Dr. Joel Diamant reviews important updates from literature and clinical trial studies as well as updated USPSTF recommendations for practice.
Back to Symposium Page » Yeah, Good morning. Welcome to the 37th Primary Care Conference in San Diego. We're going to begin by going over a conference agenda and materials. The conference agenda and course materials can be found in the scripts, Health, CMI, Conference app and on the Livestream event page. The APP is available free of charge for all participants and will be continuously updated during and after the course. Today's program is also being recorded and will be available to assess approximately one month after the event. For Livestream details, all participants must be muted during the lectures to avoid bracket background noise and for the best dreaming results, be sure to close all other Web pages and APS on your computer that may slow down your Internet connection. Please submit questions using the Ask a question button on the live feed and they will be shared with the faculty and be sure to participate in the polls during the lectures. The exhibit hall. Please be sure to visit the virtual exhibits during the break time, and you will be able to network with colleagues using the Attendee Discussion Board in the mobile conference App Connect to connect with colleagues, faculty and exhibitors. Contact information for everyone could be found in the attendee tab CMI certificates. To receive your CMI certificate, you must complete the online course evaluation and be sure to claim your credits. Instructions for taking the course evaluation will be emailed to you at the conclusion of the course. Upon completion of the survey, you will be redirected to your CMI certificate, which you will need to print and keep for your records. The survey will be available for four weeks after the conference. Thank you for attending and we hope to see you next year in San Diego. I would like to go ahead and introduce our first speaker, Dr Joel Diamont, as an internal medicine specialist, Dr D. M. A. Diagnosis and treats all types of diseases and medical conditions in adults with expertise in health promotion. In addition to his clinical practice, he has research focus on the impact of various interventions on the quality of medical education and genomic implications of staff. A cockle infection. He is also a fellow of the American College of Physicians. He believes the best patient care occurs in a setting that emphasizes clinical education for the patient as well as educating young physicians in aspects of disease, math, vacations, manifestations, prevention strategies and the most effective treatments. He serves as the executive vice president of Scripts Clinic Medical Group, assisting the organization as a whole in providing the highest quality medical education and care to our community. Doctor Demon also leads a team of scripts, clinic staff, physicians and residents in regularly staffing ST Leo's Mission Medical Clinic and the state visit to Paul Medical clinics. Welcome, Dr Dama. Good morning, everyone. It's a pleasure to be with you here at the summer conference in primary care, I have the privilege of providing an update in general internal medicine, reviewing some of the landmark papers over the last year and how they could or should impact our primary care general medicine, family medicine practices. As we go forward, I have no disclosures to share, and so we'll begin most of the papers with a case scenario. And so I'm going to run through the case and ask you to select what you believe is the best answer to this question. The paper that we then discuss will hopefully provide insights into what might be the best answer to the question. So here we have a 24 year old woman who is transferring her care to you. She reports that she has mild asthma with use of albuterol 2 to 3 times per week. She has 2 to 3 nocturnal awakenings per month and has had one exacerbation last year requiring systemic corticosteroids. She's happy with her level of control and states that she's afraid of the long term effects of inhaled corticosteroids and also can't afford them. The best recommendation for her is which of the following a continue as needed albuterol and provide Orel Prednisone for her next exacerbation. Be continuous albuterol as needed. And ADB You destiny died as maintenance. Two puffs twice daily. See stop albuterol and recommend the use of Butte. Destiny died for motor all as needed instead of as needed. Albuterol or d. Recommend a long acting beta agonist such as Salma drawl or for Motorola as a primary controller therapy and finally e recommend continuing albuterol as needed. But ADB, you destiny it and from motor all twice daily as a controller or maintenance drug. Once you take a moment to answer that question, and I believe the answer can be found in two papers that came out a year apart. The first one is entitled, Inhaled Combined You Destiny for Motor all as Needed and mild Asthma. This was published in May of 2018. The follow of paper a year later in May of 2019 was entitled Controlled Trial of You. Destiny died from motor, all as needed for mild asthma, so these are also referred to as the Sigma trials. That is our first paper in 2018, and the second paper is referred to as the start trial in 2019. In terms of a background for these papers, mild, persistent asthma is defined as asthma symptoms greater than two days per week or nighttime awakenings greater than twice per month. Short acting beta agonists use twice per week, or asthma that produces mild interference with regular activities. It's a common disease, with over 25 million Americans suffering from asthma, and approximately two thirds of them have this mild, persistent asthma. That standard recommended therapy for such individuals has been to use a low dose inhaled corticosteroid with, as needed short acting beta agonist for rescue therapy. Unfortunately, daily inhaled corticosteroid compliance is thought to be quite poor, and most patients actually only use their short acting beta agonists as rescue agents. Patients with asthma frequently wind up in the emergency department, and, in fact, 30 to 40% of emergency room visits for asthma are in this group of patients. The mild asthmatics. Yeah, forgive me. My screen seems to be stuck. Here we go. So the background for the start Tri ALS, the main trial that was published this year, is found in the Sigma trial. The Sigma trial one year ago demonstrated a revolution in approach to mild asthma, and here the investigators found that the use of an inhaled corticosteroid and a special long acting beta agonist from motor all as rescue therapy alone with no use of maintenance therapy was actually superior to the use of maintenance therapy on a daily basis. There were a number of criticisms of the Sigma trial, arguing that it may not really parallel riel world experience, and therefore the start trial, published into in May of 19, was undertaken. This was a 52 week randomized open label trial and mild asthmatics. There are three treatment arms in the trial, one arm is an albuterol rescue Onley arm. The second arm is a daily Buddhist Sinead maintenance program with as needed albuterol for exacerbations, and the third arm is Buddhist, emitted from motor, all as a rescue agent alone. The primary endpoint the investigators were looking for was the annual ized rate of exacerbation, which is defined as urgent medicine, consultation er or urgent care. Any systemic corticosteroid use or very high use of inhalers meaning greater than 16 inhalations of albuterol in a day or eight view destiny for motor all inhalations in a day. The secondary endpoint was defined as severe exacerbations, and that is determined as systemic glucose glucocorticoids for at least three days or hospitalization for the asthma. And here are the findings of the study. There are three sets of findings. We're going to focus on the first one for a moment, and this is the number of times exacerbation criteria were met. And we're going to compare the albuterol group to the view Destiny did maintenance group to the rescue you Destiny died from motor all group, and what we can see is the albuterol group obviously did not fare as well in terms of number of exacerbations. But if we look at BJU Destiny need maintenance vs view. Destiny died from motor all rescue. We see that if we look at use of systemic corticosteroids, that be destiny group is better. If we look at urgent medical care visits, we see that the rescue arm is better on Lee would in use of a number of inhalations in a day was the maintenance group better? If we look at the annual ized exacerbation rate, we see that the Buddhist Sinead maintenance arm here is equivalent to the Buddhist Sinead for motor all arm, which is depicted in the blue color. And if we look at the severe exacerbations in this arm, what we find is that the view destiny for Motor All Rescue group is the group that clearly does the best in terms of severe exacerbations, fairly startling findings. So we're gonna try to go to the next page now. This is what is referred to as the Gina Scale or the Global Initiative for asthma treatment. It's the step up scale. That address is how we should treat asthma in a step wise fashion. And this is the new 2019 version of this, and it is dramatically changed from prior versions based on the Sigma and Stark trial. And what we can see is Step one is no longer a short acting beta agonist, but is really now low dose inhaled, corticosteroid plus for motor. All we can see also in step to it, is the same thing as needed. Low dose, inhaled corticosteroid plus for motor all or daily maintenance therapy. We also see is the preferred reliever. Agent is no longer a short acting beta agonist alone, but rather the inhaled corticosteroid plus for motor, all as the preferred way to approach acute exacerbations or acute symptoms episodes. So the conclusions of these trials are that mild, persistent asthma is common. Patients typically prefer a maintenance program instead of a maintenance because we prefer a rescue program instead of a maintenance program and low dose inhaled corticosteroid plus for motor. All is now the preferred rescue agent. The reason why, for motor all is the preferred rescue agent is unlike other long acting beta agonists, it has both short acting and long acting beneficial properties. So this is what we should now be thinking about as our rescue agent, and we should be thinking about eliminating maintenance therapy in our patients who have mild, persistent asthma. This is not validated his approach for arm or severe asthmatics. Let's go on to another case scenario. Here we have a 58 year old man with COPD who presents with two days of increasing shortness of breath cough and a significant increase in thick yellow sputum. His examination demonstrates an oxygen saturation of 93% on room mayor. His temperature is 99 degrees. Blood pressure 1 35/85 his lungs demonstrates scattered rank I minimal wheezing as well as prolonged exploration. The chest radiograph demonstrates no infiltrate. He had a negative cove in test yesterday. You elect to begin corticosteroids and increases bronchodilator regimen in selecting antibiotic therapy. For this patient with COPD exacerbation, what would be the next best step begins to throw Meyssan 500 on day one, followed by 250 for an additional four days. Be withhold antibiotics until fever or other clinical deterioration occurs. See obtained a CRP level de begin ciprofloxacin, 500 mg for seven days or obtain a sputum culture. Take a moment to think about the best approach to this patient. Yeah, sure, but yeah. Okay. I think an interesting answer to this question comes out in a July 2019 paper in the New England Journal entitled C Reactive Protein Testing to Guide Antibiotic Prescribing for COPD exacerbations the background for this paper and what is entitled the pace trial is that COPD is common with greater than 6% of Americans having COPD. And in fact, one half of C. O. B dears will have an exacerbation yearly, and the large majority of those will receive both corticosteroids and antibiotics. In fact, 80% of exacerbations are treated with antibiotics. Antibiotic utilization is typically based on a combination of symptoms of increased sputum production. Increased spewed Imperialists as well as Despina and most physicians will add antibiotic therapy if two of these three criteria are present. Yeah, but a legitimate question for us is what if we could more reliably predict bacterial infections as COPD precipitate er's and then target antibiotic therapy for just that population? Well, that was the hope of the investigators in this pace trial. Their hypothesis was that if they used a C AARP level during an acute exacerbation, they could safely substantially reduce antibiotic prescriptions. Mm. Okay, So the set up of this trial is that this is a multi center, randomized, open label controlled trial conducted from 2000 and 15 to 2000 and 17 in 18 primary care practices in the United Kingdom, enrolled were 653 patients having COPD exacerbations going to their primary care physician. There is a one toe one assignment in the trial where one arm receives usual care and the other arm receives usual care from the physician. But the physician is made aware of a CRP level and may use that to help guide his or her antibiotic decisions. Yeah, patients have telephonic followed as well as office followed during and after their exacerbation. The physicians were provided with general guidelines about how to use the C AARP, and they were informed that if the CRP level was below 20 benefit from antibiotics would be unlikely. If it was between 20 and 40 there might be benefit to antibiotics, and if it was greater than 40 it was likely that antibiotic prescription would be beneficial. The physicians were instructed to evaluate the use of antibiotics globally but include the carp in their thought process if they were given the CRP level. Okay, The primary outcome in the trial was the reported use of antibiotics by patients and COPD related health status Questionnaire. Yeah, and some of the results that were found is if you looked at all of the 650 patients with COPD exacerbations, 76% of them had a low CRP level, 12% had an intermediate CRP level and 12% had a high CRP level. In terms of the Anthonys and Criteria, this is the criteria of COPD exacerbation one criteria being increased sputum to being increased Piri Alliance and three being increased Despina In these exacerbations, 24% of the patients had only one criteria, 30% met two and 45% met three criteria. And here are the findings which are kind of interesting to look at. And what we're gonna look at on the vertical axis is the use of antibiotics by the physician. How many times are antibiotics, what proportion of patients receiving antibiotic prescription and then on the horizontal axis. We see the number of Anthony's in criteria that were present and we see that if Onley one criteria is present, the blue bars are the usual care. The red bars or red brown bars are sharp guided care, and we see that these two lines, in essence, overlap almost entirely. So if you had only one criteria present, the physicians did not find that the use of a sharp level actually changed their prescribing behavior. But if to antonius and criteria are present, we see that if you were given the CRP level on Lee 45% of the time which the physician adding an antibiotic. But if the tarp was not given, we find that the physician was using antibiotics 85% of the time. If three criteria were present and you received a CRP level, antibiotics were dispensed a little over 60% of the time. But if no CRP is available, antibiotics are used at 95% of the time. So the conclusions from this trial was that the Sea AARP as a point of care test resulted in a 22% reduction in antibiotics At the initial visit with the physician. In terms of at four weeks, there is a 20% drop in antibiotic use. Basically, if our patients have Onley, one exacerbation criteria present The AARP level was not particularly helpful to the physicians. The greatest impact is when two criteria are present and we see that there is almost a cut in half in antibiotic use, 85% down to 45%. And there's a moderate impact when three criteria are present. There was no difference in COPD questionnaire to the patients. No difference in adverse events, no difference in hospitalizations. So conclusion here is that the use of a sharp level at the time of visit or on the day of visit could substantially reduce our prescription of antibiotics safely to COPD exacerbation patients. Let's try another case scenario. Here we have a 62 year old woman who is presenting for cardiovascular disease risk reduction. She had an interior wall m. I two years ago and had a PTC at that time. She's been symptom free ever since her myocardial infarction. Her medications are atorvastatin. 40 mg nightly lie since April, 20 mg daily and aspirin, 81 mg daily. Her blood pressure is 120 over 17. Her lipid panel demonstrates a total cholesterol, 150 mg per deciliter. Her HDL is 50 and her LDL is 62. Triglycerides, 175. She seeks your advice about fish oil and reducing her risk of cardiovascular death. Our recommendation to her should be which of the following a recommend over the counter fish oil tablets 1 g daily. Be recommend Nyhus and 2 g daily instead of fish oil. See advised that she consume more fresh fish but not oil tablets, because oil has not been found to reduce cardiovascular events. De recommend prescription fish oil 2 g twice daily. Brand prescription is vest Sepe or e. Recommend garlic, red yeast, rice, astrologists and Bergama at instead of fish oil to reduce her cardiac death risk. So think of this patient with known coronary disease, the lipid panel that we have. Can we use one of these interventions to reduce her risk of death? But yeah, and the answer, I think, is found in two papers that came out in the New England Journal simultaneously in January of 2000 and 19. The first one is entitled marine and three fatty acids and the prevention of cardiovascular disease and cancer. It also goes by the name of the vital trial. The second trial is encountered. Cardiovascular Risk Reduction with Picasso Print Ethel for hyper triglyceride e mia. This is also known as the Reduce it Trial. The background for these papers are the cardiovascular disease. As we know, the risk of this persists despite excellent lipid control or cholesterol control, and our patients with known coronary disease. Numerous observational studies, observational being the key have demonstrated a primary prevention benefit. Patients who haven't had an m i yet in the use of fish oil tablets. Secondary prevention trials, however, in patients with known coronary disease, have demonstrated highly inconsistent results regarding the benefit of using fish oil. There have been no large primary prevention randomized trials looking at fish oil, and so the first one we're going to talk about is this vital trial. And this is the use of vitamin D 2000 international units daily as well as omega three fatty acids, 1 g daily. This is a typical over the counter fish oil tablet entitled The Vital Trial. There are almost 26,000 patients enrolled that men are over 50 and the women are over the age of 55 for enrollment. These people do not have known cardiac events, however, 50% of them had hypertension and 30% of them had were on lipid lowering drugs, suggesting that this was an at risk population. The second trial is a little bit different. They're using a purified fish oil entitled a Casa Pent Ethel, and it's used at a moderately high dose of 2 g twice daily. This is the typical prescription dose, and it is called the Reduce a trial. Hear about 8200 patients are enrolled who have established or known cardiovascular disease. Or they may have diabetes plus multiple risk factors for coronary diseases. And all of them have hyper triglyceride anemia, triglyceride level fasting of at least 150 mg per desolate er. So the findings from the tri ALS are depicted here. Try to go back one if I can. Here we go. And so this is the vital trial findings. This is the omega three fatty acid over the counter tablet in a relatively high risk primary care prevention population. And if we look at the vertical axis, we're looking a cumulative incidence of major cardiovascular events. The horizontal axis is years since enrollment in the trial, and what we see is that the two arms, the black solid line, is the placebo arm, and the dotted line is three fish oil arm. These two arms are essentially entirely superimposed. There was no cardiovascular event benefit from taking fish oil in the primary care prevention capacity. Looking at major cardiovascular events, same finding in essence and looking for cancer. There was no benefit to the use of the fish oil and the vitamin D and cancer prevention. In terms of this not graphically but numerically in chart form. What we're going to see here is something interesting in terms of total myocardial infarction. Ziff, we look at the placebo group. There are 200 m eyes, but the Fish oil group there are 145 m eyes. This is a 28% risk reduction myocardial infarction. In this group, we can see that it's statistically significant because this result range does not cross the one line. But if we look at strokes, there is no meaningful difference. We seethe. Hazard ratio is 1.4 If we look at death from cardiovascular cause. There is no difference than hazard ratios 0.96 And if we looked at the combined cardiovascular events, we see that there is no meaningful difference. But there was a reduction that is modest in terms of myocardial infarction. So the conclusions from the vital trial was that omega three fatty acid supplementation does not result in a meaningful cardiovascular composite benefit. There's no stroke benefit, no death benefit. There was no invasive cancer benefit. This 28% risk reduction in myocardial infarction translates into a 0.443 absolute risk reduction in M I. For a number needed to treat of 233 with 5.3 years of fish oil therapy. So a relatively high number needed to treat in order to find gain. So conclusion being there is minimal apparent benefit from fish oil, uh, capsules in the primary prevention of cardiovascular events. Do you guys not hear me or see me? I just received a note from Carlin saying they don't hear me. I don't know how to get feedback here when you're dark. Hey, Scott, have we lost me? I can hear you. You come up with something and you're reducing slight. I can hear you. Okay. Thank you. So I want to go back to the slide. Julia, how do I get back to that? Yeah. Okay. Thank you, everyone. Sorry, I got a message that I was lost. I get that message from my family frequently. All right. Now, if we turn to the reduce it trialing this is the secondary prevention trial patients who have known court cardiac disease and there, given the high dose of fish oil tablets. Yeah, Let's see if I can get this to come up. So here we're gonna look at our primary endpoint again in terms of number of adverse events. And what we see is there is a meaningful difference between the placebo arm and this prescription fish oil arm of the Casa pinned Ethel. And if we go out five years, we see that in the placebo arm, there is a proximate 28% event rate. But in the Casa pin ethel group, there is an approximate 18 or 19% event rate. And so this is the combination of cardiovascular death, non fatal M I non fatal stroke coronary revascularization and angina. If we look at a harder, secondary endpoint, if we just look at cardiac death M I and Stroke, we see similar findings that the placebo arm fares not nearly as well as this vest SEPA or prescription fish oil arm for a 26% reduction in events at five years. If we look at a forest plot in terms of the different types of events and note that are vertical arm means there is no difference in the Icaza pinned group versus the placebo group. And if we look at the Icaza Pent group, this side being better than placebo, we see that for every single outcome, the Icaza Pin group fair substantially better Okay, whether that's cardiac death and M. I, whether it's fatal or nonfatal, am I whether it's revascularization, whether it's hospitalization for angina, whether it's stroke. The Onley area, where there was not a statistically meaningful benefit was death from any cause where there was actually a trend to favor the i Casavant group. So the conclusions from the vital and reduce the trials are difficult to reconcile. How do we reconcile that one trial shows no benefit from fish oil and the second trial shows a substantial benefit, and I think the way to think about these is that the vital trial is the primary prevention trial. The reduce its trial is really a secondary prevention trial. The vital trial includes all patients, um, the vital trials demonstrating including all patients within it. The reduce A trial on Lee looks at hyper troubling variety. Make patients the vital trial uses Onley, low dose omega three fatty acids and the reduce of trials using a high dose of enriched fatty acids. So reasonable conclusions are there is limited benefit from over the counter fish oil products in primary prevention, but a substantial benefit for the enriched fatty acids in a population that has known coronary disease and has hyper triglyceride denia. Well, let's try another paper. We're not gonna have a case scenario with this one. This paper is entitled the Association of Unrecognized Obstructive Sleep Apnea with post operative cardiovascular events in patients undergoing major non cardiac surgery. This came out in JAMA in May of 2019. It is also called the Posts, a study. The background. For this, the poster stands for post operative vascular complications and unrecognized sleep apnea. As we all know, obstructive sleep apnea is defined as the cyclic alternation between foreign JAL collapse and then arousal from sleep, eliminating that collapse. It is by far the most common sleep breathing disorder, and we also know that general anesthetic, sedatives and narcotics exacerbate this sleep apnea problem. Hypothesis of the investigators WAAS that unrecognized obstructive sleep apnea would be associated with a significant increase in cardiac complications in surgical patients. So the methodology for the Post a tri ALS, is that this is a multi center prospective cohort trial. In major non cardiac surgery patients, 1200 patients are enrolled, and every single one of these patients without known sleep apnea undergoes a portable overnight study of their oxygenation on the wards or at home within 30 days before the surgical procedure. The severity of sleep apnea is based upon what is called the respiratory event index, and a low index, or a normal index, is considered five or lower. Mild sleep apnea is 5 to 15 events per hour. Moderate ISS, 15 to 30 events per hour and greater than 30 is considered severe sleep apnea. The patients were then followed for 30 days the primary end points the investigators were looking for or am I cardiac death, heart failure, thrombin, symbolic disease, atrial fibrillation, fibrillation and a new stroke. Amazing findings. In this trial, all these patients do not have known sleep apnea, 67% of them when you did an overnight ox symmetry were found to have unrecognized sleep apnea, and 11% of them had severe sleep apnea. Here's a complex graphical description of what happened with the patients. We're gonna look at the percentage of patients with events this'd is in terms of adverse events that were considered major cardiac events on the vertical access and then on the horizontal access we have days after surgery. And so, if you did not have sleep apnea, we see that there is somewhere around a 12% event rate in that population. If there was moderate sleep apnea, we see that event rate is closer to 22%. And if you had severe sleep apnea, that rate was around. 29% of 29% of patients with severe sleep apnea that was unrecognized had major cardiac event following surgery within 30 days. If we look at the post hoc analysis of individual events. We're going to go through them here. We're gonna look at cardiac death and what we find is that in the severe sleep apnea X, they had a 17 fold increased rate of death compared to the non sleep AP necks. Highly, statistically significant with this P value that is minuscule. Even the moderate sleep ethnic patients. They had a 13 fold increased risk of death compared to the non sleep AP necks. In terms of myocardial injury measured as an elevated troponin level, those with severe obstructive sleep apnea had a twofold increase in evidence of myocardial injury. In terms of congestive heart failure, there's an almost eightfold increase in the severe sleep apnea X and a three fold increase in the moderate sleep. AP necks for new atrial fib Relation four times the rate of event in the sleep AP necks that are severe in unplanned admissions to the I C U or readmission to the I c U. We see that in the severe sleep apnea X, that risk is 6 to 7 fold higher in the moderates, it's fivefold higher, and even in the mild sleep AP necks, there was an elevated risk of winding up into the I. C. U in terms of unplanned intubation. Similar findings about a six fold increase in intubation that was unanticipated and the patients who had severe or moderate sleep apnea. So they're important conclusions from this post to trial. One is that unsuspected obstructive sleep apnea is extremely common. Secondly, that severe obstructive sleep apnea is associated with a dramatic rise in severe, serious cardiac events. There's a 30% event rate in the severe sleep ethnics. There's a 4.4% cardiac death rate in the severe sleep apnea X. There is a 28% rate of M I increase or has a ratio of 1.8. And there's a 5.9% rate of congestive heart failure in these severe sleep apnea X. We also found from this trial that obstructive sleep apnea could be easily detected with a portable device. Now, the drawback of this trial is that this is not an intervention trial. The best treatment of what to do with these sleep ethnics remains unknown. And should we be delaying elective surgery for these patients? Should we be beginning, CPAP therapy should reduce narcotics or sedatives. Should we elevate the head of the bed? Should we provide continuous oxygen and carbon dioxide monitors? We don't know the answer to that yet. But what we do know from this trial is that optimization of obstructive sleep apnea, maybe just as important as diabetes optimization and cardiac risk reduction prior to major surgery. Let's try another case. Here we have a 60 year old woman who is presenting, seeking routine preventive care. She is healthy. She takes no medications. She had menopause 10 years ago. She had a negative mammogram three months ago with moderately heterogeneous Lee dense breast tissue. She has a family history of breast cancer in her mother at the age of 55 a personal history of a benign breast biopsy five years ago and an unprovoked DVT 10 years ago. The best recommendation for breast cancer prevention in this patient is a annual Marie scanning of the breast be by any old mammography. See XMS stain, 25 mg daily de tamoxifen, 20 mg daily or e drink one glass of wine per day. So here we have a 60 year old woman with a family history of breast cancer What is the best recommendation for cancer prevention in her case? Yeah, so yeah, and I believe the answer lies in this paper, which was published in JAMA in September of 2000 and 19. It is one of the U S. P s t f recommendation statements in town medication used to reduce the risk of breast cancer, the U. S. Preventive Services Task Force recommendation. The background for this recommendation are that, as we all know, breast cancer is incredibly common, with one in eight women eventually developing breast cancer. It remains the number two cause of cancer, death and women in this country and in this country. In 2018, there were over 260,000 cases of breast cancer and about 41,000 deaths from this disorder. So the need for a preventive strategy in patients is quite clear. What has been advocated? His lifestyle modification with increased activity, reduction in weight and alcohol reduction, these all have limited data endorsing their benefit. The dense trial in November of 2000 and 19 demonstrated that memory scanning in women with very dense breasts resulted in a reduction in breast cancer. But our patient did not have very dead suppressed. She had heterogeneous lee dense breasts. So what is worthwhile for helping us understand the risk of breast cancer in our individual patients as the use of a breast cancer risk calculator? There are two very good risk calculators of readily available to us. One is called the Breast Cancer Risk Tool from the National Cancer Institute, which you can get at b R Risk to BC risk tool cancer dot gov And what this includes is whether or not your patient has a history of carcinoma. Insights you previous biopsies, her age, her family history, the age of monarchy and the age of menopause. Yeah, there's another tool, which is slightly different but also very useful, that can be found on the APP store. And it's called the Breast Cancer Surveillance Consortium. Risk calculator and includes some different data inputs. Includes age, race, family history, history of breast biopsy and the buyer adds debt, breast density. So that's the real difference. The Cancer risk tool includes monarchy and many part menopause data, and the consortium tool includes the bi rads, brisk breast density data. So our patient, when you plug her into these calculators. Her risk of breast cancer at five years is 4.13% but the average risk for a woman her age is only 1.8%. So she is a substantially elevated risk for developing breast cancer because of her family history and because of her prior biopsy. Well, now, data that was used by the U. S. P S. T. F is demonstrated here, and what they're gonna look at are the benefits and the harms of using a prophylactic medication, a risk reducing medication. And we're looking to look at the number of events per 1000 patients over five years. We'll compare tamoxifen tour Alak Safin to an aroma tase inhibitor such as XMs stain. If we look at breast cancer, what we're going to see is that in the patients with invasive breast cancer, tamoxifen reduced the number of events by seven. Relax a feen by nine and the aroma tase inhibitors by 16. And this was true Onley for estrogen receptor positive cancers. There is no difference in estrogen receptor negative breast cancers, but substantial reduction and out of 1000 patients meaningful reduction in the risk of breast cancer if we look at fracture, what we see is that tamoxifen results in a reduction of three and non vertebral fractures. RL oxytocin in seven results in seven vertebral fracture reductions. But the aromatase inhibitors had no benefit in terms of reducing osteoporotic fracture. If we then look, it harms the main harm comes in the form of Venus rumbling Bolic events. The tamoxifen arm has five Mawr Venus, Trumbull anabolic events. There were locks, Afeyan groups seven. But the aromatase inhibitors no impact on Venus rumbling Bolic events. And then the final one is actually looking at endometrial cancer and cataracts. Tamoxifen associated with a modest increase in endometrial cancer and a substantial increase in cataracts, whereas the other drugs did not have those adverse effects. So the recommendation from the U. S. P S. T. F is dictated here, and that isn't that women over the age of 35 increased risk for breast cancer, it is recommended to offer risk reducing medication if we calculate that they are at elevated risk. Okay, this is given a Grade B recommendation. If women are not an elevated risk, it is not recommended to use preventive or prophylactic medication in this population. So our patient who had this 4.8 risk of breast cancer but had a hiss History of Venus Trump Symbolic event. This is somebody we would not want to give a selective estrogen receptor modulators such as tamoxifen or raloxifene. And rather, she becomes an excellent candidate for one of the aroma tase inhibitors to reduce her risk of breast cancer. Okay, so here are the recommendations from the USPS TF is we should be assessing or can't breast cancer risk in postmenopausal women using one of the calculators? A greater than 3% risk at five years is the general threshold at which we should be considering prophylaxis. The drugs we touched on in terms of their dose ing would be tamoxifen. 20 mg per day for five years were lock Safin, 60 for five years, XMS stain 25 mg daily for five years or in Astra's all 1 mg daily for five years. Recall the tamoxifen and raloxifene increased Venus Trumbull embolism. The flip side is tamoxifen and raloxifene. Reduced osteoporotic fractures and tamoxifen has this unusual set of side effects of any material cancer and cataracts. The aromatase inhibitors can induce significant. My al Jas and all of these drugs can induce Vaso motor symptoms in our patients. Let's go. One more paper here. This came out in July of 2020 so just a month ago. So this is entitled Block Severe Marbach slur two months ago. Block severe marbach sel for prophylaxis against influenza and household contacts. The background for this paper is that household contacts are a common source of influenza transmission patients. At risk for serious adverse consequence from influenza are those over the age of 65 women who are postpartum women, individuals who resided, skilled nursing facilities are asthmatics, individuals with severe neurologic disorders, cardiac disease, sickle cell diabetes or immuno suppression or advanced renal or liver disease. As we all know, vaccine is the mainstay of prophylaxis for influenza, but after exposure, neuraminidase is inhibitors can be effective and are indicated for daily use for twice daily use for one week after exposure. There's a new drug that was FDA approved in 2018, called Ballack severe, which is an endo nucleus inhibitor, and it is effective against influenza A and B. This trial is a multi center, double blinded randomized placebo controlled post exposure prophylaxis trial after exposure to a confirmed positive household contact. In Japan, single dose of blocks of fear is used. That's the advantage to block severe 1 40 mg dose for everybody under the age under the weight of 80 kg or a single 80 mg dose for anybody over 80 kg. There are 749 patients are that are enrolled. They all are exposed to influence that house household contact. But the size of the inoculation that each one receives is unclear. And here are the findings from that trial. If we look at the vertical axis, we're gonna look at the percentage of patients that develop influenza that develop influenza versus the time since the initiation of treatment. And what we see is when we get out to 10 days, the individuals that receive placebo there somewhere around a 13% rate of contracting influenza. But those that received the block severe prophylaxis they're rate is somewhere around 2% at that time frame of contracting influenza. In terms of the numerical findings, we can look at them here. So here, if we take everyone who had a negative nasal PCR result for influenza at baseline and the contact has this negative. And then the contact converts to a positive PCR. We've seen the Block Severe group at 10 days on Lee, 1.5% are positive. But we see in the placebo arm, 11.6% are positive. This results in an 87% risk reduction in developing influenza. If you were given the block severe if we don't look at PCR but we look at PCR or Ciro conversion, we find that the bloc severe group 6% are positive in one or the other. But 23% in the placebo arm are for a 73% risk reduction of developing influenza, as measured by PCR for the virus or serial conversion to antibodies for the viral infection. So the conclusions and limitations of this study is the relative risk reduction for PCR confirmed influenza after a household exposure is 87% this is an absolute risk reduction of 10.1 or a number needed to treat of 9.9 very low number, comparing it to our fish oil as primary prevention, where we're looking at 233. If we look at either PCR or serological reduction. We see the absolute risk reduction is 16.8% but the number needed to treat is becomes then Onley 5.9 by utilization of one dose of block severe. Interestingly, in this trial, 72% of patients receive their block severe within 24 hours of the onset of illness. In the index patient, we don't usually get to family members that quickly, which they're capable of doing in Japan. For some reason. In this trial on Lee, 3.5% of the patients are elderly over the age of 65. Good news is no major side effect of difference, and what this does show is that a single dose of block severe and household contacts can result in a dramatic reduction in influenza risk. Yet let's remember that vaccine is our primary mode of prevention, but in very high risk household contacts, we might want to consider single dose block severe for prophylaxis. So, in terms of a summary of this year's trials that start trial demonstrated that mild, persistent asthma, the use of as needed you destiny, it and for motor all this superior to daily maintenance therapy. The pace trial demonstrated that the CRP can help guide our antibiotic decision. In COPD exacerbations, the vital trial demonstrated that there is a minimal fish oil benefit in the general population. The reduce it trial demonstrated a substantial secondary prevention benefit in hyper triglyceride MCT patients. The Post To try Aled demonstrated that un obstructive undiagnosed obstructive sleep apnea is very common and a major surgical risk. The new U S P S T F guidelines indicate that there is clear utility for selective estrogen receptor modulators or aromatase inhibitors in reducing breast cancer risk and bollocks. Severe can be effective in post exposure prophylaxis for influenza. So I want to thank you all for sitting through this with me and open the table. Two questions, and I believe that I'm gonna be able to pull those up here momentarily, and I'm gonna have to put my glasses on to read those, okay? And oh, my, I have a helper here. Who's gonna help me read these? Thank you very much, Julia. All right, so in the first K patient, uh, it was mentioned that so this is our first case. This is our patient with asthma is that she cannot afford the combination. Regardless of the New England Journal study, I would continue to use albuterol for cost reasons. And they asked me question here was Please comment on this individual who actually could not afford the inhaled combination steroid, and that is an excellent point. One of the beauties is that there is a dramatic reduction in utilization of product when individuals were using both the essence. The Symbicort debut Destiny died from motor all on as needed basis. And so this became much cheaper than the use of daily maintenance therapy. If somebody hardly ever needs their albuterol, it remains true that that individual would be able to more easily afford albuterol. However, if she makes one visit to the urgent care center because of her asthma, the cost of her care rises dramatically and will likely exceed the cost of her Symbicort. Let's see, Do I have another question? Uh, Michael, I'm not seeing additional questions. I don't know if you are for me. No, I think that was the no more questions. Terrific. Thank you All have a fantastic conference, and I hope to see you next year as well. But