Two UCSF pediatric hematologist-oncologists discuss COVID risks for pediatric patients with sickle cell and other blood diseases or cancer. Guidance includes which children need hospitalization, when to give preventive therapies for coagulopathies, and when to delay – or not delay – regularly scheduled treatments.
mm. Thank you for allowing us to uh come chat with you about the impact of COVID-19 on our pediatric hematology oncology patients. Uh I also wanna uh send a thank you for being patient with robert. And I I think this is our first tag team zoom talk so um appreciate the patients as we go through this. But uh while we've all been besieged with Covid virus information um we certainly um think that are the pediatric hmong population deserves special attention. So thank you for and uh listening. So without further ado so where are we? Um Well while we all wish we were done with Covid, Covid 19 is certainly not going away anytime soon. So we um wanted to give you a little historical perspective and uh if you look at the pandemics over the centuries, uh Covid 19 is certainly the worst pandemic of the 21st century. And with over a half a million people dying from this virus um uh in the third in the 14th century, the black death killed about a third of the world's population And more recently AIDS uh killed uh 35 million people. So um it's a serious problem. And uh this is all within the last uh six months essentially that we've lost a half million people in the United States. We've lost about 130,000 people. Um and that that's again um it seems that those numbers seem to continue to be going up. Sorry mike. What about the impact of Covid on Children will have that 100,000. Um Over 100,000 people who have died from Covid in the United States on C D C dot I'm sorry on data dot CDC dot com. Ah They show that only 29 Of those 100 over 100,000 individuals that have died were under 14 years of age at the time of death. So very few Children are dying of this disease. Uh information from China shows that less than 1% of the cases where Children under 10. There's a number of publications now showing that Children have less severe clinical manifestations and are more often asymptomatic. The those that do get sick and require ICU care often have pre existing comorbidities. Uh and it's really important for pediatricians to be aware of this multi system inflammatory syndrome and Children which is that Kawasaki is like uh condition. It's very rare but very serious manifestation of Covid 19. This graph over here just highlights The difference by age. In terms of hospital hospitalization rates. Those over 65 uh requiring hospitalization much much more frequently than those under 17 years of age which very rarely require hospitalization. So, uh there's a number of therapies that are being developed for uh Covid 19. The uh we're all aware of the uh lack of efficacy of chloroquine or hydroxychloroquine that was initially promoted. Um The only therapy that is FDA authorized is Remdesivir and that's through an emergency use act. It is not FDA approved. Uh it's FDA authorized using that emergency use act. This is true for both adults and Children. The Children that get Remdesivir have to get a different formulation. It's um it's a one without a preservative. And so that's that's important for pediatricians to be aware of dexamethasone. And you know, module A Torrey therapy was recently promoted by a study done in the UK. That again is in pre print but hasn't been formally published. And this showed a reduced mortality in patients on ventilators, uh or ventilatory support. So, these are two therapies that we do consider using in Children. There are a number of other therapies that are in development. Likewise, there's a number of vaccines that are being developed. Most of these target the spike protein which uh dr Bernick at Children's Hospital. Oakland Research Institute has shown that this uh, spike protein is the best area to elicit neutralizing antibodies. So most of the vaccines are focused on developing antibodies against the Spike protein. Uh many of you may have read this week, our government spend another $2 billion dollars just this week on vaccine development. So the bottom line for kids in terms of treatment um there there um all All Children with COVID-19 should receive supportive care. The decisions of when to admit are tricky. Um uh initially I think most of us were thinking all kids with COVID need to be admitted or at least watched very closely. Uh those things have changed over time. Again if there's underlying health conditions that may make them more prone to more severe disease, uh uh they should probably be admitted. Remdesivir are being used for patients that require oxygen and dexamethasone is considered in certain situations, especially if they're requiring intubation. But again, this is exceedingly rare that that's needed. The therapies are evolving and we're following much of the adult work in this area. So with that, um um, I'd like to pass the baton to Dr. Rafael to discuss the impact of COVID-19 on some of our hematology patients. Uh so, my section of the talk is going to focus on what we now know about COVID-19 and the world of pediatric hematology. The short answer is not very much, but I have to say something. So, what I will discuss is what we've managed to learn so far about patients who have chronic blood diseases, who may be at risk disproportionately for complications due to Covid 19, uh particularly patients with sickle cell disease. Uh and then I'm going to spend a little time talking separately about the Hema to logic aspects of COVID-19 in general and specifically about the coagulant apathy and the thrombin, symbolic risks uh that have been increasingly described. And then I will pass that baton back to Dr. Goldsby is going to take over uh talking about the impact of COVID-19 on the world of pediatric oncology. Um so as I started to research this talk, um I discovered quickly when I did a pub med search looking for Covid and pediatric hematology that I had rather only a few results. Uh fortunately I went to the American Society of hematology website where they have a whole section dedicated to frequently asked questions about specific patient populations. Uh those who may be at increased risk. And so that helped me to start to formulate my questions and to figure out what we know so far about the impact of Covid in what I'll call benign hematoma, logic disease as opposed to things like leukemias and lymphomas that will be covered in rob's section of the talk. So, in the left hand column Then, as I looked to categorize these patients, um those who are sort of called out on the ash website and have been uh described to some extent in the literature who have some definitely or possibly increased risk include patients with hemoglobin antipathies that is mainly patients with sickle cell disease, which is bolted because I'm going to talk more in depth about that group of patients. I wish I had time, but I don't to talk about patients with fallacy with transfusion dependent thalassemia, who also appeared to maybe be at some increased risk for reasons. I'll talk about sort of generally some other groups of patients who made the list includes some with inherited or required bone marrow failure syndromes you might imagine would be at risk because of their pants. It a pina and generally patients who are receiving immunosuppressive therapy for whatever their underlying neurologic disease might be patients with splenectomy may be at increased risk as well. Uh For reasons that I'll get into and patients with P. NH who have a baseline risk of thrombosis disease may have a higher risk if they happen to get coronavirus. Um importantly though, are the patients who sort of didn't make this list. So the list on the right includes the patients that you're rather more likely to see in a general pediatric practice. Most of the patients in these disease categories on the left are going to be primarily followed by their hematology specialists. Uh in contrast with patients on the right here and these are the patients that we kind of see in your office every day, patients with iron deficiency anemia or thalassemia trait. Um probably there's no reason to think that these patients that you see more commonly are at any increased risk for coronavirus compared with the general pediatric population. Similarly, patients with bleeding disorders. Although I'll talk about the coagulant apathy in a little bit. Um most of that coagulate apathy relates to uh difficulties with clotting and thrombosis symbolic disease and bleeding seems to be not a major manifestation. So if you have any patients who have hemophilia or Von Will Brandt's disease and they're asking you questions, they're probably not in any significantly increased risk. I would say the same thing about I. T. P. Patients unless they're getting immuno suppressive treatment and those have chronic benign neutropenia. So having discussed the groups of patients who might be at some increased risk, the next question is, well what what are we talking about? What exactly are the risks to these patients? And again I thought I would break this up into a couple of broad categories. There are some general risks that in the era of COVID-19 patients might be at risk for related to their underlying human logic diagnosis. So one thing we're concerned about is that patients may delay seeking care for complications of their underlying disease if they are developing if they have a fever. If they have a new symptoms they have whatever they may be reluctant to actually come into the doctor's office and seek care. They may also be reluctant to come in and get their routine regular follow up care that they need whether that's follow up physical exam laboratory studies but they don't want to go to the lab imaging studies or all the other things that we normally are doing to try to keep these patients healthy. You can also imagine a concern about delay in a new diagnosis. So some of the patients on that list, maybe you don't know they have some of those conditions on that list. Uh And there might be a delay in seeking care for uh the onset of some concerning new symptoms. Um patients may also have reduced access to their routine care. Maybe they want to come in but the office is closed or they're having a hard time getting an appointment or they are having a hard time getting there. Regular medications for example, there was a certainly a run on uh some of the drugs that dr Goldsby mentioned earlier when um uh plaque when ill was touted as a possible cure all for covid 19 patients taking that for their uh rheumatoid logic disease, had a hard time getting access to it. That's another story, patients who do come into the healthcare setting, they're not wrong to be concerned. They may be at increased risk for nosocomial infection for actually contracting coronavirus in the healthcare setting. Um and then the group of patients who receive chronic blood transfusions were certainly worried about these patients because we maybe dealing with limitations in the blood supply as the pandemic worsens. And particularly as it worsens in certain pockets of the country globally. This has proven to be a problem. The uh there was a survey internationally of thalassemia treatment centers around the globe, and a majority of those outside of the United States anyway, reported having some restrictions in their blood supply that led to changes in the way that they are transfusing patients compared with normally at their baseline. So, those are some of the general risks at the bottom of the screen then are some complications uh that are potential of patients if they actually have the misfortune of contracting covid 19 on top of their underlying disease. So, some of those could include an increased risk of secondary infection for some groups of patients that might be a bacterial secondary infection, like a bacterial pneumonia or bacterial sepsis, particularly in patients who've had a splenectomy, or those like with sickle cell disease who have impaired splenic function, patients who are neutral Penick or immuno suppressed as I mentioned, and also those chronically transfused patients who are receiving iron population. Because the regulation therapy itself puts patients at risk for back terranea with certain organisms. As I also alluded to earlier, some patients may be at baseline, uh, having a higher risk for thrombosis tick disease. So, those who had a splenectomy or have P NH and those with sickle cell disease. And then you may add on top of that, the uh secondary risk of thrombosis in the setting of a severe covid infection. Some of these patients could potentially be at risk for cytokine release syndrome or cytokine storm. This hasn't particularly been well described in the world of pediatric hematology, hematology in general, but certainly this is a theoretical concern and we'll need to be vigilant for that. And some patients may also be at risk for complications of their underlying disease in the setting of a COVID-19 infection. So at the same time that they may be at risk for a more severe course of covid having Covid may put them at risk for a more severe course of their underlying disease. For example, complications of sickle cell disease, like the acute chest syndrome, like Visa inclusive pain, crisis like stroke and like pulmonary hypertension. And so with that setup I'm going to spend a little bit of time delving a little deeper into um COVID-19 and sickle cell disease. You can think of a few different reasons that patients with sickle cell disease um might be at higher risk uh if they were to contract Covid 19 or a SARS COv two infection. Um and that has to do with the interplay between the path of physiology of COVID-19 and the path of physiology of sickle cell disease itself. And it turns out the path of physiology in both cases has a lot in common. There's a lot of overlap because in both settings, what you have is sort of a hyper inflammatory response combined with endo vascular damage, End ophelia will damage and activation, resulting in microvascular occlusion. Those things are common to both severe COVID-19 disease and to the basic underlying path of physiology of sickle cell disease. So here you've got a patient at their baseline steady state that got healthy lung but they have the misfortune of contracting the SARS cov two virus that causes a viral pneumonia, possibly a secondary bacterial pneumonia as well. And this pneumonia causes regional hypoglycemia with shunting causing those red blood cells to sickle in the vasculature prompting a bazooka inclusive crisis which causes of course this feedback loop that we recognize as the acute chest syndrome. More hypoxia results in more cycling, results in more vascular occlusion, which results in worsening of the acute chest syndrome and worsening hypoxia. All of this can result in downstream and Oregon effects and cause a pretty sick patient pictured here in the I. C. U. So that's all true in theory. But what if we learned in practice, there's been a number of case reports and a few small case series describing the experience today of COVID-19 in patients with sickle cell disease. And I wanted to highlight one of these. The largest series that I could find Came from a national survey of sickle cell disease providers across 24 different treatment centers in France during what turned out to be the peak of their COVID pandemic from about a four week span in March into April. So they collected data on 83 patients in total that were reported and hospitalized during this period with uh both sickle cell disease and with COVID-19. And I'll highlight here that they did include some pediatric age range patients. They had 12 patients below the age of 14. They had another number Of adolescents who got lumped in there with the young adults. And I don't know exactly how many fell into the adolescent uh-age range. But you can see the median age of all the patients here that they had was 30. And what I'll highlight down here is the actual complications that were reported for this group of patients. About half of them had Aviso inclusive crisis. 28% of them experienced acute chest syndrome. A little over a third received at least one transfusion during their treatment course. They stayed in the hospital for an average of a little over a week. And down here, you'll see that 17 out of these 83 patients were admitted to the icu. And what the report here is that half of those patients, nine out of the 17 required mechanical ventilation while they were there in intensive care. Another interesting thing, when you look at the breakdown across the age spectrum is that none of the youngest groups of patients, the pediatric patients required mechanical ventilation at all. Um, And the proportion of those that did increased with increasing age. So 43% of those in this middle category and 71% of the admittedly small number of patients in the higher age group category. Um, required mechanical ventilation. This doesn't come anywhere close to achieving anything like statistical significance, but it's intriguing and it certainly makes sense in the context of what we are now learning about coronavirus and its disproportionate impact on older patients. They went on to do a comparison between the 83 patients admitted to hospitals with sickle cell disease during this time period and the overall French population who was hospitalized during this uh same period of time. And they looked at the rate of ICU admission and the fatality rate. And again, what I'll point out here from this chart, that kind of struck me was the difference in age where you can see in this younger half of the patients that they looked at. Uh the younger two groups that the sickle cell patients were actually a little bit less likely than the general french population in this time to require ICU admission or to die of their disease. In fact, they had no deaths in this uh, in this age group as opposed to what we saw for the older age group of sickle cell patients when they were a little bit more likely, 50 uh, to require ICU admission compared with 36% for the overall french population as well as a fatality rate of 14% among this particular age group, compared with a rate of 5% for similarly aged general french population. Again, I wouldn't consider much of this to be of great statistical significance, but it kind of makes sense. And the trend is certainly intriguing and goes along with what we know about COVID-19 and uh, patients in general. So the sickle cell Disease Association of America as well as some other organizations, including the american Society of hematology, um, were very proactive getting out in front of this and issuing a set of recommendations for hematologist and others who care for sickle cell patients with the recognition that they may well be at increased risk complications from Covid 19. 1 thing they emphasize is continuing routine clinical care, not canceling the doctor's visits, but encouraging a transition to telemedicine visits when possible. Making sure patients are adherent with their medications and considering adding disease modifying agents to patients who are not already taking them agents like hydroxyurea for example. Uh they recommend triaging patients who develop symptoms that suggest possible. COVID-19 like fever or respiratory distress with evaluations in the outpatient setting as opposed to the er whenever possible to avoid extra exposures. Uh and then providing the standard of care for management of fever and acute chest syndrome when they do develop and admitting these patients when clinically necessary. I'll mention that some of the European guidelines that came out actually recommended admitting all sickle cell patients who have a diagnosis of COVID 19 on the right here, a little word about pain management. Again, just with an emphasis on outpatient management whenever possible. Uh the recommendations continue discussing a little bit about treatment of any sickle cell patients who are actually diagnosed with COVID-19 infection that they should be monitored for acute chest syndrome as well as for pulmonary hypertension and pulmonary emboli and that those things should be treated aggressively with the usual standards of care which includes Anyway, transfusion. But early on to be vigilant and consider transfusions for patients who are worsening. And especially to consider exchange transfusions if they're worsening. In spite of receiving a simple straight transfusion hyper co arugula ability, I'll talk about in another couple of slides. But these patients should be monitored and prophylaxis as appropriately uh in accordance with the adult guidelines or the pediatric guidelines, depending on how old the patient is. Um a word about chronic transfusions that we need to be vigilant and monitor the blood supply. And we might need to consider modifying the transfusion plan for patients who are getting transfused for lower risk indications. And some have advocated starting hydroxyurea therapy for those patients who are now being transfused for primary stroke prevention because they're at stroke risk due to an abnormal transcranial Doppler. Um as a hedge against the scenario that the blood supply might be impacted, might need to be rationed. And if those patients are no longer able to receive transfusions at the frequency that they normally need, that at least they'll be covered by having something on board that is known to be effective in reducing their stroke risk. And then finally, a word about research uh that this is an active area of research. The American society of hematology has an ongoing registry to collect data about COVID-19 infections among six sickle cell patients in the United States. Um they advise perhaps deferring elective clinical trials unless those are deemed to be in the patient's best interest. That makes sense. But some of these trials really are in the patient's best interest. So I can say here at benning off Children's Hospital Oakland, we've had at least two patients who were admitted as originally planned for a gene therapy trial uh to cure their sickle cell disease. These are things that were long in the works and it was decided that it was certainly in the patient's best interest to proceed with those plans rather than to delay them because they were already so well um in hand. So I'm going to shift gears a little bit now in the time I have left and talk now about the Hema to logic aspects of covid 19, generally not just in patients with underlying blood diseases, but in general. And one thing that's been increasingly recognized and well described is this phenomenon of a covid 19 associated co arugula apathy. Uh and so we start here in column a in this little graphic on the left with patients who bring to the hospital with them some risk factors, some of those are acute risk factors for thrombosis related to their acute illness being bedridden, being federal, perhaps being septic or dehydrated. And then whatever risk factors of their underlying disease, maybe malignancy or heart disease or we could add sickle cell disease conceivably to this list in any event, that's their baseline risk and then you add to that the inflammatory response that you see in the setting of a severe SARS. CoV. Two or covid 19 infection which results in this endothelial dysfunction. Um And some of this may be related to uh direct effect of the virus on the vascular and Ortho liam. Because as it turns out the SARS COv two that spike protein that dr Goldsby mentioned, its receptor is the angiotensin converting enzyme er ace two receptor that as we know, is present in the mucous membranes in the respiratory tract which is how the virus gets into you. But there's also a lot of Ace two receptor expression in vascular and Ortho liam. And so it may be that a Viren IQ patient gets a lot of this virus causing endothelial damage within the micro vasculature. And that may be the reason that you get this particular hyper inflammatory response uh that affects um and causes abnormalities of the coagulation system. So as a result you see these laboratory abnormalities that will describe in a moment and him a static and real logic abnormalities that can include pulmonary micro thrown by or intravascular coagulation apathy with micro thrown by elsewhere in the circulation and over D. I. C. And those things can lead to the clinical outcomes that we would certainly like to avoid like venus thrombosis embolism like stroke which isn't described here like myocardial infarction and D. I. C. So it's a brief summary of what we know is that this kogelo apathy is manifest as a combination of elevated fibrinogen as an acute phase reactant um elevated D. Dimmers and relatively mild or minimal changes in the PT and PTT. And some mild decrease in the platelet count at least in the early stages of infection. Going along with this if you happen to check it are rising levels of pro inflammatory cytokines like L. Six as well as general inflammatory markers like crp and said rate. Um And this coagulate apathy does appear to be related to the severity of illness and the resultant they call it Trumbo inflammation rather than the intrinsic viral activity. Though the virus of course may be at the root cause of it elevated d. Dimmers at the time of admission or rising di di MERS after admission are associated with increased mortality and may precede the development of multi organ failure and D. I. C. And in spite of the foregoing as I alluded to before, bleeding manifestations are not common in spite of the coagulant apathy. Rather. Um Rather what we see is an increased risk of thrombosis symbolic disease. And one series described this showing a rate of 35 to 45% among critically ill covid 19 patients in the ICU compared with the baseline rate of about 5 to 15% in other critically ill ICU patients who don't have covid. 19 As a result of this. A number of societies have recommended prophylactic anti coagulation for all adults hospitalized with COVID-19. Um which you can see down here in this uh in this table. And in fact, some experts have recommended considering it even for high risk groups of out patients who have covid 19 infection. Or to consider escalating what is our usual standard dose venous thrombosis? Embolism, prophylaxis with drugs like cloven hawks, Kogyo apathy, they note in the absence of bleeding, is not a contra indication to anti coagulation for those who should otherwise get it. And conversely, the laboratory abnormalities alone do not require corrective treatment. So they advised not to go pouring FFT into patients just to try to get an abnormal PTT, for example, into the normal range that we should reserve blood products for patients who actually have bleeding or about to undergo a procedure with risk of bleeding. Now, those guidelines are all well and good for adults for whom adult providers are well used to the concept of prophylaxis for admission for a whole variety of conditions. But it's not necessarily clear that those guidelines are appropriate for a pediatric population. To be honest, we don't have a lot of data about this. So, um a group of experts convened a task force to publish a set of recommended guidelines for Children as we continue to gather more data and I'll briefly summarize what they advised here. They recommend that all pediatric patients admitted for SARS cov two infection should be evaluated on admission and then throughout their stay for their risk of thrombosis tick disease. And they recommend that all patients who are deemed to the at risk for thrombosis um should be initiated on mechanical or probably pharmacologic prophylaxis with drugs like Lovenox if appropriate, what's appropriate? Well, they don't really say, but they sort of give a few guidelines here, they say to consider anticoagulants in patients who have a strong personal or family history of venous thrombosis embolism. Those who have the presence of a central line as well as two of the risk factors that are delineated here Or a combination of four or more of these same risk factors. But these are just general sort of advice and guidelines not very well backed up yet with evidence and it would not be unreasonable to consider prophylaxis for any patient or at least an adolescent or young adult patients Um who is admitted with a severe COVID-19 infection in the absence of a contra indication. They also recommend obtaining these laboratory studies. I mentioned before at admission and continuing to follow them serially during a patient's hospital course. Because these maybe early predictors of a worsening course and of further risk for thrombosis symbolic disease with that. Now I will pass the baton back to my colleague and I will yeah, so uh thank you robert and I'm just gonna transition a little bit into the oncological diseases of pediatrics. Um so what is the impact of covid on childhood cancer patients? Well, we know that infants are at higher risk of developing more severe disease. And some feel that that's related to their immature immune system. Uh We also know that adults with cancer are at higher risk for more severe diseases shown in the graph here, where adults are almost uh 3.5 times more likely to have uh more severe events. Um So the concern is that immuno compromised patients may be at higher risk for more severe disease. However, the data and Children with cancer is very limited and some good news. Ah A report out of Memorial Sloan Kettering Cancer center, uh which was right in the heart of the initial pandemic uh where the peak incidents of Covid was very high. Uh they found that the Children with cancer were at no more risk of severe disease as other Children. And they also had um the same rates of being infected as other Children. So, their bottom line was that Children with cancer are not really at higher risk than other Children. Very important. Uh, some other reports out of other countries that uh sort of went through the pandemic and an earlier phase than we did. Uh study out of France showed that in 33 patients that were COVID positive uh and also had a pediatric he monk diagnosis. Five of those 33 positive patients required ICU admission. Now, they don't say how many were intubated and how many were just followed in the ICU due to these uh concerns of their imminent compromise states. So not sure how serious those five cases were in spain, They had 15 cases of COVID positive pediatric oncology patients and seven of those 15 ended up hospitalist and two required oxygen and none of them were required icu admission. So about half or six of them required delays in their therapy due to the covid virus at bending of Children's hospitals. We've had two cases admitted. Um one in Oakland and one in San Francisco. Um Some funny, they both were 17 years of age. Um one was male, one was female. Both were had a l l acute lymphoblastic leukemia. And both were in maintenance therapy. Both presented with fevers and respiratory symptoms. On on the side here you can see the an example of the X ray was showing bilateral infiltrates and then the C. T. Corresponding cT showing uh or more clearly showing these uh covid virus related infiltrates. Both required temporary oxygen supplementation. Um Both were treated with Lovenox. One was treated with remdesivir. Neither required a pick you admission and both were discharged within 10 days of their admission, one at seven days and one at 10 days uh and maintenance chemotherapy was empirically held on these patients uh for two weeks. So similar to the hematology group, the oncology group put together an expert panel and came up with some guidelines as well. The main emphasis was on new patients and that they should be evaluated immediately. There's concern that there's delays in diagnosis due to covid virus. Um and uh we certainly don't want delays in diagnosis because that can impact both morbidity and mortality. Um The most commonly affected diagnosis is going to be acute lymphoblastic leukemia, mainly because it's the most common cancer in kids and it also has the longest duration of therapy. Um It's really important that we try to avoid interruptions of care as much as feasible. Uh We do offer some tell amount of some visits but most of these patients need to be seen in person. And then the other question that we don't have a good answer for is what to do with asymptomatic positive patients. Uh There is some uh suggestion that holding therapy uh is the right thing to do. But again there's not any data to support that. The other thing that pandemic has done is it's altered our resource availability. So um surgeries are obviously a very important part of of cancer therapy and Children with cancer. Uh The highest risk of transmission of this virus is during air civilization of procedures. So the anesthesiologists are very careful in who's getting procedures during this pandemic. So some modifications and timing uh and practice are needed for safe surgery without compromising both the patients and the providers. So during this resource limited time we have to be smart about how we're using those resources. What's the impact on the people? Well the nurses and frontline providers, there's absolutely increased stress uh in what we consider an already stressful job. Um the front line providers are at 12 times the risk of the general population of developing COVID virus. So um obviously this increases stress. There's also been studies showing increased psychological distress among among health care workers. So the healthcare worker group is especially the nurses are really taking the brunt of this pandemic uh family psychological challenges. Uh the changes that have been required in pediatric oncology and hematology uh include um restriction and visitation and reduced face to face, uh evaluations and reduced face to face conversations, I think limiting the understanding of some of the families of what's uh their cancer diagnosis and the necessary follow up. Um So it's changed our educational approach. Um and this is obviously an enhanced the challenge of a very challenging time for these individual families. So what are some of the practice changes we've done? And I'm sure many of you have been involved with these sort of decisions but reducing the number of people in the hospital, so no shared rooms, no shared environments, no shared playtime's uh in the hospital, um reduce people on rounds. Uh you know, presumed participation of other providers like pharmacy, social work, dietitian in a child's life and et cetera. Um uh It's changed our structure of rounds. We now round by the primary care provider, whereas before we just sort of did it in the the most efficient room sequence uh restrictions on visitation have been huge for our patient population. Uh imagine having your child diagnosed with cancer and only one parent can be there very challenging times for these families. And then the restrictions on providers limiting the number of people in specific conference rooms, the mask wearing policies have evolved. And we sent a questionnaire about that at the beginning. Hopefully guys have answered that daily symptom checks as we come into the hospital. And then covid testing of all admitted patients is another area that deserves special attention in this patient population. We've had three patients tested for covid that have developed severe episode axis because of their underlying condition in their therapies. So, a very uh somewhat unique population. So I think in summary uh the main community management is uh we're concerned about possible delays in diagnosis and treatment and I'll mention a patient that was admitted last night, a kid with severe lymphedema apathy uh probably over the past six weeks. I think the family initially delayed going to see their doctor because they didn't want to be around covid patients. And then about three weeks ago had a telemedicine visit with their doctor. Uh and they said it's probably infectious, but I wonder if that doctor had been able to feel those lymph nodes and and see they were mad at lymph nodes and needed to be assessed more urgently that kids uh now admitted uh and and likely has a leukemia lymphoma syndrome. Uh so and then the psychological impact of patients as an outpatient are really uh likely immense. Um so our emergency room visits are markedly down. And again we're worried that our patients may not come because of fear of covid. So we have to educate them that are er is safe, it's a safe place to come. Everybody is treated as if they have covid and that's to protect everybody. And in patients the patients are sicker. The isolation practices have changed, the restrictions have changed and the guidelines are constantly evolving. And again, for outpatient management we certainly have had increased telehealth visits and we have had to address some of these educational issues I've mentioned before. Um Again, we've all been besieged by covid virus information. I hope you recognize that this population is uh somewhat special and these specific attentions and again, we certainly recognize it's key for us to work with our community pediatricians to make sure we're providing the best care possible for our patients. Yeah mm mm mm.