Characterizing PRN Use of Psychotropic Medications for Acute Agitation in Canadian Long-Term Care Residents with Dementia Before and During COVID-19.

Background: Agitation is a disabling neuropsychiatric symptom of dementia. Pro re nata (PRN) injections of psychotropics can be administered for severe acute agitation, but little is known about the frequency of their actual use. Objective: Characterize actual use of injectable PRN psychotropics for severe acute agitation in Canadian long-term care (LTC) residents with dementia and compare use before and during the COVID-19 pandemic. Methods: Residents from two Canadian LTC facilities with orders for PRN haloperidol, olanzapine, or lorazepam between January 1, 2018- May 1, 2019 (i.e., pre-COVID-19) and January 1, 2020- May 1, 2021 (i.e., COVID-19) were identified. Electronic medical records were reviewed to document PRN injections of psychotropic medications and collect data on reason and demographic characteristics. Descriptive statistics were used to characterize frequency, dose, and indications of use, and multivariate regression models were used to compare use between time periods. Results: Of the 250 residents, 45 of 103 (44%) people in the pre-COVID-19 period and 85 of 147 (58%) people in the COVID-19 period with standing orders for PRN psychotropics received ≥1 injections. Haloperidol was the most frequently used agent in both time periods (74% (155/209 injections) pre-COVID-19; 81% (323/398 injections) during COVID-19). Residents in the COVID-19 period were almost two times more likely to receive injections compared with those in the pre-COVID-19 period (odds ratio = 1.96; 95% CI = 1.15-3.34; p = 0.01). Conclusion: Our results suggest that use of PRN injections increased in LTC during the pandemic and contribute to the mounting evidence that agitation worsened during that time.

A CASE OF COVID-19-ASSOCIATED PULMONARY ASPERGILLOSIS

SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: COVID-19 patients requiring admission to an ICU have a higher risk of invasive pulmonary aspergillosis (IPA) with a reported incidence of 19.6%-33.3%. CASE PRESENTATION: A 63-year-old male presented with progressively worsening dyspnea for one week. He has a past medical history of atrial fibrillation, hypertension, and obesity. He was tested positive for COVID about two weeks prior. He did receive a single dose of Moderna vaccine. Initial chest x-ray(CXR) showed diffuse ground-glass opacities. He was initiated on Remdesivir and decadron, and later received a dose of tocilizumab. He was intubated on hospital day 3 for worsened hypoxemia. Repeat CXR suggested some improvement but a new left lower lobe airspace haziness. He also had new-onset leukocytosis with elevated procalcitonin level. He was started on cefepime for concern of superimposed hospital-acquired pneumonia. A second dose of tocilizumab was administered. No clinical improvement was seen, and additional workups were obtained. Serial CXRs revealed increasing diffuse airspace opacities concerning for ARDS. Tracheal aspirate culture grew coagulase-negative staphylococcus and Aspergillosis Fumigatus. Cefepime was changed to vancomycin, and voriconazole and caspofungin were added. Unfortunately, the patient's respiratory status worsened with increasing ventilation requirement. He also developed septic shock and acute renal failure requiring CVVH. He became even more hypotensive after CVVH initiation, and multiple vasopressors were required to maintain his hemodynamics. Unfortunately, he continued to deteriorate and he also developed profound respiratory acidosis. He died shortly afterwards after family decided to withdraw care. DISCUSSION: In this case, in addition to superimposed bacterial pneumonia, pulmonary aspergillosis likely also contributed to his clinical deterioration. The mechanism by which fungal infections develop in COVID-19 infection is not well-understood. Severe COVID-related immune dysregulation, ARDS, and high-dose steroids use are potential culprits for the increased risk of IPA. Tocilizumab, an IL-6 receptor monoclonal antibody used in patients with severe COVID-19 infection, may also predispose the patient to IPA according to post-marketing data. The mortality rate from current case reports is as high as 64.7%. Diagnosis and treatment in such a scenario remain a challenge. Sputum culture, serum Beta-galactomannan, Beta-D glucan, and aspergillosis PCR have low sensitivity. Tissue biopsy and CT scan in critically ill patients are often not feasible. Voriconazole is usually considered the first-line treatment in IPA. CYP3A4-mediated drug interactions between azoles and antiviral agents require further investigation. CONCLUSIONS: Clinicians should be aware that severe COVID-19 patients are at higher risk of IPA. The prognosis is poor. Early detection and treatment in clinically deteriorated patients are warranted. Reference #1: Borman, A.M., Palmer, M.D., Fraser, M., Patterson, Z., Mann, C., Oliver, D., Linton, C.J., Gough, M., Brown, P., Dzietczyk, A. and Hedley, M., 2020. COVID-19-associated invasive aspergillosis: data from the UK National Mycology Reference Laboratory. Journal of clinical microbiology, 59(1), pp.e02136-20. Reference #2: Lai CC, Yu WL. COVID-19 associated with pulmonary aspergillosis: A literature review. J Microbiol Immunol Infect. 2021;54(1):46-53. doi:10.1016/j.jmii.2020.09.004 Reference #3: Thompson Iii GR, Cornely OA, Pappas PG, et al. Invasive Aspergillosis as an Under-recognized Superinfection in COVID-19. Open Forum Infect Dis. 2020;7(7):ofaa242. Published 2020 Jun 19. doi:10.1093/ofid/ofaa242 DISCLOSURES: No relevant relationships by Jason Chang No relevant relationships by Jason Chang No relevant relationships by kaiqing Lin No relevant relationships by Guangchen Zou

Hyperactive delirium in an 11-year-old boy with juvenile neuronal ceroid lipofuscinosis and a SARS-CoV-2 infection

An 11-year-old boy with juvenile neuronal ceroid lipofuscinosis (JNCL) is admitted because of acute agitation and hallucinations. Upon admission, the patient takes lorazepam, which does not induce the expected rest. A PCR-test had a positive result for SARS-CoV-2. Juvenile neuronal ceroid lipofuscinosis (JNCL) is a rare neurodegenerative disease in children and adolescents. Hallucinations are a known symptom in the course of the disease. In the case discussed in this article, however, the pronounced hallucinations fit within a broader clinical picture of a hyperactive delirium. A delirium is by definition provoked by a physical cause. In the presented case, JNCL was an existing risk factor for a delirium, the SARS-CoV-2 infection and lorazepam were presumably the triggering factors. Recent literature shows that an asymptomatic or mildly symptomatic SARS-CoV-2 infection can also trigger a delirium. Treatment consists of treating the physical cause (if possible), supportive measures for the patient and context, as well as medication. The antipsychotics risperidone and haloperidol are recommended. Within the context of JNCL, cautious initiation of a second-generation antipsychotic, such as risperidone, along with great alertness to possible side effects, such as extrapyramidal symptoms and neuroleptic malignant syndrome, are advised. For the young patient in the discussed case risperidone was started, supplemented with olanzapine as rescue medication. The medication had a good effect and no side effects were observed.

A Case of Cotard Syndrome and Neurosyphilis

BACKGROUND: Cotard syndrome is a rare neuropsychiatric condition in which individuals have delusions of being deceased or losing their organs. It is often seen in patients with severe depression and is associated with catatonia.1 Neurosyphilis is a severe sequelae of untreated treponema pallidum infection in which the paretic form of this disorder commonly has a psychiatric presentation. 2 We present a rare case of Cotard syndrome in a patient with neurosyphilis with successful treatment. OBJECTIVE: To understand Cotard syndrome and underlying neuropsychiatric conditions, and characterize the diagnosis and management of psychiatric symptoms in a patient with neurosyphilis. METHODS: Review of a case using electronic medical records and relevant literature. Key terms searched: 'Cotard syndrome,' 'neurosyphilis,' 'COVID-19 infection' using Medscape and Google Scholar. RESULTS: We present a 49-year-old male with a history of alcohol use disorder in remission, depression, and history of COVID-19 (asymptomatic) 6 months prior. The patient presented to the emergency department for recent changes in behavior. He was agitated, threatening, and required chemical and physical restraint. Evaluation was notable for illogical thought processes with somatic delusions. He repeatedly stated, 'I am already dead, my organs have died,' and had an episode of catatonia. All tests including drug screen and COVID-19 were negative. Rapid plasma regain (RPR) titer was 1:64. Neurology and Infectious Disease were consulted. Lumbar puncture revealed positive venereal disease research laboratory (VDRL) titer of 1:4. The patient was diagnosed with neurosyphilis and major depressive disorder with psychosis with Cotard syndrome. He was treated with intravenous (IV) penicillin G and was discharged on oral mirtazapine 30 mg and olanzapine 20 mg nightly at bedtime, oral donepezil 5 mg daily, thiamine, and folate. CONCLUSIONS: Cotard syndrome is often seen in depression with psychotic features.1 Neurosyphilis can present with depression, anxiety, psychosis, and dementia. Early identification is the key for successful treatment. This is a unique case of neurosyphilis with features of Cotard syndrome in a patient with a history of depression with treatment noncompliance. Studies show that quetiapine and risperidone improve psychosis in neurosyphilis.5 In this case, neurosyphilis was successfully treated with IV penicillin G for 2 weeks. The patient was also tried on antipsychotics and mood stabilizers ' specifically aripiprazole, valproic acid, and haloperidol ' and was eventually stabilized on oral olanzapine 20 mg taken nightly at bedtime. Our differential diagnosis also included COVID-19 delirium with Cotard syndrome, which was ruled out due to a negative COVID test. To our knowledge, there are 2 cases of COVID-19 delirium with Cotard syndrome.6 We present this case to inform clinicians of rare manifestations of neurosyphilis in patients with comorbid psychiatric illness and to advance research into treatment options for psychosis in neurosyphilis.

Increased Mental Health Needs in Pediatric Admissions During COVID-19: The Epidemic Within the Pandemic

Background: Pediatric patients with increasing psychiatric needs introduce a substantial challenge for inpatient care. This study illustrates how the COVID-19 pandemic has influenced the number and acuity of psychiatry and psychology consults among pediatric inpatients at a tertiary care hospital. Methods: The study population included all pediatric patients (ages 0-25) admitted to University of Michigan's C.S. Mott Children's Hospital between March 2019 and March 2021 who received a psychology and/or psychiatry consult. Three time periods were defined: pre-pandemic, 3/1/19-3/15/20;early pandemic, 3/16/20-6/30/20;and steady-state pandemic, 7/1/20-2/28/21. The patients were described demographically and clinically. To assess differences among time periods, ANOVA testing was conducted for numeric variables and chi-square tests were used for categorical variables. The number of pediatric inpatients receiving psychiatry and/or psychology consults was reported for each month of the study period as a count and as a percent of all pediatric admissions. Psychiatric acuity was described in terms of length of stay and use of restraints and as-needed medication. Logistic regression was used to estimate the odds of requiring restraints based on time period, controlling for relevant demographic and clinical variables (age, sex, race, length of stay, and use of benzodiazepines and psychotropics). Logistic regression was also used to estimate the odds of patients requiring as-needed medications (midazolam, lorazepam, diazepam, clonazepam, alprazolam, haloperidol, chlorpromazine, quetiapine, risperidone, aripiprazole, olanzapine, and ziprasidone) based on time period, controlling for clinical and demographic variables (age, sex, race, length of stay, and restraint use). Results: Among the 1,636 patients in the study, average age was 14.0 years (IQR 8.1 to 17.2) and 57.9% were female. Overall, 68.6% were White, 13.6% were Black, and 2.4% were Asian. Among all races, 5.7% identified as Hispanic. Percent of pediatric patients receiving psychiatry and/or psychology consults was higher on average during the pandemic months (71.2% during steady-state pandemic compared to 47.9% pre-pandemic). Across all participants, 2.1% required restraints, 34.4% used psychotropics, and 42.6% used benzodiazepines. During the pandemic, admissions became proportionally more female (64.1% during steady-state pandemic vs. 55.3% pre-pandemic) and older (average age 14.8 years during steady-state pandemic vs. 13.4 years pre-pandemic). During steady-state pandemic, children admitted had 5.70 times higher odds of requiring restraints and 1.78 times higher odds of using psychotropics, compared to children admitted pre-pandemic. Length of stay decreased during the pandemic, and was associated with psychotropic use, benzodiazepine use, male sex, and younger age. Conclusion: A higher proportion of pediatric admissions during the COVID-19 pandemic required psychiatry and/or psychology consults. Additionally, these patients were of higher psychiatric acuity, based on increased use of as-needed medications and restraints. These findings highlight the dramatic changes experienced by individual patients and their healthcare teams during the pandemic.

SARS COV-2 AS A RISK FOR ANGIOEDEMA

CASE: This is a 41-year-old man who was admitted to the medical floor with mild COVID-19 symptoms without hypoxia. He had End Stage Renal Disease (ESRD) on Hemodialysis (HD), failed renal transplant, Hypertension and Schizophrenia. Patient had no relevant family history. Medications included Aspirin, Atorvastatin, Nifedipine, Benztropine, and Haloperidol. Patient had allergy to shellfish products. He tested positive a week prior to admission with mild cough no fever or hypoxia. As symptoms worsened, he presented to emergency department and was admitted because of his immunocompromised status. The night of admission, he developed wheezing and stridor, swelling of face and lips, and altered mental status. It was difficult to pass endotracheal tube due to swollen airways. Vital signs were stable except for a low oxygen saturation. Physical examination significant for stridor and swelling of the face and lips. Laboratory values were not significant. We reviewed and none of them was newly started or associated with risks of angioedema. He had no history of previous similar episodes. Patient was given anti-histamines and steroids with slight improvement. Flexible laryngoscopy was performed showing swollen epiglottis and aryepiglottic folds. He ended up getting a tracheostomy as he was regarded as a high risk to be liberated from intubation. IMPACT/DISCUSSION: Few other cases of COVID-associated angioedema have been reported in the literature, majority of the cases explained were in African American patients. The features of angioedema reported like the traditional angioedema, swelling of the face, lips and airways. This angioedema developed within 7 days of detection of COVID-19 in our case and >10 days in the previously reported cases. Angioedema develops due to increased levels of Bradykinin (BK) and its metabolites due to increased expression or decreased degradation. Angiotensin Converting Enzyme (ACE) with other enzymes prevent angioedema by degradation of BK and its metabolites . African Americans, have genetic susceptibility which leads to lower levels of other enzymes involved in the Bradykinin metabolism, thus ACE blockade put them at a higher risk of angioedema. The association of COVID-19 with ACE2 and its subsequent disruption of ACE activity is thought to be the reason behind the development of angioedema. Most of the published articles are either observational or sporadic case reports. More thorough study might help identify further mechanisms and if there is a direct true causal relationship between COVID-19 infection and angioedema or if it is the result of a “second hit,” as it was called by authors of another case that involved a Caucasian male with hypertension who has been using Lisinopril for years with no previously reported complaint. CONCLUSION: SARS CoV-2 should be suspected as cause for angioedema. Further studies needed to establish modalities for diagnosis, management and prevention in high-risk patients.

Understanding the Palliative Care Support Needs of Hospitalised Patients With COVID-19;Are Subcutaneous Infusions Associated With Improved Symptoms?

Background/aims: Recent systematic review of symptom management for adult COVID-19 patients approaching end of life (Heath, 2021), identified 7 studies (493 patients);only 4 reported if symptom management was effective. Over 2/3rds patients needed subcutaneous infusion for symptom control. We aimed to identify if subcutaneous infusions for adult COVID-19 patients approaching end of life was associated with improved symptoms. Methods: Two UK acute hospitals. Survey of all adult patients with COVID-19 seen 1st April 2020 to 31st March 2021 by the hospital advisory palliative care teams. Symptom data was prospectively collected. Approved by the clinical audit committee. Results: 252 COVID-19 patients;mean age 78.9 yrs (range 42-98), 56% female;mean duration of care 3.2 days (median 3, range 1-35). 200 (79.4%) died in hospital;25 (9.9%) were discharged and remained in hospital;12 (4.8%) were discharged to inpatient hospice care;15 (5.9%) to own/care home. 147 (58.3%) patients required continuous subcutaneous infusion for symptoms;of these, 36 (24.5%) had pain when first seen;82 (55.8%) had breathlessness;92 (62.6%) had agitation/ distress. Of those who had or developed pain (n=43), 26 (60.5%) improved with morphine or oxycodone infusion;17 (39.5%) worse or unknown. Of those who had or developed breathlessness (n=82), 50 (61.0%) improved with morphine or oxycodone infusion;32 (39.0%) worse or unknown. Of those who had or developed agitation/distress (n=92), 50 (54.3%) improved with midazolam, haloperidol, or levomepromazine infusion;42 (45.6%) worse or unknown. Mean doses were: morphine 14.2mg/day (range 5-60mg);oxycodone 21.4mg/day (range 5-80mg);midazolam 15.4mg/day (range 5-80mg);haloperidol 2.4mg (range 1-5mg);levomepromazine 23.75mg (range 6.25-50mg). Conclusions: Despite deteriorating illness, over half of all patients managed with often low doses of common medicines administered by subcutaneous infusion had improvement of their symptoms.

A Review on Schizophrenia: Outline and Treatment

Schizophrenia is a debilitating, genetic brain condition caused by anomalies that appear early in infancy and interrupt normal brain development. It has a lifetime risk of 1% and affects people of all ages, with around 10% dying by suicide. COVID-19 may raise the risk of mortality and morbidity in people with schizophrenia. Although antipsychotic medications of the first, second, and third generations are the most commonly prescribed treatments for schizophrenia, they are linked to major side effects such as tardive dyskinesia, oxidative stress, and EPS. Ayurvedic herbal medications and some dietary supplements score well in this category since they can be taken for a long time without causing major adverse effects and have antioxidant properties. Low potency first generation antipsychotics, sedating antihistamines, and benzodiazepines, as well as inhalable antipsychotics, oral and short acting injectable olanzapine, and ziprasidone, as well as low potency first generation antipsychotics, sedating antihistamines, and benzodiazepines, should be avoided or closely monitored for patients with COVID-19. Mentally ill patients with COVID-19 should be segregated if at all possible, and employees should be adequately protected.

Psychotic Disorders and Structural Racism: On Considering Complexity

In a policy statement issued in October 2020, the American Public Health Association officially declared that structural racism is a public health crisis, and in April 2021, the Centers for Disease Control and Prevention followed suit in declaring racism a "serious public health threat. STRUCTURAL RACISM AND MENTAL HEALTH Nowhere is the impact of structural racism more directly relevant than in considering mental health problems, which are filtered directly through the cultural lens of society in ways that can exacerbate its effects. Because they are so highly stigmatized, psychotic disorders are particularly sensitive to "racial and political currents" that underlie the evaluation, diagnosis, and management of these conditions.4 In this issue of AJPH, Misra et al. In my clinical experience, I have witnessed my Black patients who were hospitalized for stabilization during a mental health crisis removed from their second-generation antipsychotic medications and switched to high doses of haloperidol, a firstgeneration antipsychotic medication that was specifically associated (via print advertisements from pharmaceutical companies to prescribers) with images of aggressive and hostile Black men in the 1 960s.5,6 I have directly observed psychiatrists and other mental health providers misinterpret adaptive suspicious behaviors and symptoms of distress in Black patients as paranoid delusions, leading to misdiagnoses of psychotic illness. The structural level of discrimination within the health care system has effectively penetrated all other levels, including institutions (such as the institution of psychiatry) and individuals.5 The history ofthe reconceptualization of schizophrenia from a psychotic illness affecting docile White women who did not meet gendered, patriarchal expectations for their roles in society to an illness centrally defined as one in which Black men were hostile, aggressive, and "delusional" for seeking to assert their civil rights and rejecting notions of White superiority is well documented.5 However, one cannot overstate the impact that this reconceptualization, codified into various editions ofthe Diagnostic and Statistical Manual of Mental Disorders,11 has had on the modern conceptualization of schizophrenia and other psychotic disorders. [...]the bias that clinicians bring to their assessment, including misdiagnosis and overdiagnosis, is the foundation for inequities through racialized perceptions ofthe very definitions of what psychosis is and how it presents in different populations.

Kritik COVID-19 Hastalarında Deliryum için Haloperidol: Bir Olgu Serisi

Amaç: Haloperidol deliryum tedavisi için kullanılmaktadır. Haloperidol molekülünün mekanik ventile edilen hastalarda sitokin fırtınasını hafifleterek mortaliteyi azalttığı ve in vitro koşullarda SARS-Cov2 virüsü üzerine antiviral etkinliğe sahip olduğuna dair bazı kanıtlar yayınlandı. Bizim amacımız deliryum için haloperidol verilen kritik COVID-19 olgularını incelemektir. Gereç ve Yöntem: Üçüncü basamak bir hastanede, hastane etik kurulu izni alınarak, Mart 2020 ve Eylül 2020 tarihleri arasında bir yoğun bakım ünitesine kabul edilen, SARS-Cov2 virüsü için reverse transcription polimeraz zincir reaksiyon testi pozitif olan ve COVID-19 ile ilişkili ARDS nedeniyle mekanik ventile edilen kritik hastalar retrospektif olarak incelendi. Entübasyon öncesinde, hastanede yattığı süre içerisinde deliryum için haloperidol verilen hastalar tespit edildi. Veriler hastane medikal kayıtlarından elde edildi. Bulgular: Entübasyon öncesi haloperidol verilen yedi kritik hasta tespit edildi. Yedi hastanın beşi erkek, ikisi kadın cinsiyette idi. Hastaların yaşı medyan 60 (min: 38-maks: 96), vücut kitle indeksi medyan: 23 (min: 16-maks: 35) idi. Komorbid hastalıklar diabetes mellitus üç hastada, hipertansiyon üç hastada, koroner arter hastalığı iki hastada, konjestif kalp yetmezliği bir hastada, KOAH bir hastada ve inme bir hastada mevcut idi. APACHE II medyan 19 (min: 10-maks: 44) idi. Entübasyon öncesinde PaO2 /FiO2 oranı medyan 106 (min: 85-maks: 122) idi. Haloperidol günlük dozu medyan 3 mg/gün (min: 1-maks: 15) olarak tespit edildi. Hastanede yatış süresi medyan 24 gün (min: 7-maks: 29) ve yoğun bakım ünitesinde yatış süresi medyan 21 gün (min: 4-maks: 24) idi. Hastalardan üçü yoğun bakım ünitesinde takipleri sırasında öldü. Sonuç: Biz deliryum için haloperidol verilen kritik COVID-19 olgularını inceledik. Bu çalışma olgu serisi olduğu için sınırlı bilgi sağladı ve sebep sonuç ilişkisi kuramadık. COVID-19 hastalarında gerçekleştirilen gözlemsel bir çalışmada haloperidol verilenler ile verilmeyenler arasında ölüm açısından önemli fark olmadığı gösterildi. Bu konuda geniş kapsamlı ileri çalışmalara ihtiyaç vardır (Turkish) [ FROM AUTHOR] Copyright of Turkish Journal of Intensive Care is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

A comparative study of long acting injectable antipsychotic agents and oral agents during covid-19 pandemic: Quality of life, adherence and shortage of supply

Background: Long-acting injectable antipsychotics improved markedly patient adherence to psychotropic agents during the past decade. They were used mainly for long-term treatment of schizophrenia. However their role in short term or intermittent use or their effect on quality of life was not elucidated clearly. Objectives: To assess the impact of Long Acting Antipsychotic agents on quality of life of schizophrenic patients. Methods: This is a retrospective cohort study of psychiatric patients who were taking LAIs and/or oral antipsychotic drugs at Mohammad Said Kamal Hospital for Mental Illness in Bethlehem and Mental Health Clinic of The Ministry of Health in Hebron city during the period of September 2019 to March 2020. Results: Fifty one patients were included in this study, 74% males, age 50.69 ± 11.14 years old. Average duration of psychiatric disease was 17.78 ± 11.4 years. It was found that 9.6% patients were on oral dosage form (category I), 80.4% were on LAI and oral antipsychotics (category II), and 10% were on LAIs (Category III). Chi square test showed a significant difference between the 3-categories and GAF score (functionality), p=0.003. However, there was insignificant difference between the three categories and CGI-S(severity of symptoms) scores, p=0.170. When it comes to side effects, there was a significant difference among the three categories and DIEPSS, p=0.049. Kruskal–Wallis Test showed a significant difference between patients in the three categories and number of all drugs, p=0.007. There was also a significant difference between CGI-S-normal group and CGI-S-severe symptoms group and overall number of drugs used, p=0.02. Mann-Whitney test showed a significant difference between number of all drugs used and the use of trihexphenidyl, p=0.001. Also there was a significant difference between number of antipsychotic drugs alone and thrihexphenidyl use, p=0.001. Patients were prescribed LAIs for the following reasons: non-adherence (47%), no reason at all (27.4%), patient dissatisfaction (13.7%), adherence and patient dissatisfaction (5.8%), side effects, convenience (ease of use), and availability of drug, (1.9%), for each. Conclusion: Improvement in functionality of schizophrenic patients goes along with use of LAIs either alone or in combination. LAIs improved adherence and minimizes polypharmacy.

Acute food refusal in 12 year old with anorexia nervosa requiring sedation and mechanical ventilation for enteral feedings

Case Report Anorexia Nervosa is a mental health disorder with significant morbidity and mortality. Acute food refusal is one of the indications for admission. We present a patient who went to extreme lengths to restrict food intake, requiring intensive care sedation and ventilation to enable enteral feedings. 12 year old male, was admitted with symptoms of anorexia nervosa and BMI of 12.0, (<1%ile) with baseline BMI of 16 (25%ile), K of 3.3 and glucose of 54. He was treated with supervised eating on an inpatient pediatric floor with no need for enteral feeding. Psychiatry consultation confirmed the diagnosis of anorexia nervosa and recommended the addition of Olanzapine to his Sertraline. He was discharged pending placement in an eating disorder center after 21 days of hospitalization with discharge BMI of 14. He was followed as an outpatient by his pediatrician, dietician and counselor but unfortunately, he required readmission 11 days after discharge due to acute food refusal, with BMI that had dropped to 13.1. Patient was readmitted and started on nasogastric (NG) feeds but he became severely agitated, pulling NG out multiple times and continued to lose weight with BMI dropping to 12. Sedation was attempted to facilitate maintenance of NG feedings, with Benadryl, Haldol and Ativan, but was ineffective at levels deemed safe without compromising his airway and breathing. Due to severe malnourishment and unsuccessful NG feeds he was transferred to PICU for sedation, endotracheal intubation and continuous nasoduodenal (ND) tube feedings on two separate occasions while inpatient. He was able to wean from the ventilator but once awake he found ways to manipulate delivery of his calories, even finding scissors and cutting the ND tube. The patient ultimately agreed to eat in order to avoid replacement of the feeding tube. He was finally transferred to an eating disorder facility, with a BMI of 13.9 and persistent anorexia thinking with restriction of eating anything but pizza. Patient completed three months of an inpatient program and had significant improvement in BMI to 19.3 (70%ile). He was subsequently discharged for continued outpatient follow-up and since discharge from the eating disorder center, his BMI has shown steady improvement in outpatient follow-up. He shows no signs of food refusal and is doing well with Family Based Therapy. This case highlights several unique characteristics in management of eating disorder patients. The age and being male along with extreme food refusal and resistance to enteral feeding that led to the requirement of deep sedation are quite unusual and not well described in the medical literature. The severity of his illness was a significant barrier to inpatient placement. In addition, despite a nationwide attempt to find an inpatient facility for him, which took several weeks, we identified shortages in eating disorder beds that have been exacerbated by the COVID-19 pandemic.

P.0177 Partial ornithine-transcarbamylase deficiency, autoimmunity and psychosis – a complex case report

Background: Ornithine-transcarbamylase deficiency (OTC) is the most common type of urea cycle disorder, and it is the only one with X-linked inheritance. The clinical presentations can vary from severe symptoms caused by hyperammonemia in childhood or adolescence to milder cases with late-onset in adulthood (similar to delirium or acute psychosis) [1], in the context of precipitating factors such as pregnancy, high protein intake, acute stress, infections, certain medications (valproate, steroids, haloperidol) [2]. Method: We present a case of a 31-year-old female, with no history of mental disorders, with a personal history of Hashimoto thyroiditis and urticaria, and a family history of OTC deficiency (her two-year-old niece). She was also a heterozygous carrier for the OTC deletion, reporting periods of meat avoidance and anorexia. She was single, lived alone, and complained of work-related stress, mainly as she worked from home during the COVID-19 pandemic as an IT consultant. The patient presented at our clinic in emergency for psychomotor agitation, slurred speech, complex auditory and visual hallucinations, and mystical delusional ideas. Furthermore, one week before her presentation, she started fasting because of her Christian orthodox religious beliefs (before Easter celebration), but she also complained of insomnia, fatigue, and tachycardia. The patient reported being vaccinated with the first dose of Pfizer's SARS-CoV-2 vaccine one week before the presentation. Results: Laboratory tests showed iron-deficient anemia and ketonuria;hepatic function was normal. Thyroid function was also normal, but anti thyroperoxidase antibodies were elevated. Serum ammonia levels were normal, and urinary orotic acid levels were within normal range. The result of head CT was unremarkable. Neurological examination was normal. She was started on 10 mg i.m. Haloperidol per day, but given the possibility of inducing hyperammonemia in urea cycle disorders patients, she was switched to Risperidone 6 mg/day, which was gradually reduced to 3 mg/day. Also, she was started on a protein-restricted diet. On the second and third days of admission, she was partially disoriented and somnolent but showed no signs of metabolic encephalopathy;therefore, metabolic treatment was not initiated. On the sixth day, she was almost completely recovered, with no psychotic symptoms. After the remission of psychotic symptoms, the neuropsychological evaluation showed significant cognitive deficits: executive functions (impaired performance on Tower of London task), deficits of focused and distributed attention, and decreased immediate verbal memory, even though the patient had received higher education, being at the top of her class during her studies. Given that metabolic profiles were normal, we discuss the complex interactions between autoimmune disorders, genetic factors, precipitating factors, and psychosocial factors that could have contributed to the psychotic episode. Conclusion: Clinicians should consider various factors that can influence the psychological state of a patient, paying attention to atypical factors or symptoms. Also, regarding the treatment of psychiatric symptoms in patients with urea cycle disorders with a normal metabolic profile, psychiatrists must avoid certain medications (haloperidol, valproate) that can worsen the patient's status. No conflict of interest

Olanzapine versus haloperidol in CoViD patients

Background and Aim: Haloperidol is the most widely used drug for the prevention and treatment of delirium in the Operating Units of Internal Medicine. New generation antipsychotics are a possible alternative often with fewer side effects. The objective of this study is the evaluation of a single-center observational retrospective study to compare the efficacy and tolerability of oral olanzapine versus haloperidol for the management of delirium in CoViD-19 patients. Materials and Methods: 97 patients were enrolled. The analysis of all data is retrospective as a single-center observational study approved by the ethics committee. Two groups were identified: the first of 49 patients treated with haloperidol, 48 patients treated with olanzapine. Results:We observed lower efficacy and safety of oral haloperidol than olanzapine in the management of delirium in elderly patients with CoViD-19-related pneumonia. In particular, we observed a reduction in the number of episodes of delirium, a reduction in hospitalization and greater compliance with ventilatory therapy with fewer adverse events in the group treated with olanzapine. Conclusions: Oral olanzapine therapy may be indicated as a better alternative for the management of delirium in the fragile high-risk geriatric patient.

Probable haloperidol decanoate-induced fever in an African American with benign ethnic neutropenia: A case report.

We present a case in which a patient developed fever and leukocytosis subsequent to each monthly haloperidol decanoate injection, an adverse reaction that does not meet the diagnostic criteria of neuroleptic malignant syndrome (NMS) or any previously reported adverse reaction for this medication. A patient being treated with haloperidol decanoate for psychosis experienced a fever within 3 days of injection and leukocytosis along with swelling, pain, and a "knot" feeling at the injection site. This recurred after each injection for several months. Muscle rigidity or changes in vital signs other than temperature were not noted. Temperature and injection site reactions resolved with administration of acetaminophen and ibuprofen. The elevation in temperature was discovered as a result of universal twice daily temperature monitoring implemented due to the COVID-19 pandemic. Reports of fever with antipsychotics are typically associated with NMS or heat stroke; the details of this case do not meet the clinical criteria for either. Similar reactions are reported for other antipsychotics, such as clozapine and olanzapine, but not for haloperidol. The recommendation was to discontinue use of the medication due to an unclear mechanism of the reaction.

Insights into the biased activity of dextromethorphan and haloperidol towards SARS-CoV-2 NSP6: in silico binding mechanistic analysis.

The outbreak of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus continually led to infect a large population worldwide. SARS-CoV-2 utilizes its NSP6 and Orf9c proteins to interact with sigma receptors that are implicated in lipid remodeling and ER stress response, to infect cells. The drugs targeting the sigma receptors, sigma-1 and sigma-2, have emerged as effective candidates to reduce viral infectivity, and some of them are in clinical trials against COVID-19. The antipsychotic drug, haloperidol, exerts remarkable antiviral activity, but, at the same time, the sigma-1 benzomorphan agonist, dextromethorphan, showed pro-viral activity. To explore the potential mechanisms of biased binding and activity of the two drugs, haloperidol and dextromethorphan towards NSP6, we herein utilized molecular docking-based molecular dynamics simulation studies. Our extensive analysis of the protein-drug interactions, structural and conformational dynamics, residual frustrations, and molecular switches of NSP6-drug complexes indicates that dextromethorphan binding leads to structural destabilization and increase in conformational dynamics and energetic frustrations. On the other hand, the strong binding of haloperidol leads to minimal structural and dynamical perturbations to NSP6. Thus, the structural insights of stronger binding affinity and favorable molecular interactions of haloperidol towards viral NSP6 suggests that haloperidol can be potentially explored as a candidate drug against COVID-19. KEY MESSAGES: •Inhibitors of sigma receptors are considered as potent drugs against COVID-19. •Antipsychotic drug, haloperidol, binds strongly to NSP6 and induces the minimal changes in structure and dynamics of NSP6. •Dextromethorphan, agonist of sigma receptors, binding leads to overall destabilization of NSP6. •These two drugs bind with NSP6 differently and also induce differences in the structural and conformational changes that explain their different mechanisms of action. •Haloperidol can be explored as a candidate drug against COVID-19.

SARS-CoV-2 orf1b Gene Sequence in the NTNG1 Gene on Human Chromosome 1.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus. It is contagious in humans and is the cause of the coronavirus disease 2019 (COVID-19) pandemic. In the current analysis, we searched for SARS-CoV-2 sequences within the human genome. To compare the SARS-CoV-2 genome to the human genome, we used the blast-like alignment tool (BLAT) of the University of California, Santa Cruz Genome Browser. BLAT can align a user sequence of 25 bases or more to the genome. BLAT search results revealed a 117-base pair SARS-CoV-2 sequence in the human genome with 94.6% identity. The sequence was in chromosome 1p within an intronic region of the netrin G1 (NTNG1) gene. The sequence matched a sequence in the SARS-CoV-2 orf1b (open reading frames) gene. The SARS-CoV-2 human sequence lies within non-structural proteins 14 and 15 (NSP14 and NSP15), and is quite close to the viral spike sequence, separated only by NSP16, a 904-base pair sequence. The mechanism for SARS-CoV-2 infection is the binding of the virus spike protein to the membrane-bound form of angiotensin-converting enzyme 2 and internalization of the complex by the host cell. It is probably no accident that a sequence from the SARS-CoV-2 orf1b gene is found in the human NTNG1 gene, implicated in schizophrenia, and that haloperidol, used to treat schizophrenia, may also be a treatment for COVID-19. We suggest, therefore, that it is important to investigate other haloperidol analogs. Among them are benperidol, bromperidol, bromperidol decanoate, droperidol, seperidol hydrochloride, and trifluperidol. These analogs might be valuable in the treatment of COVID-19 and other coronavirus infections.