AUTOPHAGY AND Acyl-CoA-BINDING PROTEIN INFLUENCE COVID-19 SEVERITY

Background: Autophagy, a cytosolic-structure degradation pathway, allows production of IL21 by CD4 T-cells and efficient cytolytic responses by CD8 T-cells. Autophagy is in part regulated by acyl-CoA-binding protein (ACBP) which has two functions. Intracellular ACBP favors autophagy, whereas secreted extracellular ACBP inhibits autophagy. Herein, we assessed whether autophagy and the ACBP pathway were associated with COVID-19 severity. Method(s): Through the BQC-19 Quebec biobank, somalogic proteomic analysis was performed on 5200 proteins in plasma samples collected between March 2020 and December 2021. Plasma from 903 patients (all data available) during the acute phase of COVID-19 were assessed. COVID-19 severity was stratified using WHO criteria. In vitro, ACBP intracellular levels, autophagy levels (LC3II) and IL21 production were assessed by flow in PBMCs after a 24h stimulation with IL6, phorbol myristate acetate (PMA)+ionomycin or lipopolysaccharide (LPS). Plasma levels of anti-SARS-CoV-2 (full spike protein or RBD) IgG were assessed by ELISA. Result(s): Median age of the cohort was 62 yo, 48% were female, 55% had comorbidities (see table). Increasing plasma levels of ACBP were found with severity (mild, moderate, severe and fatal groups having 5.3, 7.3, 9.5 and 10.6 RFU/50muL of plasma, respectively, p< 0.001 for all comparisons). Patients with comorbidities had higher plasma ACBP levels (7.4 vs 6.4 RFU/50muL, p< 0.001). Plasma ACBP levels were higher during the delta and omicron-variant periods (8.4 vs 6.8 RFU/50muL;p< 0.001). Plasma ACBP levels correlated with LC3II levels (r=0.51, P< 0.001) and IL6 (r=0.41, p< 0.001), but neither with markers IL1beta nor IL8. ACBP levels negatively correlated with IL21 levels (r=-0.27, p< 0.001), independently of age, sex, and severity. ACBP levels were not associated with levels of anti-SARS-CoV-2 IgG levels. In vitro, IL6 stimulation of healthy control PBMC induced extracellular ACBP release. Moreover, adding recombinant ACBP: 1) reduced autophagy in lymphocytes and monocytes upon polyclonal stimulation with PMA/ionomycin or LPS;2) reduced intracellular production of IL21 in T-cells after PMA/ ionomycin stimulation. Conclusion(s): Plasma ACBP levels were inversely linked with IL21 levels, suggesting that autophagy and IL21 allow control of SARS-CoV-2 infection, independently of the level of SARS-CoV-2 antibody secretion. ACBP is a targetable autophagy checkpoint and its extracellular inhibition may improve SARS-CoV-2 immune control. (Table Presented).

Effectiveness and Safety of Nirmatrelvir/ Ritonavir in Real Life Setting

Background and Importance On March 28th 2022, nirmatrelvir/ ritonavir was marketed in Spain. The Spanish Agency for Medicines and Medical Devices (AEMPS) established criteria to prioritise its administration in patients at high risk of progression to severe COVID. Data regarding the effectiveness and safety of nirmatrelvir in preventing severe coronavirus disease outcomes are limited. Aim and Objectives To assess the effectiveness and safety of nirmatrelvir/ritonavir in patients at high risk for severe COVID-19. Material and Methods Prospective descriptive study from April to August 2022 of patients treated with nirmatrelvir/ritonavir. Sociodemographic variables, vaccination status, hospital admission, high risk factors for progression and concomitant treatment were recorded. Readmissions were recorded within 30 days of the end of antiviral treatment. Results 53 patients were included with a mean age of 64 years, 51% women and 49% men. 57% were vaccinated with 3 doses, 17% with 2 doses, 9% with 4 doses, 6% with 1 dose and 11% were not vaccinated. 34% (18/53) were hospitalised at the time of initiation of treatment. The most prevalent high-risk criteria were: 24% active treatment with myelotoxic chemotherapy, 21% treatment in the previous 6 months with anti-CD20 drugs, 14% over 80 years vaccinated with some risk factor for progression, 7% patients with onco-haematological treatment and 7% in treatment in the previous 3 months with inhibitors of the proteinkinase. 3 treatments were performed off-label for persistent covid. The mean number of days from the onset of symptoms to the start of treatment was 1.6 days. 23% of patients required dose adjustment due to renal impairment. 53% required adjustment of chronic treatment for interactions, mainly with metamizole, statins, fentanyl and diazepam. 2 patients received remdesivir and sotrovimab, 2 remdesivir and another two sotrovimab. 4 (7%) patients were readmitted within 30 days after the end of treatment with nirmatrelvir ritonavir, 1 of them with persistent covid. One patient stopped treatment for hives. Conclusion and Relevance Nirmatrelvir ritonavir has been shown to be a safe and effective drug in high-risk patients of progression to severe covid.

A fall in isolation: reflection on a complex case

This case review focuses on a male patient who had fallen and was found to be profoundly hypothermic, with an altered level of consciousness and evidence of seizure activity. With multiple time-critical features, this clinical presentation was made particularly challenging by the presence of several human factors. A reflective model that considered these human factors in the context of the COVID-19 pandemic, when this incident occurred, was employed. Reflecting on this incident revealed how some subconscious (intuitive) thinking led to a degree of unconscious bias compounded by availability heuristics and human factors present. This meant that the author encountered difficulty when trying to obtain peripheral vascular access and, although several alternative interventions were identified, the majority of these were unavailable at the time and some would require a change to standard clinical practice for many paramedics. The only intervention that could have been used earlier in the management of this patient was rectal diazepam, but the need for this was removed by the patient's seizure activity self-terminating. Given the increasing prevalence of falls, social isolation, mental health problems, alcohol and substance misuse, especially in the pandemic, this type of case was unlikely to be an isolated event, strengthening the argument that the range of clinical interventions available to paramedics should be increased.

CAN THE SYSTEMIC IMMUNE-INFLAMMATION INDEX, THE NEUTROPHIL-LYMPHOCYTE RATIO, AND THE PLATELET-LYMPHOCYTE RATIO HELP ASSESS PROGNOSIS OF SARS-COV-2 PNEUMONIA?

SESSION TITLE: Late Breaking Chest Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: To identify the association between SII, NLR and PLR and the prognosis in SARS-CoV-2 pneumonia. METHODS: A cross-sectional study that took place in Tacuba General Hospital, Mexico City. Adults hospitalized with SARS-CoV-2 infection were included. Descriptive statistic was made using Mann-Whitney's U test. Spearman’s Rank correlation coefficient was calculated. The risk of invasive mechanical ventilation (IMV) and mortality was calculated for each index with logistic regression. The analysis was made using the STATA 14.0 program. RESULTS: The current analysis included 295 subjects, 64% men. There was difference in SII and NLR levels between subjects who died and those who did not. Females with acute respiratory distress syndrome had a positive correlation for each index and length of stay: for SII rs=0.739;for NLR rs=0.689;for PLR rs=0.649. Males had weak correlations. The risk of IMV with SII exceeding its cutoff value had an odds ratio of 2.50 (95% CI 1.38-4.51);a higher risk for IMV with NLR above its reference was detected (OR 2.34, 95% CI 1.36-4.05). Also, the elevated SII and NLR levels had an increased risk of mortality;for SII an OR 2.54 (95% CI 1.55-4.15);for NLR an OR 2.16 (95% CI 1.35-3.46). Statistical significance was considered with p=<0.05. CONCLUSIONS: These indexes are an accessible and low-cost tool that can help assess the prognosis of patients hospitalized for SARS-CoV-2 pneumonia. CLINICAL IMPLICATIONS: The SII, NLR and PLR could be useful in identifying patients at risk of death or severe illness who require invasive mechanical ventilation in the earlier phase of SARS-CoV-2 pneumonia. As these indexes are easily quantified from blood sample data, they can reflect the body’s immune status and help assess the prognosis of SARS-CoV-2 pneumonia. DISCLOSURES: No relevant relationships by Amaury Bravo Rodríguez No relevant relationships by JAVIER FIESCO PIÑA No relevant relationships by José Antonio García Cuéllar No relevant relationships by Ruben Antonio Gomez Mendoza No relevant relationships by Damayanty Gomez villanueva No relevant relationships by Karen Hopf Estandía No relevant relationships by Eduardo León Guadarrama No relevant relationships by Alma Daniela Martinez Carrillo No relevant relationships by José Peña Ramírez No relevant relationships by José Pérez Nieto No relevant relationships by Mariela Rosas García No relevant relationships by Fernando Sánchez Mata No relevant relationships by Damayanty Solis Contreras

ACUTE DIGITAL GANGRENE TRIGGERED BY COVID-19 COAGULOPATHY

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: As the coronavirus pandemic continues to burden the global health care system, strong associations have emerged with hypercoagulability. Recent reports of Covid-19 support both venous and arterial thromboembolism, thus coagulopathy emerging as one of the most severe sequelae of the disease, which has also been associated with poorer outcomes. CASE PRESENTATION: A 71-year-old female with a past medical history of hypertension, type 2 diabetes, and obesity presented with progressively worsening shortness of breath and cough. She was found to be hypoxic to 80% on arrival and tested positive for COVID-19. She was subsequently intubated and admitted to the ICU. Her D-dimer was noted to be 9.04mcg/mLFEU (0-0.55mcg/mLFEU), ferritin 256ng/mL(10-291ng/mL), LDH 707 U/L(130-270U/L), CRP 138mg/L (< 10mg/L). She was treated with a ten-day course of dexamethasone and a five-day course of Remdesivir. On Day 7, purple discoloration was noted in the second to fifth digits of the left hand, concerning acute ischemia. Left upper extremity ultrasound revealed intraluminal heterogeneous echogenicity likely occlusive ulnar arterial thrombus with no flow to mid or distal segment and normal flow in the radial artery into a complete palmar arch. This was seen to be classical for micro-embolic phenomenon attributable to the hypercoagulable state associated with Covid-19 infection. Treatment with Heparin drip was initiated along with the local application of nitro paste. The patient was subsequently discharged home but re-presented a month later for gastrointestinal bleeding. At this admission, her left second digit was noted to express purulent drainage. Imaging confirmed osteomyelitis in the second through fifth digits and was referred to a tertiary center for definitive treatment. DISCUSSION: Covid-19 has been shown to provoke catastrophic inflammatory responses by triggering a dysfunctional cascade of thrombosis in the pulmonary vasculature leading to both micro and macroangiopathic manifestations. The quick progression of ischemia to digital gangrene, despite collateral circulation and early intervention, indicates severe microangiopathy. CONCLUSIONS: Thus physicians must always have a high index of suspicion for thromboembolic complications in patients with Covid-19. The development of severe complications despite prompt anticoagulation highlights the need for alternative or newer therapies like targeted immunotherapy that would effectively manage these complications of SARS-CoV-2. Reference #1: Digital Gangrene as a Sign of Catastrophic Coronavirus Disease 2019-related Microangiopathy Jessica S. Wang, MD,* Helena B. Pasieka, MD, MS,† Vesna Petronic-Rosic, MD, MSc, MBA,† Banafsheh Sharif-Askary, MD,* and Karen Kim Evans, MDcorresponding author Reference #2: Galván Casas C, Català A, Carretero Hernández G, Rodríguez-Jiménez P, Fernández-Nieto D, Rodríguez-Villa Lario A, Navarro Fernández I, Ruiz-Villaverde R, Falkenhain-López D, Llamas Velasco M, García-Gavín J, Baniandrés O, González-Cruz C, Morillas-Lahuerta V, Cubiró X, Figueras Nart I, Selda-Enriquez G, Romaní J, Fustà-Novell X, Melian-Olivera A, Roncero Riesco M, Burgos-Blasco P, Sola Ortigosa J, Feito Rodriguez M, García-Doval. Classifications of the cutaneous manifestations of Covid-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020 Jul;183(1):71-77. doi: 10.1111/bjd.19163. Epub 2020 Jun 10. Reference #3: Mouhamed Yazan Abou-Ismail 1, Akiva Diamond 2, Sargam Kapoor 3, Yasmin Arafah 2, Lalitha Nayak 4.The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management Thromb Res. 2020 Oct;194:101-115. doi: 10.1016/j.thromres.2020.06.029. Epub 2020 Jun 20. DISCLOSURES: No relevant relationships by Navyamani Kagita No relevant relationships by ABHIGNA KULKARNI No relevant relationships by Rajesh Thirumaran

Prescribing practices in a UK Intensive Care Unit during the first wave of the COVID-19 pandemic

Introduction: Comparatively little is known about drug requirements in patients admitted to ICU with COVID-19 pneumonitis. We analysed drug usage for patients admitted during the first wave of the pandemic, comparing these with a retrospective cohort admitted with Influenza pneumonia. Methods: Forty-nine ventilated patients with COVID-19 pneumonitis were identified through ICNARC, ten were excluded as duration of stay < 7 days or not needing ventilation. Further three were excluded due to missing data and one due to ECMO escalation. Results: The median age was 61 years;length of stay 22 days and 68% survived ICU. Table 1 describes the use of Infusions and enteral medications. Discussion: Propofol was used in most (43% patient-hours in ICU/median duration = 234 hours). All patients received opiate infusions (mainly morphine or alfentanil in similar proportions) and 91% received muscle relaxants, for prolonged periods. Over half received Midazolam (median 106 hours) as an adjunct or substitute to Propofol as patients were difficult to sedate, required longer ventilation, paralysis and concerns with Propofol associated hypertriglyceridemia. Over two-third received alpha agonist infusions (median 68.5 hours) as adjunctive sedation or delirium management. Three quarters of patients received a furosemide infusion (median 90 hours), the evidence extrapolated from studies such as FACTT.1 Around three quarters received Human Albumin (median 100 grams over 3 days). Nearly a quarter received nebulized Prostacyclin for refractory hypoxia, often associated with saturation of HME filters and ventilatory difficulties.2 Over half of patients received Carbocisteine (median 13 days). Clonidine and Risperidone to manage delirium were used in a third (median 10.5 and 11 days respectively), as was Acetazolamide to restore pH and aid weaning. Over a third were prescribed enteral opiates and nearly a quarter received benzodiazepines to manage withdrawal symptoms. Just under a half of patients received Melatonin. Antibiotic usage was high with a median of 3 Antibiotics used (median duration 15 days/61% of patient days). Diagnosing superadded infection such as VAP was challenging3 and we did not routinely monitor serum Procalcitonin levels. We also compared prescribing habits with 12 influenza patients (11 survivors) identified using similar inclusion criteria and found patients with COVID-19 were older (61 versus 51 years ) with longer ICU stays (median 22 versus 20 days). They were also more likely to receive enteral Carbocisteine, Clonidine, Acetazolamide, Morphine and Diazepam. Conclusion: We were able to generate valuable data on prescribing in ventilated patients with COVID-19 pneumonitis during the first wave. Through this, we are able to use drug usage as a surrogate for issues such as delirium, drug withdrawal, antibiotic prescribing and nursing workload in general.

Alcohol Use and misuse during the COVID-19 pandemic

GPs can play a pivotal role in the identification and management of alcohol problems at any time, and their role is even more important during the COVID-19 pandemic as more and more patients are resorting to alcohol to manage the stress and anxiety created by the pandemic. © 2021 Medicine Today Pty Ltd. All rights reserved.

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.

Patterns of benzodiazepine consumption before and during the COVID-19 pandemic in the azores archipelago population

Background: The Azores, an autonomous region of Portugal, is an nine islands archipelago in the Atlantic Ocean, were mental health concerns have long been present. The pandemic of COVID-19, declared in march 2020, has put additional strain health systems. Moreover, there are initial signs that depression and anxiety's prevalence is expected to increase. Monitoring consumption can be an indirect way of assessing medicines' adherence and accessibility. Purpose: To explore how the pandemic of COVID-19 impacted the consumption of anxiolytics, the aim of this study was to assess patterns of Benzodiapezine consumption in the Azorean population, one year before and one year after the beginning of the COVID-19 pandemic. Method: For this ecological study, the Benzodiazepines consumption database was obtained from hMR, a health market research company. This database contains information relative to the total number of all benzodiazepines acquired in the Portuguese market, organized by Anatomical Therapeutic Chemical (ATC) classification, and information relative to dosage and package size. The number of total sold packages per drug was obtained for the years 2019 and 2020. Azorean population was obtained from government official data. The defined daily dose (DDD) was obtained from the WHO ATC/DDD index website, and the DDD/1000hab./day was calculated. Only oral dosage forms were analysed. Descriptive and inferential statistical analysis was performed to assess yearly, biannual and quarterly drug consumption and uncover seasonal trends. Findings: Total benzodiazepine acquisition pattern in DDD/1000hab/day was not different between 2019 and 2020 (p = 0.987). The most consumed benzodiazepines were alprazolam 69.5 DDD/1000hab/day (± 4.3), followed by diazepam 27.1 (± 1.7) and lorazepam 26.7 (± 1.5).Only clonazepam and potassium clorazepate showed a significant increase from 2019 to 2020 (p = 0.001 and p = 0.003). The maximum of total DDD/1000hab/day was registered at the onset of the pandemic (march 2020). For the remaining of 2020, higher standard deviations were observed. Two other peaks are noticed in july 2019 and july 2020, exceptions to the apparent seasonal effect with a biannual period of higher DDD/1000hab/day in the winter months (r2 = 0.567). Conclusion: The pandemic of COVID-19 did not aggravate the consumption of benzodiazepines in the Azorean population. However, a change in the pattern of benzodiazepines' acquisition during 2020, was noticed. Patients might have avoided frequent visits to health services and pharmacies in order to decrease the risk of COVID-19 infection. Nevertheless, the adherence is unclear, and should be further investigated. A weak seasonal pattern in benzodiazepine consumption in the Azorean population was also found.

Impact the pandemic by the new Coronavirus on the consumption profile of anxiolytics and antidepressants in the Primary Health Care of the Federal District, Brazil

The new Coronavirus pandemic provided an increase in psychosocial vulnerability and the aggravation of preexisting pathologies, such as depression and anxiety. This work aimed to evaluate the impact of theCOVID-19 pandemic on the consumption of anxiolytics and antidepressants at UBS 4 in Recanto das Emas - Distrito Federal through an observational, cross-sectional study that analyzed the consumption of anxiolytics and antidepressants in the period between February and August 2019 and 2020, using the average monthly consumption and the number of visits. In addition, information on sex and age was also verified to draw a profile of consumption of these medications. Of the 7 medications evaluated, all showed an increase in consumption in 2020, this being 181.90%, 124.36%, 325.33%, 125%, 12.80%, 22.18% and 6.45% for fl uoxetine 20 mg, amitriptyline 25 mg, imipramine 25 mg, clomipramine 75 mg, diazepam 5 mg, clonazepam 2 mg and clonazepam 2.5 mg/mL respectively. There was a predominance of females and the population aged between 20 and 59 years as major consumers of these drugs. In general, there was a greatimpact on the consumption profiles of psychotropic drugs in the period evaluated.

Assessment of alprazolam abuse: Data from the French addictovigilance network

Introduction: Alprazolam is a high potency and short-acting anxiolytic benzodiazepine. Alprazolam was one of the most misused benzodiazepines during the first lockdown related to the Covid-19 pandemic [1]. Thus, an evaluation of the abuse of alprazolam was requested by the French Medicines Agency. Material and methods: Analysis of the epidemiological tools of the French Addictovigilance network (FAN) over the period 2011-2020: spontaneous notifications (NotS), supplemented by data collected in addictology care centers (OPPIDUM), false prescriptions (OSIAP), substance-related deaths (DRAMES), and chemical submission data. Results: During the study period, among the 675 NotS analysed, women were slightly in the majority (51.7%), and the median age of users was 39 years. The desired effects were the intensification of the therapeutic or recreational effects, a euphoric effect and the management of withdrawal from other substances (opioids, psychostimulants). Regarding tools, a male predominance (60-72%) was observed with an age of approximately 35-39 years. Alprazolam was the 3rd benzodiazepine listed in OPPIDUM after diazepam and oxazepam. Analysis of NotS and OPPIDUM showed a recent increase in the combination of alprazolam and opioids. In DRAMES, alprazolam was found in 10 deaths/11. Regarding CHEMICAL SUBMISSION, alprazolam was the 1st benzodiazepine reported in 2019. Finally, in the OSIAP survey, alprazolam was in 2020 the 5th drug cited and the first benzodiazepine ahead of bromazepam, diazepam and oxazepam (citation rate: 7.8%, slightly increasing since 2019). It should also be noted a rejuvenation of this population and an increase in the proportion of men during the study period. Discussion/Conclusion: Analysis of FAN data showed an increase in criteria for abuse: false prescriptions and users seen in drug addiction care centres. In addition, the increase of the alprazolam-opioid combination and the significant part of this association in deaths constitute a signal already observed in the international literature and to be investigated [2].

INCREASE IN THE PRESCRIPTION OF BENZODIAZEPINES IN THE CONTEXT OF THE SARSCOV- 2 PANDEMIC

Background and importance The most frequently recorded mental health problem is anxiety disorder and in the context of the SARS-CoV-2 pandemic, where an increase in anxiety cases has been evidenced, benzodiazepine derivatives (N05BA) have been one of the most prescribed pharmacological groups in most developed countries for this problem. Although their short-term benefits have been demonstrated, increasing their consumption may have longterm risks. Aim and objectives The main aim of this study was to find out the prescriptions of benzodiazepine derivatives from 2018 to 2021 in the context of the SARS-CoV-2 pandemic and the variation in them. A secondary objective was to learn which benzodiazepine derivatives varied more. Material and methods Retrospective, observational and crosssectional study. The study period included June 2018, June 2019, June 2020 and June 2021. The study population included the 710 581 inhabitants associated with the prescribing doctors of benzodiazepine derivatives from the study province. Results Total study population N=710 581;21.61% (153.574) with a benzodiazepine prescription, 67.33% (103 416) women, between June 2018 and June 2021. The prescribed benzodiazepine derivatives were: alprazolam, diazepam, diazepam/pyridoxine, clotiazepam, lorazepam, ketazolam, clobazam, pinazepam, clorazepato dipotassium, bromazepam, bentazepam, diazepam/sulpiride and diazepam/sulpiride/ pyridoxine. June 2018: 35 800 prescriptions, 67.30% (24 085) women;June 2019: 37 601, 67.20% (25 262) women;June 2020: 39 547, 67.30% (26 622) women;and June 2021: 40 626, 67.60% (27.477) women. From June 2018 to June 2019 prescriptions increased 5.03% (1801), from June 2019 to June 2020 they increased 5.20% (1946);and from June 2020 to June 2021 they increased 2.73% (1079), which represented a 13.48% increase in prescriptions (4826) from June 2018 to June 2021. The largest prescription increases were diazepam +23%, lorazepam +18%, bromazepam +12.5%, and alprazolam +12.3%. The largest prescription decreases were clotiazepam and bentazepam -100%, pinazepam -96.43% and clobazazam - 22.45%. Conclusion and relevance In the context of the SARS-CoV-2 pandemic we have seen a progressive increase in benzodiazepines of 13.48% (4826 prescriptions) from June 2018 to June 2021, with women being the users of 67.33% of prescriptions on average. These data allow us to know the current situation of the prescription of benzodiazepine derivatives to the population and to focus on mental health both in the validation of treatments and in pharmaceutical care.

42nd International Congress of the European Association of Poisons Centres and Clinical Toxicologists

The proceedings contain 209 papers. The topics discussed include: an illicit drug early warning system utilizing comprehensive toxicological analysis of emergency department presentations in Victoria, Australia;4-fluoroamphetamine (4-FA) intoxication results in exaggerated blood pressure effects compared to 3,4-methylenedioxymethamphetamine (MDMA) and amphetamine: a retrospective analysis;single nucleotide polymorphisms of mu opioid receptor gene OPRM1 in emergency department patients with acute opioid overdose;ketamine in acute recreational poisonings in the Balearic Islands;the neuro-respiratory effects of pregabalin and the potential deleterious effects of its combination with diazepam or morphine ? a rat investigation;cobaltism from metal-on-metal (MoM) hip implants: how to manage and treat with acetylcysteine;analytically-confirmed polydrug use is more common in drug misuse patients attending emergency departments in Scotland compared with those in England and Wales;and it is not always COVID-19: a case of respiratory failure from lung damage associated with electronic cigarettes (EVALI).

Proposed protocol for the investigation of the safety and efficacy of the COVID-19 vaccine for patients with psychosis, with pilot safety findings from a Chinese psychiatrist's self-experiment

We present a study protocol designed to test the safety and efficacy of the 2019 coronavirus disease (COVID-19) vaccine in patients with major psychotic disease. A secondary objective is to investigate optional vaccination methods for these patients. In a self-experiment, a Chinese psychiatrist examined the safety and efficacy of the COVID-19 vaccine under clinical use of typical antipsychotic agents and sedatives (olanzapine, duloxetine, and diazepam). For patients with extremely drug-resistant conditions, the safety of the COVID-19 vaccine under electroconvulsive therapy was also investigated. The entire study process was recorded on high-definition video. This clinical study protocol is, to our knowledge, the first of its kind. Our findings will shed new light on the protection of patients with psychotic diseases from COVID-19 infection.

The use of phenobarbital in ECMO

INTRODUCTION: A high prevalence of critically ill patients have difficulty obtaining an appropriate level of sedation. Additional challenges may arise in patients requiring extracorporeal membrane oxygenation (ECMO). The utility of phenobarbital, a barbiturate sedative hypnotic that produces sedation through GABAA receptor agonism, in adult ECMO patients has yet to be described within the literature. DESCRIPTION: A 46-year-old male (95 kg) with asthma, hyperlipidemia and recently diagnosed COVID19, was admitted to the ICU for acute hypoxic respiratory failure and subsequently initiated on VV ECMO. By day 13, his sedation regimen consisted of the following: hydromorphone 12 mg/hr, midazolam 15 mg/hr, ketamine 1.4 mg/kg/hr and dexmedetomidine 1.4 mcg/kg/min, along with oral diazepam 15 mg every 6 hours. Propofol use was limited because of hypertriglyceridemia. Despite this, he was dyschronous with the ventilator. A recommendation was made to use phenobarbital. The patient was loaded with 10 mg/kg using ideal body weight (IBW), followed by 1 mg/kg twice daily. At steady state, a serum level was checked and resulted at 10.8 ug/mL. Simultaneously, the patient was more synchronous and did not require any escalation in sedation. Following a decompensatory event, a repeat bolus of 5 mg/kg IBW was given, followed by a 2 mg/kg twice daily regimen. A second steady state level was checked and resulted at 16.7 ug/mL. DISCUSSION: This case highlights the potential role for phenobarbital in ECMO patients refractory to conventional sedation, and sheds light on pharmacokinetic (PK) considerations. Phenobarbital is a relatively lipophilic drug with a LogP value of 1.47 and limited protein binding (48% protein bound). Given this PK profile, we anticipated that the degree of sequestration in the ECMO circuit would be low. We performed therapeutic drug monitoring and obtained serum levels at steady state and compared the findings to non-ECMO patients. Although no optimal phenobarbital level for sedation has been defined, extrapolation from therapeutic levels for epilepsy (15-40 ug/mL) was made. Based on our results, we concluded that limited drug sequestration occurred within the circuit and no dosing adjustment may be needed. The standard dose may be similar to non- ECMO patients and should be guided by therapeutic drug monitoring.

Treatment of Catatonia with Asenapine in a Patient with Schizotypal Personality Disorder, Psychotic Depression and Septic Shock from SARSCoV- 2 - A Case Report.

INTRODUCTION: Catatonia is a psychomotor syndrome that presents with severe symptoms which can lead to dangerous and lethal conditions if not diagnosed and treated properly. SARS-- CoV-2 is a positive-sense single-stranded RNA virus that can occur in severe cases with acute pneumonia, ARDS, sepsis and septic shock. In these cases, ICU admission is necessary. CASE SUMMARY: A 59-year-old Caucasian man with septic shock and bilateral interstitial pneumonia from SARS-CoV-2 and schizotypal personality disorder presented with catatonic behaviour manifested by soporous state, response to intense painful stimuli with the opening of the eyes, execution of simple verbal commands, maintenance of the same position, catalepsy, immobility, rigidity and mutism. At the same time, there were symptoms of septic shock and catatonic symptoms, causing greater difficulty in the correct formulation of the diagnosis. During the course of his hospitalization, he was treated with asenapine 20 mg/day. The catatonia responded rapidly and significantly to the asenapine. DISCUSSION: To date, the pathophysiology of catatonia is unclear, and few guidelines are available for the treatment of catatonia. In the literature, studies have reported the efficacy of benzodiazepines such as lorazepam and diazepam, GABAA agonists such as zolpidem, NMDA receptor antagonists such as memantine, antidepressant SSRIs such as fluoxetine and paroxetine, and antipsychotics such as olanzapine, clozapine and aripiprazole. We demonstrate that the antipsychotic asenapine is also effective in treating catatonic symptoms in psychiatric disorders. CONCLUSION: Asenapine produced a rapid and significant reduction in catatonic symptoms in our patient with schizotypal personality disorder.

Utility of Hypertonic Saline and Diazepam in COVID-19-Related Hydroxychloroquine Toxicity.

BACKGROUND: Hydroxychloroquine (HCQ) poisoning is a life-threatening but treatable toxic ingestion. The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and the controversial suggestion that HCQ is a treatment option have led to a significant increase in HCQ use. HCQ poisoning should be at the top-of-mind for emergency providers in cases of toxic ingestion. Treatment for HCQ poisoning includes sodium bicarbonate, epinephrine, and aggressive electrolyte repletion. We highlight the use of hypertonic saline and diazepam. CASE REPORT: We describe the case of a 37-year-old man who presented to the emergency department after the ingestion of approximately 16 g of HCQ tablets (initial serum concentration 4270 ng/mL). He was treated with an epinephrine infusion, hypertonic sodium chloride, high-dose diazepam, sodium bicarbonate, and aggressive potassium repletion. Persistent altered mental status necessitated intubation, and he was managed in the medical intensive care unit until his QRS widening and QTc prolongation resolved. After his mental status improved and it was confirmed that his ingestion was not with the intent to self-harm, he was discharged home with outpatient follow-up. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: For patients presenting with HCQ overdose and an unknown initial serum potassium level, high-dose diazepam and hypertonic sodium chloride should be started immediately for the patient with widened QRS. The choice of hypertonic sodium chloride instead of sodium bicarbonate is to avoid exacerbating underlying hypokalemia which may in turn potentiate unstable dysrhythmia. In addition, early intubation should be a priority in vomiting patients because both HCQ toxicity and high-dose diazepam cause profound sedation.

Chloroquine, hydroxychloroquine and COVID-19.

The media have featured the antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) to treat coronavirus (COVID-19). Political leaders have touted their use and recommended availability to the public. These anti-inflammatory agents have substantial human toxicity with a narrow therapeutic window. CQ and HCQ poisoning cause myocardial depression and profound hypotension due to vasodilation. Bradycardia and ventricular escape rhythms arise from impaired myocardial automaticity and conductivity due to sodium and potassium channel blockade. With cardiotoxicity, ECGs may show widened QRS, atrioventricular heart block and QT interval prolongation. CQ may also cause seizures, often refractory to standard treatment. Of concern is pediatric poisoning, where 1-2 pills of CQ or HCQ can cause serious and potentially fatal toxicity in a toddler. The treatment of CQ/HCQ poisoning includes high-dose intravenous diazepam postulated to have positive ionotropic and antidysrhythmic properties that may antagonize the cardiotoxic effects of CQ. Infusions of epinephrine titrated to treat unstable hypotension, as well as potassium for severe hypokalemia may be required. Current scientific evidence does not support treatment or prophylactic use of these agents for COVID-19 disease. Regulatory and public health authorities recognize that CQ/HCQ may offer little clinical benefit and only add risk requiring further investigation before wider public distribution.