episode in the series. We are honored to sit down with actor. Oscar singer Lonnie the director of the hypertension center at the Johns Hopkins Hospital to help work through new information relating to old medications and his thoughts on navigating uncharted territory. And friends. Just remember this. Podcast is not meant to be used for medical advice. The views expressed here do not necessarily reflect the opinions or policies of our employers. The goal is to simply enjoy learning more about cardiology in the covert era directly from expert. Cardi innards hey cardio nerds. There are so many unanswered questions surrounding Cova. One thousand nine hundred information both good and bad as flooding our. Tv's twitter feeds. Newspaper is an pubmed searches. This timely episode is meant to help guide clinicians on the front lines doing their best to take good care of their patients today. We are so grateful and excited to learn about the interplay between aces and arbs with cove in nineteen. We are so excited to be joined by Dr Oscar. Singer Lonnie a true expert on the subject matter. Dr Singer Lonnie earned his medical degree from the National University of La Plata Argentina and completed his internship in internal medicine residency at c. e. m. i. c. Barness Argentina and Hypertension Research Post Doc Fellowship at Henry Ford Hospital Detroit Michigan after completing his internal medicine residency at the Reading Hospital and Medical Center in Pennsylvania. Dr Singer Lonnie joined the Johns Hopkins Hospital as a cardiology fellow where he remained on faculty after his training. He is currently the associate director of the Johns Hopkins Hospital Cardiac Care Unit and the director of the hypertension center doctor single on his research interests focus on hypertensive heart disease and its transition to heart failure. Honestly Guys Dr. Milan is one of my most favorite people to work with. And he's so beloved by all of our fellows he's as cool as a cucumber during the most stressful times and his work life balance is something to strive for besides for all of his academic accomplishments factor. Single on is a passionate sailor and master photographer. Dr Singh Lonnie can go on and on but thank you for joining us today. Oh thanks for such a kind of introduction and I'm very happy and honored to be hard cardio nurse now this is the pleasure and honour singularity and we are so that you're here right now because we can definitely use your advice for our next case. Sarah as Ovid's is a twenty nine year old woman with a history of familial dilated cardiomyopathy with an ejection fraction of twenty five percent satisfied. Primary Prophylaxis single-chamber icy her doctor. Dr Spikes listened to Carter's episode number thirteen in which Dr Randall starling taught us all about guideline directed medical therapy and Hef Ref. Accordingly Kovic is on the Senate bill twenty milligrams daily Metropole Sexy twenty-five millions daily and sparing electron twenty five milligrams daily in the clinic. Dr Spikes is about to discuss searching her from the center pill to secure certain but she walks into the room as his Co. is having a coughing fit it turns out that she ominously returned recently from family cruise and has been having a few days. A fever and cough recognizing scenario darker spikes immediately dones personal protective equipment and activists her hospitals covert Action Plan. I sound suspicious. So the burden of cardiovascular disease has been high in patients affected with Cova did with hypertension and diabetes concurrently being the most common co morbidity. He's there to recently published papers. We will reference on our website finding increased risk of covert in patients with pre existing cardiovascular disease diabetes zoo at all published a paper in the. Lancet recently that included a retrospective description of one hundred ninety one. Cova nineteen patients in this cohort. Thirty percent had hypertension nineteen percent had diabetes and eight percent had coronary artery disease another publication by Guan at all of about a thousand or so covert patients in the New England Journal. Found that of the one hundred seventy three individuals with severe illness about twenty four percent had hypertension sixteen had diabetes and six percent had coronary artery disease. It's hard to really deduce causal inferences with out prospective data. But there's a lot of talk about the biological plausibility that individuals with hypertension or diabetes. Me Be more predisposed to contracting cove in nineteen the basis of this possibility is the role of Andrew tencent converting enzyme to Dr Singh. What IS AC Two? What is it's role in the SARS covy to biology? And could this contribute to infection in those with hypertension or diabetes right going? That's a very interesting question. And as you said The data suggests that patients with hypertension and diabetes and also coronado artery disease where more severely sick than others. I think that to begin with before getting into the age. We need to make sure to know that these are studies coming from single country very sick and few look into those patients who are sick regardless of why. They're sick the majority of them. We'll have hypertension diabetes in quarter nutty artists. We don't know exactly. How many of these were taking eighth. Inhibitors OR ENGINE. Reset some bloggers but some of those are certainly taking the problem with this and let me started by the chasing This from the get go. There's an enzyme that converts engine tensing one to end you tensing too and that ends in school and detention converting enzyme or eight. There's another is a form of that in time which is called as to that is also in the lungs and it has some actions that protects the long. But it's also a receptor in the Numa sites type. Two that facilitate the the entry of the Corona viars to the cell and this happens when grown virus with protein that SKULD S. That is a little you know. Round the ball in the in the crown Touches the age and that together with another protein proteges called P. M. P. A. S. S. Two together. They internalize the virus into the cell and they fuse. The ad end of the buyer is with the nuclear information of the virus with the cell and then propagates the infection. So ace inhibitors as well as a RV's all the drugs that ends with a certain drugs that ends with Krill are known to produce an increase in ace two levels so in theory if you think that the virus needs a stew to penetrate impact the cells and these medications increase ace two medals. Then naturally we need to think that this could be bad for us because he's might propagate infections but that is not as simple as it sounds so first of all all. This data comes from animal studies. And if we take for example a mouse that We knock out a stew that means that genetically they don't have as do those mice have lower contract. They have high end attention to expression and they don't have as but those minds even though they're less prone to develop viral infection with the Prior Cobra virus to two thousand to two thousand three virus They were more likely to there. A art yes because ace to say protective mechanism and I'm going to explain in a bit so let me silly that I not only. The data comes from animal. Mainly from rodents but second. There's controversial show studies suggesting that it could be worth in theory but in practice animals exposed to Cobra virus treated with low certain developed less A. R. E. S. then Those who were not so now we can. If you want we can go and tell you. Complicate matters a little bit more. Yeah so there are two states and they in humans and patients one is a low state and the other one is high entertaining to stay so and attention One is cleaved by the ace in Nj attention to and whether you have high or low entertaining to levels they mechanising between engines and two and ace two is a little bit different for example in cases where you have naturally no entertaining to stage and they say for example in a patient who takes ace inhibitors though stations by blocking the conversion from one to two they naturally have low and Japan to do so that in that scenario enter tensing two binds to the eighty one receptor and the receptor binds to the ace to and that ace to because of that catalytic site occupied but the entertaining one receptor produces more of a substance known engine fencing. One two seven and that engine one to seven seems to protect from a rds protecting inflammation and protecting vascular permeability so that se is a protective mechanism on the other hand. If you have high end attention to which is if you stop the ace inhibitors and defensing to go. Hi Two things happen. First of all and your tendency do goes to the CORTEX of the ADRENAL glands and Producers Industrial Dr Lowest Potassium and elevate sodium producing hypertension. Well guess what those patients who did the worst and who died had higher blood pressure that does recover. And a third of those have hypoc lenient on the other hand when the engine sensing two levels are high that age attention. What we said that that I told you advise ace to it separates allowing the virus to bind to a stew and internalize yourself so visit per optical response and number three in something that we are also trying to report in the next few days. Is that if you look at aging road and the older you are the less engines into you have so you can argue that. Actually the elderly gets more civilian festive because they have lower levels in their lungs and then therefore are more prone to developing a yard and other hypo visit and the gene that codifies for engine for ace to the gene that is responsible for as to if the x chromosome so women have more ace two levels than men for that recent. Well guess what women tend to be less impacted and less severely infected than men. So there's just another reason. I say that this could be something in fact that are trials ongoing in the US right now that are treating patients with MILD CORONA COVA. Nineteen infections with low to see if that can protect them from becoming to be released. So again all. This is based on a single hypothesis and most of the day comes from mice so what happening humans. Well guess what if you measure from blood as two levels. It doesn't matter if you're in a nice or in a RV or nothing you're ace. Two levels are the same in the last night. We don't know what happened in the lungs but emplacement. We know that there's no major difference so this is a classic example where one can think of a hypothesis but until we have more data we cannot tell somebody with heart failure or the prior. Am I with hypertension to stub their medications? Now because we actually don't know what's GonNa Happen. Talk About Jacqueline Height. So it sounds like a stew has the propensity increasing infection by virtue of being the portal of entry but then also may have a protective effect against some of the more severe complications. Correct that's exactly correct to therefore if a patient is already on a throwing arm prior to infection they may be more susceptible to catching the infection but when somebody has the infection there is a potential benefit of actually being on a Nacer in Arab. Because you yes. That was. That was what I was thinking last week but now that we know that most of the people who are thirty years old or younger I are actually infected. Asymptomatic probably is not about getting impacted. Maybe everybody gets infected the same degree but those who are you know in the in that age range about sixty they really get more severely sick and those are the ones that we are testing the most so it might be that it doesn't matter if you have as two levels high or low for the infection you might actually have a little bit of base too and that's enough to get infected but one thing is for sure if you do not have a stew you're more likely to develop a or at least that is what the animal data suggest so so far. I am just using commonsense if you are on a medication because you have heart failure prior am I or hypertension. Why stopping it because you can actually do worse if you get the virus but it actually you can do warriors if you don't get the virus because you know you can have more heart compensation or or something know related high blood pressure so I you know. We don't know how long this is going to last. We might be talking about from few months hopefully to a year or more and are we willing to leave our heart failure patients without a RV's or without an ace inhibitors for forty years. I don't think so so I feel we have more data out knowing all this complex Mechanisms we should probably follow the guidelines and the consensus statements from the a feet and European Society of cardiology all of which are actually recommended to continue with treatment with these medications and I think it's worth emphasizing again ducking linear saying that all afar understanding of how trip hypertension with aces and arbs impact as two levels really is derived from animal data. And the only way that we have from humans is suggesting that maybe doesn't have an impact to begin with correct correct. I think that that's very very true and very important. The difference is that you know all all the trials that we've done humans were preceded by animal data But we have the data in humans that time. The problem is that now we are in emergency but we don't have time so he be very cautious in how we act upon this I think that we need to wait. and we will have some more information. I know that the Chinese and Italians are looking into this. And we're going to hopefully have more and more data coming to that is incredible and fascinating and really reminds us that you can't latch onto one side of a pathophysiology coin until you really appreciate the fuller picture. And sometimes that means waiting it out and going with what we know and then actually implementing treatments based on what we know what is tried and true and then eventually lowering other options but it seems like you make a good point if we pull everybody off of such lifesaving medications for heart failure we may not even anticipate the damage that we could potentially due to. Our patients who we know would get real benefit from these medications. Such as as an arms in patients with chronic heart failure absolutely absolutely and that will also underscore the importance of clinicians you know reaching out to basic scientists and vice versa because this is the way to solve problems just not working silos But you know kissed. Collaboration between different specialties is very important and I'm learning a lot about in technology in microbiology and I people are learning a lot about cardiology. And this is the beauty of medicine and taxing money. I think the public service announcement here is for clinicians to not latch on to these preliminary reports and really hypotheses into keep patients on the medications. There are on now but you did mention that. There may be some Something to suggest that there may be a therapeutic role of Engine Receptor blockers. This obviously too early for prime time for that discussion. But do they really have any merit in your opinion? I don't know I know that there's also trials with Combo Stat. Mesylate which you say suppressor of this other proteins that works together with the ace to because the problem seems to be the can be there or not but if you don't have the coach as very few in his approach as the d. m. p. r. s. two That is the key one that actually you know makes the the entire complex. Go into the south so it. It's very complex. But the other thing is that I read this the The Lancet paper. I'd read it relaxed and you know two weeks ago and when I read it it didn't occur to me that we should stop this because I read a little different. Is You know if you re that in the absence of this damage you read the This coming Turning Lancet and they actually raises the issue of NEAT requiring more research of this In this topic but a week later when people are panicking you know you read it and you look at what you want inside the article and say Oh we should stop everything and know. The article was not meant to suggest that it was the media that suggested that and the people who just read it very rapid me in trying to you know make this condemning A little bit worst enemy. It is I think that we should be very careful. When we read the data because It was just a hypothesis generating and thanks to this Article that came and landed and another one that came in British Medical Journal. We're now learning a lot about this mechanism. And maybe you know we'll help to come up with a solution. It Dr Single on certain engine. Tencent converting enzyme two gene polymorphisms have been linked to diabetes hypertension and stroke. Do you think there may be ace to polymorphisms which may result in increase or decrease except ability to the virus That's a great question. It's under investigation. So the quick answer is I don't know and I'm not sure that anybody knows we do know that diabetic patients especially might have a polymorphism as to and we don't know that polymorphic change It's the same one that the virus is using to get into the cell so again. This is another Major stone that We should not Assume things and think that by inhibiting or enhancing a stew we're going to be targeting that ace to that the virus neat so a lot of data coming down the road also in that regard. It's really interesting. How are clinical observations feel basic science and basic science fuels are our clinical endeavors? And wondering. Do you have any thoughts about the therapeutic use of soluble form of as to let me preface this by saying that rather there might be an idea that soluble as to might not only help neutralize the virus itself by competitively binding the spike protein. But there's also thought that may help increase the protective role of the membrane bound form of as to and There may clincal trial underway looking into that. I know the same thing that you know but so I haven't heard any more Beatles about that but I heard about that. Big The complex issue is that the The binding of the ace depends on the state of the engine. See too so you. You're gonNA have a completely different Response in those with high levels compared to those with low end attention to levels so and and even if you are not treated with an ace inhibitor. Even if you don't heart heart failure we treat hypertension with low or high Rennes dates. So there's patients who have high levels of engine to and others who have low level engine thanks to and we are now trying to measure certain substances to tailor therapy accordingly interesting. Thank you with regard. There's also a lot in the media about Ibuprofen and and said is that. How is that related in? What are your thoughts on that? Propane is one of the medications that increase his expression crunchy. I probably until this is the other thing I've heard from actually from Argentina. I I'm going to have a So I'm they're going to do an interview. Bs Sky Tomorrow Point Eight four the TV channel in in Argentina and because in Argentina. There's this boys going around gossip thing that nobody takes appropriate because it increases as to and. Actually it bleeds for and they're confused because they are having an Argentina's also dandy which produces from the side opinion. You can't make but the truth is that ibuprofen increases as to to the point that. I'm not sure if I should not be appropriate right. If it's the same mechanism that we talked about with the ARBS. Yeah very interesting by taking ibuprofen. I can raise my eighth to expression in the lungs by by actually get impacted by not developed yet again hypothesis. Interesting so Dr Singh Lodhi. We know that you've been using telemedicine Pretty broadly even prior to this pandemic now with with the pandemic of cove nineteen A lot of people in healthcare providers are turning to tele-medicine. Can you share with us? Any S- tips and tricks with regards to the experience. You've had this far with telemedicine. Yeah so I think that you know we. We as a healthcare providers are moving into telemedicine. And I've been practicing telemedicine basically in my hypertension patients who I see than the first sign. I they get the you know the physical exam that blocked work and we follow them via telemedicine and I found that very very promising and we are having great great results in in terms of especially when discussing side effects of medications and when discussing titrate medications we we have been preventing patients from Stopping their their treatment. Thanks to tele-medicine so I think that this called nineteen condemn ick is actually beating us up to deploy this system and it's GonNa be terrific. I think that the one of the things that I've noticed is that you know. A lot of people. Think that telemedicine is unpersonalised and you lose connection with the patient. But I've been surprised of how relaxed I can have a conversation Through skype or through phone for half an hour talking about how things that I don't talk in the clinic and and making a connection with the patient that goes beyond they connection that we make in the clinic. Sometimes he doesn't you know we're we're not relaxed or there's noise or somebody else in the door or or the patient needs to rush through another Appointment so. I think that there's a great opportunity and we should take advantage of this Endemic to rapidly deploy telemedicine service and instant. That's well no. I absolutely agree. That will definitely be at least one positive thing. That will hopefully come out of this. The building that infrastructure so that it's more seamlessly utilized. Donna do anticipate telemedicine being used as kind of like a silver lining. Potentially this pandemic if we can even see a silver lining at this point something that we will learn to use an implement so saving a lot of our patients time and hassle of coming into to the clinic. And do you see that as something that can possibly happen? Going forward. I predict will happen. I'm hope I'm right. I predicted this is going to happen. And between those I received an email to go through my co by patients for the next month and risk. Try to fight them and decide which of those can be followed by telemedicine and we go should be rescheduled. So we are Hopkins. It's actually working very very aggressively with this. In trying to implement by the end of this week a telemedicine platform started being active allow. It's so nice. He does plan being put in action. So this has been a wonderful discussion. Document Lemme thank you so much for taking the time to teach us in this time of fear uncertainty and really ubiquitous misinformation. We are so grateful for experts like yourself keeping grounded in the facts and guiding the care we give to patients like Ms Cove and just to emphasize the main takeaway for clinicians on the front lines. Taking care of patients is essentially in agreement with a major society guidelines to not preemptively take patients off aces Arabs and other such really life saving medications until or unless we have more information so thank you thank you guys. Moving terrific in night totally agree with your closing remarks. Yes and by the way because you have been so generous with your time on the cartoon show as they say. No good deed goes unpunished. We hereby officially invites you to join us in a few weeks down the road for critical update on what we learn about the roles of ace to and the Cova virus officially. Except that thank you. Thank you awake. Green has an update for us absolutely so friends. Despite our best efforts MS Kovic takes a turn for the worst on her way to the emergency room. Stay tuned to our next episode where we learn about critical care management of the cardiac patients in the ICU. With Dr David for Farro from Columbia University. And Dr Sam Brusca from the NIH are show so it's time to make like an s to split. You can follow us on twitter at cards. Don't forget to check out the amazing illustration the Korean prepares for y'all at www dot guardian dot com and please share what made your heart flutter this week so does the clip two Carbonari gmail.com if you enjoyed shall be a nerd and spread the word and now aflutter Guardian Air. It's just want to say that I love the show. My Name's Steven and I'm an orthopedic surgery resident at Georgetown. University Hospital will makes my heart. Flutter IS COMING ON POST. Call the see my wife and baby daughter. She just turned three months old and is the best part of every day. I'm just going to get up recording. I Love Dance family way for me to sound proof studio suite when people's families come in and like in the middle of the interview.
#69 Inpatient Heart Failure: 5 Pearls Segment
"I everyone this car episode. This month will count for Sammy credit with ACP. Yeah, Hey, we will link the executive. Elon the showed so click on the link answer three questions and get cme credit, and with that cue the intro. This is Dr Marty free to primary care physician. At the Ohio State University Wexner Medical Center, and this is Dr Sharia Travek Internist at-bat, Israel Deaconess Medical Center and Dr Michael Dunleavy a clinician Educator Fellow Ohio state. This is the core I am five pearls podcast bringing you high yield evidence beings pearls. Today we're kicking off a two part series on advanced heart failure. All, right? Our first episodes can address pearls around heart failure on the general medicine floors. In our next episode. We'll tackle more ICU level care with discussion on advanced therapies. We are super excited to introduce a new friend of the pod Dr Michael. Patrick, Dunleavy, great to be here right on all right? Let's get started with the pearls. We'll be covering in this episode. Test yourself by pausing after each of the five questions for member. The more you test yourself, the deeper you're learning games per one initial clinical assessment, what are some key clinical variables to evaluate when you first meet a patient with acute de compensated heart failure? Pro To initial lab workup. What are some of the most important lab findings to pay attention to in a patient with de compensated heart failure? Pearl Three home runs, which medications can be continued during a heart failure admission, and in what circumstances? Pearl four loop diuretics. What are some dosing strategies and monitoring tips to help us? Guide initial volume removal. And Pearl, five diarrhea says two point Oh advanced topics in volume removal. What role do thighs is an ultra filtration plane India Rhesus? And why does diuretic induced metabolic alkaloids happen? And what should you do about it? Okay before we deep dive. Let's just take a moment to make sure we're on the same page when we talk about heart failure. Heart failure is a clinical syndrome meaning it's a constellation of signs and symptoms that lead to a diagnosis and de compensated heart failure refers to someone who has the clinical syndrome of heart failure with elevated cardiac selling pressures. That's Dr Greg Cats. Are Core I am in house. Cardiology consult and cardiologists and cardiovascular intensive EST at vassar Brothers Hospital in Poughkeepsie New York. So I think about a heart failure exacerbated as being the result of elevated injured cardiac filling pressures, and that leading to a cascade of a neural homeowner response that causes vasoconstriction, an and fluid retention, and all of the subsequent symptoms that people have those things will develop all right. That's a perfect place to start. The initial clinical assessment of a patient we suspect is having a heart failure exacerbated. All right so Mike. Dunleavy you get a call from the D and You're next. Admission is a middle aged gentleman history of Corner Disease Post. Some stands his objection fractions in the twenties. He's reporting. Some worsening lurks swelling shortness of breath after binging on some net flicks. End My favorite Roman noodles for about two weeks. What's the first thing you're looking for? When I'm getting an admission and I'm suspecting it to Hartfield exacerbating. My spidey senses are way up when I'm looking at the vitals after all vitals vital. So the pressure is going to be a sign of a patient's perfusion status and I think what helped determine what your next steps of therapy are I mean the hypertensive patient he's may be poorly profuse and could need an Aina trope, also hypertensive patients, and is more blood pressure control that they need relations and afterward reductions. That's Dr Aisha Sean from Ohio State Dr. Hassan is the medical director of the heart failure, program and section chief for heart, failure and transplant. Her point here is easily overlooked obviously crucial to triage. What is there pressure and what does that? Tell me about perfusion status, and when I'm listening for the blood pressure I'm also tuning in to what's the pulse pressure, which is the difference between the systolic diastolic blood pressure. Pulse Fresher. Can Be assigned that somebody is in a low output state, and if you are not taking that seriously, occasionally, you will miss a vulnerable patient because their blood pressure is one thirty over one ten, when they're normally one eighty over one forty, and you will take someone who is relatively hypertensive, but as a pulse pressure of twenty and just create damage unique. Listening to those numbers. Your spidey senses must be. Be Tingling all right. Peter Parker walk us through the pulse pressure, so Paul's pressure is usually determined, enlarge, part, Bay, aortic elasticity, but if someone with a reduced ejection fraction comes in with a low pulse pressure, it's more likely assigned that they're sick. Heart has a poor systolic function and can't generate enough force to even get a normal pulse pressure rather than it being related to their a arctic elasticity. All right and the other variable, not to lose track of is heart rate. Remember that old equation cardiac output equals stroke volume time, heart rate, sometimes resting sinus tech, a cardiac might mean that that heart is on struggle street and making up for the low cardiac output by working overtime. The to me rookie mistake is interpreting the heart rate without looking to see hey, is that patient on an AV nodal blocker or not? I think we've all been fooled by normal heart rate, but they have motto Pearl. Onboard one strategy I've seen. Is people including this in their documentation or hand off so they might say something like heart rate in the nineties on home. Home tope sucks nate one hundred milligrams. Yes, I appreciate those qualifiers to take objective data into context winning. They're all right, so that's the vitals moving onto the rest of the physical exam. I mean with heart failure. There's just there's lots of signs to look for. If we had to focus on one aspect of the physical, the and heart failure. What would that be? You are committing malpractice. If you are not looking at someone's neck means when they're admitted with heart failure. Okay not to sell I might be thinking twice about asking Greg for expert witness testimony in the future, so the reason I focus solid life physical exam on Jugular Venous distension is because that is your window into cardiac selling pressures are. The, absence of Pulmonary Dima or lower, Tremonti's swelling all of these traditional physical exam. Doesn't tell me that patient doesn't have. You can have heart failure without swelling and swelling without art. Vedder your jugular venous pressure. Is your bedside swab? That tells you what you're right. Atrial pressures okay so. JVP is our window to see. How backed up are in the heart. If you look at the medical literature, you'll see that JD is often not considered to be a super important sign of heart failure I'm completely persuaded that the reason why the evidence doesn't back. This up is because nobody does jv. All you need to do spend one week rounding with a heart failure attending who is able to figure out patient who medical team stop diary sing still twenty pounds out just at their neck hands. You will be persuaded to. You can't just do it once or twice and watch a couple of youtube videos easel thousand neck's. All right well, I don't know about you all, but I'm pretty convinced out J. P. now, but that's a pretty tough exam and I've heard of at least eight different ways to do it. The real question is how can we accurately find the JVP? The simplest quick and dirty way to do it is you sit somebody up at ninety degrees and you see do they have any palpable jugular venous pressure above their above their clavicle, and if you see anything Venus, above the clavicle in the absence of severe tr. That's elevated. Right atrial pressure assuming that it's not like SBC Syndrome or TAP, and then the second thing that I'll do is I'll put someone at forty five or sixty degrees to sort of like super flat, but also not completely upright and I'll look to see that they have a pulse ation their ear, and you need to look at both sides, because sometimes only one side will show it for whatever reason, okay, yeah I've definitely been guilty of only looking at my patients right side. The other thing is I always feel like I'm trying to figure out the pulse I'm seeing is Venus or arterial when you're finding someone jugular venous pressure your finger on their wrists. Find the pulse. Your jugular venous pressure should have to pulsating for. One Halsey that you feel at someone Chris, and if the up stroke of what you're feeling on the rest corresponds to the stroke of a pulse station the neck. That's the karate pulse, and it's not the one that you want us. Great Cirri kept my big takeaways from the initial clinical assessment is at blood pressure, specifically low pulse pressure can clue us in at the heart squeeze is. Isn't that great and the patient might? Might be in a low perfusion state and I'm all for changing our culture in terms of how we present our document vitals and say Hari in the eighties on hundred milligrams daily, so we don't feel reassured by a normal hurry for a patient who's on ebay nodal blocker and I will ever be terrified about not looking at a ged, because that is as Greg pointed out the window to the right atrial pressure. All right guys. Can we also just be real and talk about all the times we've been at the bedside with our interns or mets? Houston's shining iphone light on the patient's neck and the JV exam is just limited by hazardous. Sometimes, we just need a little bit more objective measures, so let's talk about the labs in heart failure. Yes, the happens all the time. And a lot of attention gets paid to the BNP or brain, natural peptide, and for good reason. Greater than a thousand supports the diagnosis of congestive heart failure. BNP less than one hundred makes way less likely and BMP's in the hundreds are just not that useful. For example, one paper noted a BNP of three fifty has a likelihood ratio one which doesn't change your pre test probability at all. For me, the trend is important as well as the actual numbers I love when patients coming in with the Hartfield exasperation have had an outpatient bnp when they were feeling. Well. That way I can compare what the BNP is when they're sick on admission to the hospital to what it was when they were feeling well outpatient, and the reason why that trend is important, and I'd argue even more important than the actual numbers itself is that there are factors that lead the BNP to either be higher or lower for example patients with chronic kidney. Usually tend to have higher BNP's so it's even more important to compare that current BNP to where that patient usually lives when they feel well, and there are few other conditions to be aware of two. and. Then BMI is important when it comes to assessing the BNP, because morbidly obese patients tend to run a lower looking more at the trend, if patients are on the new drugs, sexual betrayal the Nepalese an inhibitor. Then BNP will be elevated, have to approve Ian P. Yeah that knepper Lisin editor BNP. Bump can be significant, even tripling from the baseline levels, and the reason is not licensed breaks down. BNP SO BNP levels will rise. If you're on an upper lisin inhibitor, instead you actually want to order a probe, emp and patients on knepper license inhibitors since it's not a substrate for knepper lifespan, so listen. BNP gets a lot of attention, but when I'm talking about the heart failure work with Meyer interns and residents, I always try to impart a healthy respect for the trip ponant indeed. Heart. Failure especially if they're post, pressures are low, and you're concerned about shock. You don't WanNa. Miss an opportunity to ask. Your is somebody when you had that opportunity because that's the only intervention that we know seems to make a difference ENCARTA genyk shock. Exactly, if there's any consideration for acute coronary syndrome, being the culprit of that compensated heart failure. Again especially if they're pressures are low getting them to the Cath lab to see. If ACS is causing, it can one of the few things we do to actually improve their mortality. Love it all right. Let's move onto the next most important lab dunleavy. What else is on your list of never misses? Let's talk about Sodium Fun Fact Hi Tony actually associated with a worse prognosis. Yes, sodium corresponds really closely with somebody's mortality and their degree of chronicity of illness when I see somebody come in with the compensated heart failure and a sodium of one twenty nine. I think about them in a completely different frog. Place than I do in someone who comes with sodium of one thirty eight. And those data to back that up admission hypoglycemia is of all cause mortality. The risk of death was especially worse. I was less than one twenty five in heart. Failure exacerbates even a sodium drop of just three. Per leader during the admission was associated with increased mortality. Wow Okay respect sodium respect, the trope I feel like we do a pretty good job of that already, but yeah, for real respect the sodium. Okay any other labs to respect their definitely others, but we might be respecting labs a bit too much like the Craton. Yeah so like I don't think you're talking here about critically ill patients who arrive in extremists and you're rushing to this E. I mean true kidney injury like eighteen or cute tubular crosses can, and does occur in really sick folks and we definitely care about that. I think we do respect cranny and a little too much when it comes to small bombs that occur during diagnosis exactly. Yeah happens all the time, but we know the answer. Just keep diary. Sing right through that acute kidney injury. This is not really acute caen injury. It's hybrid the out in the name Ya. Yes, that is Dr Swap, Neil her ma to their rescue nephrologist the Ottawa, hospital and from twitter's Neff JC, but wait. What's he saying here? So that hypercritical? That's why not mentions is referring to the work of Dr Steve Coca who wrote a great paper on this idea of permissive Aka I in the treatment of heart failure. And he's playing with boards yet. It's a question of semantics but the this kind of framing changes said from thinking of it as a kidney injury. That is unclear and you should be falling principle of but massive hypothetically academia so leading Cleveland go up, look at the patient. Volume overload. LET THEM BE DIET EAST INSTEAD OF CLEVELAND. One point five. It is one point eight. That's okay they could be breath. Clinically the patient is getting better that sort matters. All Right? Yes, take a deep breath be brave and channel your inner swap. No! So. If you see a Croat named bump reassess, what else might be going on? Are they obstructed? Need a Foley, or was it just a small bump in patient who's otherwise clinically improving but still overloaded and needs more diagnosis. The knee jerk reaction is often to just hold the died Roddick's, but if it's a small creating bump in a patient, who's otherwise improving continuing the course might actually be the best thing for them. Yeah I think we can all do better and channel are in inner spot melanie situations. Art To summarize this per all. Number one when looking at the BNP it's great if we can compare it to the outpatient setting or the last time they were admitted with heart failure exacerbation again there are other things like obesity. Chronic kidney disease patients on knepper license inhibitors that can make be MP's either higher or lower number two hypoglycemia remember it's an independent marker for mortality in patients with cf, especially if it's worsening. Worsening during the admission number three remember to check a trope if there's any concern for acute coronary syndrome as a cause of de compensated heart failure, especially if they're in that cold category, we discussed in Pearl. One because there are significant benefits to earlier vascular ration- and finally Cardio Renal. Syndromes important and complicated, but if your patients still dominates the answer to a small crandon bump is. Continue Diaries. Okay guys can I tell you. What really grinding my gears? When you call someone back within seconds of missing a phone call and the person doesn't answer the fact that it costs more to replace in in cartridge than it does to buy a whole new printer. Chris Harrison's Murtha mercy. Sins Mercilus pre-commercial teasers during Bachelor Season Finales. You've got a lot there like. You could just pick you. Well, obviously, those are bad. But we're talking about maybe even worse than that. The fact that some people still believe flat earth conspiracies Occa-. No not not that bad. That's bad. That's that's bad. But I really can't stand it when my primary care patients have, their guideline directed medical therapy held. During an admission, and it never gets restarted he i. do work on changing this habit that I picked up overtime I think most of the time. We're like all right. Let's be precautionary in just in case because we don't know what direction this patient's GonNa go. In most cases, we wouldn't hold the Beta blocker and I think that's the biggest thing we see. When patients are admitted at night holding a Beta blocker, every compensated patient, so we try not to. It just sat there in shock. If they're tax KARTIK very low blood pressure, you think in shock that would be the time I would hold it otherwise. I would continue the Beta blocker give lower doses, and interestingly are quote unquote just in case holding of those home meds. and not wanting to do harm can actually do more harm. There's data that shows when we hold betablockers with patients coming into the hospital. It's hard to get them restarted on it back to their target does especially came on twenty five milligrams twice a day of Carlo, and when patients were seen six-month post hospital discharge. oftentimes, they weren't back on their Beta blocker. So that's why we need to continue it unless it's truly a shock situation. Thank you, Dr his son, and that is what I'm talking about. Stop Stop in my Beta block. Just big picture. What do I look at? Are, they altered or somnolence? What are their extremities? Feel like cool clammy. Do they have any libido ridiculous? What is their pulse pressure? How threat is their radio pulse and the combination of all of those things is going to give you a sense of. Should you stop their Beta, blocker? Should you continue their Beta blocker? Okay, so that's the Beta blocker story I'm guessing things get a little bit more dicey with what to do. About holding or continuing ace inhibitors for patients who are admitted for heart failure exasperation. Well Yeah. It's the kidneys. It's obviously going to get more complicated here. Tell me we have a swap. No sound bite for the win. I don't blame anyone for stopping this stopping these innovator is the easy way elk. No one is going to blame you for doing that the path of least resistance. So I just met swap now, but I feel like this isn't the whole story. So I would encourage people to become courageous and believe and nonstop the inhibitor. Yup knew it, but what if someone's Craton Nina's rising? That is little data about what should be done. The geographic means to stop be. The best data have is there was A. Study from Albert a couple of years ago and actually showed that patients was acs Suez stop and high mortality. Now Swap nor did acknowledge that the paper he's referring to here is not a trial, and despite propensity score, matching and other stats was DRI. There is a high probability that sicker patients had as held. You can't just eliminate all that confounding. Yeah. I think there's a similar logic with the Beta blocker argument to. All right so if I may try to summarize this Pearl. There's this knee jerk reaction to stop ace inhibitor is when someone is. D- compensated in heart failure, and there's certainly situations where that is the correct answer, but it sounds like there's a lot of situations where aces end? Betablockers can comfortably left on or even dose reduced to ensure that we don't lose that mortality benefit of all those meds if they aren't restarted on discharge. What you commonly see is a patient comes in on a certain AARP or Aaron I or an MRI. And then we'll have their normal held when they're compensated and they're lasix does direct does increase, and then they're discharged without the nor homeowner lucky, but with a higher dose of the diuretic, and if you're thinking about the long term survival of the patient, that's the exact opposite thing that you WanNa do. All right, so at this point we've diagnosed are patient with heart failure. We've completed a thorough evaluation of their perfusion and congestion status. We've considered which if any of their home medicines, we need to hold during the admission. Let's bust out the diuretics and get this Man Ping for while you're seeing everybody getting forty milligrams Ivy lasix when they got admitted regardless of. Of the home does, but now I think people are better at looking at the home. Those of Lasix tour semi whatever and trying to our rule of thumb is double. It is so it's forty milligrams. Tour some I'd that they're on home twice. A day can give him eighty IV twice a day coming in or something like that to figure it out. Yeah, I mean everyone has their own practice right some cardiologists. They really advocate for that initial diuretic dosing to be one big per in the hospital. But let's back up here and ask ourselves. What is a good does for a loop diuretic? Or don't of spirits, tonight could result in an effective diuretic episode. For a single dose, it's considered effective if you excrete from that single dose about two to three liters of water with that proportional amount of Sony port in. That's Dr. Sav Essien. Listen APD at Baylor. Every patient has different goals depending on how much you want them to be for the day and how much they can, he moved an eminently tolerate. But what peeves me? Is that what you Wehrley back? After six hours and see was that an effective dose or not? Did we hit that threshold for that patient to get effective decreases, doctors broke this down beautifully in a recent material where he astutely asked. What's the better dose here? Patient Forty Milligrams daily Earth Twenty milligrams, VIP, and it depends on what that person's individual dose threshold and does ceiling is. Yes so basically, this idea is that the dose threshold is the diuretic dose where you will start seeing meaningful diarrhea, sis, meaning about two to three liters of urine per dose, and the does ceiling is the point where you start getting diminishing returns on your diuretics, so further increases in dose beyond that will no longer need to more urine output. Actual dose for a given patient in. Eighteen milligrams. Then giving them twenty B I d. will result in two episodes of effective diaries in. Each causing the patient to p true to have leader said for a total daily diaries the five litre. Whereas if you give that patient, a single forty milligram does. Sure? They might be a little bit more than to the twenty p three leaders, but they only have one of those episodes and their total daily diaries readers. All right. Let's put this together with a couple of cases now it is going to be a few numbers here but I think it's GonNa be worth going through the exercise, so if you can, you might WanNa. Pause or slow down the PODCAST. Right patient, a got lasix forty milligrams, IV twice a day and his daily urine output is one point five leaders now, considering that output dunleavy Howard you adjusting his diabetics, so forty milligrams clearly isn't reaching this patient's threshold. If total urine output is one and a half leaders after two doses that means with each forty milligram dose. The patient put out only seven hundred. Hundred and fifty sees that's not near our target of two three liters per dose, so we need to up the dose eighty milligrams all right, so let's say patient be who's on forty milligrams of Ivy, League six twice. A day has a urine output four leaders over the whole day. He's tolerating it well, but still quite a bit overloaded now, what are you doing? So each dose of forty milligrams, Ivy is leading patient. Beata put out almost two leaders per dose that means increasing amount given per dose will likely hit the ceiling for that patient, so we'll only have a marginal effect instead of going up on the dose I'd increase the frequency of the medication to Ti, and maybe for the sake of the patient consider giving it at six am newman and six PM, so they aren't up all Night Ping! That is very thoughtful of you. There Dr Levy. All right sometimes. You weren't in those situations where tracking urine output is like inconceivably difficult. So if you're not sure whether somebody who responded to a dose of diuretic, either because they can't tell you qualitatively if they beat a lot or because you have poor tracking of is knows you can send a spot urine sodium if that has over a hundred. They probably responded to diuretic. If it's under one hundred, they probably didn't ninety five. You can like take some poetic license and say it's probably fine, but. In general one hundred is a decent cough. Yes so the point here is that if someone did not have a significant urine output, or they have a low urine sodium after their diuretic dose, you probably need to increase the dose of the diuretic. And at what point do you reach for? The furious might infusion they all Lisa Strip. Yeah, we asked all of our experts on this, and it really came back to style I'm a very low threshold to start extracting, and if they're not responding to a bowl of eighty. That's usually when all star Mata Drip And it's also okay not to have a strong opinion here. So I'm a little bit agnostic aboard. They want to use A. Infusion but if you cannot do an infusion, it's completely fine to us in a multiple doses. Okay thank you swap now all right so to summarize this Pearl if we can loop in our patients that are nurses. If we can loop in our patients about their loops. About getting urine outputs, and if we can get that, that's great, so you can either adjust the dose if we haven't hit that patients threshold dose and we have hit that threshold we can think about increasing the frequency of diuretic to get more volume off and remember a good effective output per dose is going to be about two to three liters of urine. And if it's hard to get that accurate urine output, which unfortunately happens more often than we'd like. Try a spot urine, so if you're hitting that threshold dose, and then when it comes to. In versus continuous dosing of Euros It's more of a style question. So with most patients, all you really need is a splash. Fears might, and they are going to be just fine hopefully, but sometimes things don't always go so smoothly. What if that Fierro semi just cutting it? If, you're up to eighty one hundred milligrams three times. A day on lasix adding is is is is very appropriate, until usually turned him toll zone just because it's relatively inexpensive. Yet the ideas that thighs I'd such as chlorophyll down and thighs. I liked diuretics such as Matola zone work in the distal convoluted Tubul, which is downstream of to loop Hanley. Where furious might does it steady work? And thighs are especially useful in situations where term presence of loop, diuretics are causing diuretic resistance. All right anything specific about the addition of thighs is that we should know about? We return to Mottola zone five milligram, sometimes ten milligrams, and use a on a pure and basis that thing about Matola is lasts up to seventy two hours the effect from it, so it's not something that we need to stay late when we use todd, Mataya Rhesus. All right so the point here is that we shouldn't just be right in Matola Zone Q. Day, and Senate, and forgetting it. The risk of adding as is is that you get way more electrolyte disturbances particularly hypoglycemia yet. We see this commonly some definitely checking lights twice daily. If I'm reaching for thighs, I'd or thighs I'd like diuretic. Yeah, and while doubled erasing with loops and is I'd some other electrolytes to keep an eye on? Is that chloride and that by carbonate? There's that Pesky diuretic induced metabolic. alka losses that we sometimes mistakenly call contraction alkyl assists. The Ocean of the! Way of putting it. Is that everything else contracts, but the bike hub remains the same, so the backup concentration goes up right to that the It makes unduly. It's nice to think about contraction ankylosis that way sodium goes down goes down, but the potassium goes down, but the bicarbonate concentration for somebody stays the same, but as we know, that's not the end of story. Okay I. Don't think I ever realized exactly why it was called contraction of. And be I feel like I've been lied to my entire life, but as usual credit swap for completely opening, my is something I definitely had not appreciated before. The minority has evolved from volume contraction analysis to depletion in depleted uncles. Eight that he's in contraction on close is not right is because if you these patients albumin for example, you will cutting their volume state, but it doesn't make the Colossus. It's only when you give them chloride. The Colossus seems to get corrected. And without much chloride and being in a metabolic alcohol estate for a bit, it can have some quite significant implications for our patients particularly if they have obstructive lung disease. When you're retaining bike are. Metabolic Alkaloids Fan caused a respiratory compensation, and when you have patients who have COPD and have baseline twos in the fifties or sixties, all the sudden for them to be retaining more co two is a really bad thing. When that bike arps starts to creep up to thirty, six and thirty eight, and then forty one, and every once in a while, there will be a really catastrophic outcome, because somebody has a metabolic alcohol induced diarrhea, and then they have respiratory compensation. To shoots up to ninety, and then they get to Nar coasts, and so you need to be cautious about. Yeah I actually saw this very recently on the wards we had a patient whose by car was slowly increasing over several days of diarrheas, but thanks to our conversation with Greg. We got on top of it. We treated the diuretic induced metabolic al closest by repeating their chloride using potassium chloride, the by carbon proved, and fortunately the patient didn't develop any respiratory issues. Nice I guess we could just memorize metabolic. Give, ACL, but I kind of want to channel my inner Tony Brew and ask why the? Has Really Changed Ronald the key channels. Is this thing called Mandarin? It's took chloride bicarbonate exchanger. So it will throughout the bike hub and reabsorbed right. This chloride by carb exchanger allows our kidneys to remove access bicarbonate in the urine by Zorg ing a chloride. Basically if there's chloride available pending can pick one up and toss out by carbon to the urine. Right, the one we're diaries, patients with loops and thighs sides. They're losing a lot of their chloride. So pendragon doesn't have it's Mojo doesn't have that chloride around and can't correct that metabolic. L. Closys. And Penguins activity also shuts down more with hypoglycemia and when there's elevated out astro. Think about problems with patients in heart failure, elevated rast system diuretic induced hypoglycemia and chloride depletion. It's almost like we're doing everything we can to shutdown pendragon. Oh, dear, okay, so, is there anything we can do to actually prevent this? In situations where you know, you're to need out to us either high doses of fewer semi on your adding on zone. Or a diabetic I would I always through actively add ons by an electoral. Oh Wow that makes so much sense. HYPOGLYCEMIA is bad for Penguin, so preventing that with a potassium sparing diuretic helps keep pendragon going yeah. All Right Quick Pearl Recap where we add on thighs I'd like diuretic two loops. We can cause a lot of electoral issues like hypoc Alenia, chloride depletion and resulting metabolic alkaloids. And that metabolic alkaloids, this is largely due to decrease activity of Pendragon that chloride bicarbonate exchanger that spits out by Carb, if can reabsorb chloride, but in heart failure patients when we're aggressively diary seeing them when there is not much chlorate around, there's not much spitting out of bicarbonate. And pending activities further decreased with hypoglycemia and hyper astronaut. So one worker on his preemptively giving spinal lactones something that's good for these patients anyway. Well, push right all right. Let's finish out this Pearl with a quick discussion of what to do when we have started a lube. We've added a thighs I'd and maybe even a potassium sparing diuretic, you'll total neff Ron blockade and we still aren't getting. The diary says we want. If you have given enough of that any assume not having enough response than go to the. Moving fluid by. Mechanical means by. Barbadian manners like dialysis uncovered tuition. Yes, ultra filtration is definitely an option when we're running out of more sophisticated ways to get volume off using medications. But yeah, there are definitely situations where we might reach for ultra filtration earlier. Sometimes we start with ultra filtration right away on some of the patients who come in on severe on massive doses of towards Meyde at home hundred be ideal up thirty pounds, or so that might be a patient. You go straight to ultra filtration because you know they're going to be very diuretic resistant. but otherwise as your escalate in the hospital. You're on big bowl of a lou or a drip. As I would try ultra filtration, and you get a higher sodium removal with. Asian, and also you don't have some of the electrolyte issues because it doesn't pull off potassium and magnesium, so you can usually these that situation we somebody recently we put on ultra filtration because they terrible out with early diuretic, seleted ultra, filtration and everything. Went pretty well. How pretty cool, so true allows us to remove fluid manually without mucking with all those other electrolytes. So to summarize this section on troubleshooting diaries us once you're on a fairly high dose of diuretic, and not achieving significant diary, says consider adding a thighs diuretic fell down or thighs, I like diuretics such as Matola Zone, remember these can cause substantial electrolyte abnormalities and contribute to chloride depletion, metabolic alka losses, which as we saw can be a major issue when diaries patients, especially those who have copd in those patients reach for the potassium chloride to replete their chloride, and prevent worsening of their chronic respiratory acidosis or even consider adding sperone a lactone to prevent the cascade from the start. And finally ultra filtration, Stephanie, an option, if all else fails there cases where you might want to reach fruits sooner like patients who've demonstrated significant diuretic resistance, and you just know you're going to have a tough time managing only with medications. All right well, that is all for us. We are now going to have Dr Michelle Kilson. Give us an expert recap of our pearls as well as a few awesome teaching nuggets of her own. Doctor Kitson is a professor of medicine at Ucla in the director of the advanced heart, failure and transplantation fellowship at Sinai Medical, center she also tweets from at 'em Kitson MD, so definitely give her a follow over there all right Dr Kitson. Take it away. Okay, let's start with Pearl. One be initial clinical assessment. Signs of buying overload are well known. In elevated Jugular Venous Crash Clinton s three Gallup. Are the most specific signs of congestion now crackles, or rawls are knee either sensitive nor specific for Pulmonary Emphysema and chronic heart failure there may be no rawls, due to up regulation of pulmonary lymphatic or lots of rows, due to add elect assists so the best way to irritate your heart failure. Attending is to base your assessment of volume status on the lung alone. Okay, let's move onto signs of poor perfusion, which are just as important. If there's a low pulse pressure that's concerning. Batak Accordia is important, too, because it's a symptom, not a disease. Don't move to knee jerk lower the heart rate in a patient ricard failure, instead respect that the high heart rate is an attempt to compensate for low stroke volume in a tenuous patients. Girl to what labs can tell you about the severity trajectory of the patient? I were stranded on a desert island with the heart failure patient and could only choose three labs well, maybe that analogy stretches credulity, but let's run with it. I would want sodium potassium and. Sodium, and create with. Tell me how sick the patient is low sodium and high creating means it will not be a straightforward set it and forget it ride, and a high or low potassium helped me decide on how much of the running and you tend to strain system, inhibition and loop diuretic therapy. The patient can tolerate. Hurl three guideline directed medical therapy in a heart failure exacerbated. What about the whole mets? We'll the task. Blood pressure can take it. Don't be afraid to continue. All the wonderful guideline directed medical therapy. The patient came in on. Remembered that the acute Hema dynamic benefit of after load reduction with the Andrew Johnson Receptor knepper leads an inhibitor or the ace inhibitor or the AARP, as well as the natural effect of the Angie tencent receptor knepper lights inhibitor can only be a good thing. The scrotal tone is also essential, not just for long-term remodeling, but potassium sparing properties. Have you ever swallowed a potassium horse pill? You don't want to heat up the potassium in the least offensive way that continuing disgruntle acton. Now finally as noted, these observational studies did indicate that discontinuation of Betablockers during hospitalization results in reduced Beta, blocker usage it follow up, which likely contributes to poor a long term outcomes, so unless you think the patient is sick enough to need a pulmonary artery catheter in on atropine. Support that is they are so advanced that there's little benefit. The guideline directed medical therapy and imminent discharges unlikely anyway. There's no reason to stop these wonderful medications. Okay Pearls and five volume removal and additional tips and tricks. My favorite topic is IB. Die Rhesus and I have three rules. So the right answer is what works I love. Loop diuretic drips because I find in my experience. Get More Bang for my buck. Yes, there was no difference in the dose trial, but they tested global improvement in symptoms at seventy two hours. I'm not even sure what that means. So my room. If lasix. twice daily doesn't give me what I want. Just usually a minimum of two leaders diary in the first twenty four hours a drip it is. As for MOTTOLA zone. It's a big gun to be used sparingly given the hype, Oni Premia and hyper Kalian yet that inevitably results the patient isn't responding to a lasix chip at eighty makes our reach Matola zone, but I also start talking advanced heart failure therapies with a patient is meeting Matola. Zone to achieve decongestion is a bad sign. Alright rule to the longer you stay, the longer you stay. My sense? Is that for every plus of Dima. It's five to ten pounds so someone with three US bilateral lower extremity Dima thirty pounds to lose. Let's say fifteen leaders. If you make them slow leaders negative daily. Go be there four days. If you make them to leaders negative daily, they'll be there twice as long which gives them more time to fall out of bed or get. She did so in the warm and wet patient with a stable blood pressure potassium in creating. Don't be afraid of rapid diarrhea. Let the patient guide. You not fear of the INS and outs. And finally it's mean to disrupt sleep. I, turn off loop. Diuretics from eleven pm to five am an unless a patient is insignificant. Respiratory distress never thought diuretic doses after six PM. The night float will thank you and the patient will thank you. It's yet more reason to be more aggressive with morning dosing. Well that's probably enough for one expert recap. Here's to lots of liquid gold and guideline directed medical therapy and smooth sailing for your next heart failure admission. And that is a wrap for today's episode. If you found this episode, helpful, please share with your colleagues. Your team's give a rating on apple podcasts or whatever podcast APP you use. It really does help people find us. Thank you Dr. Cathy's is Sean from UCSD for the accompanying graphic to Salon Kelleher for audio editing. Especially all the edits the day before the publication to our peer review is Dr Steven Fan in Dr Eugene did ski as well as many of the hospice and residents for reviewing episode and thanks to you. And as always we love hearing feedbacks who email us at. Hello at Cory M. Podcast, dot com opinions expressed our own and do not represent opinions of any affiliated institutions. Need to look at the markers of our they refusing and what's going on before you can say yes. I did a great job. You're not like trump with the covid response. Just because you say you're doing a good job doesn't mean you're doing a good job. I don't know if you want to include a line like that. You're. I said it and I didn't say should be off the record, so it's fine. Shreds is a the the the diplomat diplomat here so. We'll see if that makes the final per.
COVID-19 Miniseries Episode 9: Recommendations on Ibuprofen
"This is the Mayo Clinic. Talks of curated weekly podcast for physicians and healthcare providers. I'm Gauche and into medicine physician at the Mayo Clinic in Rochester. Minnesota one talks about covert teen and they infections resulting from it. A lot of trust among providers among lay people and almost all over the world people are worried about what is going on. Why is the confusion so rampant with nineteen? When you look at any illness that I usually some to not change in covert nineteen. It involves patients with age. Sixty me gender poor economic status etc. That cannot be changed by us or by anybody else. However the modifiable risk factors are access to hospitals with critical care facilities like ventilators What medications can be given and be heard about a lot of new medications being considered smoking so on and so forth? There is increased emphasis on the risk which is posed by the patient school market conditions and the medications that they're taking are not taking during the speed as we already know that there are a lot of medications which are being considered like chloroquine has a tremendous and an antiviral treatment like loping original there. And they're still waiting on the results however what has really taken over the world and has caused a lot of anxiety in the last week is a report committee came out that I do. Profound could possess a could could present with great risks to patients who have covered nineteen infections. Today we are joined over phone by Dr Back. You run KAIK. Who's one of one of our Goto individuals and the Department of Pharmacy and he also sees the Medication Knowledge Management Program. Whenever we run into this problem in Medi- in medicine when we have a question regarding medication side effect I go to Matt Run. Kite because he does possess the knowledge and resources do Even information to me in a very speedy fashion as to what I need to do because I'm beginning to medicine doctor on the front line. So thank you for joining us. Today Matt. Thank you for having me I wanted to ask you about. Could you describe the recent events in the media that led to the suggestion that call covert patients to be taking Ibuprofen That they could be having a worse outcome. Yeah so With a lot of things these days It started off Primarily with social media so it started off with a tweet actually and to kind of get to that tweet. We need to go back a little bit. Further so on March Eleventh Twenty Twenty The Lancet respiratory medicine actually published a correspondence That hypothesized why. A single centered. Retrospective observational. Study observed. Poor outcomes in critically ill patients who had this novel. Corona virus in China who also had cardiovascular disease hypertension and or diabetes so in this correspondence the authors hypothesize that the medications that these patients were commonly taking could be leading to worse outcomes. And we'll get a little bit into that hopefully later on in this talk about why that might be be hypothesized but subsequently on March fourteenth the French Health Ministry issued a covert Nineteen Recommendation Update. In this updated guidance the ministry recommended against the use of non steroidal anti inflammatory drugs and said such as ID Profane due to serious adverse events related to the use of Ed in patients with known or suspected cases of Kobe. Nineteen and I think one important thing to mention at this point is there have been Several case reports or case studies out in France Looking at Ibuprofen in viral infections. And so even before this whole cove in nineteen Pandemic there has been questions in France about the use of Ibuprofen in infectious diseases. So keep that in mind And this recommendation that that came out on March fourteenth was partially based on this March eleventh correspondents in the Lancet respiratory medicine as well. Let's some anecdotal evidence of young individuals with the novel. Corona virus having poorer clinical outcomes while they were taking Ibuprofen so shortly after this tweet or this notification from the French Health Ministry The World Health Organization actually came out and recommended against the use of profane actually said that if given the opportunity you should be using Acetaminophen over Ibuprofen now. They quickly turned around Less than twenty four hours later actually redacted that statement and since since that time other other well-known institutions such as the United States Food and Drug Administration have come out also saying there's just not enough evidence to support saying that I'd be profiled should not be used however Once that that you know horse it Kinda left a barn. The damage had already been done and the media had informed the general public That health authorities across the globe we're recommending against the use of ibuprofen. It's great that you mentioned about the tweet. Devil's just Today morning looking at the number of website hits on when I typed in covert nineteen in Google. Got Five point. Four billion hits Today and for when I when I combine Kobe. Nineteen with either prevent I came up with twenty five million. Hitch just to give you an idea. About how great the sizes at whenever you Add anything to Coleridge like what to do what not to do And had some Miniseries in the past where we talk about covered nineteen all these new events which are coming getting huge response in the media. For example known things that we know it's certainty absolutely certainty we've and we studied it and randomized trials and big meta-analysis like us up non steroidal. Anti inflammatory medication. And it's causing kidney disease. It's five point. Six million hits using on pumping Liberte or long term studies. A long-term use a proton pumping bitter resulting in osteoporosis. Point three million H. Compare that with covered and Ibuprofen of twenty five billion hit. So you're absolutely right that this article which I see a one page document. It's a it's a cross. It is coming the correspondence section. It's not even the main journal and just based on some hypothesis which has been placed Mealy dealing with the pathophysiology of these medications but one of the rich math. I was intrigued by is it. They mentioned about few medications they postulated that few Medications Increase Danja tencent converting enzyme to An enzyme and you tell me why does and your attention. Converting enzyme to suddenly has come into limelight during the covert crisis. Yes Oh NGO THOMSON CONVERTING ENZYME. Two or ace two. I'll probably refer to it Throughout the rest of this really came into the limelight. Because it's one of the main entry points for some of the corona viruses including the novel Corona Virus Which is the cause of the Kobe? Nineteen disease so east to can be found on the epithelium of the lungs intestines kidneys and blood vessels. And as you've kind of alluded to hear some of the drugs can cause an up regulation To these these Epithelial ACE to And 'cause potential issues because it's the main entry point for the the novel Corona Virus here and by some of the drugs. You mean ace inhibitors that the Arab or engines intercept are You Bet there's as well as I do. Profane has also been one of the medicines which has been linked to up regulate engine to and has has a using diabetes but these are physiological changes. Which I've been which have been late to These medications but via found out that anytime in the past whenever you use pathophysiology and and and conduct studies based on the physiology not often right for example in New England Journal in March Twenty First Nineteen ninety-one they had performed a study hypoth- hypothesis that if you suppress the ventricular topic after Michael Infarction. It could reduce our in depth. Made sense that optimize. Our little infarction heart is unstable as swinging all their topics. And if you give him some medications and slow that the topic or stopped at the topic maybe the prognosis is going to be better. But the randomized trials which was published in any gym on March Twenty First Nineteen Ninety. One should completely the opposite when they use flex tonight and in fact the number of patients who are dying. We're dying meows. Were much more on patients. Taking these two and make medication so similar -ly The whole concept that if you award injured insulin receptor To innovators like ace or arbs You might show a benefit in patients with covert but there are other studies. Can you talk about the study? Which that about naproxin which is also an innocent and that is I mean influence on influenza Yeah exactly so So kind of you've done a great job of summarizing why it's maybe not the best Some of these smaller studies may be one thing but we can get conflicting data and I think Naproxen and actually the methods that are great examples of this so In in a study with Naproxen they found that it actually inhibits the nuclear protein of Influenza A. Which is a protein that's necessary for viral replication? And so that's an end. Said that has antiviral activity there and so this kind of compounds this whole Are you know pro viral or antiviral that type of thing but also In in my studies and looking some some of the information up for you I found that into medicine is actually shown. Antiviral activity against other corona viruses in Vivo So based on these observations a Lotta clinicians have questioned the hypothesis. That protein is harmful Because there's other medications in the same class like we like. We just talked about into methuen as well as Naproxen. That actually turned antiviral activity. Now the other thing which I would ask as a general physician I take off hundreds of patients with diabetes hypertension than just heart failure and chronic kidney disease for these patients and for millions others. That my colleagues were listening to our podcast treat as has been short beyond a doubt that met analysts systematic analysis and systematic reviews one after the other great benefit in fact outcomes of hard outcomes like mortality Limiting heart failure Decreasing admission to the hospital all of these benefits are showing with ace inhibitor. So bit stopping. Suddenly there's some suggestion of stopping even ace inhibitors in patients with diabetes hypertension on congestive heart failure. Unfortunately these patients also get a lot. More of them are suffering from covert because of other reasons but the mentioned was that stopped his medications because yes The the Kobe dividers using Andrew converting to a receptive to get in and he's these receptors. Are Operas alleged? When somebody's speaking an ace inhibitor or an are are are ibuprofen or is it alone so just stop medications and maybe that'll be benefit of which we have zero evidence but the harm. I wonder do you specify the harm that could happen if you just blondie take some guidelines adopted to these funny patients? Yeah so I think you've done a great job of pointing out the numerous benefits. So numerous studies have shown that ace inhibitors reduce mortality and cardiovascular and points unstable coronary artery disease they also have beneficial effects in Congestive heart failure type two diabetes and chronic kidney disease and so this is actually been a topic that's come up in In some of the more well known societies and so Everyone kind of saw this coming that we're there would be positioned out there. That might WANNA stop these. Just because of this hypothesized. Up Regulation of ace two on March seventeenth. Twenty twenty the American College of Cardiology and the American Hyper Chin Association as well as the European Society of cardiologists strongly recommended that patients with chronic. Who are already taking ace inhibitor. Or arbs should continue to take these medications and so this recommendation is in part because of the benefits of the reduced mortality. That that both you and I mentioned earlier but it's also because there's been some studies that have actually suggested that aces and arbs might be beneficial intriguing or preventing pneumonia. Thank you. That's that's very useful that now. We have statement from the national and international guidelines. You become like American colleges physicians American heart and the European Society of cardiologists stating that Do not do not stop these medications. In fact they have gone. I was reading it after I discussed with you last week. I was reading some of the guidelines and he mentioned that ace inhibitors have been have been shown to cause beneficial effects in patients with severe lung injuries in in several cases so because of the anti inflammatory effects of this They have been found to be of benefit apart from their benefit to the kidneys and heart and everything else. So these are. These are good things to know That we should not stop. I not predict how many patients had these medications have been stopped and that is that is something to be to be concerned about the other thing which comes about which. I don't have the answer. I don't know whether you is supposed somebody somebody who comes or somebody with this Who have all these quality heart disease or anything comes to the audience gets one? Does how much of up regulations of and you've been converting enzymes happens anyway with one medical one tablet and already admitted in the hospital. He chronically. Giving them Ibuprofen. How much up regulation of these enzymes happening and Debbie Chemicals significance because Ibuprofen? There are alternative medications like Acetominophen One is not really limited in once armaments just through Ibuprofen so one can always say well. If you're having some pain give give them enough in which has does not affect the engines in converting enzyme stu but apart from that Are you aware of any studies Mitchell? But you have to take Ibuprofen for a week or two weeks or three days before. It causes up regulation. Yes so I looked into this problem particularly It was really only animal studies that I was able to find it in and unfortunately You know just because of the way that study was designed they They were not able to actually check these. After one does it was generally after several doses and so it's really hard for us to extrapolate out and say you know after one does. You're GONNA see this immediate up regulation of ace to and you should worry about it So yeah unfortunately. There's just not good data like with a lot of things coming out with Kobe. Nineteen There's still a lot of a lot of questions that we have to answer. That's great that leads me to a much more complex question. This is not going to be the only time. I'm sure you you have been tapped by The doctors here the male clinic and by public. I mean the patients using these moments during similar moments of uncertain or challenging times. And this is kind of almost unprecedented. What we're going through You are the first line of defense sometimes in the providers when the physicians don't know I lift up the phone and call call you or pharmacist saying hey help me out. What does this mean? What does this medicine mean? How do you respond? Or how do you communicate with one? War is the doctors and patients saying Then been via than there's so much noise in the press. A border medications. What do you follow? Yes so I think with all healthcare workers at this time. It's particularly important for all of us to stay abreast of kind of developments with the cove in nineteen But it's particularly important with pharmacist. Because we've been hearing about a lot of different Developing Sciences. That may change our response to the novel virus Even in press conferences. That you hear probably daily from the president. You've heard about a lot of different medications. That are in the pipeline So for pharmacists specifically. There's actually a lot of work that has been done There's there's a great society that we have called the American Society of Health System. Pharmacists are HP. They've done a great job of putting out a variety of pharmacy related resources. So these include a summary of medications that are being discussed in the scientific community as well as the lay press. It's nice table format so I would encourage even Healthcare provider so primary care physicians to periodically check that because they are updating it on a regular but in addition to that that that table that I just mentioned they have a comprehensive database of drugs that are currently on shortage so this might be useful outside of the pandemic In in some instances they actually do provide appropriate alternatives. That are available so I found that this has been particularly useful when we do have a drug shortage if they can in the right direction. Maybe it's a disease that I don't know everything about or maybe there's something that I do know a lot about but I'm just not sure what is available so that's another resource that I would definitely recommend that S. H. A. S. H. P. puts out here at Mayo Clinic specifically though we have developed an internal websites dedicated to covert nineteen for the Department of Pharmacy and before Kovac's even became a thing. We had a weekly newsletter. But we've been using that more and more often to highlight important information as it relates to the pen. Dammit I would urge everyone Pharmacist particularly to check reliable sources such as the CDC cove in Nineteen website eighth. Hp website that I spoke about earlier the website is eighth HP DOT ORG and there'll be links in these specific resources For this podcast. Because what we're saying on this podcast today or You know kind of what's going on in a week from now might be completely different than than what we're thinking right now so it's really important especially in this rapidly evolving situation for everyone to keep as knowledgeable about the situation as they can by checking these reliable resources. There's one in particular that I think is really valuable for everyone. All the healthcare professionals out there and it's called the assessment of evidence for covert nineteen related treatments. And so again that's A. Ps that is in table format. I think is a really great job of giving you the rationale for why why were even looking at something it also tells you about the clinical experience the doses that are being studied as well as some comments about you know some interpretations of the studies that have been put out how maybe some of their flaws. That's very very helpful and so I would check on a S H sp dot org website And actually look at look at exactly The information that you're saying but I would like to add one more thing which actually the confusing and sometimes like understanding a lot of us really struggle with how to communicate risk and why different wider risks which are which bitches which we are exposed to. The particular moment varies between the city which we live The county which we live at the hospital that is close to us all even the country which we live. I've because risk is a risk communication and I'd do. I'd lock out here in mail and I've learned that I have to communicate risk. It has two different object information. One is objective information. Which people want to know that? What is the risk of undesired outcome and often? Does it happen for example. I looked at the numbers today. We have over one hundred and forty four thousand positive cases and twenty six hundred. That's in us. Which would mean that one in fifty five individuals test positive Might have fatally rent. So that's really bad. It's the one point. They were sixty years old obese individuals the other higher risk that they want to know how bad that can be. And that's why there's so much fear so talking about some of these emotions which are associated with risk communication. We need to understand. Why some wrist acceptable? It's somebody's car voluntaristic. When an individual tends to smoke or decides to smoke or have an unhealthy lifestyle. They're taking the risk on themselves and they don't take that as risky as opposed to an involuntary risk which then one minute is putting on us like the White House has done ten so again. You're worried about manmade risk worse off than a man-made risk which I would encourage myself guy happened to small again wrist which is unfamiliar like the current situation as opposed to familiar with a familiar risk would be like driving and getting into a situation where the more I drive. The chance of my ending up in an accident is high right now. The risk of dying in a car accident is one in ten thousand and be very view. Okay with it because it's it's a small risk and and it is a familiar risk but this unfamiliar thing which is happening every county in. Us different particular particular. Risk of developing. And once we develop. What's the chance of hurting us from just being in the hospital through really ending up in a ventilator divorce case scenario that that's very scary any risk which is supposed to children and pregnant? Women are considered more risky than anything else. Catastrophic risk is again fell to be very very Problematic both occasions as well explaining risk which are which are taught to be unfinished And I was just watching the videos over all over the world and I saw some really Saudi state of affairs in India where there was a huge migrant population who just were fleeing a particular City to go to their own own houses because of the risk possessed by cove it and that was felt to be very unfair because poor and they didn't have the resources so there's a lot of Elementary which goes into understanding risk the other bigger elements becomes as contradictory statement which happened in this case The WHO say yes Ibuprofen as risky and then taking back within within a day saying nor does not that again because this pose to Kind of makes people confused as to really what is going on and who is doing what so. These kind of things one has to be as a physician. I'm very often. I use this Element on a US. All the strategy to explain understood myself. I I need to understand the competence for this before. I'm in a position to explain a risk so I keep it very simple. I sit down with a patient. I listen to you on this. I is it be talking about. His pain is a disability. Is a debt for chloride could be either one of the three if he symptomatic which eighty one percent of the patient? You know. You're you're better off. Not Taking Ibuprofen. Better off. Taking tylenol and If it is if you get in the hospital again you're not you. Regardless of what the evidence and what I participate we are talking about taking Saddam. Offend is probably beneficial and its debt. All of this all hands on deck. That's when we are trying to prevent it. That's the WHO whole different situation. Then is temporary or permanent. This seems to be temporary event for most most most of the cases. That's what we're talking about. The flattening of the curve. Most of these issues will resolve within two or three weeks but for some cases of course death is permanent. Event is early then the third thing which I talk about is the timing. Is it going to happen early or is it going to happen? That's right scary. Because it is an early event things happen very suddenly as opposed to hypertension diabetes heart failure. All these things all even smoking. That's why people are okay. We're taking the risk of smoking because It'll happen ten years from now. Twenty years from now so they worry about it and then the probability what is the likelihood of this even happening which that's why knowing the numbers of ar which city you are and in Male clinic. Working Day and night you include Manhattan nursing staff and a front end to absolutely even use the probability of adverse effect. I be no. You're going to fail at times. You're going to feel the patient we're GonNa feel the family have. You're probably GONNA lose some cases but can be a lot more patients understanding Our resources on what we need to do. And that's become so useful. Pharmacy become so helpful and vacating us as to what medications need to be used not used. What are the best format and thank you for to you and your team get that message out with your websites and And also letting US know about the websites that you mentioned here. The fifth dimension of risk his badness. What is the badness of what is the value to this patient so most chronic diseases how slowly slowly they get worse? So it's we don't we don't really see what's going on Till the patient comes back about a year or two. The patient has no idea what's going on but the doctor or somebody seeing them because in a year or two finds out that the numbers are changing the hemoglobin. Even he's getting worse or hot phidias going to get worse even though the patient is living through it. Everyday Coronado. It's not like that. It's now it's within the next two to three weeks. So that is why we getting so many websites and hits and Google Everybody's trying to find a cure but with the cure. There's a lot of information I wouldn't call it misinformation everybody's trying to help the patient But we are trying to establish here to our meal. Miniseries is trying to find out each of these elements which are being discussed in great Detailed everywhere all over the world and try to figure out how clinics exports are pushing it. So if you're talking about Ibuprofen use uncovered nineteen with Matt when Kaik thank you for your time Matt. These remember right now if you're diabetic patients a diabetes if your patient has hypertension patients. Connie can you disease on? If your patient has chronic congestive heart failure please please please do not do not stop. Is the ARBS. This patient comes to you. Can WORSEN KIDNEY DISEASE. It can borsen heart failure. No big deal you will. I know you will not give it give to these of patients and there are many alternative medications which you can but you can use. But I think understanding how to communicate Chris out to understand risk is an important aspect which internists have to face on a daily basis. And hopefully our discussion has been helpful to you. do understand what's going on with risk communication with the patient. We will continue to bring you updates on the situation as events unfold. If you've enjoyed the Mayo Clinic podcast up. Sprite held the next week and above all he physical and social distance.
NEJM This Week June 18, 2020
"Welcome, this is the. New England Journal of Medicine I'm Dr Michael, bearer this week June eighteenth, two thousand twenty, we feature articles on systematic or test guided treatment for TB in issue, an observational study of hydroxy chloroquine and Covid nineteen trust ABC to Ken for her two positive gastric cancer Reenen Angie attention Aldo dostram system blockers and covert nineteen, reconsidering PSA screening and a new twist on RNA vaccine's a case report of a man with acute respiratory failure and unclear goals of care and perspective articles on grading changes for US l. e. step one. Systematic or test guided treatment for Turkeys losses in HIV infected adults by false Waza blow from Naught University Hospital France. In regions with high burdens of tuberculosis and HIV, many HIV infected adults begin antiretroviral therapy when they are already severely immuno-compromised mortality after a Rt. initiation is high in these patients and tuberculosis and invasive bacterial diseases are common causes of death. This randomized trial compared the benefits and risks of tuberculosis screening strategy, involving a combination of. Urinary Lamb, test expert MT B. R.. I f. test and chest X, ray and targeted treatment with those of a strategy of systematic empirical treatment for tuberculosis in HIV infected patients with severe immunosuppression at week, twenty, four, the rate of death from any cause or invasive bacterial disease, calculated as the number of I events per one hundred patient years was nineteen point four with systematic treatment and twenty point three with guided treatment. Treatment at week forty eight, the corresponding rates were twelve point, eight and thirteen point three at we talked for the probability of tuberculosis, was lower with systematic treatment than with guided treatment, three percent versus seventeen point, nine percent, but the probability of grade, three or four drug related adverse events was higher with systematic treatment, seventeen point, four percent versus seven point, two percent, serious adverse events were more common with systematic treatment. Among severely immunosuppressed adults with HIV infection, who had not previously received a RT, systematic treatment for tuberculosis, was not superior to test guided treatment in reducing the rate of death or invasive bacterial disease over twenty four or forty eight weeks, and was associated with more great, three or four adverse events. Richard Jason From Johns Hopkins. University School of Medicine Baltimore writes in an editorial that this trial fits into a suite of studies, regarding the strategy of Empirical anti-tuberculosis treatment for patients with established and advanced HIV infection, and firmly shuts the door on this intuitive, but apparently incorrect concept what can be done to reduce to burke ulises, incidence and mortality in patients with HIV infection, particularly those with advanced immunosuppression, rather than empirically treating. Disease in this population, a better approach might be to incorporate an algorithm established by the world, Health Organization, in which populations at risk of late in Turkey losses are identified, screened and offered preventive therapy continued concerted efforts to diagnose HIV infection as early as possible and initiate antiretroviral and tuberculosis, preventive treatment are essential to diminishing the burden of HIV and tuberculosis globally for persons with severe immunodeficiency. When HIV infection is diagnosed, the best approach may be too promptly. Start a RT and tuberculosis, Berkeley preventive therapy and monitor them closely for opportunistic illnesses, but it is now clear that empirical anti-tuberculosis therapy for persons with advanced. HIV, infection is a pound of cure that is worse than an ounce of prevention. observational study of hydroxy chloroquine in hospitalized patients with covid nineteen by Joshua glares from Columbia. University New, York. I dropped see chloroquine has been widely administered to patients with covid nineteen without robust evidence supporting it's use. These authors examined the association between hydroxy chloroquine US and incubation or death at a large medical center in New York City data were obtained regarding consecutive patients hospitalized with Covid, nineteen of one, thousand, four, hundred forty six consecutive patients, seventy patients were incubated, died or discharge within twenty four. Four hours after presentation, and were excluded from the analysis of the remaining one thousand, three hundred seventy six patients during a median follow up of twenty two point five days, fifty eight point nine percent received Hydroxy Corcoran. Forty five point, eight percent of the patients were treated within twenty four hours after presentation to the Emergency Department and eighty five point nine percent within forty eight hours. Hours hydroxy chloroquine, treated patients were more severely ill at baseline than those who did not receive hydroxy chloroquine, overall twenty five point, one percent of patients had a primary endpoint event of incubation or death, one hundred eighty patients were incubated of whom sixty six subsequently died and one, hundred sixty six died without integration in the main analysis. There was no significant association between Hydroxy CORCORAN USE AND And intimidation or death hazard ratio, one point zero four results were similar in multiple sensitivity analyses in this observational study, involving patients with covid nineteen, who had been admitted to the hospital hydroxy chloroquine administration was not associated with either a greatly lowered or an increased risk of the composite endpoint of incubation or death, randomized control trials of hydroxy chloroquine in patients with covid. Nineteen are needed. Eric Rubin Editor in Chief for the Journal writes in an editorial that chloroquine, anti-drug C., chloroquine, alone or in combination with Zithromax and have been highly touted as potential therapies for covid nineteen, the claims of efficacy are based largely on anecdotes and K series that have been described as being so persuasive that it would be unethical to perform studies with placebo controls on the basis of this evidence. These therapies have been recommended in many guidelines including some national policies and have been widely implemented, but is the evidence really that strong. The observational study by Galera and colleagues examines the Association between Hydroxy. Clark when US and And outcomes in patients hospitalized with Kobe nineteen and suggests that this treatment is not a panacea physicians caring for patients with Covid nineteen faced with important therapeutic choices. Should they use widely available agent such as hydroxy chloroquine, or is it through my sin? The choice to use these drugs has already been made probably in hundreds of thousands of patients, but with scant evidence about the risks and benefits. We have chosen to publish this report so that clinicians will have some information that is based on rigorous analyses of available observational data. However, this observational study is in no way. A substitute for randomized placebo controlled trials. TRANSDUCER ABC Directa can in previously treated her two positive gastric cancer by cohash Atara from the national cancer. Center Hospital East Sheila Japan. Trust, who's a mob DIRECTA can is an antibody drug conjugate consisting of an anti her two antibody a cleave -able Tetra Peptide based winker and a cytotoxic Topa is. One, inhibitor, this randomized phase, two trial evaluated director Ken as compared with chemotherapy in one hundred eighty seven patients with her two positive, advanced gastric cancer, an objective response was reported in fifty one percent of the patients in the trash student APP. Direct stand group as compared with fourteen percent of those in the physician's choice group, overall survival was longer with transducer Mab Directa Ken then with Chemotherapy Median, twelve point, five versus eight point four months, the most common adverse events of grade, three or higher, where a decreased neutral fil count in fifty one percent of the Trustees Emad Group and twenty. Twenty four percent of the physician's choice, group anemia, thirty eight percent and twenty three percent respectively, and decreased White, Cell Count Twenty one percent and eleven percent, a total of twelve patients had trust. ABC Directs to Ken Related Interstitial Lung Disease or Newman Itis as adjudicated by an independent committee. One drug related death, due to pneumonia was noted in the trustees Mab Directa. Ken Group therapy with ABC Directo can lead to significant improvements in response and overall survival as compared with standard therapies among patients with her two positive gastric cancer, Milo suppression and interstitial lung disease were the notable toxic effects. Reenen NGO attention, Aldosoro, system blockers, and the risk of covid nineteen by Giuseppi Mancha from the University of Milano Be Coca Milan Italy. A potential association between the use of NGO receptor blockers, ARB's and NGO tencent, converting enzyme ace inhibitors, and the risk of covid nineteen has not been well studied. This population based case control study in the Lombardy region of Italy evaluated the association between the use of blockers of the Reenen Andrew tencent Al Dostram, system and the risk of covid nineteen a total of six thousand. Thousand Two hundred seventy two case patients in whom infection with SARS, covy to was confirmed between February, twenty first and March eleventh were matched to thirty, thousand, seven, hundred fifty nine beneficiaries of the regional health service, the use of ace inhibitors. Arby's was more common among case patients than among controls as was the use of other anti hypertensive and non anti hypertensive drugs and. and. Case patients had a worse clinical profile use of ARB's or ace inhibitors did not show any association with Kovic Nineteen, among case, patients overall adjusted odds ratio, zero point nine five for rb's and zero point, nine six for Ace, inhibitors, or among patients who had a severe or fatal course of the disease adjusted odds ratio, zero point eight three for a RB's and. And Zero Point nine one ace inhibitors, and no association between these variables was found according to sex in this large population based study, the use of ace inhibitors, and Aarp's was more frequent among patients with Kobe nineteen than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that H. inhibitors or a Arby's affected the risk of covid nineteen. Rian NGO tencent doctrine system in hidden hurts and risk of covid nineteen by Harmony Reynolds from New York University Grossman School of Medicine New York. This study assessed the relation between previous treatment with hitters and tencent receptor blockers, Beta blockers, calcium, channel, blockers or thighs, I diabetics, and the likelihood of a positive or negative result on Covid, nineteen testing, as well as the likelihood of severe illness defined as intensive care, mechanical ventilation or death among patients who tested positive. Among twelve thousand, five hundred ninety four patients who were tested for Covid, nineteen, forty six point, eight percent were positive. Seventeen percent of these patients had severe illness. A history of hypertension was present in thirty four point, six percent of patients among whom fifty nine point one percent had a positive test. Twenty four point, six percent of these patients had severe illness. There was no association between any single medication. Medication class and an increased likelihood of a positive test, none of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. These authors found no substantial increase in the likelihood of a positive test for covid nineteen or in the risk of severe covid, nineteen among patients who tested positive in association with five car in classes of anti hypertensive medications. In an editorial, John Jarkko Deputy. Editor for the Journal writes that taken together. These studies do not provide evidence to support the hypothesis that ace inhibitor or AARP use is associated with the risk of SARS covy to infection, the risk of severe covid, nineteen among those infected or the risk of in-hospital death among those with a positive test, each of these studies has weaknesses inherent in observational data, but we find it reassuring that these studies in different populations and with different designs arrive at the consistent message that the continued use of ace inhibitors and ARB's is unlikely to. To be harmful in patients with COVID, nineteen several other smaller studies from China and the United Kingdom have come to the same conclusion, professional scientific societies and experts have spoken with one voice in advising that patients should not discontinue ace, inhibitor, or AARP therapy out of a concern that they are at increased risk for infection, severe illness or death during the covid nineteen pandemic, the data from these studies support those recommendations, ultimately, one or more randomized trials will be needed to answer definitively the question of whether ace inhibitors or AARP's pose a harm to patients with covid nineteen. Seventy four year old man with acute respiratory failure and unclear goals of care, a case record of the Massachusetts General Hospital by Juliet Jacobson and colleagues. A seventy four year, old man with lymphoma was admitted during the covid nineteen pandemic, because of rapidly progressive respiratory failure one day earlier productive cough and Disney developed the next day when the patient was being evaluated at home by visiting nurse. The oxygen saturation was eighty five percent while he was breathing ambient air emergency. Medical services were called. Patient was first evaluated by Dr Jacobson. It was apparent that there was little time to talk before the patient would require intimidation and mechanical ventilation. Doctor! Jacobson reviewed his chart and paged his oncologist for additional information. In order to better understand the medical aspects of his case, she learned that this patient had some viable treatment options for his cancer, but would probably die from the disease in less than a year, the oncologist said that the patient had expressed the desire to try additional courses of cancer treatment, and that integration would be consistent with the patients goal of getting back to baseline. However they were concerned about the possibility that the patient had respiratory disease due to Covid nineteen, in which case he would probably not survive several years earlier. When he had been critically ill, he had expressed a desire for. Do not resuscitate status more recently. He had indicated that he would try all therapies. That may be helpful. An urgent palliative care consultation was requested. Reconsidering, the trade offs of prostate cancer, screening a medicine and society. Article by Jonathan Shock from Weill. Cornell Medicine New York. After the widespread adoption of prostate specific antigen PSA screening in the early nineteen nineties, prostate cancer diagnoses increased rapidly while death rates have to over the course of the next quarter century, initial results from randomized trials and recommendations against screening from professional societies, which were recently moderated, probably contributed to screenings, falling out of favor over the past decade decreased screening has been associated with a sustained fall in prostate. Cancer diagnoses, although not necessarily reflective of a change in the number of men in whom metastatic disease will ultimately develop some evidence suggests that the incidence of metastatic disease at diagnosis which had been decreasing until two thousand ten may now be rising. The decline in SAG screening has a number of contributing factors, but appears to have been precipitated in part by misinterpretation of existing randomized data and lack of attention to follow up time when the calculus of harms and benefits is evaluated. Shoghi and colleagues reviewed the long term results of PSA screening from randomized trials and raise questions about whether the risk benefit ratio is as strongly in favor of risk over benefit as currently gauged. Amplifying are N, a vaccine development, a clinical implications of basic research article by Deborah Fuller from the University of Washington School of Medicine Seattle. Recent, interest in Messenger R. N. A. M. R. N. A.. Vaccines has been fueled by methods that increase Mr Rene stability and protein production and improve delivery. There are several strategies to elicit immunity with an RN a vaccine. They all involve coaxing host cell to replicate and translate and exogenous are a and coating. The Vaccine Antigen. A recent study describes a new versatile approach. The authors describe strategy. Strategy that is based on two are in vectors, one retaining the replicates and coding gene and the other coding the Antigen the replicates machinery is therefore provided in trans that is to genes acting together, but on different RNA's by a self amplifying aren A or non replicating MRI and mediais replication of the Antigen. Encoding are in a the authors found induction of robust and protective neutralizing antibodies. In mice after immunizing them with Antigen encoding are in a expressing the influenza protein Hema gluten at Nanno gram doses, although comparatively high numbers of replication coating. RNA's were required. NUCLEIC ACID vaccines have been a major hope for solving the Kobe nineteen pandemic crisis, the ability of self amplifying our innate vaccines, and now trans amplifying aren't vaccine's to provide amplified and durable production of Antigen in Vivo coupled with potent inherent innate immune stimulating properties adds to these powers and may provide the dose sparing that will probably be needed to meet global demands. Grading changes for US emily step won a golden opportunity to recalibrate medical education priorities a perspective article by Charles. Proper from Stanford University California when the Federation of State Medical Boards and the National Board of Medical Examiners announced that results on step one of the US medical licensing examination will soon be reported as pass or fail rather than a three digit score, the jubilation expressed by many medical students who haven't yet taken step one was countered by the frustration of a similar proportion of students who see a graded exam as an opportunity to prove to residency programs, their relative merit, facing in two thousand and twenty two target date for implementation. Some students are pondering ways to delay. Test until it becomes pass, fail while others want to take it as soon as possible so that they may shine this focus on step. One highlights the degree to which exam scores affect the educational journey and decisions of today's medical students and their schools in the author's view, the intense focus on step one test scores can stifle medical curriculum development when students prioritize memorizing, what's likely to be tested over seeking other knowledge without the US l.? Step one exam exerting undue influence on our curricula. We have the opportunity to work as a community to redefine what it takes to train, scientifically grounded and exemplary caregivers in today's world, such collaborative action is overdue. The impact of a pass fail step one. A residency program directors view a perspective article by Lisa Willett from the University of Alabama at Birmingham. Although the Invitational Conference on us, Emily scoring was intended to have a broad representation of key stakeholders medical education. The Graduate Medical Education community felt underrepresented and many residency program directors voiced concerns about unintended consequences for both students and residency programs already overwhelmed with the current process for residency recruitment. Some program directors believed that the change will further dilute the transparency and trustworthiness of the information that medical schools provide to residency programs to understand this concern. It's important to see the process of residency matching from the GM perspective. Medical students match into. Into residency positions through the national resident matching program, which changed its policy in two thousand thirteen to require residency programs to fill all positions through the match under the match process program directors must create a rank order list that task necessarily involve comparisons between students and requires a holistic review of the academic and personal attributes of each candidate. The changed a pass fail scores means among other things that residency programs will lose the ability to compare students performance across schools leaving step to ck scores as the only objective measure for comparative data. Poor scores on that test or a failure on any US test may doom a student. Objective measures needed program directors perspectives on a pass fail us. Step one a perspective article by Alan my cool from Vanderbilt University. Nashville. I administered in one, thousand, nine, hundred, ninety, two, the US Steph one results have evolved into a benchmark for various selection processes, including those for honor societies away rotations and residency positions faced with more applicants than they received in the past and variable medical school evaluation systems us. Residency Program Directors now rely on step one scores as one of the only universal standardized metrics in the residency application process binary step one scoring represents a dramatic change in medical student assessment, which will have consequences for the residency application process to characterize residency program directors responses to binary. Binary step one result reporting these authors developed and validated a nineteen item survey through phases of pre pilot and pilot testing, only fifteen point, three percent of program directors agree with changing step one to pass fail and seventy seven point two percent expect this change to make objective comparison of applicants more difficult. The results suggest that step to CK will largely replace step one in importance in the residency application process, whereas students currently have two opportunities to perform well on a USO. Emily examination before applying for residency after the change, they will have only one. These authors believe there should be more not fewer objective measures available for assessing applicants. A test of diversity what US MLB pass fail scoring means for medicine, a perspective article by Quentin humans from Northwestern University Feinberg School of Medicine Chicago. Two hundred two. Years of anticipation months of preparation hours of practice testing, all score of two hundred, two of a possible three hundred such laments are common among us. Medical students who put their personal and academic lives on hold each year while preparing for step one. The stakes are high for all students taking the first step examination, but students from racial and ethnic groups that are underrepresented in medicine experience, great angst, although the effect of pass fail us. Emily step one exam on trainees from underrepresented groups remains uncertain. The change may help diversify the medical profession, opening a world of possibilities for. For Physicians and patients alike, the odds are stacked against students from underrepresented minority groups, starting early in their scholastic journeys and structural factors have resulted in a leaky pipeline for medical careers as many talented potential physicians choose other fields. Instead these authors appreciate that there may be unintended consequences associated with any change. Particularly want is bold. Is this nevertheless they believe that holistic review will be tied. That raises all ships equitably, although there's much angst about a pass, fail step one. A change was clearly necessary. The change brings great opportunities for innovation in residents selection and should catalyze. Improvements in diversifying our physician workforce. Our images in clinical medicine features a seventy eight year old man who presented to the emergency department with weakness on the left side that had developed ninety minutes earlier and his schemic strokes in the territory of the right, middle cerebral artery was diagnosed and intravenous tissue plasminogen activator TPA was initiated fifty four minutes after the infusion was initiated, swelling of the left side of the tongue was noted, and the TPA was stopped the swelling progressed, he had no history of use of NGO. tencent, converting enzyme ace inhibitors. The patient had no shortness of breath pain, and there was no evidence of airway, compromise or lingual NGO DIMA is a known potential adverse effect of TPA. The swelling can be a symmetric had. And can develop in a location contra lateral to the schemic lesion. Or? A lingual NGO Edina may occur most often in patients who have had a stroke that involved the insular or in patients who have received treatment with an ace inhibitor. The mechanism is incompletely understood treatment in this case included intravenous antihistamines and GLUCOCORTICOID 's without advanced airway management, the tongue swelling resolved, but at a follow visit three months after presentation, some neurologic deficits resulting from stroke remained. A twenty nine year, old man, who had recently immigrated to the United States presented to the cardiology clinic with worsening exertion. Visual, blurring and headaches, these symptoms have been present since childhood, but had not received regular medical care, and the condition had not been diagnosed. The patient had found that his symptoms lessened when he squatted or after thirty minutes breast, the oxygen saturation was ninety two percent while the patient was breathing ambient air. The physical examination was notable for a harsh Holo systolic murmur at the left. Stern border with a stern will heave. There was no evidence of digital clubbing electro cardio graffiti showed sinus rhythm with a right. Bundle Branch Block laboratory studies showed a haemoglobin level. Level of twenty grams per deciliter echocardiographic showed the your two, overriding a large ventricular Septum, defect and right ventricular hypertrophy with subprime Onyx NOCES, all of which confirmed the diagnosis of tetralogy of follow. The characteristic murmur is due to right ventricular outflow obstruction, squatting maneuvers increase systemic vascular resistance, resulting in reversal of shunting at the ventricular Septum defect, and therefore a reduction in symptoms. The patient underwent surgical repair, including Pulmonary Valve Academy closure of the central defect reception of muscle bundles in the right, ventricular outflow tract and patch augmentation of the infant, debut and main pulmonary. Two months later. He was recovering well. Without further episodes of Disney visual, disturbance or headache listen to an audio of the sound of tetralogy of fellow at any J. M. Dot. Org This concludes our summary. Let us know what you think about our audio summaries. Any comments or suggestions may be sent to audio at any J. M. Dot Org. Thank you for listening.
Episode 106 - March 15, 2020 AFP: American Family Physician
"Hey this is Steve. It's March Seventeenth. Twenty twenty when I record this before we start this episode. I wanted to provide a brief comment about the Cova nineteen public health crisis affecting our world right now as you know lots of things are cancelled the NCWA tournament the Masters Golf Tournament. Movie releases and Broadway shows graduations weddings. But you know what's not cancelled family medicine now more than ever. We see the importance of family medicine. You all are on the frontlines. Caring for the health and wellbeing are patients and communities. Thank you I'd like to share some thoughts. I saw on twitter from Rene crisslow. Md A full spectrum family physician on faculty at the University of Minnesota. Here's Dr crisslow with advice to her graduates entitled Breathe. So this one is for you folks. You know who? You are the grads. I've taught family medicine physicians and Medical Students for more than twenty years. I'm talking to you. We are in the clinics hospitals emergency rooms and the ICU's remember what I used to tell you. People don't need us when it's easy. They need us. When it's hard will. It looks like it's going to get harder for awhile in when it does. I want you to remember your training. I don't expect you to be perfect. I don't expect to know everything. I expect you to do what I do. And what we've taught you to do. We step up every time we do our best we then evaluate and injustice indicated by the results. We expect you to remember as you were trained. These are not cases. These are not advocates. These are people and they are your patients. They are someone's daughter. Someone's mother someone's father someone's son and we have the honor to care for them. It is a sacred duty. There will be a time many years from now when they will tell the stories of the time of Code Nineteen. That's not why we're here. No one may ever hear what you've done. Just do your best. Now take care of each other. Now take care of yourself now. Tomorrow is a hope for a better day made real by every choice that we make in the present you will need to have faith in yourself and each other and when you can't believe in yourself remember that I believe in you breathe much love Krige. Thank you Dr Crisslow for sharing this with us at this crucial time in our personal and professional lives of course. This crisis is ongoing and rapidly. Changing family. Medicine is here and we will always be here and on March Twentieth Twenty Twenty match day we welcome more than four thousand new family doctors to our ranks. I'm sorry to all of you that your match day celebrations were likely canceled. Consider this a small celebration welcome. We are so glad you're joining us. Finally I'd like to refer people to to resources for family doctors. That might be helpful as we tackle. Cova nineteen risk in our communities. Check out the link on the homepage at www dot af p dot org and check out to recent blog posts from two of our American family. Physician Editors Doctors Middleton and Lynn the first ones entitled Corona Virus Disease Twenty Nineteen updates and resources and the second is optimizing mental health during the covert Nineteen Pandemic. You can find both of these at. Afp Journal DOT BLOGS DOT DOT COM. Okay folks that's it. Take care of yourselves and each other. Here's the episode. The AFC PODCAST is supported by the American Academy of Family Physicians and by UNC network physician recruitment currently recruiting for UNC healthcare and thirteen other UNC affiliated hospitals throughout the State of North Carolina for open opportunities more information please in an email to physician recruitment at UNC health dot USC DOT EDU man. Hey and welcome to the American family physician PODCASTS FOR THE MARCH. Fifteen twenty twenty issue. I'm Jake I'm Michelle I'm Melissa. And we are residents faculty mostly residents of the University of Arizona. College of Medicine Phoenix Family Medicine Residency. Today on the podcast. We're GONNA be talking about managing hypertension using combination therapy. We'll have a steps look at a practice guideline on GPS. We'll talk about medication. Used TO REDUCE RISK OF BREAST. Cancer Will Review Genital Ulcers. And we'll wrap things up with an. Afp clinical answers rapid fire round the opinions expressed in the podcast our own and do not represent the opinions of the American Academy of Family Physicians. The editor of American family physician or banner health do not use this podcast for medical advice instead sear doctor for medical care. I on the docket managing hypertension using combination therapy and this comes to us from doctors. Dustin Smith Robert Linen and Peter Carl's guard. Thanks Michelle and Jake for volunteering contestants in combination anti hypertensive Trivia Ready. Let's start with a softball. Can someone remind our listeners of the J. Eight criterias hypertension treatment thresholds and the general first line medications to us? Oh I definitely know this one. Treat to a blood pressure. Goal of less than one forty over ninety for adults aged eighteen to fifty nine and patients at any age with diabetes or chronic kidney disease entering otherwise healthy adults over the age of sixty two a goal of less than one fifty over ninety for general all comers first line medications include ace inhibitors or arbs. Thi- as I diabetics or calcium channel blockers but there are some caveats in special populations in which you may want to choose one of the other classes over another okay so with those blood pressure goals in mind. It seems obvious that one indication to start a second anti hypertensive would be in patients who have inadequate control with monotherapy but in patients. Not already on anti hypertensive medication. At what blood pressure would you consider outright initiation of combination? Therapy two hundred over three hundred. That blood pressure. I guess I would treat it if that was a blood pressure. I'M GONNA go one sixty over one hundred. Yeah SO SYSTOLIC. Blood PRESSURE GREATER THAN ONE. Sixty or greater than twenty above goal or diastolic blood pressure greater than one hundred or greater than ten millimeters of mercury above goal would be the reason to start outright combination therapy or two hundred two hundred hundred. Yeah it was close next question. The combination of which two classes of first line anti hypertensive should be avoided is an arbs. I was GONNA say that. That's right. You should avoid ace inhibitor. Plus Arb- in combination as this can increase the risk of NC dream disease and has not been shown to have any mortality benefit. Moving on the Jhansi. Eight found witch strategy superior with regards to initiation of combination anti hypertensive. Therapy patriation of monotherapy to maximal dosage. Before adding second agent or adding a second agent before reaching maximal dosage with a single agent definitely adding a second agent before eating maximum reaching maximal dosage. I'm going to support Michelle and not answer trick. Question who neither strategy has been shown superior likewise for adding a third agent. Let's talk more specifics. About some special populations in black patients. At least one anti hypertensive should be from which to classes of first line? Anti hypertensive medications thighs. I'd calcium channel block thing. We're a good team Michelle. That's right speaking of Diet sides. The preferred that is II. Diabetic is close allies. That's right patients with heart. Failure with reduced ejection. Fraction should receive a witch classes of anti hypertensive medications to improve morbidity and mortality. Going back to the ACE inhibitors Beta blocker. Nice in ace inhibitor. Orb Or Andrew tents receptor knepper lisin inhibitor or Arnie plus a Beta blocker. Once the patient no longer has symptoms of volume overload are indicated the addition of sperone lactone or Appel reknown to ace inhibitor therapy decreases morbidity and mortality in these patients especially after acute myocardial. Infarction consider a diuretic based on volume status. How ABOUT FIRST? Line anti hypertensive medication for patients with chronic kidney disease with protein area. Feel like I'm just repeating myself but ace inhibitors. Ace inhibitors or arbs have been shown to decrease progression to end stage. Renal disease finally for our diabetic patients does it. Matter which of the sign medications you choose. Maybe yeah sure about that. Answer of a maybe like Depending on their property screening right right so not unless they have protein area. In which case use an ace inhibitor or an Arab next up we have steps remember? Step stands for safety tolerability effectiveness price and simplicity. This steps looks at s. Ketamine or name-brand Bravado. Vodka for treatment resistant. Depression as Ketamine is an isomer of ketamine and acts as an antagonised on the in. Methyl D aspartame receptor. Its exact mechanism is unknown and it's labeled uses for the treatment of resistant depression in those already. Taking an oral antidepressant. Jake what do we know about its safety? There are a few safety concerns to mention here so the risk of abusir diversion with this. Medication is quite high in caution is warranted in those with a history of drug abuse or dependence. Dissociation and sedation are the most commonly reported side effects and after administration patients should be observed for two hours and not allowed to drive until the following day. It can also raise blood pressure so patients with a history of vascular inr `ISMs ATM's or Intra Cranial Hemorrhage should not receive it s ketamine should also be avoided in children adolescents pregnant or nursing mothers or those with a paddock impairment. Eliza is it tolerable. Well Ma- adverse effects are actually pretty common dizziness. Vertigo and nausea happens in twenty to thirty percent of patients. You also mentioned the blood pressure issue. Seventeen percent of patients will have a substantial increase in their blood pressure within two hours of administration to other common side effects are Hypospadias Asia and anxiety. One in twenty patients will discontinue the medication due to these side effects. Will that's not super reassuring. Hopefully it's effective I them. It was studied in two. Rcti's against Placebo where patients depression was not responding to at least to appropriately dosed antidepressants. And the addition of s Ketamine did not show a clinically significant difference in achieving remission. Although in patients that did achieve remission significantly fewer patients relapsed while taking ketamine with a number needed to treat a five. Please tell me it's redeeming. Quality is that it's affordable. Though right you would be incorrect. A one month supply of the induction phase ranges from five thousand to seventy five hundred dollars depending on the dose maintenance doses range from the slightly better twenty five hundred. Thirty seven fifty I don't think I even want to ask him about its simplicity. Yeah the International S Ketamine must be given under direct supervision of a health care professional that is enrolled in the manufacturer's risk evaluation and mitigation strategies the initial doses fifty six milligrams and then either fifty six milligrams eighty four milligram. Dosages should be given twice per week for four weeks then it should be given weekly for four weeks and finally after nine weeks it can be given every one to two weeks want to bottom line. This one four streak. No I don't but I will and here it is. It's costly their safety concerns and requires pretty substantial monitoring plus. It doesn't even sound effective so it really should be reserved for patients with resistant depression. Who can't undergo other things like e C T receive IV Ketamine? Okay guys. I'm excited. Let's hit this practice guidelines and this one is group. B. Streptococcus disease updates guidelines for the management of at risk infants this kind of replaces the CDC's two thousand ten guideline for GPS and is based on evolving epidemiology new data and changing practice. Standards this comes from the AARP and endorsed by Aycock. Gbs disease is the most common cause of newborn early onset sepsis and a major cause of late onset sepsis in infants there are two flavors epidemiologically early onset. Gps is from birth to six days of life and late onset is one week through three months of age. I let's screening screen. All pregnant people with vaginal rectal culture. Thirty six to thirty seven weeks or for any pregnant person with preterm labor premature rupture of membranes before thirty seven weeks rectal. Vaginal culture isn't needed if into natal urine culture was already positive for. Gps NUCLEIC ACID amplification. Tests are not recommended for GBS screening in February. Twenty Twenty Cog published a committee opinion on the prevention of GPS early onset disease in newborns that reported that GPS nucleic acid amplification tests can have a false negative rate of seven to ten percent therefore acog recommends against routine use of this test if NASA T. results are obtained for an intra-party impatient with unknown. Gbs Status Aycock recommends that patients receive antibiotic prophylaxis if they have a positive. Gps result or a negative GB S. A. T. result with risk factors of justiciable age less than thirty seven weeks rupture of membranes longer than eighteen hours or maternal fever a negative. Gps N. A. T. Results can eliminate the need for antibiotic prophylaxis if none of these risk factors are present. Let's talk prevention of early onset. Gbs disease who should receive intra-party antibiotics for prophylaxis all patients with a positive antenatal. Gps SCREEN GPS bacteria at any point in the pregnancy a previous infant with GPS disease or those with preterm Labor or premature rupture prior to thirty seven weeks. Additionally those in Labor at thirty seven weeks or greater who have not been screened should get intra-party prophylaxis if they develop a fever or have ruptured membranes for eighteen hours or more. Lastly and this one is new current recommendations state that have. Gps status is unknown. But the patient is known to have had GBS colonization in a previous pregnancy. In part in prophylaxis can be considered the committee. Opinion points out that those would be colonization and one pregnancy. Have an estimated fifty percent risk of colonization in a subsequent pregnancy. So it's reasonable to offer prophylaxis as shared decision making process in this scenario. Okay so you've determined that profile is indicated. What's the antibiotic of choice? Penicillin remains the drug of choice. Ampicillin IS AN ACCEPTABLE ALTERNATIVE FIRST GENERATION. Cephalosporin for those penicillin allergy and low risk for NFL axis and Clinton Mason for those with high risk for NFL axis. But only if the susceptibility the Clinton Mason is known and if there is a high risk for NFL axis and there's Clinton Mason resistance go with vancomycin newborn assessment for early onset. Ubs disease involves looking for clinical indicators of disease like vital sign instabilities supplemental Oto requirement or need for. C-pap mechanical ventilation or blood pressure support. Cbs's should not be done routinely to assess for risk due to their lack of clinical. Utility hypoglycemia should not be considered a sign of early onset. Gps disease all right guys. Let's talk about assessment of the newborn once they're out and this is where the guideline is a little less clear. They give us three options for infants at thirty five weeks gestation greater recommendations now include the option to use a multi variant risk assessment with the neonatal early onset sepsis calculator which considers risk factors and clinical condition to identify the level of risk and provide recommendations based on that level the calculators available online through Kaiser Permanent Day recommendations also include an option for risk assessment based only on the clinical condition of. The newborn. Antibiotics are administered. Only if the infant is ill appearing this is based on the fact that risk of early onset infection is reduced by sixty to seventy percent if the new warren is in good clinical condition at birth. The third option for risk assessment is what previous guidelines have recommended the so-called category goal risk assessment in this approach a maternal inter-parte fever. It would result in blood. Cultures Impact Antibiotics for the well appearing infant or for the infant born in the setting of inadequate intercomm. Pardon Prophylaxis they would be clinically observed for thirty six to forty eight hours for infants. Born earlier than thirty five weeks obtain a blood culture and start and pick antibiotics. If the cause of preterm birth was cervical insufficiency preterm Labor premature rupture of membranes enter amniotic infection or acute or unexplained non reassuring fetal status this regardless of intrepid on prophylaxis. All right and so then for the infant. That's born before thirty five weeks but falls in the low risk group like those with maternal or fetal indications for the preterm birth birth by C. Section in the absence of labor attempts to induce Labor or rupture membranes before delivery. What do you do with those ones Elissa? If the MOM has received adequate inter-party prophylaxis than the infant does not require empirical antibiotics if there are no signs of sepsis or maternal intra-party Fever. Great thanks for that overview. This is a big change because it replaces that two thousand ten. Cdc Guideline that we've been using for so on like ten years K guys we're GONNA put prevention into practice here. This putting prevention into practice looks at medication used to reduce risk of breast cancer. And it comes to us from Dr Tina Fan from arc and Addio faulk laid. Who's a general preventative? Medicine resident at Case Western the USPS CF recommends offering to prescribe risk reducing medications to ASEM dramatic patients who are at increased risk for breast cancer and at low risk for adverse medication effects. This is a grade. B recommendation although there is no specific cutoff for defining increased risk for all patients. Those with at least three percent risk of breast cancer in the next five years are likely to derive more benefit than harm from risk reducing medications and should be offered these medications if their risk of harmse's low the. Us does not endorse any particular prediction. Tool to calculate a patient's risk though various risk calculators are publicly available for use you can also use combinations of risk factors to identify patients at increased risk of developing breast cancer. Examples include patients over the age of sixty five with one first degree relative with breast cancer patients. Forty five years of age or older with more than one first degree relative with breast cancer or one first degree relatives who developed breast cancer before age. Fifty patients forty years age or older with a first degree relative with bilateral breast cancer or a personal history of a prior biopsy results. Showing atypical doctor or Labile. Hyperplasia or Lobola Carcinoma insight. You Okay Jake. Tell us about the meds to mock sutphin relaxing and aroma taste. Inhibitors have been shown to provide benefit in reducing risk for breast cancer in patients at increased risk only tomography is indicated for use in pre menopausal patients to mock. Sutphin AND RELAX. Athene may decrease the risk of fractures in patients with osteoporosis. Eliza what about the harms to mock Sutphin and relax iffy in have an increased risk of thromboembolic events to mock seven has also been shown to increase the risk of development of endometrial cancer and cataracts the risk of enemies. Israel cancer and thromboembolic events are higher in older patients. All three classes of medications may increase the risk of visa motor or musculoskeletal symptoms in some patients determined to be at increased risk of breast cancer. Should be offered risk reduction medication however these potential benefits should be balanced against the potential harms of adverse medication effects. Great let's on a main topic. Genital ulcers differential diagnosis and management. And this comes from Dr Michelle Rohit from Georgetown. When you guys think genital ulcers what comes to mind that's a question for the ages Michelle but really I think. Hiv Syphilis Hueco. Just named the most common causes infectious causes are much more likely but there are some non infectious causes. Well we'll start with the most common herpes simplex virus one and two Jake. What would you expect? On history and physical for herpes. Simplex the classic genital HIV is most reliably diagnosed with observation of painful shallow ulcers investigators on an earth space. These are commonly preceded by pro drill. Symptoms of Tingling for some infections can also cause constitutional symptoms and lymph at an apathy and notably impatience. That have recently started antiretroviral therapy. There's an increased risk of outbreaks a presumptive diagnosis can be made by observation of these lesions or definitive diagnosis by pr of the ulcer or vesicles fluid. Elissa had we treat hse Eisai Clavier Valley. Cyclo viewer or Fan. Stickler can all be used with varying doses durations. Physicians should treat without waiting for serologic results. Treatment has been shown to prevent HIV transmission reduce healing time and relief pain. Suppressive therapy should be offered to prevent transmission as patients with HIV to have viral shedding up to ten percent of the time in the absence of an outbreak. This has agreed B. Recommendation. Even on suppressive therapy there is still a viral. Shutting and transmission can still occur in pregnant women. Suppressive therapy reduces the risk of recurrence by seventy five percent and reduces the rate of c-section due to H S V by forty percent. All right. Let's move on to the second most common syphilis. Jake what do we expect here on? Ancient be the characteristic. Lesion here is a single painless indicated ulcer with a clean base otherwise known as Shankar. These patients can also have tinder. Inguinal lymphatic apathy. Men who have sex with men have the highest prevalence of syphilis and the physicians should routinely asked US population about sti symptoms trap. Nima Paladin can be identified from the schenker or lymph node aspirin. Whoever is doing that on dark field microscopy or by direct fluorescent antibody a presumptive diagnosis can be made with a positive non trapani will test like our PR and confirmed with a trip minimal test as the RPR can be falsely positive with certain conditions. Eliza what can you tell us about this treatment? All phases of syphilis should be treated with intramuscular penicillin G Benzathine. Two point four million units. This is one of the few times that if the patient has an allergy to penicillin. They should actually undergo desensitization. And then treat with penicillin. Sexual partners exposed within ninety days before diagnosis should also undergo treatment due to the high prevalence of syphilis in men who have sex with men presumptive. Treatment should be initiated prior to results. Nontraditional Antibody titre are used to monitor response and treatment is considered successful with a four fold decrease in these tigers in pregnancy if syphilis is untreated it has an eighty percent fetal infection rate and forty percents stillbirth or miscarriage rate other infectious officers. Include the Schenker oid which usually presents as a non-integrated painful lesion with Pigeons border and FRY will base with an acrostic imperialist exceed eight painful unilateral lymph at an apathy can occur and it may transform into those scary booze a whopping seven patients were diagnosed in the US. In two thousand seventeen though the non infectious causes are pretty rare but include psoriasis. Shed Syndrome fixed drug eruption sexual trauma or Wagner's granular matosas and to rounded out Elissa. Tell us about prevention and screening the US pse F recommends screening for syphilis in those at risk pregnant women but against HIV screening and ace symptomatic patients including pregnant patients and remember to offer pre exposure prophylaxis for patients at risk of free HIV which includes those previously diagnosed with syphilis. Bottom line here. Most genital ulcers diagnosed in the. Us WILL BE H v one or two or syphilis. Our guys under ready. We're going to wrap this episode up with. Afp Clinical Answers quickfire round. Remember listeners if you want more information about any of these topics checkout a p dot org slash. Atfp here we go. What therapies are effective for the common cold over the counter? Analgesics Andy Congestions with or without antihistamines. Not antihistamines alone and for kids. Nasal ceiling irrigation menthol. Rub An honey. If they're over twelve months no cold meds in kids under four for maintenance fluid in hospitalized. Children should hypo tonic or ice. Oh tonic solution. Be used as tonic to prevent hypo natrium. Ya with a number needed to treat of eight. How should you counsel patients about e cigarette use e cigarette use is not recommended for youth? Talk to adults about the hazards and Safe Storage. And try evidence-based cessation methods. I is cognitive behavioral therapy an effective treatment for postpartum depression. Yes the addition of CBT reduces depressive symptoms more effectively than usual. Care alone like medication and other therapies. What is the best approach to treat multiple Actinic toasties of the head topical five percent fluorouracil once weekly for four weeks? And that's Rep. Nice job guys. This is renee crisslow from the University of Minnesota Department of Family Medicine Community Health. Go gophers please. Email us at a p podcasts at W. P. DOT ORG or tweet at AFP podcast. Please rate and comment on Apple podcasts. Our podcast team is Jake. Anderson Caroline Blogger Stephen Brown. Sarah Coles Elissa Cori- Gene Victoria Herbert's Rosenbaum Michelle. Somare and Hilary. Tamar are sounding technical guru is tyler. Coles theme song is written and recorded by family. Physicians Bill dabs Ryan Evans and Justin Jenkins. This podcast is brought to you. By residents and Faculty of the University of Arizona. College of Medicine Phoenix Family Medicine residency. We'll talk to you soon for the next edition of the American family physician podcast.
Is Dapagliflozin aDAPtAble to Treating HFrEF in Patients Without Diabetes?
"Greetings and welcome to the I former ex podcast where we explore the evidence that informs Imlay Tori Care Pharmacy Practice. My name is Stuart Hanes and your host and in this episode. We're GONNA be talking about the Sodium Glucose transporter two inhibitors or more commonly known as the SGLT two inhibitors. This class of medications is indicated for the treatment of type two diabetes and have been shown in the landmark cardiovascular out controls to reduce the risk of cardiovascular events in patients at high risk of atherosclerotic cardiovascular disease. We've previously posted commentaries and podcasts about these landmark trials on. I former expert today. We're going to be focusing. On the potential use of these agents specifically deputy flows in to treat patients with reduced ejection fraction heart failure. Perhaps you've already seen and read the data H. S. study which was published in the New England Journal of Medicine on November twenty first in two thousand nineteen undoubtedly. This study will generate lots of discussion and quite possibly lead to changes in the way we treat patients with low E. F. Heart failure. I'm delighted to welcome to the IPHONE X. Podcast today Dr John. Andreas Dr Zieger. And Dr Michael Kelly Doctor Andrea and Zieger are pg way one pharmacy practice residence with Cedars Sinai Medical Center in Sunny Los Angeles California and Dr. Kelly is a member of the Chapman University School of Pharmacy Faculty and an ambulatory care specialist. Together they co authored a commentary for I former ex cleverly entitled is Dan Lewis lows in adaptable to treating reduce. Es Harshly Michael. It's great to have you back on the I former ex podcast. Indeed Michael You were a guest on our very first podcast episode back in two Thousand Fifteen Alexa and Jonah. I'm so pleased to have the two of you on our show today and I hope I'm welcoming you back five years from now. Thank Stuart Glad to be back. Thank you so much. Probably not happy to join you on the podcast by Dr Hanes. We really appreciate the opportunity to be here and talk about this exciting study before we get started. I I WANNA revisit a case we talked about in our last podcast episode. I want you to imagine you're seeing in be a seventy eight year old African American man and the Primary Care Clinic today after his discharge from hospital a few days ago the the patient was admitted due to increasing shortness of breath in poor exercise tolerance and was treated for heart failure exacerbating now. This is his third mission in the past year. In addition to reduced ejection fraction heart failure. He has a longstanding history of high blood pressure and dyslipidemia and he's obese. According to his medical record he's been prescribed Corbeta all twenty five milligrams twice a day Lysenko Pearl Twenty milligrams twice a day. Hiroshima Twenty daily tasks. Him Chloride tablets. Twenty million twice-daily resume. Staten Ten milligrams daily Aspirin. Anyone milligrams daily and his most. Recent Echo performed three months ago indicates that his left ventricular ejection fraction is approximately thirty percent. He weighs two hundred thirty four pounds in his. Bmi is thirty two point two blood pressure. Today was one twenty eight over sixty eight and the most recent labs that he had performed were drawn a day before his hospital discharge a include a serum potassium which was four point. Two Blood Glucose of ninety six his a one C was five point two percent and his cholesterol panel. Ldl OF SEVENTY-SIX HDL forty-eight and triglycerides of one. Oh seven and the patient states to these feeling much better since they got rid of all that fluid from me so Alexa before we talk about the study that you reviewed in your I former ex commentary. I wonder what's going through your mind case like this. What additional information would you want to collect and assess during this encounter in? Are there any additional treatment option? So you'd be considering at this point. So most of his labs in vital signs look normal to me however he is overweight and the number of heart failure exacerbated. He's had in this past year. Indicate that his heart failure isn't well controlled by like to ask him more about his lifestyle and things like whether or not he's active and if he takes in a lot of sodium and his diet and if he drinks an excessive amount of fluids which would contribute to lack of symptom control. I'd also like to see if he weighs himself regularly and if he uses a lot of pillows to sleep on it they in terms of his medications. There are few other things. I'd like to ask whether or not he uses over the counter products like end sets or herbal products which may have a negative effect on his heart failure. I would also like to get more indepth medical history to see if he needed to continue the daily baby aspirin as far as his heart failure regimen. He's pretty good. Starting point with the ace inhibitor and Beta blocker for that morbidity and Mortality Benefit and he also has a diuretic to help with symptom relief but before adding anything on. I wanted to make sure that. He's taking these regularly and address any adherence issues. After all of that I think potentially I'll dust thrown antagonist or even eyesore by DNA trade with hydraulic zine would help as they have been shown to have morbidity and mortality benefit with the latter two medications the ice assert by nitrate with Hydraulic Zine showing specific efficacy in the African American heart failure population. So John in the commentary wrote for I former Ex. You reviewed the study entitled adaptive flows in in patients with heart failure and reduced ejection fraction which was published in the New England Journal and medicine now for those in our audience who haven't had a chance to read the paper yet. Can you give us a brief synopsis of the Study Methods and the results? Debra H F was an international face. Placebo controlled study compared to standard of care in patients with reduced ejection heart failure. The patients were followed for a median duration of Eighteen. Point two months now the primary endpoint was a composite of worsening heart failure further defined as hospitalizations or urgent care visits resulting in IV therapy or cardiovascular. Death as you mentioned earlier we've seen positive heart failure results with impact with lows in empire egg and connect with lows in canvas. But what makes this study very unique? Was that the patients did not have to have diabetes to partake in this study. In fact almost sixty percent of the patients in this study did not have diabetes also. An overwhelming majority of patients were on guideline driven medications more than just rest hitter and Beta blocker over seventy percent of them were also on an industrial antagonised. The primary outcome occurred in sixteen point. Three percent of the Paco flows in Group and twenty one point two percent of the placebo group resulting in a statistically significant hazard ratio of zero point seven four a secondary outcome also showed that patients onto pegos and had a greater reduction in symptoms compared to placebo. Subgroup analysis of patients without diabetes showed similar outcomes and safety. That was one of the exciting parts of the study. Even patients without diabetes had a reduction in heart failure hospitalizations and death so the study concluded that the packers lows in may be used to reduce risk of cardiovascular death and worsening of heart failure in patients with or without diabetes Michael. I I'm also wondering what you perceive to be the key strengths and potential limitations of this study so some of the strengths of the study that I found were the In the design it was a randomized double blind placebo controlled trial that was multi-centred international study was powered with an adequate sample. Saw is to detect a difference between treatment groups. The analysis was done on an intent to treat principle and like John mentioned that majority of patients were treated with guideline directed medical therapy. Ninety five percent of patients were receiving either an ace arb- or an army ninety six percent of receiving Beta blocker over seventy percent of patients were treated with DASA and antagonist so patients. Look like they're actually Adhering to kind of the standard of care limitations. This study was mostly comprised of men and mostly white race amid minority of patients were from North America about fourteen percent. So that may limit the generalize ability of the results to patients That we actually treat here in the US. I would like to point out though that Paradigm Jeff another heart failure trial had even smaller proportion of patients in North America so also limitation there. The inclusion criteria for the study did require patients have elevated in T. pro BNP perhaps selecting out for patients who were volume overloaded or perhaps even sicker patients. I know in our practice. We don't routinely measure BNP level before adding medication so whether we should be checking or sesing BNP levels and patients before changing the medicines is is something unknown and then lastly I think the low use of the Cuban starting in this study previously been shown to reduce hospitalization for heart failure including vascular death. Compared to ace was something of note however it did appear that despite low numbers of patients using secure patrol belts are the benefit of adding the pegos and was their Alexa. Some might argue based on the fact that the SGLT two inhibitors produce glucose urea and fluid loss that they are just very expensive. Diuretics and really. Don't offer anything more than what can be achieved with a good loop diuretic edit adequate dose. So do you buy this argument? And it's not one not so. That is a good point in this study as Dr. Kelly mentioned participants needed to have a high BNP to be included suggesting that they are likely fluid overloaded however when we look at the effect that loop diuretics how we don't see the same results in reduction in hospitalizations they only have been shown for symptomatic relief although the diuretic effect of the start two inhibitor. Class makes it a useful drug for heart. Failure patients they are also thought to have cardio protective effect so this cost of medications are thought to change the way that the heart metabolise energy by reducing the interest Elliott sodium calcium load and increasing that might have conjured calcium levels in failing heart cells so they thought to improve the dog function as well and for this reason. I think that the utility of the class goes beyond just Dia Rhesus so John. Let's go back to the case recall that. Mb has been hospitalized. Three times this past year. Do you think that would be a good option in this case Getting their generally favorable side effect profile. Would you recommend using SGLT two inhibitor? Instead of and al-dostur on Antagonists. And lastly do you think empathy glue flows in or Canada flows and would be reasonable alternatives. If that flows in was not available on drug formularies. Barring any other contraindications I would say to Paphos. Indefinitely is an option for 'em be even though he doesn't have diabetes. He would likely see some benefit in both symptoms and his risk of yet another hospitalization however at this point in time. It's not my go-to option for him. I would choose an al-dostur and antagonist for M. B. As long as his blood pressure could handle it both dossier and the combination of eyesore by died nitrate anhydride housing in an African American patient. Also has statistically significant reduction in morbidity and mortality unless the Paphos and had much stronger data than an Australian antagonised or there was a head to head study showing superiority. The price of the medications would lead me to initiate the generic al-dostur antagonist prior to the Brandon Deepak Association that being said if I was inclined to using sglt two inhibitor and Pagu flows and was not on the drug formularies. I personally would be okay with using impact. Closing are connected with lows in the effect to me seems class white. Especially after looking at impact in and connect with lows in diabetes data. I think further studies will allow practitioners to feel more comfortable using the other medication soon regardless of what happens. Sglt two inhibitors seemed to be a promising tool for practitioners to use a difficult heart. Failure Disease States Michael Alexa. John I WANNA to thank all of you for joining me today to discuss the treatment of heart failure and the potential role of the sglt. Two inhibitors as a class in patients with low. E. F. Heart share. I think it's clear from your comments that you believe that. This class of medications has a real impact and has a real potential to change the way we treat patients with heart failure. Certainly it's another option that could be used. We'll tell us what you think should an Sglt to inhibitor. Be routinely considered impatience with low E. F. Heart failure. And if so when should it be added should be added before or after an al-dostur on Tagore's well only I former ex members can leave comments and use the interactive features on the site. You can become a member of by former ex. It's free so sign up today and good news. If you are a board certified ambulatory pharmacists and want to earn recertification credits. This program you can. We've partnered with the American Pharmacists Association to offer. I former ex content for board recertification credit. Click on the link. Posted below the commentary on our website. Learn more lastly and want to thank the many volunteers helped make. I former ex possible. A special thanks to Michelle by from the University of Arkansas for medical sciences. Michelle reached out to me a few years ago wanting to get more involved with I former Exxon. Since that time she's written commentaries performed pure reviews. She's maintained our. Copd clinical trials webpage served on our advisory board and recently joined our editorial board. So thank you Michelle for reaching out to me and for being such a great volunteer and contributing in so many ways and until next time. This is Stuart Hanes editor in chief. Marex signing off.
#109: ENCORE Breakthroughs in Cancer Research with Dr. David Hong
"This is an encore presentation of healthcare rounds. Today, we are rebroadcasting episodes forty four and forty six with Dr David Hong Associate Vice President of Clinical Research at MD Anderson Cancer. Center. This episode was originally uploaded on April eleventh two, thousand and nineteen. Welcome to healthcare rounds the podcast serving you the INS and outs of health policy and business topics as well as our take on the rapidly evolving healthcare delivery ecosystem. I'm your host John Marceca Co Darmon Research Group and faculty associate at the W. T. Carey School of business and the College of Health Solutions at Arizona State University. This week I'm speaking with Dr David S Hong Deputy Chair of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center. Where he also serves as associate vice president for clinical research and clinical medical director of the clinical. Center for therapy. Dr Hong received a bachelor's degree in biology, from Yale University and a medical degree from Albert Einstein, college, of medicine, he completed an internship in residency at Thomas Jefferson University Hospital, and a medical oncology fellowship at MD Anderson during which time he was appointed chief medical. Oncology fellow. In two thousand and five, he joined. MD Anderson's faculty. Dr Hong is the recipient of many awards including the two thousand four young investigator award from the American Society of Clinical Oncology he has published more than two hundred and seventy articles in peer reviewed journals. So To kick US off. Tell me a little bit about your role. Within MD Anderson Oh I am the deputy director of what's called the Department of Investigational Cancer Therapeutics. It's a specific unit within MD Anderson dedicated to doing early drug development studies in cancer, and these studies are really the first in human studies oftentimes phase ones that they have evolved in some sense. over the last several years. but the steps after animal testing. That goes into cancer patients, and so we run that unit or department within the institution and I'm also the associate vice president trump research. And in that role I, I've played a number of different roles Do a number of things. One is one of the important things. I think one of the challenges I. Think Academic Medicine is. You know we have large bureaucratic structures have been trying to get some of these trials up and running as quickly as possible and I'll talk a little bit about that in context of how changing. But also some of these emerging challenges overall in oncology drug development it's it's been a challenge for us here to get trials of growing fast but we we have just recently. Relate implemented some. Key changes as that has. A. Lot to shrink our timelines. And I. Called in a number of things in that role, I help with managing grants, the internal grants that are being distributed to junior investigators and involved in kind of going through our clinical trials process. Here we have a huge number studies. You have close to three thousand files at Anderson Different Trials with our survey or treatment trials in. So a lot of details have to go through. In trying to help manage the infrastructure here at Anderson, which is one of the probably I would argue probably one of the largest in the world. So anybody WHO's watching the pharmaceutical industry has noticed a surge in cancer drug approvals in recent years, and some of these drugs are showing remarkable results and that's one of the reasons that I wanted to speak with you. was to get your insight from a research perspective how and why things have changed and can you talk about what's new in the last five to ten years and why the research landscape is so different today. Good question one you're absolutely right There's been really a record number of. Kinda new molecular entities, orphan drugs, both new and also generics by similar two, thousand eighteen. There was a total of. Oracle seventy six new indications for new drugs in cancer over the last five years and right now There is close to a thousand. Of Thousand Two hundred different agents or new molecular entities in clinical trials as of two thousand eighteen. But that's been that's been growing over the last. Decade. In two, thousand, eight, there was about seven hundred fifty but has been slowly climbing. Now it's close to twelve hundred and why is that? While part of that is too large extent is because we are reaping the harvest of molecular science and investment that has been in discoveries that have been. Implemented, over the last several decades, right At the Hanna Hanna Dot. Weinberg are scientists in college who wrote this a seminal review called the hallmarks of cancer in their first time occasion was in two thousand time they had listed the classic hallmarks, six hallmarks of cancer. But they republished the publication again in two thousand eleven. In the added, an additional four hallmarks cancer. tickly avoiding immune destruction that was one of their emerging hallmarks since then the discovery under pinning of the understanding of how cancer is so destructive has led to ways to target it. So you know I'm in Texas. So we talk about oil a lot, right? Right and We had we had a fracking event in two thousand eleven and that fracking event on that new technology was immunotherapy that was the first time when bloom Mab was approved in. Melanoma. And soon, afterwards, we had a number of. new immunotherapy agents, particular PD one inhibitors that augmented the Anti Taylor for bloom APP that led to obviously even more activity. And also then has emerged other things such as car t-cells, etc.. These numbers are probably out day but as of March of two thousand seventeen, there was close to a thousand one, hundred, twenty, two cancer immunotherapy combination trials while again, this is the individual agents I talked about the twelve hundred agents in two, thousand eighteen. So, there's been really an explosion of new trials new agents. In particular therapy, it's really transformed landscape for cancers that we never. Ever thought were GONNA be amenable immunotherapy such as long such as bladder I. Mean we we had some indication that melanoma was responsive to immunotherapy such as I'll to high-dose too but. those are oftentimes limited in really patients who can tolerate that drug, but these drugs are now. Have some side effects have relatively well tolerated. Third thing beyond the new molecules on immunotherapy in number three as rolling been in parallel to immunotherapy has been just the refinement and the ability to cut have molecular phenotype tumors. and. That's all the way from things like Brca mutations which we knew for a long time. But until just recently had been able to target patients with Bracken ARP inhibitors. And also other mutations that are relatively rare but are truly transformative such as entrance fusions. I was involved in the phase one, but also the New England journal Phase to and kind of. Paper. That was pivotal nor the studies that were pivotal in the approval of colour threatening, which is the first intrigue fusion inhibitor. And what's unique about this approval was that it was approved across all tumor types. irregardless of the type of cancer you had as long as you had entered fusion and so this was really the second type of that was approved What's call independent of histology or tumor type? The I was actually was called. pendulism have won the immunotherapy checkpoint inhibitors in a subset of tumors call MSI high. I'm coining this phrase but I I'm sure if you talk with other experts would say it truly is kind of this golden era of oncology drug development that we haven't seen for a while. So that that personalization that you're talking about I had a I was at a conference in their two doctors one that was. Really strong on clinical pathway development and the other one that was speaking about more the precision medicine, and it was really interesting to see these two different perspectives that they're mutually exclusive. But seeing these these two physicians talk about the advantages of. Ver- either standardization or personalization what are your thoughts on that I agree with you they're not mutually exclusive and I'm both of them are valuable in in many ways I think they will intersect as we become more personalized. So imprecise therapy I think one of the the reason that this is happening more and more is because actually know profiling molecular profiling tumors have become much much cheaper I remember when I was in resident in I think it was Around two thousand, two Francis Collins? Think Bill. Clinton and. Craig venter made an announcement that they was on national. TV. That they had done some Then this incredible, a- profiling of a human, a whole Xm sequencing or whole genomic sequencing of a person's whole genome right and I remember the reporter saying that it was a mere two billion dollars to to make this happen right? In what what they didn't really full tell it was they hadn't done i. think it was only the Exxon's I I may be in criteria, but they hadn't really fully profiled everything. It was they had profiled the vast majority of the genome. In and that technology has gotten increasingly better and cheaper than even silicon chips. You know there's that Moore's law. And you can get online now and you can get your whole xm sequence or a whole genome sequence for like under a thousand bucks. and. So that technology has just incredibly evolved to the point where we are. You know routinely getting that and all of our patients here in the Anderson. Recently made that announcement that they would pay for the mutational profile in there have been some incredible examples like the Lehrer tracking. Of example, that I mentioned to you that truly has shown that the advantages of kind of profiling tumors etcetera. The are still skeptics a the skeptics would argue that only a percentage of the patients were maybe even a small percentage of those patients actually benefit from personalize therapy, but that's an assumption that that's assuming the current technology and. The current drugs will stay the same and obviously that in my opinion is short-sighted, we will develop new drugs and they're all V more knowledge imitations that personalized therapy approach. I suspect will be much more a approach that we can follow, and this is being or out particular lung cancer or lung cancer for example, is really been being sliced into smaller pies as suit targeted therapy. So it's important to note that that that trend in technology impresses will continue and I suspect that. You know five years from now there will be many more targeted therapies, many more patients who may benefit from personalized therapy than than they are right now the vast majority of patients are still Kinda using standard you know chemotherapy in for example, the NC, guidelines are a very good guideline as to how we treat patients all the way from early stage later stage. So they're not necessarily mutually exclusive. I helped develop a something called a pourquoi protocol green tea constitutes member home that's actually a combination targeted therapy plus chemotherapy. Regimen that we we identified high activity and benefit in patients would be Rafi six, hundred, eighty colorectal cancer that has been now incorporated into the guidelines for colorectal cancer, and that is a pathway which on colleges used to make determinations as to how to treat patients. So these aren't mutually exclusive pathways. I suspect though that you know not just five years from now ten years or even further down line there may be even more nuance ways more complex ways in which we. Live pathways, personalized pathways. Whether it's using a guy right and use it utilizing things like whole genome profiling identified drugs that may cause too much Choksi or may Ashley and also benefit. The data that we use in the context of profiling tumors or using a profiling patients is really determine which patients may actually. Benefit rather than which patients may Ashley Gain Toxicity. So all of that is going to be incorporated in the future to make maybe even personalized pathways. So there may be really a convergence of the both of those. Processes. Interesting. I. Noticed. You're actually published MD Anderson actually publishes all of your pathways on on the website. Why find that's remarkable is as part of our research into different institutions I often run into people who I don't know if the word is proprietary, maybe it's third they're secretive about their pathways within their organization which I don't understand. Why that would be the case when certainly MD Anderson is. As I said publishing them for the world. So ahead, a an a recent conversation with another academic institution where many of their docks their careers advancing through research publishing and sometimes. At least according to this person, they struggle to get them to spend time with patients. Obviously MD Anderson is known for world class care as well as being renowned research institution. Do you find it difficult to do both wealthy face the same kind of challenges with your researchers. Yeah, I think I think that's that's an increasing challenge given the current reimbursement environment. But you know if you look at the vast majority of revenue and what you need to kind of cover operating costs think eighty five to ninety percent of that. Still comes from clinical revenue. Don't don't quote me on I. Don't think I know the exact number, but it's around there. Right. So the other like seven percent I think is like is research NCI. I'd sponsors, it's address the other three percent is philanthropy. We know the most academic centers recognize. Where their bread is being buttered Sir they you know continuing push academic. Departments and chairs ensure that they meet their clinical revenues targets, but as a academic institution and in order to attract people are interested in research. US Chair, need to kind of balance. All of that ensure that you know you have some time to do research but I will tell you that it is becoming increasingly more difficult. I mean, I you know if you don't have a grant in some of our departments, you're you know you're seeing patients four days a week, and that's essentially the same same amount of. Clinical effort you put in usually in private practice, you do four days a week in the day off to try to catch up and follow patients in order sets, orders, and stuff like that. Right the challenge though is for an academic senators they can't pay them pay these colleges for pay the physicians as much as they as they will get in private practice, right? So, if you increasingly make it equivalent, you know time that you're spending son doing clinical care as you would do a group practice or outpatient practice without giving them time to research than what incentive is there to stay in an academic institution I've seen that happen with a number of my colleagues who actually graduated from the inner cells which I did went off to academia. Brilliant people who were you know had really promising early careers got lasko CDA's etcetera or ask a young investigator awards but their respective institutions would require them to see a lot more clinical care than they initially signed up for. Eventually, they just said you know what's the point you know and they leave and usually they leave for two areas. One is private practice or industry. I'm seeing more and more colleagues of mine leaving for industry that has pharmaceutical companies etcetera who need on colleges need that these experts that help them develop their molecules. So I don't I don't know the answer. What is the right answer to? How do you make this balance? I think it's a very it's a big challenge for chairs and administrators to try to ensure that academics have some time because you know you can't do research with like. One day a week off I. Really. It's really hard because you know you're spending some of that time already on clinical care follow up with patients at. CETERA. into try to actually write papers, write protocols beyond teleconferences or run a lab it's almost impossible and so you have to give some margin of time to for these researchers but understandably, if these researchers not bringing grants or Rian protocols or funding. Institutions are losing money on every single one of them right? Not entirely sure which direction this is gonNA. End Up going for academic year in the United States, I think there are different challenges particularly if you're outside the United States but I'm seeing more and more trials actually moving outside the United States for a number of reasons one. It's cheaper for drug companies to actually do trials outside the united. States. And to there are more investigators or clinical trial has to know how to run a clinical trial or even even early clinical trials. In Asia in Europe in eastern Europe particularly and so companies are moving towards their so. some of these new novel ages may not become available for patients here in the United States in the future. So finally, just to wrap things up before I got on the call, I saw a New York Times propublica article about a another cancer center where they've had some issues with conflicts of interest in. To comment on on that, you may be aware of it but but rather, how do you partner with industry in? What's Pharma's role as a partner in research in caring for patients? Yeah. That's a really good question. Former is I would argue instrumental at least in the in the clinical aspect of research I think the NIH in the has a very obviously central strong role in preclinical research. and. and to some extent Pharma is having increasingly there. There are needs for affirmative also have increasing role or by TechNet forming biotech role in also preclinical research. Most of the drugs. That are currently approved in the United States was not developed by the government. It was developed by the pharmaceutical industry, the vast majority of new drugs whether it's an oncology. Those seventy-three indications came from drug companies who invested in poured out, argue billions of dollars into research. Now, one can argue I'm not gonNA argue about drug pricing, which is I think complicated her and nuanced here. But part of the reason that they're able to do research is the money that they've poured into this area. We do have collaborations the NCI in doing clinical trials with them but the vast majority of clinical trials are done in this country in the world are conducted by pharmaceutical companies in what what I think Propublica, some of the other ten of venues that are trying to that out this conflict of interest they may or may not realize this is that this research probably would not be conducted if it wasn't for Pharma trying to, you know get drugs approved and investing the money in order to try to get these drugs improved. Clinical trials isn't incredibly expensive endeavor and that's also very complicated reason as to why but you know the numbers ranged from phase ones from twenty to fifty million dollars of phase one, and then you get into large phase randomized phase two can run up to one, hundred million, and then doing an international phase three study can be up to three hundred million. There's debate as to how much this whole process costs. But if you look at the institude Joe, democracy has been working in this area for decades. And their data suggests that capitalized cost that means the cost incurred to get one drug approved, which is usually a a ten percent. Likelihood of a drug, one drug that only one drug out of ten that gets into the clinic gets approved that capitalized cost is probably three billion or more Again, one can debate as to why these drug costs are so high, but without Pharma, the United States government does not have. That kinda cash. To invest in research and getting new drugs out there. So fortunately or unfortunately, that's just the nature of the reality of drug development at this well and Pharma wouldn't be able to implement those trials unless they were in partnership with the the Anderson's of the world right I mean, yes and no increasingly Pharma is moving outside of academia. There's a one of the largest conch proud units in the world or in the United States at least is something called Sarah Cannon Cancer Center and they're not necessarily affiliated with the university. they're part of a C-, a dedicated oncology practice that is really kind of focused on clinical trials in oncology. And they are Juggernaut in oncology trials, but they're not affiliated with any university of any sort and so that that allows them to have low lower overhead costs and also them to have faster implementation clinical trials, which which always leads to decrease research costs. Right. So to date, we know on average from drug getting into the clinic in getting approved still takes about eight years before FDA. approval. Things have gotten faster in the last couple of years but. You know the last paper I read on this still the average was like eight to nine years. and. So if you're for example small biotech. You are burning through incredible amounts of cash to pay for your staff, the clinical trials, etc.. into the faster, you get that up and running and completed the better and so. The Anderson's and Danafarber Casey see they're still very important in the KHL trial infrastructure. But there are other alternatives that drug companies farm are looking at not including Sarah. Cannon. But also outside of the United States. There are other entities now outside the United States that are also doing these kinds of clinical trials. Now, you know the FDA singer their mandate is is that you know long as the data's good right and it's it's been audited and vetted appears good. They're not going to necessarily disapprove a drug because it's not done it in the Enersen caring right? They just WanNa, make sure that the right protocols have been followed in all the essentials of running clinical trial is done properly is essentially. So you're all in competition with each other for those those clinical trials. Right I mean ideally, we should. We shouldn't be in competition, right ideally, we should all be working together towards You know getting these trials up and running and completed for cancer patients but there is some level of competition I would really academic competition but also trying to get slots for patients who are at your institution. I wanted to pick up where we left off on our discussion of Pharma and the cost to bring a drug to market I think you throw to figure something like two billion dollars. That's the number that I've seen something around that, and we're talking offline about the decisions that Pharma companies need to make whether to even enter clinical trials or move from phase one to two. To, three bringing drug markets on every stage of the every step of the way in stages decision needs to be made it go no go decision what are your thoughts on that process and the the issues that people think about when making those decisions? Yeah. That's a really excellent question. So I had that same question to my colleagues in Pharma, and so I actually pitched A. A Educational Session on this very topic and we titled at the art and Science of go no go decisions in oncology drug development. And the reason we titled that is, is because I, it's not a science scientific process, right? There are many different factors that make a decision about whether a drug will move into not only into the clinic but from each step in the process and there were three kind of industry veterans who are part of that educational session. If some of your audience were at a CR, they can log onto the website and actually it was recorded. Nancy Cole, who is was kind of the head biologist or head she scientific officer blueprint biology. She's now consulted for a number of companies institutions. The second person was David fell quite who is the head of early drug development at ems the last person was Sandra Horning who's chief medical officer at Genentech. And so I posed this question to all three of them who how do you make these decisions in each step from the preclinical to the early and late? Nancy. Obviously shared there are a number of key decisions. Is there activity in certain models? Can you actually create a molecule that will have the right stability and characteristics in a clear environment that we can? Can you scale it? Right? Can you make enough drugs so that you can get this into the clinic and what in the context of all of this you know what are your competitors out there? What drugs already in that space Dave had a really interesting perspective. He's a huge fan of economists. Named diversity, who was a behavioral economists? Who won the Nobel Prize in the and and really believed that in complex decision processes you really need clear try to make as much objective decisions as possible outside of your own personal kind of agenda has I think we're all whether it since to some extent in science, but also in complex decision process such as drug development in your all we all have biases right for and Dave has tried at least in his processes still eliminate that by looking at certain. He's actually got an algorithm where he looks at the characteristics of that molecule in clinic. So I in early trials. So does this is their activity is there does inhibit what we think it does in biomarkers a both what's called proximal biomarkers and distant biomarkers, and what level of activity are we seeing is safe for less toxic and human beings all these criteria he kinda posed and he uses somewhat of an algorithm to make to help their team make decisions. Sandra was much more broad and she posed a number of challenges. I think that the industry is facing and that is you know we have gone from this period of scarcity where we had very few drugs and entries can into a clinic now with a huge abundance of new trials and new molecules what's challenging for somebody like Santa? Horning is there is a lot of competition out there. Right? There are at least there's already five approved pd one or Pedia one inhibitors. There's another ten in the in in the space. Where do you go right? There are multiple agents in every single class. How do you proceed? and. So She just post a lot of questions and for them I think how do you navigate the process? In the context of the larger challenges such as patient enrollment research cost. How much is this GONNA cost us to eventually get an approval. I would argue the regulatory framework she brought up the regulatory framework which has has really changed over the last several years and I I give credit to. Our colleagues at the FDA, they've really tried to look at alternative ways to get approved in a way that we hadn't seen before the breakthrough indication histology, agnostic trials, real world data et CETERA. And so I think a lot of what Sandra in one of a large Pharma and so forth are doing is how do you navigate that? How do you best execute your go? No go decisions in that in that environment. So. Yeah. So it is truly I would argue more of an art right now there's not a sign if it was a science and it was easy enough that you you did this and add this and mixed up this and you'd get an approved drug. We'd have a lot more drugs approved, but that's not the case at this time follow up question and this is going to really show my lack of drug knowledge. But in the in the simple what I would call the simple space rather than in the biologics during the cancer space. Let's say blood pressure drugs. In that space, you have your calcium channel blockers. Ace inhibitors are some Alpha blockers. Are Trying to think I'm probably forgetting a few diabetics. and. It's always been my sense that physicians view. The category is the drugs in the category being relatively interchangeable and how this relates to go decisions. As you know, once you hit the fifth ace inhibitor, do we really need a sixth or seven or eight days? And especially in in these days when formularies are tightening up and putting products and preferential position. So my question is, is it different in the world of oncology? Do you view products in a given category as being relatively interchangeable or does it go to our last conversation about? Precision medicine and maybe one particular drug is better than another. That's a really good question. I mean today to most of these drugs are oftentimes approved any specific indication. For example, you know like I said, there's like five different PD, one inhibitors out their PD L. One inhibitors, but each of them have taken different niches, right so for example, value MAB which is PD L. One inhibitor I think AstraZeneca owns at is approved in from a large say which was called the Pacific trial, which was in the context of Ashvin therapy after Chemo Experti- Chemo, radiation radiation in in lung, cancer patients. I'm pretty sure I'm sure that there are other drug companies now like Merck and B. M. S. looking to use that space. But at this point, I don't think you can just ask. Your Insurance Company to add Nivo in that context of that setting. Because these drugs are so expensive right satellite. Change out one ace inhibitor for another right right and some of these drugs have only indications in certain specific disease states. So I think one of the reasons that there's not kind of interchangeability is that these drugs were so expensive and specialty pharmacies are becoming much much more strict about what indications who can use did what setting etcetera etcetera off label use in this country is legal, right? In fact, I think the formation, the FDA, their their intent was never to tell doctors exactly how to use this drug they were initially. Commission to really say drugs are safe right? But but because of the expense of these drugs specialty pharmacies, sherm plans, reckon very strict about how these drugs can be used in not used. And what indications and so I see that being different than just standard other drugs like ace inhibitors. CETERA. What implication. Application does that have for biosimilars? Well so biosimilars will I. Think we'll be increasingly be used I. Think they they will I mean I mean you know the it'll be a while before I think anybody can develop a bio similar to some of these PD one inhibitors but there's now by similars now rolling out for like Redux mad which has come off I think patent and there's other biosimilars for, for example, the GMC F. and Jesus analogs. So in those settings are pretty straightforward I. I don't think anybody's done large scale studies comparing you know the boss similars as to whether they're any lesson essay in fear to like Rotunda Mab or whatever. Theoretically, they should be very almost exactly. The same right because these molecules are are the all by complex you know the they're very precise. So I'm assuming that they will have a role because the cost will go down They're not going down as much as like you know if you had a generic of in ace inhibitor partly because they're just much more difficult to make a more complex to make. I I do think that biosimilars will and they are beginning they are taking off I mean we The institution here at the Anderson I think oftentimes uses biosimilars. or by Bison wish because they are cheaper than than the other standards. I think that that has been a good change for overall drug costs, but remember the patent life or at least the the drug exclusivity rights of a drug right give it a forget exactly what the time point is. But give give it a exclusively for a long period of time. So I. Try to or Nivo we'll have drug exclusivity for many more years and they're gonNA charge what the market will bear. Right right. Right as talked about last time the drug pricing is a very complicated. Very trying to explain somebody how drugs are paid for in the US is and why they're priced the way that they are. Is a challenge it is complicated. You know I think that this is one of the things I posed in that that that educational session as you are I I do think that Pharma is coming upon their kind of tobacco moment right from suitable companies used to be an if they ever. But they you know they weren't necessarily seen like the bad guys like tobacco companies, right? But. Then you have the whole March skelly story. You have this whole stories about the EPI pen. You now have the whole stories of the purdue family, and then you know just recently the CEOS of the Pharma companies were all brought forward the in front of Congress right if you look at Gosh any survey looking at particularly Medicare and Medicaid drug pricing in negotiations. Despite the fact that we as a country are divided almost every major issue. The only thing that we're actually united about is drug pricing right Republicans and Democrats Liberals, and Progressives, and conservatives they are and I think that what's going to end up happening whether it's trump next year in two thousand twenty or whoever there's GonNa be a push towards somehow you know. Allowing Medicare to negotiate prices. And I think if that happens, you know the other the shoe falls, which is insurers will fall on that. Also, I mean, there is already. Drug pricing negotiation going on particularly with a church companies. But I think that Medicare pricing comes into the plays GONNA drive down costs even more. So drug companies are going to have to figure out how do they you know given the increasing research costs and maybe likely drug reimbursement is going downwards. You know, how do they make decisions based upon that right and they you know? As much as we'd like to think that drug companies purely make decisions on science alone and efficacy of drugs they don't they have to be fiduciaries to their stockholders and they have to make decisions based at that will make revenue, right? Yeah and I think today it's It's an even bigger issue but the the example that I used to use is Zithromax saw three mice now. Granted. We're talking a much much lower scale in terms of dollars. But I always just to say Pharma has a hard time selling value. You know here you have you can take for your sinusitis you can take. A Salon for mock cicilline three times a day for ten days not sure if that's exactly accurate, but if you look at the Z pack. You know you load up on the first day and then you take something for four more days than you're just much more convenient. You're much more likely to be compliant. But when you go to the pharmacy and you see this, it's off pat now that you see this, you say, well, wait a minute I'm going to pay seventy dollars or this cost a hundred dollars for six pills and people just think and it's the same kind of thing with the Gilead drug or suite of drugs for Hep say. People look at that and they say their the value can't be there for what I'm getting and I. Just I don't disagree at all by the way that they're having their tobacco. Moments here with a string of these kinds of things hitting the news and I also think that they just haven't done as an industry a good job explaining the value of of what it is that they bring to the table. I agree. You know I mean it's it's a it's a part of the larger story of healthcare here in the United States right? I don't know what the right answer is. I definitely envy some aspects of like kind of centralized. Manage systems like Canada or in Europe but at the same time like I, tell you the number of clinical trials number amount of research says being done here in the United States number of drugs that are available. Are Not available to cancer patients in Canada or the UK? UK. has something called the Nice System Right which is a committee that makes decisions based upon the value of life year right? Whether or not that drug is going to be of value to a cancer patient. You know how do you put a price on that? I it's hard to put a price in my opinion it's hard if it's especially if it's your if your wife or your son or whoever right? The committee, a government committee says, we know that this drug can extend possibly extend the life of a somebody by six months, but we don't think that is enough for us as government to pay. Well, that's a curve right? That's that's a curve. Some of those patients who may benefit six months may also benefit five years right? It's it's it's the tail end, but there's still that chance I, I don't know. If Americans are GONNA want to to make those kinds of decisions or want somebody in a central government to make that kind of decision right and there are number of health economists? Is You we all know who argued there are three things in healthcare and it's it's different than most other economic kind of markets. One is quality availability and then cost in most health economists would argue you cannot have all three. It is very hard to have all. Even, in socialized systems like the UK or Canada, their costs are skyrocketing. And so it's a balance and I it's it's one of those things where I. It'd be hard for me to see. Consumers Union, the United States Oh, you know what I'll. I'll wait I'll wait three months for my hip replacement right or or you know what? I'm not going to get the latest drug because you know it's too costly the government's as to but now you can have it two tier system where those who could pay into that system. You know have a private insurance which does occur in like Canada to some extent in other countries. But at the same time, also I could see just an uproar about the inequality of something like that inevitably would draw inequalities because no matter how much. Money, you pour into a system like healthcare which were pouring tons of money into they're still going to be inequality. So I don't know the right answer to you. John I don't know the answer either I certainly have my my opinions. I mean the reality is using the Canada Canadian example in the UK. I would imagine that the people that you see. Down, MD Anderson who come from those countries are wealthy right I mean. They have the ability to to come to you know top medical institution have their care and no matter what direction we go in its I, don't see that changing yes. Yes and I you know I can't speak to the full population patients that come to the tonight. We definitely do of kind of indigent care here in the Houston community because it's a Texas mandate but you're correct in the sense that a lot of patients who do come here from. Outside of Houston have the resources to come right especially if you're from another country, we're seeing a whole lot of patients actually coming from China you know it's a socialist system in China. There says, says a kind of a videography essay on Chinese healthcare. It is abysmal about what's going on there and there's there is going to there likely is probably already two-tiered system. But the system. Currently of those who get socialized healthcare there is is abysmal I mean it's just it's just really sad. On that article. But we are seeing yes we are seeing lots of plenty of patients from other countries coming here is because. A lot of them are from socialized countries. Right? We have the the best potentially the best care here in in the US but then there's the question about why is it that we're not at the top of the list in outcomes in just about Agree that you look at why is that well show? So in cancer care, we actually are better than like social systems like UK and so forth. If you look at life expectancy and so forth I think it's far more complex than just Oh, you know our healthcare system I mean you'd think about health health is the human bodies. Health is a very complex system right? I mean like we Americans eat crap. and. If you're seriously, if you were to bring the full Japanese population here to our healthcare system, I bet our life expenses would be a lot better right because Japanese eat much healthier than us they way lot less than us. Probably Habits they're better than us, but we Americans eat a lot of fatty fried food and we were overweight. And we overwork by the way. I think a lot of people like to compare healthcare systems by those outcome saying, APP, apples, oranges, but apples, apples but that's not true because our populations are entirely different. You know a lot of the socialized systems exist in very smaller countries Sweden. Whatever they have populations. I think is Norway has has north. Finland has a population of Houston. Right right. I didn't bring you still how do you? How do you come in? You say while you know they're they're they're they're such higher life expectancies. Well, that's hard to compare three, hundred, million to five, million population you know and and much more headed much more homogeneous population relative to heterogeneous, population. And so you know I kind of oftentimes take those kind of comparisons with somewhat grain of salt because I don't think that you can just throw the United States population say well, you know therefore the healthcare system is failing them. I totally agree that there are definite aspects in Christie's of the current modern are American, modern healthcare system that is failing the American populace but there's also many aspects of American healthcare that is truly benefiting us as a nation particularly innovation if he talked with people in Pharma. To large extent and I'm not saying that this is the the major reason. But you know a lot of the research costs are borne by the fact that we have higher drug prices here in the United States right now people don't want to say it. And but that's the truth right? You know a few say, okay we're GONNA now not allowed drumbeats to make profits or whatever will the money flowing into research decline I bet it will. I'm just making my best assumption that probably likely will will they make it up by increasing prices in Canada and the UK and other places? I doubt it because those governments will just say, no, we're not paying more her night they've already those agreements I'm not sure what the right answer is. We haven't cured cancer for and we still need new drugs and we as many new drugs are out there we need to you know every day I you know I see patients were dying, right? I mean most of my patients. Despite these new drugs die on me and And it's easy to say I think if you're a critic when you don't have a a mother or a father or a life or a child who is suffering from cancer, say you know what it costs too much and it will make sure that the drug companies don't make any profits or just reasonable prophets. But when you have somebody who has cancer, it's not that easy to say, no, I lost both parents to cancer different types, cancer and watch them. In the last days of of their their lives and it was horrible. In a needs to tell you, you see it every day. Yeah. Yeah. Well, this is an enlightening. Yet. Again I'm sure we could talk for another half an hour but I think I be wearing out my welcome Dr Hong Thank you. You know this obviously our opinion piece. Obviously, this is my opinion that the opinions Anderson Suppress. Pathetic. But yeah, it's it's fun. It's fun talking about this. This is stuff that have a passion for you know alternately, you know why do what I do is because I really want to help our patients and ultimately I really believe that clinical research particularly new innovations will transform not only cancer but you know health in general in the world, and so I'm you know I'm I'm I'm passionate about that. Thanks for interviewing me a happy to do this again sometime. At some point leader in. Whenever you have this and so happy to talk about other topics. That sounds great. Thanks again, Dr Hong Terrific. That's all for this week from all of US Darwin Research Group. Thanks for listening. If you haven't yet done. So please rate and review healthcare rounds wherever you listen to podcasts. Healthcare rounds is produced by Deanna Nicolaj and engineered by Andrew Roja. The music by John Murcillo. Darn Research Group provides advanced market intelligence and in-depth customer insights to healthcare executives. Are Strategic Focus is on healthcare delivery systems and the global shift towards value based care. To learn more about us, go to Darwin Research DOT COM or send an email to insights at. Darwin. Research Dot Com. Or. If you'd like to get right to it, cost eight, four, zero, two, three, four, six, five, see an extra round.
"Hey all welcome back to the real life. Pharmacology podcast. I'm your host pharmacist christianson. You can track me. Down linked in erik christiansen. Farm d be cps gp or. You can also find me at med education. One zero one at g mail dot com if you have questions or suggestions or curious about different resources as far as drug interactions or case studies. I can definitely Send you to those links. If interested there. I hope you enjoy the the episode today today. I'm going to cover finance brand name of this. Medication is pro scar. Or it's also known as propecia and i'll get into the different Indications there for each of those agents. So i this drug is categorized as a five l. for reduc taste inhibitor. And what this means is by blocking five. Elfriede reduc tastes. This prevents the conversion of testosterone to die hydride dihydrotestosterone. Okay so ultimately what this drug is going to do is reduce the levels of dihydrotestosterone. Now what does hydrotestosterone do. Dihydrotestosterone plays an important role in causing or contributing to the growth of the prostate. So as you can imagine a five reductive inhibitor. Like finance dried can be used to help shrink the prostate in manage symptoms of bph. Now you might ask yourself. Why don't testosterone increases the size of the prostate as well so on thirty more of that around and that is true to an extent however die. Hydrotestosterone is much much much much more. Potent androgen than testosterone is so essentially. You're reducing the overall androgen burden on that patient which again can help shrink the prostate and help symptoms of bph. In addition die had dihydrotestosterone causes hair follicle damage. So what that means. is it's associated with baldness. So if we reduce that agent or that molecule hormone. We can actually help. Treat hair loss. And that is indeed one of the other Indications for an asteroid. So those are the two most common indications that i see it used for Bph out say first and foremost and then Rarely you may see. It used in hair loss as well now. The dosing is different for those indications. For bph we're gonna uses significantly higher dose of five milligrams for hair loss We're gonna use a one milligram. Typically how about adverse drug reactions. So you know thinking about Testosterone and dihydrotestosterone in the androgen effects. One of the most common in major adverse effects. That patients are gonna report is evidence or sexual dysfunction can. So that's something we gotta look out for in patients It can potentially also lower blood pressure as well I would say it's probably more so associated with Alpha blockers which may be used in combination with finance dried But there is some potential for lower blood pressure just from finesse to ride as well k. I do want to Also mentioned that in my practice a primarily have have worked geriatrics and long-term care And i've been around a lot of younger female caregivers of childbearing age in. It's really really important to remember that. This drug is toronto janik k. So the pregnancy risk historically using that the categories it. It is category acts gays even handling Getting powder you know handling broken or crushed tablets getting that powder on hands and things like that I is definitely not a good thing. for younger females of child bearing age to do because of those risks In pregnancy. So i think that's a really really important education point To remember there. Let's talk a little bit about onset of action and kinetics so in both shrinking the prostate and hair growth. It takes a really really long time for finance. Drive to work so you really spent some time in educate patients and let them know hey. This isn't an instantaneous. Miracle cure for your symptoms of bph or symptoms of Alopicia so again takes time to work. How long does it take to work. It can take months for this agent to work in both hair loss and bph Typically inadequate trial For the management in shrinking of the management of bph shrinking of the prostate You're probably looking at six to twelve months for hair loss and that type of thing you're probably looking at Three to six months of taking the medication and seeing if it's actually going to provide some some benefit so in bph specifically What's often done is far as patients who are really symptomatic. Have trouble with urine flow and things of that nature Alpha blockers will often be given with so drug like tam solution for example k so that tam slauson has a much much quicker onset and hopefully with symptoms to a modest extent. There all right. So let's take a quick break from our sponsor and we'll finish up with drug interactions in the market for pharmacists board certification. Study material like nap. Plex. bcs ambulatory care geriatrics or bbc. Mt m s definitely. Go check out our exam resources that can help you prepare and pass your exam. We've got lots of Testimonials and and satisfied customers over the years. Been doing this content for several years now so hopefully it's Tailored well Towards your specific exam and can certainly help give you a little edge as far as trying to pass these exams. If you're a nurse. Med students or other healthcare professional looking to learn more about medications medication. Safety definitely go checkout one dot com slash store of got a growing list of amazon books. audible books and different resources. Along those lines that you can certainly Check out and Help maybe your education about patient safety and medication management. So again everything located admitted one one dot com slash store all right so finishing up on drug interactions. Let's talk first about anti cholinergic. So anti cholinergic can definitely oppose beneficial effects in the management of bph. So if you remember anti cholinergic they can facilitate essentially clamping down or blocking urine flow. And when we do that that can lead to worsening symptoms worsening urinary retention which again kinda counteracts and opposes any beneficial effects. You might be getting From your five alpha. Reduc ace inhibitor. Like finance dried game. Another class of medications are the decongestants so these have elf agonised activity and again can kind of restrict urine flow out of the body in increase the risk of urinary retention and exacerbating symptoms of bph and as far as drug interactions go and increasing concentrations of finance stride There really aren't a ton of a drug interactions that way. Whether it's you know the cyp enzyme system usually we don't have to worry about that too much There is a supplement called saw supplemental that may have five. Alfred duct tastes activity so that could potentially have some additive effects to finance jeroen. So i i would say most often what i've seen in clinical practice. Is you see a patient that has prostate issues and maybe they read online. Maybe they hear from a friend. Whatever the case may be that all salt palmetto is is supposed to help with prostate issues. Well they try to take it and you know maybe get a little benefit. Maybe they don't but then they go to their physician they prescribed for now stride and now all of a sudden you've got The patient potentially on both of those agents and having additive of potentially so i'm typically in most situations going to recommend discontinuing that saw palmetto If a patient's on a five alpha reduc ace inhibitor like finance deride so those kind of wrap up the drug interactions. There's not a ton of drug interactions with finance right which is definitely a nice thing But the primary thing i think about is drugs that potentially exacerbate bph symptoms or oppose Those beneficial effects that we might see from finance stride. All right so that's going to wrap up the podcast for today. leave a rating review on. I or wherever you're listening. Definitely go subscribe at real-life pharmacology dot com get your free thirty one page Study guide of the top two hundred drugs. Great little resource for any healthcare professional or aspiring healthcare professional. And of course sheriff's with friends. Colleagues students your precept in In help us grow the podcast yet. Support the sponsors admitted one one dot com slash store. Help us keep this podcast free and educational for all to enjoy. And i'm going to sign off for today. Thanks so much for listening at take care and have a great rest of your day.
ACE2: The Coronavirus Gateway
"This is sarah scenic hosted the serial podcast. I wanna tell you about our new show nice white parents. Reporter hana joffe. Walt spent years looking into this one middle school in her neighborhood. She must've gated the school's history and finally realized she could put a name to the unspoken force that kept getting in the way of making the school. Better white parents. How white parents can mess things up for everyone else without even knowing it. Nice white parents is made by cyril productions a new york times company. You can find it wherever you get your podcasts. Hello phil sense here listener. Are you one of the many people who take ace inhibitors. Or aarp's to treat high blood pressure or to help with heart issues or diabetes in the uk. This should be about one in seven view because these are some of the most common prescription drugs out there and recently people have been worried that they might make a corona virus infection worse. The link between them is a thing that's inside. Everyone's bodies could eighty two on today's show meet as to the protein in the spotlight the bastion of our defenses in our walls. Protector turned betrayer. This is naked genetics. It's important to say i that there's no evidence at all that either ace inhibitors or airbase. Put you at more risk of virus and in fact. There's some evidence that they even help you. I don't wanna leave that issue hanging and you can hear why they might help later in the show but before that let's dive into what all this stuff actually is. I want to introduce you to a big system of hormones in our bodies. That controls blood pressure called the reenen and gio tencent system. It sounds complicated. But the crucial parts are this hormone called angios tennyson. And some enzymes that convert it ak antea tents and converting. Enzymes is one of the people who i discovered a lot of. This is australian researcher. Joseph henninger and he explained it to me in more detail. The system called entertainment system and this system. For instance they go late so blood pressure regulates hot functions or kidneys. It's one of the most fundamental systems file basic. Zoology and two enzymes which i go late. This as and as to ace constricting blood vessels and as to does the opposite it opens to blood vessels and keeps us. Healthy keeps multiple of organs healthy. Can you help me picture what it kind of looks like yes. So the ace to basically Produce inside sales and then it goes to the surface of the soft parts of it is still in the south. The business amd is outside of to sell. It sits many many tissues because the system has multiple functions up all the why do viruses come into all this so the viruses came into this because after being founded than we found the total novel system that as to actually protects against lung failure at this time when we start working on this visit built in icu for mice which took us years to do. Did you consider calling it a might see you. It's a great idea. My see is so we built in my seal and found two hours applies to to like in. The hot is good guy. Miss out as to blood vessels started to leak. The holy land became full baseball. Tough full of russian and then a goping. Boston said that as to could be a candidate receptor for the first sauce. Files live basically clicked because if as to protect plunged into saas virus causes various lung disease. Maybe the to fit together. What exactly is the relationship between these viruses and ace to is as to the thing. The viruses are attacking as is to four into our body for the virus. The virus can only live if it enters our cells in our body and to enter the cells in all. It needs a gate ace. Two is the essential interrogate for the first and now second saskatchewan vials. Are you saying that this is the reason that these corona viruses do the damage that they do because they're using this as to which ordinarily would help against lung infection cooked. It's evil you know. There's no morals for viruses but did surreal evil virus to hit on the phone central protective systems. And when they hit that game today also sort of use it up exactly so they don't just open it. Actually take the gate with them inside the house and that's why we believed to particular viruses became so dangerous. So you're saying this kind of this double whammy of both the damage inside the cell and the damage you get from losing this helpful as to which is sort of wind. This current virus has been such a problem cooked stubborn miami and because the gate doubles is a good guy in our body. You mentioned that to does all this stuff to getting for example high blood pressure if the current is is getting rid of that are we seeing patients with the current virus who've got blood pressure. She's or something like that. Give a really interesting. Is you know if you look. At the cases people who died unfortunately of covid nineteen most of them have actually headed deceased before and the diseases to head before diabetes which affects the blood vessels of cardiovascular diseases. Hypertension exactly where is twos has actually a critical it's very suggestive and now it turns out in the latest stage of kobe. Nineteen the infection of more or less old blood vessels so it does explain a lot talk. Joseph henninger currently head of life sciences at the university of british columbia but right now stuck in austria until flights resume. As joseph explains eight two is the doorway. The the virus uses to get into ourselves. But not everyone's cells have the same number of doors so to speak to find out what this means. I got in touch with another biologist. Whose long research ace to and then i made her wonder rent her house trying to find the best possible sound quality. I'm patricia gallagher. I'm a professor in the hypertension research at wake forest university in winston salem north carolina and i have to say you sounding pretty good right now. Where in your house are you. I'm in a closet. You have put me in the closet. I feel bad when you put it like that. That's all right. So tell me about ace to what are the primary functions of ace to is to maintain the proper balance between two hormones and attention to an in one to seven. Now these two hormones coursing through your body as we speak and attention to constricts or narrows blood vessels while engines. One two seven dilates or opens. Blood vessels up. That's kind of a funky naming system. Why isn't andrew attention to andrew jackson. Three well engine to is eight amino acids. Long an ace to cleaves one of those amino acids to produce entered since one seven. Okay engine hinson to also promote inflammation while into tunes. One seven has anti-inflammatory properties. Ace to insurance that the levels of these hormones balanced. So there's proper defense against invaders and so that your blood pressure is not too hard to low so it's out of a yin yang thing. How important is it in the grand scheme of your body. Well we think of as to an answer. Tens of one to seven as part of a pathway that projects against chronic diseases such as hypertension heart failure cardiovascular lung disease and diabetes sars and cova have hijacked this essential protein as their host receptor and in the process wreak havoc in the patient. Does that mean then that if you reduce the amount of this as to that you have that might protect you against coronavirus. Well it's a complicated issue before or in the initial stages of infection. That might be a good thing but later on when you've got that severe pneumonia high levels of systemic inflammation increase in ace to maybe a good idea. So you're saying that even though it's what the virus uses to get into you it's still useful to have when you've got the virus because it does all these good things in the latter stages definitely i would think higher levels of as to maybe a good thing and there are actually clinical trials right now looking at drugs that causes increase in to it gives the patients in the latter stages of disease now to different people naturally have different amounts of ace to to start with. There's a lot of data accumulating now. On as two levels their studies. Showing that asians particularly asian females have high levels of ace to compared to other ethnicities men have higher levels of women as to also increases as we ate this increase in ice to with age may in part explain why covid nineteen has such devastating effects impatience over sixty but also these patients and to have chronic disease. This is a complicated process patricia. Gallagher there from wake forest school of medicine. North carolina explaining why it's so unclear whether mores to helps people with coronavirus or hurts them. We've heard about how ace to is sort of the way in for the coronavirus but there's a crucial distinction between that protein as to starve. Today's show and ace as an ace inhibitors. Both first and foremost seem to affect blood pressure but in opposite ways. Let's take a look now at ace. The one without the to human camry is an intensive care specialist at university college london and he spent a long time trying to understand. What does what ace inhibitors might do. And what role. The genetics seem to play an old. This we will have to ace jeans. And we can have one of two flavors once known as the i or insertion varied which is a tiny little extra chunk of dna in it and one school the deletion or d variant which has a little bit missing that changes. How much of this protein. The gene makes which is called ace so this. This isn't something that breaks gene and stops it from doing stuff. This just changes what happens. That's essentially it changes. How much of this active protein you've got and for a long time. We thought the only reason this system existed was to control your blood pressure and for that very reason a bunch of drugs amaze these cold ace inhibitors and they lower the amount base activity and that lowest blood precious. These drugs are widely used now but it is true that is turns out not just to be something that regulates blood pressure but it regulates the growth of cells and it also regulates that metabolism you. Dvd's new bit like me a likely to find that you can stack muscle on very easily with training. Whereas the i. I people the ace activities activity people a very much better generally speaking as endurance. The i version of the gene is much more common and long distance runners and the debate is much more common in. Powerlifters rose for instance. What's the version. That's really really good at sitting down for long periods of time even genes livingston's whether you want to sit in the rear end washer netflix's all day at better. Thank joe wicks now for helping me overcome that stuff. Good now when it comes to the coronavirus this is sort of related right because ace acts as part of the same system as the thing that the virus attach onto. Yes so this is really exciting. We were doing some work with mountaineers. These people climb of course very high and there's high you go the less oaks generators and we found. The version of the gene was very very much more coming much much more common even than in marathon runners having those same jeans massively influenced your chance of surviving from severe lung injury. In fact you were five times less likely to die which is way beyond any impact on mortality. I could have as a competent in todd. Working intend to this so there are a couple of questions the first of the maze if we just took this corona virus setup patients with very bad lungs and low oxygen would they benefit from us. Giving them an ace inhibitor and lowering. Would we find a similar reduction in mortality. We don't know but the data a suggesting that it might if we look at the distribution of the i and d versions of the ace gene around the world the places that have much more ivers gene do seem to have less severe disease with corona virus. And secondly there's a threefold reduction in mortality in people taking an ace inhibitor. Or actually something that blocks the product-based is angie attention to now. That's not enough to prove the effect. These data fit together to suggest that lois activity might work and we think this may give us potential treatment that works in facts. We're just about to stop those trials hopefully soon with using those very same cheap effective drugs that treat blood pressure and heart failure if there were no such trial and there were no other options. My money were betting would be the ace. Inhibitor would work but we found out this is such a far cry for when people were worried that these drugs would make the condition worse. Yes and of course. That was the first story so when we first heard that as to was the protein respect the spike protein of the corona virus. We rule a bit anxious. Should we be stopping. A snippet is on the patients and as it turned out we don't see any signal for hamas soul. So i was on the next to now listening to this podcast. Continue to take it. He won't gumri there from ucla. Whose trial of ace inhibitors is just getting underway. So we've learned that the gene. You have your ace protein. Might change how badly you get. Hit by corona virus. What about the gene. Fritz cousin d crucial protein. That kicks off. The infection are star ace to that is after the break. Music in the program is sponsored by epidemic. Sound perfect music for audio and video productions. Hello sorry to button. Katie here from the naked scientists. Did you know we make other naked chose to the fraction of all humanity who has actually gotten a chance to see their own. Brain is very tiny and you are welcome to that club. So if you enjoy musing over the mind reflecting on thoughts or frankly feel bamboozled by the brain checkout naked neuroscience face hurts now so yeah let's go by. Don't go down into the creepy seller and turn the light on exactly access the full archive by a naked scientists dot com slash near science all. Subscribe to naked neuroscience. Wherever you get your podcast. Welcome back to naked genetics. Scientists right now are still trying to work out. What makes one person's krona virus infection just a bad cough. An another person's a life threatening hospital visit. There's lots of theories relating to your age sex health and more but what about your genes like the gene for ace. We discussed earlier. How much do they explain. I'm like some theorized. could this be. Why certain minority ethnic groups disproportionately going to hospital with this disease. According to you and bernie. That is unlikely. He's director of the european bioinformatics institute helping gather current of patient. dna actually mice Whether you're infected with the virus will be due to your exposure but some hops whether you progress. A weather in hospitality have a mild disease severe for disease. Those may well have genetic factors contributing to the variation that we see. And do you have an idea for this. Corona virus of how big a role. Genetics might play now. We really really. That's been some initial work using some twins. Studies says that some evidence that there's gonna be a genetic component on our experience of many previous studies would argue that we some aspects for me i think in particular between mild and severe disease is going to be on most fruitful marital cat but when we concept for sure many way one has to collect data set and do the analysis before one can be show very early. Genetic analysis is not showing much variants being attributed by genetics. But we just don't have the sample size to be. She'll that's the full story. We need to white since we have more cases coming through the system. If you do find something what's the point. What can you do with that. Yeah potentially it can point us to ponder the jeanine different individuals in the population vary on if we're lucky. That pot of the gene is in a pathway. that we've already go to drug foam. That would be the best results now if we find something in the jeanine that there isn't a drug. There is a possibility of making a new drug. That is a long long ride. A final possibility. Is that the genetic components which are big enough that they really showed the difference between different individuals in a way that we can actually use in terms of saying what you'll you'll very much at risk and you'll know now. I don't think that's going to be a likely outcome to genetics tends to be. The genetic is very complicated but it is a possibility. if you do end up finding patterns. Are they likely to be with everyone or are they going to be patterns in specific groups of people or what human genetics is very very messy and saddam likely to be weak undistributed across all humans on the planet. That's the most human genetics works out. Incident put it to realize that although we in society we have a lot all casual use of self identified ethnic groups. So if you're presented with full while you're asked to take who you are whether you're european-american on african american or white british white our show all these other. Todd's most people feel confident about ticking boxes that prices of taking boxes since less aligned to genetics than people's intuition thanks so it's unlikely that there's going to be big differences between these self identified ethnic groups. You might be aware that. It's it's reasonably clear bite in the uk in the us that many people in minority ethnic groups african americans in the us and africa band south asians in the uk seem to be disproportionately represented in hospitalizations of covid nineteen. But what you have to remember is two things. Firstly the biggest outbreaks hunting in dense urban city centers. London new york new spices have a much higher level of of these groups and secondly many of the things that we know are involved with causing severe disease such as type two diabetes and obesity cardiovascular issues related to socio economic status which is related to. How much money you have. And that is distributed in a in a very skewed. Why in all society so. I'm relatively confident that there is not a big genetic component explaining the observed differences we see all ethnic group labels with covid. Nineteen you and bernie from the european bioinformatics institute. Meanwhile the evidence is starting to come in on whether hosts genetics that is the genetics of human hosts. Changes are response to coronavirus here in the uk king's college. London have rolled out a popular app called the covid symptom tracker app and they've recently released some of their findings using twins to figure out how big a role the genes play producer. Katie hailers spoke to one of the team francis williams about what they've found we've done what's called a classical twin study in which you can compare symptoms. Among the twin pairs we know that identical twins share hundred percent of their genetic material while not identical twins share on average fifty percent. We can compare the the identical identical 's a workout roughly what the contributions of genetic factors on what symptoms specifically talking about cough fever delirium loss of taste and smell shortness of breath chest pain. Abdominal pain diarrhea. That sort of thing. We'll the communist symptoms associated with many different viral illnesses. We combine the symptoms in a mathematical model to determine the best combination of symptoms. That predicts being positive A test for the virus. So it's a combination of symptoms such as the loss taste and fever with assistant coughing fatigue and ancient sexwale sir in that model and interestingly that model has the highest herod ability of all the symptoms that we look at fifty percent which means that roughly fifty percent of the difference in expression of those symptoms is accounted for by genetic factors. What does that mean for an individual. Well it's difficult to extrapolate to individual because habitability is all about the group differences in the population. If you like. But i think what this is telling us is that while many people consider infections to be entirely random events in fact it's not entirely random. It is some extent influenced by the individual. But we know that many symptoms of viral illnesses actually occurred because of the host immune system reacting to the presence of that fars rather than the damage that the virus itself causes directly. Do you think this could go any way to explain why some people seem to be relatively mildly affected whereas other people are severely affected. We know that the people that end up with a major illness requiring hospitalization often developed high levels of inflammatory proteins in the blood and it may well be that what we're seeing in our study is reflecting the fact that somebody's genetic makeup impact. How their immune system response to viral infection and whether or not it was sponsored by making very high levels of those inflammatory markers. What's the value in understanding to. What extent the symptoms or risks are habitable. Firstly is a better understanding of how genetic variation influences people susceptibility to the disease so it might be possible if we develop for example a test which would advise people better about their risk of developing. I it's rather than just have a blanket rule about by age or by sex. Everybody has to stay indoors. You could make it more personalized at the second big value. I think this is being able to collect large volumes of data real time and about how this infection is spreading across the country francis williams there. The paper is what's called a preprinted which means that hasn't yet been evaluated by the academic peer review process. So take it with a pinch of salt. But it's still online available on med archive genetics. In general then seems to do at least something but what about. More specifically the gene for the crucial protein ace to does variation in that ace two gene. Make the coronavirus see you as a great big bullseye or even the opposite minded actually protect you. Medical geneticists william gibson at the university of british columbia has tried to find out using a big database of people's dna cold nomad. There's just over a hundred and forty one thousand people represented in the nomad database. And are you looking at this as two gene. What it's like for all of those people we did. Not every person had reliable data at every part of the gene. Fortunately the nomad database gives us data on the quality of each person's dna sequencing at each specific site. So we were then able to look at. The number of x chromosomes both males and females. That had reliable data at each of the sites that we were looking at okay. So you've got all your people you've got twice the number because all the women have two x chromosomes and then he whittled down to get older ones. They're definitely accurate. What differences did you find in this sort of final amount of data in the final analysis. We found that there are differences in the as protein and these differences seemed to be distributed differently among different human populations and predicted to be at different levels between males and females. Told me through this. What kind of variants can you get. You can get genetic variants that are predicted to stop the protein from being made. They either break the protein or they make protein. That's too small to do anything. You could also get variants that are predicted to change the shape of the protein but not break it so the pro team likely works pretty well and we call those mis sense variance. We're looking at a small number of the variants that are specifically predicted to bind the virus as opposed to all of the missing variance overall. How many of these types of variants did you actually end up. Finding between fourteen and fifteen cents variants in the as two protein that were predicted to bind the virus. Some of them were predicted to bind the virus more tightly and some of them were predicted to bind to the virus less tightly how commoner these differences overall uncommon but not unheard of among males. Ah of european descent around one. In one hundred and seventy males would be predicted to have one of these variants. It's about one at eighty females. Interestingly enough these variants were more frequent in individuals of ashkenazi jewish descent and they seem to be less frequent among latin americans. South asians people of african descent. People finished descent people of east asian descent. Really what does that mean. It's not entirely clear what it means. What we're looking into now is whether these variants affect susceptibility to disease and disease outcome. We're not sure about that yet. Did you find that. For example ashkenazi jewish population had more of the variants that bound the virus better or more of the variants bound. The virus worse. Or neither i confess. We haven't actually split out the numbers that way partly because we're not really sure how good our prediction software is in other words. Do the predictions that remake using the software actually correlates to actual binding of the protein. Or not if they did. Is there anything you can do about it. Theoretically if someone were found to have a high susceptibility variant then that would be very useful for them to know in terms of either self isolating or of course for their healthcare practitioners. They were found to then contract the virus that someone who would need quite carefully managed care william gibson from the university of british columbia evidence on this subject is coming in all the time from different methods and sources william gibson back there used computer modelling only and now a separate study from finland karolinska institute seems to show that coleman versions of the ace two gene. Don't actually affect much in the way of body traits like blood pressure at least for people who are already healthy. Here's serena son at one of the researchers way found that none of the common genetic variation in this gene are associated with a physiological variation between individuals. So there's no impact in regulating cholesterol level or your weight. Nothing at all no not among all the hundred and fifty different measurements that we consider. How did you figure this out. So we'll look to add more than thirty thousand volunteers. They all live in the north of the netherlands so yes genetic information of those individuals would look at this. Ach to gin and there are roughly one thousand variants in that genes are common means. There are present in at least one person every one hundred we compare the different variation to their corresponding level of blood pressure or glucose or cholesterol song. If you found no associations what's the most surprising to any that you thought might be there that you found nothing for well. The first question was is this shin involved. For example in trash trash or glucose we are seeing a lot of corona virus patients. They also have hypertension or diabetes. But in reality this was not so if there is any explanation for these probably comes from other genes or from some other factors so out of all these like a thousand different versions of this gene. That a few people have. It doesn't seem to affect any of your physical stuff at all. Yes wha what does this mean for people. This means that. For the coronavirus infection decision is probably not having any role on the macon symptoms. Worse intensify pretension and diabetes. You've been talking about common variants specifically. Does that mean that they're rare one that you didn't look at yes correct. There are rare variance in this change that we didn't look because we look at thirty thousand one tears but for rare volume so Are present in one every ten thousand. Where really didn't have enough numbers so we did not look at this the civic attain gory of genetic variation which my still play a role in infection and usually rare variance in the genome have a higher impact than common. By asian serena santa from the caroline get institute who has found no link between as to variation and body traits. So time will tell if ace to variation makes you more or less susceptible to corona virus. But at the moment they don't seem to be any major effects meanwhile our first guest joseph penning Is trying something different. East testing whether a fake. Decoy version of ace to contract the virus into avoiding ourselves altogether. You can hear more about that work in his interview with chris. Smith on our website try naked scientists dot com slash covid. That's it for nick genetics. Thanks for our guests. Joseph pending patricia. Gallagher hugh montgomery you and bernie francis. Williams william gibson and serena sana if you've got any questions or comments feel free to send an email to fill at naked scientists dot com or seek us out on social media. Although i'm not super good it using twitter. I'm trying to get better. And until next time. I've been phil sanson. Buy i m peter. Demand is joined the future positive. A podcast from x prize. Holy convenience a world brightest minds unpacked. Some of the most future topics listened to feature positive. Wherever that your podcasts. Radical future optimism for your brain.
"Hey all welcome back to the real life pharmacology podcast. I'm your host pharmacists. Eric christianson thank you so much for listening as always go checkout real life. Pharmacology dot com. Go snag your free. Thirty one page. Pdf on the top. Two hundred drugs. i share a lot of Clinical pearls Regards to things that are actually seen in clinical practice as well as things that tend to show up on Pharmacology board exams finals and things of that nature. So definitely go snagged out for free as a thank you from me for simply you know listening to the podcast and of course Sharing with others who may Find it interesting and a beneficial right. So i am going to talk about. Impact flows in today. Brand name of this medication is giants Its use has definitely Escalated over the last few years at least from my perspective. And what i've seen i. It is used in the management of diabetes primarily but that is Changing a little bit as well based upon some some more recent evidence over the last few years mechanistically so we're using this medication for diabetes. How does it lower blood sugar. That's what you really want to ask yourself and it's categorized as an sglt lt to so what the heck is that right so The sodium glucose co transporter two is found in the kidney and what sglt to does. Is it basically Helps the body reabsorb glucose back into the bloodstream from the kidney and renal tubular and things like that so by using this medication we're blocking that reabsorb of glucose back into the body and ultimately lowering blood sugars if it's not being reabsorbed now. The other thing to think about with that mechanism is where does that glucose go. Well it's gotta go out Through the urine. So that can you know lead to some potential adverse effects. Which of course all. I'll talk about a little bit but Yeah that that lowering of blood sugar out through the urine is how it has its blood glucose lowering effects dosing wise pretty straightforward You know in a big advantage of the. The medication is once daily dosing. And it's oral. You know it's not an injection or anything and you know getting patients to take medications two or three times a day. I can be a challenge for for many of them so once daily dosing is definitely. Nice i usually for diabetes ten milligrams and then we can bump up to twenty five milligrams if tolerated in usually we wait for weeks To decide whether we want to Bump that up now. I mentioned that you know. This medication was obviously developed for diabetes. But we've found or they found in studying the medication that there's additional benefits so patients At risk or diagnosed with sc cd we potentially have cardiovascular protective effects from this medications. That's a potential benefit heart. Failure patients can potentially reduce hospitalization in heart. Failure patients is well. And that's patience With or without diabetes. That's definitely an interesting finding as well. And then obviously in diabetes patients Have generally over time or the potential to have that declining a renal function and impecable flows in has potentially shown some benefits In that area as well okay so just mentioned kind of that that renal protective effect potentially I wanna stay focused on renal function because we recall from the mechanism that this works in the kidney. And that's how it lowers blood sugar k. So as you could imagine if that kidney is functioning poorly Blocking sglt to probably isn't going to have that great of an effect and indeed. That's what we see with the package insert so Egfr is less than forty five. We're probably not going to have a lot of benefit on the blood. Sugar side of things with this medication. however in the studies on the renal and cardiovascular benefits side we have Potentially seen the benefits still even in patients with poor of function renal function that way. So again if we're looking at it strictly for blood sugar lowering purposes Kind of similar to metformin But i guess. Different reasoning But full isn't probably won't work that well and bringing down a one c if we're using it In patients with poor renal function again canada. The cutoff mentioned As less than forty five. Mils per minute there. Let's kinda think about that mechanism of action a little bit and i think that helps with a side effects as well. So when there's an increase of glucose out through the urine there's a couple of things that can happen with that We can send fluid off with that. So patients may be at risk for a lower blood pressure and all that could potentially be a beneficial thing. I guess but particularly maybe in our elderly patients. We've gotta be a little bit careful about this if we drop blood pressure too much They're going get dizzy. And fall another aspect of running fluid out or increasing of fluid loss through the urine dehydration again elderly tend to be more prone for this risks. So that is something that we we need to think about. coupled with that water i mentioned initially glucose is going to go out to the aaron. Now bacteria like sugar may like glucose it helps them grow and prosper and with that So do Fungus fungal infections so genital urinary. Mary infections are definitely a risk with the use of this medication. urinary tract infections Maybe a little bit of risk there as well so those caused by bacteria so as a pharmacist. Something i look out for as i'm you know reviewing medications over time with the patient If i see an sglt two inhibitor I'm probably going to ask about recent fungal medications You know yeast infections If they've had frequent. ut is those are things. i'm just gonna kinda ask about and see if they've encountered any issues with that lately And then obviously make sure to reassess that risk benefit of the flows or other. Sglt two inhibitor. Other adverse effects Probably more on the the rare side of things or associations q. acidosis risk Necrotizing fasciitis risk Bone fracture Lower limb amputation. That's more of a controversial one but these are all things that You know. I am prepared to speak to Because when patients google search medication and they google search side effects You know these are probably gonna come up on google in some way shape or form and you definitely may be asked about these again. All those are extremely extremely rare. Definitely the most common things are you know. Increase in sugar to the urine so that infection risk potentially a drop in blood pressure maybe dehydration a little bit there as well monitoring parameters. Obviously you know diabetes. We're looking at a one c anyway. Blood sugar renal function. I've i've mentioned already Blood pressure lowering effect again. Mentioned that Keeping an eye out for any type of of antifungal z- That might be used to treat genital urinary infections. That's definitely something to keep tabs on us woes Ut is bacterial infections as well. And then you know we as patients are starting. This medication may be getting used to it. Maybe increasing doses You can't keep tabs on on monitoring for signs of a key to acidosis nausea vomiting fatigue shortness of breath. Pain that that type of thing all right. So let's see a quick break from our sponsor will wrap up with drug interactions. If you're in the market for pharmacists board certification study materials like ambulatory care medication. Therapy management pharmacotherapy geriatrics nap plex or the psychiatric pharmacist. Practice exam definitely go checkout med one. One dot com slash store in addition. If you're a nurse physician. Med student Pa nurse practitioner We got a bunch of of different resources The clinicians guide common drug drug interactions. That's been a popular one amongst a lot of people just a great review on some of the more common drug interactions and just some clinical guidance. Some things to think about When looking at those interactions so again that's on audible You can also find that on amazon so definitely go check out met at one one dot com slash store All the links to to everything that we have Can be found there all right. So let's finish up on. Drug interactions now impecable frozen. Nice in that we don't really deal with many of the cyp. Enzymes your three. Fours two sixes. It's generally not going to be a big issue with this medication. the most important in common drug interactions are typically with additive effects. So i think about diuretics. First and foremost if we're promoting Fluid loss with epochal flows. Enter that that can happen. We can increase that risk for dehydration and lower blood pressure and things like that Blood sugar lowering agents. I think this is common sense. Somebody who's on. Insulin safaniah ria. We've got a obviously be aware when we add. Sglt two inhibitor. Like anglo flows in. We're going to increase the risk of lowering blood sugar which is obviously what we're trying to do But if we lower it too much we can put that patient into a hypoglycemic episode which is certainly not good. Either and then blood pressure lowering medications. You know i i. I talked about the hypertensive. Type of fact We may need to back off on. You know m load a pain or you know a diuretic or ace inhibitor. If that blood pressure drops too low when we added drug Like impo flows in right. So i think that's going to wrap it up for today. If you enjoyed the podcast leave a rating review on itunes or wherever. You're listening if you want to track me down. You can find me. At linked in eric christianson farm d g. p. cps or med education. One on one at g dot com is the other way Probably most quickly Track me down. I'm going to sign off for today. Thank you guys so much for listening supporting the podcast And our sponsor mid one zero one dot com as well take care. Have a good rest of your day.
DECLARE-ing Another Victory for Dapagliflozin
"Well hello and welcome to the i former x podcast where we explore the evidence that informs aleatory care pharmacy practice. This is stuart hanes the host of the i former x podcast in about a year ago we reviewed and discussed the data h f study which evaluated the benefits of the sodium glucose transporter two or s. l. t. two inhibitor. Adaptable flows in in patients with reduced ejection fraction. Heart failure even in patients without diabetes. And if you are not familiar with a data h f study. I strongly encourage you to read the original study. And the i former x commentary of course. The data regarding the use of the sglt two inhibitors to prevent cardiovascular events and to treat heart failure or quite compelling but can they also slow the progression of renal complications in patients with chronic kidney disease. Well i was excited to see the much anticipated data. Ck d. study published in the new england journal of medicine a few weeks ago. And i knew just the right people. I wanted to review this study for i former expert. Dr jennifer clements dr stephanie. Nitro jennifer and stephanie are no strangers to i former x. They are members of the i former x oriel board and have been frequent contributors over the years. That clements is clinical pharmacy. Specialist in diabetes transitions at spartanburg regional health. Care system in spartanburg south carolina indoctrinate grow is associate professor of pharmacy practice at the university of connecticut. Stephanie jennifer it's great to welcome you back on the i former x podcast. Thanks for the invitation stewart. Thank you for having us back so before we get started per usual. I'd like to get your thoughts on a patient case. A i think that is not unlike. What many of our listeners encounter in their practices and want to imagine. You're seeing k t a sixty one year old african american female in the primary care clinic today. The patient has a longstanding history of hypertension type two diabetes dyslipidemia and. She's morbidly obese. She also has osteoarthritis internees. She recently was diagnosed with chronic kidney disease in her primary care physician referred her to you to make certain quote. We are doing everything we can to protect your kidneys. According to her medical record katie has been prescribed lysenko pearl twenty milligrams twice daily resume astatine twenty milligrams daily metformin thousand twice daily and insulin Twenty it's bedtime and in addition over the counter. She takes aspirin eighty-one milligrams and naproxen sodium for arthritis pain. She currently weighs two hundred sixty four pounds of bmi forty point. Nine blood pressure today when thirty. Eight over seventy six and her most recent labs yesterday include a fasting glucose of eighty seven and a one c of six point seven percent. Sam crat nin of one point seven milligrams per deciliter and an estimated. Gfr of thirty seven seven potassium of four point seven. Ldl cholesterol fifty six hdl cholesterol. Forty eight triglycerides of one. Oh seven in addition. The patient had a timed urine protein tests performed and the album into creating ratio was three hundred fifty. So stephanie. Before we talk about the study that you reviewed in your i former x commentary. I'm wondering what's going through your mind in this case What are some of the key questions you ask this patient during the encounter and what additional apps if any might you want to obtain and is there any additional treatment options. Who'd be considering at this point to stewart. I would agree that. Kt really does mirror. Many of the patients that are encountered in clinical practice. And i think this case excites me because there are many opportunities for the pharmacists to intervene here and if we're going to utilize the ppc process. I would. I want to collect additional information from kt. for example. Does she smoke. How often is she using her naproxen. And at what dose. I'd also want to collect possible. Her a. one c. Blood pressure and serum craton and trends and we know how important it is to not evaluate labs in isolation so seeing her patterns would provide additional insight or care planning. It's really important to know. Kt's renal function is stable or if it's consistently fluctuating as this information would help our assessment of how we can manage. Her current metformin does since her egfr is approaching the cutoff for continue at minimum. She needed both reduction. And also story the for thinking about the potential use of sglt two inhibitors for katie ensuring that arena function is stable. What help us feel more comfortable recommending. Its use since we know that there have been reports of a two kidney injury and volume depletion upon initiation of these drugs. I don't want wanna collect a bit more information about her. Lifestyle habits including a general understanding of her dietary choices notably her sodium and protein intake and see if she is engaging in any physical activity given her need when the patient and osteoarthritis. I'd also wanna know her insurance provider and learn if she's burdened by any of the cost of her current medications in case we want to add anything in the future cd management perspective. I'm really happy to see that. She's on than a pro because she has albumin. Urea but further management is needed to help delay rano progression and when we think of good. Ck d. management. We need to consider it. I optimizing her glycemic control which looks really good for. Kt at this point and also painting and maintaining a blood pressure will have less than one thirty over eighty if we can do that safely and again. Kt is really close to the school but there is some room for improvement. Hey should be counseled to avoid smoking if she does and avoid toxic drugs like her naproxen for example and finally since chronic kidney disease and cardiovascular disease are closely linked. I'm happy to see her. Lipid panel is excellent and now she's on a high intensity. Staten but at this point stewart i would like likely recommend a reevaluation and discontinuation of her aspirin based on the findings of the ascend study container. Aspirin appears to be used for primary prevention. So jennifer in the commentary wrote for i former ex. You reviewed the study entitled deputy flows in patients with chronic kidney disease which was published in the new england journal of medicine in late september. Two thousand and twenty. And while i think everyone in our audiences should read the paper for themselves. We provide a link to the paper on her. I former x website. But can you give us a brief synopsis of the study methods and results. The data stay k. D. trial was an international double blind placebo. Controlled trial conducted to assess the efficacy and safety of day Ten milligrams orly once-daily among participants with chronic kidney disease with or without type two diabetes to elaborate on chronic kidney disease participants had macro albumen urea and stage two through four kidney disease following one. To one random association each group received stable doses of either an ace inhibitor or arb for at least four weeks. The primary outcome was composite endpoint of a time to event analysis and included declined of gfr fifty percent in stage kidney disease and reno or cardiovascular death. There was a secondary composite outcome. In this included the primary outcome with cardiovascular death or hospitalization for heart failure when looking at baseline characteristics both groups were similar in terms of age females race. Gfr as far as cardiovascular disease and standard of care the gfr main was about forty three and a majority of these participants could be classified as stage three. B in addition thirty seven percent of these participants had cardiovascular disease and ninety eight percent. Did receive the ace inhibitor. Or a are now after three years dabba cliff flows and reduce the primary composite outcome by thirty nine percent with a benefit. Sharon individual outcomes of decline jeff for fifty percent in stage kidney disease and long-term dialysis as saying other trials with dabba gla flows in. There was a reduction of nine percent in the composite of cardiovascular endpoint of cardiovascular death or hospitalization for heart failure now discontinuation was low and similar between both groups. But it's important to look at some safety outcomes volume. Depletion was statistically higher with dabba in than placebo even though there was no statistically significant finding placebo group did have a higher percentage of participants experiencing a reno related adverse event than compared to flows in and lastly there was no cases of you. Glycemic kato acidosis among those. That received Show stephanie. Every study has strengths weaknesses and potential limitations. I think many clinicians would consider this study along with the data. Hf study a landmark trial. Do you agree. Is this a landmark. Study do you have any concerns about the design and conduct of the study and can the results of this study be generalized to most patients with chronic kidney disease including those who do not have diabetes or do you think epochal flows in should only be used in selected groups of patients. I would agree with you stewart. I think this is indeed a landmark study. You know for the first time in about twenty years. We have a drug and and really a whole drug class. Potentially that can be used in a patient population where there is currently a large unmet. Need not only was the efficacy of fluids and impressive but it was proven to be safe as well and when we look specifically at the patients with diabetes. In this study there were virtually no cases of hypoglycaemia or diabetic acidosis which has historically limited the use of sglt two inhibitors and those with diabetes. I'm the fact that these drugs have benefit in earlier stages of katie like stage to further adds to their potential role and intrigue in my opinion. So yes. I definitely think that this study has the potential to change practice regarding your questions about the study design itself. I believe it was strong. And its methodology and included a diverse group of patients with various stages of katie from mild to more advanced cases but i would have liked to see more black patients in robes since we know that katie does progress to end stage. Renal disease more quickly in this patient population also. Since the was halted after three years there is some concern that the benefits may have been over estimated while some of the secondary outcome may have been underpowered and about a third of the patients enrolled in dabboussy. Katie did not have diabetes. So i definitely think the findings can be generalized to those with and without diabetes. But we don't know. Stewart is if these results would be reproducible in patients not already on pre existing razz therapy or those without macro albumin urea. So we'll have to wait and see how that plays out jennifer. Let's go back to our case. Recall that katy has been recently diagnosed with c k. D do you think that flows would be a good option in this case and if so given that the patients glycemic control is already pretty good. What changes in her anti-diabetic regimen would you make. And lastly do you think. Employee flows in or chemical flows in would be reasonable alternatives if adapted flows was not available on the patient's health plan formularies. These are all great questions. So i yes i think. Kt is a candidate for Flows in ten milligrams orally once daily. If we assume that this could be started. I would advise the patient to take this medication in the morning and i would review expected adverse events along with preventative measures before she leaves the clinic. I would also want to schedule the patient for appropriate follow-up on renal function and about one month as it will be important to monitor her renal function due to the expected initial dip with. Sglt two inhibitor. It will also be important to monitor the patient's blood pressure and weight along with her general tolerance with dapple flows in. So i mentioned this because it is important. I think to have an appropriate protocol for monitoring with the sglt two inhibitors to answer some additional questions. In terms of medications for diabetes metformin needs to be adjusted to five hundred milligrams orally twice daily due to jeer. Far i would not make any further changes within slim gorging at this time until i can determine. The trend with self monitored glucose readings now to answer your last question if data close in is not covered. By the patient's insurance i think canada flows in a hundred milligrams. Orly once-daily could be another reason based on evidence from the creatives trump. Trawl chemical applause. In reduce the risk of in stage renal disease doubling of serb croat ning and renal cardiovascular death as a composite endpoint by thirty percent among those with type two diabetes and chronic kidney disease. I would suspect that flows zone. We'll have positive outcomes win. The impact. Kidney trouble is completed a reported in the upcoming years however it may be challenging to convince providers to write a prescription for impecable flows if the full report of the trials not available compared to the published information on the created trou- with canada closing D. with dabba guus larson. Mo- jennifer stephanie. I wanna thank you both for joining me today. To discuss the treatment of chronic kidney disease and the potential role of the sglt two inhibitors to limit the progression of kidney disease. In patients with diabetes and patients who don't have diabetes. It's clear your comments that you believe that the sglt two inhibitors on are very important. Class of medications with several benefits. Not only can. They reduce the risk of cardiovascular events the development of heart failure and reduce the risk of heart failure exacerbate tensions that they also appeared to have a very significant in terms of reno outcomes. Well tell us what you think should an sglt two inhibitor. Become a routine. Part of practice is considered in most if not all patients as long as there's no contraindications who have chronic kidney disease regardless of whether they have diabetes or not and if so when should it be at it well only i former ex members can leave comments and the interactive features on the site. You can become a member of i former x. It's free so sign up today by the way. If you are a board certified ambulatory care pharmacist and want to earn recertification and continuing education. Credit to this program you can. We've partnered with the american pharmacists association to offer. I former x content as part of their board recertification program. Click on the link posted on the bottom of the i former commentary on our website to learn more lastly. I want to extend a very special acknowledgment to mary. Beth seople eric gunderson and amanda applegate for putting together and maintaining the covid nineteen resource. Page on the i former x website. This has been a rapidly changing area of practice and mary bath. Eric and amanda have made regular updates to the webpage of the past year to keep us all informed about the latest evidence. So i former xs made possible by the active engagement of pharmacists from around the globe. So thank you to mary beth. Eric amanda for being active and engaged. I former members until next time. This is stuart hanes editor in chief. I former x signing off.
#C55 (caption to capuche)
"Hello were nerds. Welcome to the dictionary regarding my song. In the last episode i went ahead and listen to a little bit of it so i could be reminded of how it went. And it's something like this. Let me over the cat It doesn't actually say captain he says captain. But there's no am in captain. So why is there an m. in there anyway february third is today it is in the. Us it is world read aloud. Day will look at that. I am celebrating by reading aloud. This book to you. Every day is world. Read aloud day for me And then it is also national signing day. Bhosle i'm clicking on the link because this could mean so many different things Let's see it is Marks the start of the college football signing season so it's college people signing two different college sports teams and then worldwide in mozambique. You don't hear a lot about mozambique not ni- don't It is mozambican. heroes day. So yes let's go celebrate some mozambican heroes okay. The first word is caption c. a. p. t. i. o. n. noun from circa sixteen seventy one the part of a legal document that shows where when and by what authority it was taken found or executed to a the heading especially of an article or document and a synonym is title to be the explanatory comment or designation accompanying a pictorial illustration. I love the cat do you have you ever looked at the the new. Is it the new york times cross. No oh boy the new york times cartoon caption contest that was a mouthful they They they post some videos of celebrities. Comedians actors whoever up trying to play this game and they often come up with some pretty good stuff. I am no good at coming up with captions for those. But i do very much enjoy hearing what people got to say. Okay so that was that. And now we have to see a motion picture subtitle. We have been basically watching everything with the captions when we can because even though we can hear it if there if it's in like british or irish sometimes their accents can be pretty heavy so that definitely helps But also you you actually get a lot more out of it than you probably would think you would You you might miss a word. That is maybe semi important Sometimes there's words in the background may be on the radio or tv and that can be sometimes kind of important. So i definitely recommend watching things with captions on caption. Lists is an adjective. I guess you can't really say caption full because if it's captioned that already means that so there are no captions on this thing. It is captioned lists so this is probably short for certificate of caption Which then in parentheses it says taking and then comma seizure certificate of caption okay. That's probably more about the number. One definition moving onto the second form of caption transitive verb from eighteen. Forty eight to furnish with a caption. Yup next is captured. Shas c. a. p. t. i. o. u. s. adjective from the fourteenth century one marked by often ill natured inclination to stress faults and raise objections as in kansas critics marked by an often ill natured inclination to stress. Faults yes critics are definitely doing that number. Two calculated to confuse entrap or entangle in argument as in a question So another synonym is the word critical. Yes you've been very critical when you're captured. Lee is an adverb. Capture snus is a noun and Let's see this is from the latin cup. Tio which means deception or verbal quibble from caparo which means to take and there's more at the word heave h. e. v. e. next we have captivate verb from circa fifteen fifty five. Looks like it's only transitive. One is archaic synonyms are seas and capture. I have captivated you with my with my words i don't know Number two to influence and dominate by some special charm art or trait and with an irresistible appeal Then another synonym is the word attract. Okay next we have oh. Captivation is a noun and captain later a noun a captive ater is using their captivation skills to captivate you. Next we have captive they are captured. They are captivating the captive This is an adjective from the fourteenth century. One a taken and held as or as if a prisoner of war one b. one kept within bounds. Synonym is confined one. Be two of or relating to captive animals as in captive breeding them. That is the breeding that is happening when they are captive but they if they are in the wild it is just regular braiding to held under control of another but having the appearance of independence especially owned or controlled by another concern and operated for its needs rather than for an open market as in a captive mine. Like is that the mind that you go digging for coal and diamonds and stuff number. Three being such involuntarily bean such involuntarily because of a situation that makes free choice or departure difficult as in a captive audience. Wow i don't know some. Sometimes these definitions just seem unnecessarily extravagant. Something i'm sure it's not. My brain is a a little slow. I hope that you are a captive audience listening to me. Teach you these things and then just captive is a noun. And i don't think there's any etymology say to you so we are going to move onto. Captivity noun from the fourteenth century won the state of being captive as in some birds thrive in captivity. Why why is that is that. Because when they're in the wild there's a higher chance that they would get eaten by something or get some illness from being outside and that's why they thrive. They have a longer lifespan. you know. I think depending on the species sometimes. They're good in captivity even though they probably shouldn't be there they live longer. They get to get health insurance. They get medical care but yeah sometimes sometimes they don't sometimes they don't live as long. Yeah that's that's a that's a whole thing okay. Number two is obsolete it is a group of captives a captivity is a group of captives people who have been captivated by somebody in some way. Okay next we have. Capped apprel c. A. p. t. o. p. r. i. l. capped apprel noun from nine hundred. Seventy eight one. No no one. An anti hypertensive drug c-9 h fifteen n three s. That is an ace. Inhibitor ace is all caps a c- And this is from moore captain plus o plus paroling plus ill Yes so they just combine a bunch of things. That mean something to somebody but not to me okay. Next we have captor c. a. p. t. o. r. It's like raptor you. I don't know. I have this envisioned of my in my head about a raptor being a captor. Ooh maybe there's a song raptor captor. I wanna be your raptor a baby. I wanna be your wrapped. I don't know what that means. But it's a song with two words that rhyme and it's a raptor. That captor captivates people wrapped debate. Now this is going on way too long. This is a noun from circa sixteen. Eighty eight one that has captured a person or thing. Yes raptors can definitely be a captor okay next. We have the first form of the word capture so a captor captures people by captivating them and then they are captives This is a noun from circa fifteen forty two one an act or instance of capturing as one a an act of catching winning or gaining control by force stratagem or guile gotta use all those things one be a move in a board game as chess or checkers. That gains an opponent's piece you have. You have captured my rook one. See the absorption by an atom nucleus or particle of a subatomic particle that often results in subsequent emission of radiation or envision. Yes that's that's the thing that happens sometime. Auburn's subsequent admission If you don't know when you when you release a particle or something That is radiation. That's where that's how radiation happens. I don't know that's that's all. I'm taken from that. One d the act of recording in a permanent file as in data capture to one that has been taken as a prize ship. I have taken this ship and it is very prized. So it is mike capture. The next is the second form of capture. It is a verb from fifteen seventy four. We are starting with transitive. And i think yes. It must only be transitive. Because i don't think there would be an in transitive way to use this word capture That i can think of so number. One a. to take captive also to gain control of especially by force as in capture a city one be to gain or win especially through effort as in captured sixty percent of the vote. I hope that's enough for you to win. To a to emphasize represent or preserve as a scene mood or quality. Oh wait there's more to emphasize represent or preserve in a more or less permanent form as in at any such moment as a photograph might capture at any such moment as a photograph might capture. That is a quote from c e montague people back in the day spoke and wrote very differently than we do now. I would never think to write something like that. I'm also just not a good writer in general but anyway another example is a seen a mood or example. That is what can be captured in a more or less permanent form. Next is to be to record in a permanent file as in a computer three to captivate and hold the interest of that is why my episodes are fairly short. Because i want to be captured and then you can move onto something else nearby soon soon. -ly sudenly yes. Within fifteen minutes you should be able to go and do something else. Okay number four to take. According to the rules of the game five to bring about the capture of subatomic particle is an example. And then a synonym is. The word catch. Next is capture the flag three words noun from circa nineteen twenty five a game in which captures not a game in which players on each of two teams seek to capture the other team's flag and return it to their side without being captured and imprisoned. I've i've played this a few times. I've never felt very good at it. I was very stressed out about how to do this. Because i always knew that there were people better than me. So is a very stressful time. Next and last word for this episode is bush or coach c. a. p. u. c. h. e. capoche noun from circa sixteen hundred It just means a hood. that's the synonym hood. Especially the cowl of a capuchin friar so we are actually going to learn about capuchin in the next episode. But maybe it's a location or something and there are fryers and they wear a cowl or a hood and that is called a push. This is from the italian capuccio which is from kapa which means cloak and that is good for that so we had caption. Oh you know what. I don't think i actually picked a word of the episode in the last episode. Did i know. I don't think i did Well let's see let's look at those real quick will do to words of the episode for this one Maybe i just wanna pick capstone as the word of the episode. Because i'm curious about where that came from okay. So in today's episode we had caption captures captivate captive captivity. Capped apprel captor capture capture the flag and bush. Well maybe i shall pick captivate as the word of the episode. Because i wou i don't know why i don't know i just picked it. Okay thank you very much for listening. And until next time this is spencer dispensing information goodbye.