All right, so we're going to gradually get started. Good morning, everyone. Thank you for joining us in this beautiful spring morning in San Francisco. We are going to talk about COVID-19, and our presentation will have discussion of the psychiatric manifestation of COVID-19 illness, and also the discussion of wellness interventions for the healthcare workforce. We do not have any disclosures to make, and this is the agenda for today. First, Dr. Joseph Keating will be talking about neuropsychiatric complications of COVID. Then Dr. Smita Patel will be presenting her original research on a large data set from multiple hospitals on COVID-19 manifestations in that data set, and also in our hospital, Leahy Hospital in Massachusetts. And then Erika Savino-Moffat will present on her reflections after three years of her work doing wellness interventions for our colleagues in the front line during the pandemic. I want to briefly introduce our speakers. Dr. Joseph Keating obtained his medical degree from University of Queensland in Australia, and he completed a dual residency in psychiatry and neurology at UMass Medical School in Massachusetts. He has presented at several meetings locally and nationally on the intersection between neurology and psychiatry, and at Leahy Hospital he is attending both in our neurology and psychiatry departments, and he teaches our trainees, residents, medical students, etc., both in neurology and psychiatry. Dr. Smita Patel obtained her medical degree from Surat, India. She completed her residency in psychiatry and additional training in addiction psychiatry and CL psychiatry in Boston. She has an extensive clinical, educational, and leadership career in general psychiatry, addiction psychiatry, and CL psychiatry in the Boston area and New England. Erika Savino-Moffat is a nurse practitioner and licensed mental health counselor. She obtained her master's degree in mental health from Boston University and a master's in psychiatric and mental health nursing from Boston College, and she went on to obtain further training in child psychiatry. At Leahy Hospital, in addition to her clinical work, she has been a champion of wellness interventions since the beginning of the pandemic and continues leading this work to the present time. So I hope you enjoy our talk. A couple of administrative issues, this talk is recorded live also, or broadcasted live, so we're going to have questions both from the audience here and from the online audience. We plan to allow for a couple of questions after each speaker, but we're going to have more time for Q&A at the end of the three talks. Thank you very much, and I'm going to leave you now with Dr. Joseph Keating. Thank you. Good morning, everyone, and thank you for having me here today. In 2019, the World Health Organization declared COVID-19 a global pandemic. By August 2022, there were 590 million cases with 6.4 million deaths worldwide. Hold on a second, I'm trying to find... There we go, I think that's working. I just lost the cursor. Oh, there we go. Sorry about that. Can you hear me now, please? Yes, absolutely. Yep. You can still hear me. No, it doesn't match. Everybody's hearing me a little bit better? No? Still nothing? There we go, there we go. So, as I mentioned before, COVID-19, in 2019, the World Health Organization declared COVID-19 a global pandemic. By August 2022, there were 590 million documented cases with 6.4 million deaths worldwide. What I am intending to do today in regards to COVID-19 is to provide a brief overview of the neuropsychiatric issues consequence of COVID-19, to provide some background information for my colleagues, Dr. Patel, as Dr. Safar mentioned, who will be talking and elaborating upon the description of the data that she collected in the Leahy Medical System, and also to allow Erika Savino-Moffitt to discuss how it is affecting healthcare workers and interventions we have engaged in that regards. For my portion of the topic, we're going to be discussing a brief overview of what the literature has said in regards to the neuropsychiatric issues of COVID-19, discussing also some of the risk factors and touching upon the potential pathogenesis of some of these conditions. First, to start it off with a question, what would we say is the most common neuropsychiatric manifestation of COVID-19? Just thinking about it for yourselves or if anybody wants to shout out. Fatigue. Fatigue, often commonly reported, brain fog is another one that's commonly reported, probably within our clinics in a more organized way. The answer is actually delirium, primarily in hospitalized patients. An important distinction to note, given the fact that delirium can often be associated with poorer outcomes, longer hospital cares, and more intensive interventions that are required. But that is not to exclude the fact that delirium is a very common symptom of COVID-19. But that is not to exclude aspects of fatigue, encephalitis, depression, anxiety, PTSD, seizure disorders, in addition to other more neurological aspects of the disease, strokes, seizures, neuromuscular complications that can arise that we won't touch upon too much here today, focusing more on the psychiatric aspect of things. So in the environment created by the pandemic has presented significant mental health challenges independent of the effects of the infection of COVID-19. This is for the general population worldwide, but there's also certain populations that are at increased risk related to this. Primarily essential workers forced to expose themselves to the virus while others remained isolated. Healthcare workers facing dangers, heartache, physical stress, older adults cut off from their networks, immunocompromised patients, and families of small children unable to return to a more normal life, and students missing classrooms, resources, and social contact. Not surprisingly, there have been widespread reports of depression, anxiety, suicidal ideation, and substance abuse, domestic abuse, and interpersonal conflicts as a consequence of this. To provide an overview of the general population, first and foremost, in regards to depression and anxiety, I found this study to be useful in comparing them to the healthcare workers that we have noticed. This is from a meta-analysis of 158 studies with an N of about 10,000 participants. As you can see here, about a quarter of the population were more likely to experience some degree of depression, anxiety, and we can see those numbers being a little bit higher amongst the healthcare workers, 31% respectively for depression and anxiety, and were less likely in regards to depression and anxiety. We also found that there was a higher percentage of depression and anxiety among healthcare workers than in regards to depression and anxiety, and were less likely in regards to report positive well-being. I'm going to start this overview of the prevalence of neuropsychiatric issues related to COVID-19 a little bit backwards, starting with the caveats and the limitations in regards to these studies. Amazing efforts of the researchers and scientists who guided and fueled our understanding of the neuropsychiatric issues related to COVID-19 had to do so in a fairly quick way, in which not much about COVID-19 was really understood. This did result in some limitations of our knowledge in this regards. For instance, there's variable case definitions. For instance, post-acute COVID-19 syndrome had a range of dates that were accepted. Some said as early as greater than four weeks after initial infections. Some define that as relative to three to six months afterwards. Yep. Can everybody still be able to hear me okay? There's also a lack of biomarker data. Biomarker data where there's no diagnostic criteria available to definitively identify COVID-19 as the underlying etiology of either acute or post-acute neuropsychiatric events. The variance of COVID-19 also differed in regards to the neuropsychiatric consequences that are understood here. So alpha, delta, and omega all had some degree of variations, and distinguishing amongst these can often be somewhat difficult. There's also an ascertainment biased with most of the epidemiological data not being representative of the entire population at risks, and may underestimate rates of neuropsychiatric issues to long COVID among populations with limited access to healthcare. There's actually, there's also a lack of longitudinal studies, where most of the studies out there were looking more at snapshots of many medical facilities to help characterize some of the neuropsychiatric issues related to this. Healthcare disparities in acute and chronic phases of COVID-19 are also well-documented amongst racial and socioeconomic groups with limited access to healthcare. That also is going to fuel some of the data. There's a lack of adequate control groups in which it was hard to match some of the age, sex, social determinants of health, and comorbidities of controlled patients, either in patients who didn't have COVID or those who presented with mild or asymptomatic disease. Differences across lifespan can often skew some of the data as well. Most of the data, at least in the initial identified, the elderly population has increased risk for neuropsychiatric issues related to this, but I think as more and more data is coming out, we're seeing more of a bimodal distribution with our adolescent populations also affected as well, as we see later on down the line, that many folks increased suicidal rates amongst this population. And then, of course, the effects of treatment, steroids, antimalarials, things like that could also skew some of the results in this regards. Despite those limitations, there is still worthwhile information that can be understood in regards to this data, primarily in regards to the acute and post-acute phases. The more common presentations that we would see were symptoms of acute and post-acute presentations that we would see or symptoms that we would see in the acute phases were fatigue, myalgia, changes in smell and taste, headaches, and as we already mentioned, delirium. Moderately common also fell in the category of sleep disturbances, cognitive impairments, lack of appetite, irritability. And then there's the post-acute phases. In a large meta-analysis of 51 studies involving 18,000 patients with a mean follow-up of about 77 days with a wide range of days after initial infection of 14 to 182, we do see the most prevalent symptoms being related to fatigue, sleep disturbances, cognitive impairments, the brain fog that we probably often seen or heard our patients discuss, increased emotional ability, and slightly less common will be anxiety, depression, PTSD, and headaches. This table is a useful table from a rapid review of literature published in PubMed and PsychInfo between January 2020 and February 2022. Here we can see that there are effects of hospitalized versus non-hospitalized patients, particularly in regards to depression and anxiety, with rates being slightly higher for hospitalized patients. Cognition, cognitive effects being notable amongst hospitalized patients, about 55% in the intensive care unit. And fatigue and sleep disturbances were both predominant issues, fatigue being an issue in both hospitalized and non-hospitalized patients. And then the data. Some of these effects lingered. We can see here in regards to depression and anxiety, there are greater than four weeks and greater than three to six months. Comparable rates, I would say, of depression, similarly for anxiety. And cognitive issues tended to persist, particularly in patients who had an ICU admission related to delirium. As we can kind of already hypothesize in regards to psychosis based upon the previous pandemics or epidemics that have been out there, H1N1, Ebola, SARS, and COVID-19 all had an increased risk of new onset psychosis of about 0.9 to 4%. In a retrospective cohort study, there was evaluating the psychiatric sequelae among 236,000 patients over a six-month follow-up, reported an incidence of about 0.42% for a first-time diagnosis. And these hazard ratios for COVID-19 in particular are higher than for ones that are identified for influenza. In a systemic review targeting case reports and case series that evaluated the occurrence of new onset psychosis or exacerbation of clinically stable psychosis, there were 57 unique cases of new onset psychosis or exacerbation of clinically stable psychosis. Sixty-six percent had no history of or no previous psychiatric history, and about 72% of the sample did respond well to antipsychotics. Confounding factors here, of course, were related to psychosocial stressors, iatrogenic effects, antibiotics, steroids, antivirals, all of which can increase risk for this as well. There's not much information in regards to bipolar disorder related to COVID-19. Some of the information that I did draw from was based upon a search performed on basic lit sites in October 2021, looking at medical records of 23 patients fulfilling DSM criteria for a manic episode that occurred on average about two weeks after the dates of COVID onset. The most common symptoms were related to increased rapid pressured speech, elevated mood and euphoria, inflated self-esteem, and decreased need for sleep were the major issues in this regards. Delusions and hallucinations are also notable in this population. Delusions are primarily related to grandiose and hyper-religious delusions, but now we had new coronaphobic-based delusions related to just fear or anxiety related to COVID-19. The study also looked at a mania composite risk score. Interestingly, looking at risk factors related to a manic episode, considering the previous psychiatric conditions, family history of bipolar disorder, or pharmacological triggers. And interestingly, 30% of the population didn't have any of these, suggesting a stronger effect of COVID-19. As we can also presume, they're going to have an increased risk of social or substance abuse after COVID-19. This is based upon data from September 2020 through April 2021, ultimately looking at 111 research studies, and noticed that there was an increased prevalence of tobacco use during COVID-19, with increased risks for COVID-19 for smokers. Similarly, increased alcohol consumption across the pandemic, related to psychological distress and COVID-19 related anxieties were associated with a high number of heavy drinking. Anxiety and depression were also related to increased alcohol use amongst those aged 40 years old. Opiate use was also higher in this regards, and was associated with increased risks of more complicated and poorer outcomes amongst people. There's also increased risks over overdoses, and to some degree related to limited access to health care during shutdowns. Suicide and self-harm were a little bit trickier. There's not a clear-cut trend that came out of the data that's associated with this. The chart that you're seeing here is related to a cross-sectional study looking at suicide-related ED encounters during 2019, and comparing them to 2020 in California. And what you see here in the red line is the 2019 compared to the blue into 2020, and we see this initial dip in regards to ED presentations related to suicide that then became comparable to 2020 and 2019. Now the differences that aren't shown here are related to the 2020 cohort did have an increased risk and correlation with substance use, and they also were less likely to report suicidal thoughts in outpatient clinics in the year prior. You see here the initial dip is also, could be hypothesized to be related to a number of factors. People being more concerned about going out to the emergency departments right after the first shelter in place in Northern California during that time. But there's also data to suggest that there, in general, there's increased suicide attempts and ideation during this time as well. And this data does get a little bit fuzzier, but in general I do think there's a trend related to increased suicide attempts and suicidal deaths in response to this. There's a cross-sectional and cohort studies looking at a lit review between December and 2019 to May 2021, analyzing the incidents and trends of suicidal attempts during COVID-19 pandemic, noticing there's about 12,000 suicide attempts, 33,000 suicide deaths reported. And other trends noticed in other data, they noticed that in 22% of a lit review that was conducted reported an increasing trend, while about 16% reported a decreasing trend or no trend at all. The data for suicidal deaths is not quite as robust either. There, about 16% of the studies noticed an increasing trend, where about 21% either repeated a decreasing or no trend, and 5% reported an initial decreased trend during the crisis, but increased after the immediate crisis passed. Associated risk factors were noted to be related to social distancing, COVID-19 quarantine, and financial constraints related to a lack of employment during this time. Trying to understand the prevalence of symptoms related to post-COVID-19 syndrome. This was a lit review conducted between 2020 and 2021, looking at symptoms that occurred greater than three months, ultimately using 18 studies and 10,000 patients, noticing that there was increased risk for sleep disturbances, memory issues, fatigue, and brain fog were the most notable issues that persisted long after COVID. This is also useful given the prevalence of midterm, so three to six months after initial COVID infection and other, or versus symptoms that lasted, persisted greater than six months afterwards. You can see here things like anosmia and myalgias were more related to the kind of subacute neuropsychiatric risks, but things like anxiety, brain fog, fatigue were the kinds of symptoms that seemed to be a little bit more prevalent as the further away they got from initial infection. Now, understanding the neuropsychiatric risks of COVID-19 is important, but also understanding the risk factors associated with the populations that we should be focused on in regards to this is also useful as well. First, we have gender. Women consistently reported an increase in mental health problems in response to COVID-19 pandemic than men with meta-analytic effect sizes being 44 to 75% higher. This was presumably or arguably related to increased demands in managing kids at home, perinatal effects related to anxieties related to that as well. As we mentioned before, adolescence showed an increased risk for suicidal ideation. Race, so non-white counterparts had a worsening mental health and neuropsychiatric issues related to COVID, presumably related to less access to healthcare. Pre-existing conditions, epilepsy, MS, these things also further increased mental health characteristics related to COVID-19 as well. Healthcare workers, as my colleagues here will elaborate upon and we've touched upon already, pre-existing mental health issues were also at an increased risk for neuropsychiatric issues related to COVID-19. The severity of infection, ICU admissions, prolonged hospital stays also affected this as well. Vaccination status, people who were vaccinated had a decreased risk of neuropsychiatric issues related to COVID-19. And then the COVID strain, the alpha variant was comparable as the initial original strain, whereas the delta variant was a little bit higher than both and omega was comparable to the initial strains as well. Now, touching upon briefly in regards to the pathogenesis of neuropsychiatric issues, COVID-19 binds to the angiotensin converting enzyme inhibitors. This is a lot, causes it to get into the nasal passage. And then from there, once it breaks through the blood-brain barrier, we have these receptors pretty much all over the place, which can explain everything. There, we can see here a nice little diagram that shows that the inflammatory reaction causes an increase in tumor necrosis factor led to endotheliitis, at least to increased von Willebrand's factor and fibrin deposition that will increase risks for strokes, DBTs, PEs that can persist not only in the immediate future, but also in the prolonged phase as well. And we also see the increased monocytes, once that breaks through the blood-brain barrier, releasing interferon gamma that disrupts synapses and results in neuronal injury. And so once these factors go throughout the brain, we can presume that there's going to be neuroinflammation related to damage to the cerebral cortex that can impact executive functioning and other areas such as the prefrontal and cingulate cortex that can contribute to symptoms of brain fog. Damage to the thalamus and brainstem can impact our sensory motor integration, vestibular processing that can relate to dizziness, disruptions of the thalamus and brainstem involved in the sleep-wake cycle can relate to sleep disturbances. Areas in the hypothalamus can contribute to fatigue. And just to kind of touch upon some of the pathogenesis related to this. One aspect of area that was difficult to really kind of tease out was related to what degree of these certain neuropsychiatric symptoms might have been functional in nature. If we remind ourselves that functional neurological conditions are the second most common presentation after headaches in neurology clinics. And some of these issues, or at least some of these things that we are identifying, could have been related to functional etiology as well. The autogenic effects are hard to kind of tease out. And gut microbial translocation is also of a notable hypothetical effect as well. For the sake of time, I'll just leave to my colleagues. These are some of the references that can be available and request. And thank you for your time. Thank you, Dr. Keating. If anyone wants to ask a question to Dr. Keating, we can take one or two questions now before we move on to the next talk. We're gonna follow the 10 seconds rule of our hospital. Okay, so we're gonna go on then to the next talk. We're going to have to put a platform for our next speaker. This presentation is in two parts. Part one is a research in post COVID vaccinated, non hospitalized, COVID negative and COVID positive patients. And also, I could not resist, so I had done research on the patients in emergency room at the Lehi Hospital, which I'll be presenting two years prior and two years during the COVID infections. Part two is the interaction of the Nirmal Telweer and Ritonavir with psychotropics. I will use Paxilovir throughout the presentation as the later one is tongue twister. My family and I have no disclosure. Now, if infection with SARS-CoV-2 follows a similar course to that with SARS-CoV, that is severe acute respiratory syndrome in 2002 or Middle East Respiratory Syndrome in 2012, most patients should recover without experiencing mental illness. But you have heard Dr. Kitting research study that COVID-19 might cause delirium in a significant proportion of patient. Depression, anxiety, fatigue and post traumatic stress disorder and rare neuropsychiatric syndromes may occur in the longer term. The unpredictability and uncertainty of the COVID-19 pandemic and associated lockdown, physical distancing and other containment strategies and the resulting economic breakdown could increase the risk of mental health problems. Preliminary findings suggest adverse mental health effects in previously healthy people and especially in people with pre-existing mental health disorder. This data collection is done by Dr. Saju Ganatra and his research team at Lehi Hospital. It is a period of post vaccination period, January 2021 to January 2022 with the cohort one is a COVID negative and cohort two is COVID positive. These are the patients who were vaccinated one to three times, either Pfizer, Moderna or Johnson and Johnson and both cohort had patients of age 18 plus. Now for the Trinix is a global research network and 76 healthcare organization and 48 providers responded to this query and final cohort matched the query with psychiatric diagnosis in the patients of 197,660 patients. These slides explain risk and risk difference and odds ratio which is for the reference. Now usually the propensity match is done. It is a statistical techniques to construct to the control groups for comparison which helps estimate the impact where we have a 171,416 patients. Now the total outcome with the p-value less than 0.05 is significant and you can see here for the white and more significant for the females, Hispanic or Latino, Black or African Americans. Total patient outcome in COVID negative patient had a lower likelihood of developing mental health problems as compared to the COVID positive patients. This is all in outpatient. Alcohol and substance, sorry, anxiety and mood disorder. COVID negative patient had a lower likelihood of developing anxiety and a mood disorder. Alcohol and substance abuse. It is an interesting finding that you see that COVID negative patient had a higher likelihood of developing alcohol and substance use disorder as compared to the COVID positive. We have found the similar findings from the study published in JAMA and it is referenced in slide 15 which I will go over later on. Psychotic disorder, delirium and personality and behavior disturbance. There are no statistical differences. Overall, you can come to the conclusion that individuals who suffer from COVID-19 may be at increased risk of mood and anxiety disorders. People with mental disorders are in general at increased risk of infection than potentially patients with the COVID-19 are also at higher risk of mental disorder. COVID-19 has presented challenges to the mental health of the population and some of the effects may be persistent. Still more data analysis for the long haul COVID needs to be researched for better treatment options. This is the reference that I had mentioned in JAMA study which was published in February 9, 2023 which concludes that alcohol disorder is the same in COVID negative versus positive. I work at Lahey Hospital and I'm proud to be working at Lahey Hospital and Medical Center which is in Burlington, Massachusetts which gave me an opportunity for this study and presentation. This is the comparison of two years prior that is March 2018 to March 2020 versus March 2020 to March 2022. You can see that when it is broken down by specific diagnosis there is an increase in bipolar disorder and mood disorder and schizophrenia and this is mainly in emergency room which had a great impact on the services as they occupied emergency room for a longer period of time considering psychiatric inpatient beds were limited during the COVID pandemic. So individual who suffer from COVID-19, I'm sorry, see how the COVID has interrupted our lives. Right now it is the electricity that caused the problem but imagine during the COVID how our patients has gone through. Anyway, Liverpool COVID-19 drug interaction checker that I have used and all the information is from the COVID-19 drug interaction checker. Co-administration of medication has not been studied in patients except Paxilovir. Rest of the medication will be in a generic form. Some of the medications are not FDA approved in USA and I'm not familiar with them. It is included in the presentation for international physicians. What are the choices when Paxilovir is given with the psychotropics? And usually Paxilovir is given for five days. The options hold the psychotropic medication and resumes three days after stopping the Paxilovir that is totally eight days. Use alternative psychotropics or use alternative COVID-19 agents. I'll be discussing two cases about involving the interaction. First case number one, this is a 64-year-old female, a professor who has been suffering from panic disorder and generalized anxiety disorder for 15 years and she had been mostly stable on Paxil CR 24 milligram QD. In the past, whenever she had the viral or bacterial infection, she required increasing paroxetine CR to 37.5 milligram for two to three months and received lorazepam 0.5 milligram PRN during that infection about two weeks. She used to use the lorazepam for flying only and after she was diagnosed with COVID-19 in December 22, she was taking lorazepam 0.5 milligram daily before she called me and then I discussed with her and she agreed to increase the paroxetine CR to 37.5 milligram. The increase in paroxetine helped her with no exacerbation of panic or anxiety and she stopped taking the lorazepam. In the past, we have the history that she used to reduce her dose back to paroxetine CR 24 milligram due to weight gain after two to three months. Now if this patient were to receive Paxilovit, I'm going to review the antidepressant with the Paxilovit. What shall we do? Continue or increase or decrease the paroxetine, continue lorazepam PRN or change to clonazepam? I'm going to just review a short about the St. John's wort because most of the people feel that St. John's wort is a natural substance and it should not interfere with anything but significantly it reduces the Paxilovit concentration and may lead to loss of effectiveness of Paxilovit and possible resistance to the COVID-19. Why this is blank? Antidepressant with the Paxilovit, paroxetine has unpredictable response. It may, Paxilovit may increase the level of paroxetine. Now lorazepam, there is no interaction and clonazepam, Paxilovit increases the clonazepam concentration and increase the risk of extreme sedation and respiratory depression. I'm going to discuss propranolol as it will come up later on in our discussion. Paxilovit could potentially increase the propranolol concentration and although to a moderate extent. So in case number one with the professor, we don't need to change the paroxetine CR as it is a weak interaction if she receives the Paxilovit. There is no need to change the lorazepam as it is in the category of no interaction. But please do not give the clonazepam even though it is a long acting and we like it during the anxiety exacerbation as it increases the level of clonazepam and cause extreme sedation. I have questions for you. Is it safe to increase the paroxetine with the Paxilovit? How long will you continue higher dose if you decide to increase? These are the questions posed to you. Now discussing the case number two. This is a 42 year old male with the bipolar disorder with psychosis, stable for many years on sodium valproate 1000 milligram per day, lamotrigine 250 milligram per day, propranol 10 milligram TID for familial tremors. I inherited this patient and he always refused to change his medications. COVID positive, he developed on January 6th and symptoms reported to be high fever, cough, increased paranoia and hallucination during COVID infection. I received the call from his therapist that he is paranoid which he has not been paranoid for last few years. I called him and suggested to consider Risperidol 0.5 milligram PRN QD which he took it on a daily basis and psychotic symptoms improved in parallel with the respiratory symptoms. He stopped his Risperidol after one week as his psychotic symptoms improved. Now he developed, give me a second, in between then after few weeks he was admitted to the psychiatric hospital for psychotic episode. In between period he was psychosis free. Inpatient team increased the sodium valproate to 1500 milligram per day and added Lurasodone 120 milligram. They discontinued the lamotrigine and Risperidone and he returned to work stable. Now again after receiving the second booster in May 7th he developed COVID positive. He calls me on June 21st but symptoms reported mild runny nose and mild lethargy. Now he has no exacerbation of bipolar and psychotic symptoms which I had followed him on almost every other day to see if anything changed. I did not want him to be psychiatrically admitted. So we have a question what should we do with the valproate and lamotrigine during episode one. Whether to continue Risperidone during episode one. Now episode two was in, I call it in June. What will be the dose of sodium valproate and whether to continue or change the Lurasodone. Let's review it next the antipsychotic with the Paxlovid. Paxlovid increases the level of Risperidone but in a milder form that is why it is in the category of potential interaction. Paxlovid increases the level of Lurasodone to the point that the potential cause will be cardiac arrhythmia hence it is in the category of do not go administer. Anticonvulsant valproate and lamotrigine are mainly glucuronidate and co-administered may decrease the valproate and lamotrigine concentration due to induction of glucuronidase by the ritonavir in the Paxlovid. However given that the induction reaches maximal effect after several days and the short duration of Paxlovid treatment, there is no prior dose adjustment is recommended for both the sodium valproate and lamotrigine. Now this is just for the review for the stimulant. I always have a question. Do they need the stimulant during the infection with elevated heart rate and also they are not active during the acute infection. They are not working, staying home. Couple of notes on atomoxetine that Paxlovid can cause the higher atomoxetine concentration and can cause the high blood pressure, nausea, somnolence and reduction in the dose is recommended. Please monitor the vitals on more regular basis when patient is on atomoxetine. Second thing is guanfacin that I will be concerned with that we need to reduce the guanfacin dose for 50% and also refer to the guanfacin product label for the further titration may be required as it increases the level of Paxlovid increases the level of guanfacin. If you for any reason need to give the medications, consider the dexmethylphenidate or a methylphenidate during the Paxlovid treatment. Now during the case number 2, episode 1, lamotrigine and valproate, no prior dose needed. Rispiridol is given in a very low dose and he responded well, I will not make changes. Propranolol has no interaction. I will not make any changes. We continue the same. Episode 2, there is no need to change the valproate but luracidone needs to change as it increases the cardiac arrhythmia and risk of cardiac complication. When I looked up on Google it up, what are the other medication we should consider instead of the luracidone, it came up as eripiprazole, quetiapine, olanzapine, rispiridone and lumatroprone. Considering olanzapine is the safe to administer, if a person has to receive the Paxlovid, I will stop the luracidone and consider the olanzapine to prevention of the psychosis. As we know, we have the history, he had a psychotic episode. And after 8 days, so 5 days of Paxlovid and 3 days for the half-life to be over, after 8 days, luracidone needs to be cross-treated with the olanzapine as he responded to luracidone and in addition, weight gain will be less of a concern. During the second episode, in June, he got again COVID positive but very mild symptom. The question is, he did not have any exacerbation of psychosis during the second episode. Is vaccination a protective factor? And that's why he did not have much of the COVID symptoms and no exacerbation of psychosis or bipolar. Thank you for your attention. I would like to thank my colleague and my family for the input for the presentation. Also, I have attached the slides of the interaction of the Paxlovid with the all psychiatric medication, how it works with the CYP2. I mean all the CYP factors 450 with psychotropics. You can, that is for your reference. Thank you. Thank you very much, Dr. Patel. Because of the time we lost with the technical problems, we are going to move on to Erika Savina-Moffat's presentation, her conclusions after 3 years of working on wellness initiatives with our workforce. Hi, everybody. Thank you so much for coming today. How are you? So, for all of the people here in San Francisco and everyone at home, let's just take about 2 or 3 seconds and take a little bit of a wellness break. I'd invite you to close your eyes and just take one deep breath. So, now we're going to pivot from what happens to COVID patients, thank you Dr. Keating and Dr. Patel, to what happens to the people who care for those patients. As you can see from my visual pun here, I, myself and my spouse have no disclosures. We're going to talk today about some of the context of the work that I've been doing, the lessons that we've learned in cross-hospital post-COVID wellness work, and then the conclusions and limitations and future directions. So, I love that dirty water. Here it is, Leahy Hospital and Medical Center, our professional home outside of Metro Boston, Massachusetts. We are a 335-bed level 1 trauma center that includes ambulatory practices as well. And then, of course, March 2020, as we all well remember, COVID set in. As with many institutions, our institutions mobilized Incident Command. As a part of Incident Command, the Caregiver Resilience and Wellness Committee was formed to address caregiver burnout. Burnout, of course, being ICD codable, as is everything else. So, burnout is chronic stress in the workplace, which is not managed successfully, and results in decreased energy, increased mental distance from one's job or negative feelings about the job, and reduced professional efficacy. So, nurses were among the first to speak up in our particular institution, and so we mobilized the Nursing Wellness Initiative, which we started first with some in-person town halls with nursing administrators. We did one for the inpatient folks and a separate one for the ambulatory folks. We also stood up, I think it was about a dozen, virtual town halls with nursing staff that included administrators, right up to and including our president, our COO, lots of C-suite folks. Certainly, I think the important thing is that the validation of staff sharing feelings in those meetings was particularly key because it allowed them to construct a shared reality of the COVID experience to that date. Obviously, with the end of the public health emergency and for quite some time, Incident Command has been decommissioned at our hospital, and in its current state it exists, we have a wellness manager, Kristen Bedrick, with whom I work closely, and wellness champions throughout the hospital. So, just quick pulse check here. What did you do more of during the early stages of COVID, and what did you do less of? So, whether your pastime of choice was a sourdough starter, a new fitness routine, or a quarantini, it's really important to think about how we as caregivers respond to stress. So, this sort of menu is a handout that was distributed throughout our hospital that contextualizes and really is a menu for all of the many wellness sources that we had available. So, that was on the local level. Above that, within the hospital system level, there were efforts there. So, hospital system, and then the hospital, and then we had this caregiver wellness, and then below that, the nursing wellness initiative. In that menu, you'll see that colleague support is a part of it, which actually comes up a lot in the literature as well. Our department also stood up support groups for staff, which are both virtual and in person. And I say a lot in this work that being together really was the most radical thing. Our department manned a warm line, which served as a place to vent, to get connected to help, and our department is needed as well. In terms of the themes, wellness works best within a culture where it's normalized. We started putting wellness into our daily routines in our hospital, with all staff emails that encouraged self-care, lots of emotional check-ins as a part of our daily huddles, which really was a shift away from that stereotype of healthcare workers as tough and we don't need feelings, and really unlikely to acknowledge or disclose, or really work to cope with the feelings that we're sitting with in any given moment. And the shift was to an understanding that the expression of our feelings is actually really important, that self-care is really important, and it actually helps patient care. When I asked how are, remember I asked you how are you, show of hands, even if you answered in your head, who said good or fine? Most of us, right? That's actually a socially conditioned response. The problem with that is that it disinvites any emotionally authentic response. So instead of saying good or fine, well, I'm mostly okay, but I'm a little nervous. It also disables our natural inclination to mobilize empathy for each other, and thus for ourselves. And so these cards, the images you see were cards that were put in mask bags to help people do self-rounds. On the back, and you might be able to see it, I'm not sure, was a list of free emotional support resources. Here was our EAP phone number, and then the Warm Line number. In terms of where we go next, wellness starts by validating where people are at a current moment. Often it was the operational stressors that really led to the uncovering of the emotional stressors. And the operational stressors, frankly, were what stressed folks out. They put staff feelings in context and really kind of clarified, okay, well, what do you need to be better? What do you need? The graphic that you see is part of a presentation given to senior leadership that summarized those town halls with the ambulatory and the outpatient nursing leadership. Then, of course, we have the good old stress continuum, which talks about stages of burnout originally adapted for the Marines, I believe, and it was the military, but very applicable to us as healthcare workers. We saw a lot of these go up around the hospital to give people some sort of gradation for how they might check in. And when we look at how nurses are, really, this 2023 American Nurses Foundation survey are saying that they're pretty stressed, 64% of them stressed, 57% of them completely exhausted. Age was a risk factor, that younger nurses with less than 10 years' service were struggling more, a full third identified being not emotionally healthy or not at all emotionally healthy. On a scale of one to five, with five being the worst, the mean emotional health score was 3.5. The worst part of that is that was actually better than when it wasn't COVID. In terms of the context, nurses face sicker patients, higher patient volumes, because of the mass exodus from nursing in a lot of areas of medicine, more inexperienced nurses, staffing issues, more abuse from patients and families. I don't know if you've experienced that as well. And then COVID. And really, when you look at the overall numbers, this becomes particularly significant because nurses make up a large percentage of any hospital. For us, it's about 24%. So for theme three, to crib from Ted Lasso, if you're familiar, all people are different people. So you have to come up with a variety of things to try and capture people wherever they might be. Our hospital health insurance vendor, whether you buy the hospital health insurance or not, offered online yoga and exercise classes, meditations. Our hospital also had, as you can see top left, a traveling wellness cart that had really small snacks, non-food wellness items, lip balm, moisturizer, little journals or colored pencils. We also had support groups for staff in any department that requested them. We had some in person. We had some virtual. I did a few hybrid. That was a little logistically challenging. And then in the DEI of it all, because we don't want to forget that piece of it all, is that it was a little more difficult, I think, for certain people to access certain kinds of employees and certain positions in the hospital. It's harder for them to access some of these things perhaps. Really, I think everybody is in a different place on their wellness journey. I certainly know I am from day to day. When we look at the seminal work from Procheska and DiClemente, we had a lot of folks in pre-contemplation. Sometimes it was because they were different degrees of psychologically minded, but a lot of it was because they were just in the middle of it all, that the onslaught of the trauma and the struggle was continuing. Not everybody was willing to engage in wellness work. There were teams that requested debriefs that we stood up, and then pretty much no one showed up. But the ones that worked the best were when we had it during a time when folks were on shift, when they had coverage, when management publicized the session ahead of time, and participated, but briefly, for the first five minutes or so. In terms of the development of wellness approaches, it really has coalesced that it moves in some pretty logical stages. So for the information stage, it's about figuring out what's happening and how people feel about it. So a lot of times we would go and talk to a bunch of people and get this sort of aggregate idea of what the stress points were. We've talked about how the emotional reactions often started with operational stressors. For the directional stage, we have to figure out what the staff delivering this information want to have happen as a result of giving this information. Is this something where they just really needed to talk to somebody and have a one-time event session that doesn't need to go anywhere? Or is it that they feel really strongly, like, no, somebody needs to know about this. And so certainly, we would inform relevant stakeholders. In case of groups, we aggregated, and certainly for all accounts, anonymized information. And then come to the sorting stage, as we've sort of discussed, is this an emotional thing or is this an operational thing? With the emotional things, some of it we could address. With the operational things, rather. With the emotional things, for the things that we could not change and cannot change, it was more about helping staff find ways to cope with that thing that we could not change. One example is that we stood up some sleep hygiene groups for folks that were really struggling with sleep. And then lastly, we have the action stage where the information gets distributed, and then interventions are planned, which I've discussed a little bit. The other thing I would add is that with some of the operational stuff, some of it was pretty heady, thorny stuff. And so then we would offer sort of tailored support groups. We would direct people to wellness resources, but if there really wasn't anything available that fit the bill, we tried to create a group around that need. It probably goes without saying that wellness only works when staff are supported both operationally and emotionally. You really can't have one without the other. The operational constraints create emotional distress, like we've discussed. And so to ignore one domain with the hopes of altering the other will substantially limit the amount of change possible in any organization seeking to improve staff wellness. And hopefully that recommendation is consistent with other institutions like Rush and that paper by the AMA right there. Power differentials are a really important piece of this work. Lots of authors have talked about how it's important to have senior leadership rounding the hospital. But the power differential, as you saw with some of those nursing groups, really does affect different staff differently. Some staff are perfectly willing to just say what they need to say when hospital leader shows up, but other folks go running in a room so they don't have to talk to them. So we do senior, and we continue to do senior leadership rounds as well as wellness rounds with staff outside the power structure. And I always say that the power in our wellness rounds is that we have little power at all as kind of deemed by an org chart. The power that we have is the power to amplify the message. Recognition is a really easy way to jumpstart wellness. It's as simple as just saying thank you for what you do. I really appreciate that you're working so hard. Rewards don't have to be complex or expensive in this age of very limited hospital budgets. You know, our wellness card items were things that were all like very low cost, like 50 cents or a dollar really. The act of giving that reward or that sort of token is a really nice touch point to see what people know about wellness. Do you know where the intranet site is? Do you know where on our hospital intranet site all your wellness resources are? Hey, there's this really great, you know, 20 second hand washing meditation. Have you tried it? So we could introduce resources specific to the person. We could see how much they knew. We could sort of tailor our recommendations. And then that sort of treat or reward that they take away from that interaction is that tangible reinforcement of not only the wellness knowledge, but also of that thank you. Certainly it stands to reason that wellness is multidirectional and that our colleagues' wellness really affects our own. It's the if you go, I go principle, for good or for bad, really. Colleagues were more likely to participate in wellness activities when they knew somebody else was coming, which kind of produced a positive cascade of wellness. We know anecdotally that one bad apple can spoil the whole bunch. I tend to believe that it's also true the other way. We know that wellness facilitates job satisfaction. They're positively and reciprocally related. And then certainly, and I think this is an important point, wellness requires a balance of personal and institutional responsibility. There have been lots of calls from lots of authors to bear some responsibility for employee wellness as a facet of sort of corporate social responsibility. You see there, Morgenstein and Flynn, occupational functioning is the responsibility of individuals, team members, and leaders. It makes sense on a pragmatic level because lack of wellness affects retention, which is super costly to organizations. So it's in the best interest of any institution to invest in staff wellness. But we know that no matter what's offered, some staff just aren't ready to engage in those offerings. And so the counterweight there really is the personal responsibility. These sort of counteracting strategy to that is to offer lots of things and lots of domains. We had things that were in person. We had things that were virtual and on demand, things that were virtual live. We had exercise. We had mindfulness. We had all kinds of things we still do. We had things that were a one-time seminar. We had other things that were a series. And in terms of our conclusion, it goes without saying that as COVID wore on, the fact that we were all getting worn down was really quite clear. Liz and other healthcare workers were at risk of high work-related stress before the pandemic started, but the pandemic really pushed that to pretty epic levels. And a lot of the features, particularly to COVID-19, made the typical coping skills difficult to impossible. So no one really had a manual for how do we get through this? We had some ideas from the military with the stress continuum. We did have some clues from Ebola as well. But it wasn't like you could go to the gym or out to a bar after work, and that we were all physically separated from our families and friends. A lot of healthcare workers talk about how they separated from families and friends by choice, that there were nurses in our hospital who, there was a nurse in our hospital who rented an apartment. She was so afraid to give COVID to her infant child. And so by shutdown and by choice, we were separated due to the fear of infecting others as a healthcare worker. You know, interventions addressing both operational and emotional factors, various staff having various needs and who they would speak to, and to what degree they'd engage with their own wellness varied considerably. And so now with the end of the public health emergency, COVID is over, I say in air quotes. But wellness still really matters, because COVID experiences have left a large number of staff with discernible mental health issues. I would love a survey, I'd love to look at the literature of how many healthcare workers as a result of COVID meet criteria for PTSD. So as we think about the future in the next slide, we have to consider the impact of all of this on the current healthcare worker population. Certainly there are limitations to this work, we weren't able to get to everybody. Those of us who do wellness work are all sort of daytime folks. So you know, hospitals is running 24 hours a day, there are a lot of folks we couldn't get to. My advanced practitioner and physician colleagues are, we're tough to reach. For the inpatient folks, they're all over the hospital with really sick patients and a lot of responsibilities, so not a lot of downtime. In the ambulatory world, they're the competing of pressure of productivity that you're seeing patients back to back all day. Before we started today, we were talking about how, as much as we enjoy each other, we don't really get to see each other a lot, because we have all pretty, a lot of patient responsibilities there. Nurses, on the other hand, are sort of area bound and sort of naturally have a little bit of downtime. As it stands currently, our wellness staff are mostly not physicians, and there's a question of whether staff relate better to wellness approaches from their own discipline. In terms of what's next, our early town halls, as you may have sort of gleaned, were kind of unintentional qualitative research with really readily identifiable themes, as you saw in that Venn diagram. We could follow up specifically on the domains that were identified. We could use quantitative measures, Maslach burnout, PHQ-9, and others to kind of assess kind of what the more general domains of stress are. Certainly, we definitely are looking for more PAs and P's and physicians to join our wellness efforts, and our current wellness department is sized at 3.5 FTE right now. It would be great to see that grow. So lots of references there for your review, and thank you for your attention. Thank you to all the presenters. We have a thinned out audience. I don't know if you have any questions for our presenters. We do have a few questions online that I can go ahead and read. So the first question is about psychosis in COVID-19. For patients who seem to develop new-onset psychosis after COVID-19 infection, and they responded to antipsychotics, how was it determined that such a large percentage have complete resolution of symptoms after one year? I assume this is data that you presented, Dr. Keating. Yeah. You know, to be honest, I'm not really 100% sure exactly. You know, you did have limitations in regards. I think it was based upon the immediate response that they had in response to antipsychotics. So I think it was more of a dosage response kind of thing, rather than complete resolution of symptoms that were monitored. The next question is about vaxxers and non-vaxxers. So let's see, now that we have additional vaccination boosters, are we seeing any increase in neuropsychiatric issues in the vaccinated as opposed to the unvaccinated? I think the data you presented, Dr. Keating, was a reduction, right, in neuropsychiatric complications in people who were vaccinated. So why don't we start with that? Do we have any data that the other way is true now? Anecdotally, I definitely have some patients who swear that the vaccine caused more neuropsychiatric consequences. So there's definitely an element of anxiety there from at least my own anecdotal information. I think there's also a distinction that has to be made between there is, I think, a general trend in regards to even the booster shots still contributing to an ongoing decreased risk of neuropsychiatric issues for those who get COVID. But there's a distinction between, I think, for those who get COVID and for those who just get the vaccination, whether it's not, I'm not sure if there's any other neuropsychiatric consequences related to the population. And then there are a couple of more, but we're going to respond to them online. In terms of the request for the slides, I think the slides for Dr. Keating didn't make it to the app. So we're going to upload all the slides to the app. There was a technical problem with that, but they will be there. Thank you very much for your attention, those here and those online. Thank you.

COVID-19

neuropsychiatric complications

delirium

healthcare workers

mood disorders

anxiety disorders

wellness interventions

mindfulness exercises

support groups

psychosis

vaccinations