Clinical use of remdesivir in COVID-19 treatment: a retrospective cohort study.

OBJECTIVES: This study investigated remdesivir's clinical use to provide direct evidence of effectiveness for a low-middle income Asian setting. DESIGN: A one-to-one propensity score matching retrospective cohort study. SETTING: A tertiary hospital with COVID-19 treatment facilities in Vietnam. PARTICIPANTS: A total of 310 patients in standard of care (SoC) group were matched with 310 patients in SoC+remdesivir (SoC+R) group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was time to critical progression, defined as all-cause mortality or critical illness. The secondary outcomes were length of oxygen therapy/ventilation and need for invasive mechanical ventilation. Outcome reports were presented as HR, OR or effect difference with 95% CI. RESULTS: Patients receiving remdesivir had a lower risk for mortality or critical illness (HR=0.68, 95% CI 0.47 to 0.96, p=0.030). Remdesivir was not associated with a shorter length of oxygen therapy/ventilation (effect difference -0.17 days, 95% CI -1.29 to 0.96, p=0.774). The need for invasive mechanical ventilation was lower in SoC+R group (OR=0.57, 95% CI 0.38 to 0.86, p=0.007). CONCLUSIONS: This study's results showing remdesivir's benefits in non-critical patients with COVID-19 may be extrapolated to other similar low-middle income countries, allowing more regimens for limited resource areas and reducing poor outcomes and equity gap worldwide.

Pregnancy exposure registries for drugs and vaccines in low-income and middle-income countries: scoping review protocol.

INTRODUCTION: Data regarding the safety of drugs and vaccines in pregnant women are typically unavailable before licensure. Pregnancy exposure registries (PERs) are an important source of postmarketing safety information. PERs in low-income and middle-income countries (LMICs) are uncommon but can provide valuable safety data regarding their distinct contexts and will become more relevant as the introduction and use of new drugs and vaccines in pregnancy increase worldwide. Strategies to support PERs in LMICs must be based on a better understanding of their current status. We developed a scoping review protocol to assess the landscape of PERs that operate in LMICs and characterise their strengths and challenges. METHODS AND ANALYSIS: This scoping review protocol follows the Joanna Briggs Institute manual for scoping reviews. The search strategy will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Checklist. We will search PubMed, Embase, CINAHL and WHO's Global Index Medicus, as well as the reference lists of retrieved full-text records, for articles published between 2000 and 2022 that describe PERs or other resources that systematically record exposures to medical products during pregnancy and maternal and infant outcomes in LMICs. Title and abstracts will be screened by two authors and data extracted using a standardised form. We will undertake a grey literature search using Google Scholar and targeted websites. We will distribute an online survey to selected experts and conduct semistructured interviews with key informants. Identified PERs will be summarised in tables and analysed. ETHICS AND DISSEMINATION: Ethical approval is not required for this activity, as it was determined not to involve human subjects research. Findings will be submitted to an open access peer-reviewed journal and may be presented at conferences, with underlying data and other materials made publicly available.

Chronic spontanous urticaria following anti-covid 19 vaccine: Is there a link?

Background: Urticarial reactions following Covid-19 vaccine were rarely reported and have a short self-limited resolution. However only one case of chronic spontaneous urticaria (CSU) after mRNA vaccine was observed (1). Herein, we describe an original case series of patients who exhibited a CSU after Sars-Cov- 2 vaccination. Method(s): It was a retrospective case series of patients referred to the department of Clinical pharmacology of the University of Monastir for exploration of urticaria after Covid-19 vaccination., between January 2021 and January 2022. Result(s): Eight patients (8 F /5M) were included in this study. The median patient age was 36.5 years. None of them had a medical history of CSU. Urticaria was reported in 4 patients following mRNA vaccine (BNT162b2 and Moderna). Viral vector vaccine (Oxford/ AstraZeneca) was offended in 2 cases and inactivated virus vaccine (Sinovac, CoronaVac) was reported in 2 others cases. The mean time interval between vaccination and the onset of urticaria was 28.5 hours. The first shot of vaccine was the mostly offended dose (n = 6). Urticaria was associated with angioedema in 5 patients after Oxford/AstraZenecavaccine (n = 2) and following mRNA vaccine (n = 2). One case of urticaria was associated with angioedema and dyspnea after the CoronaVac administration. Blood tests showed polynuclear leucocytosis in 37% of patients. Positive anti-thyroperoxidase antibodies, and elevated polyclonal hypergammaglobulinemia were present in one patient 3 months after receiving BNT162b2 vaccine. Total serum IgE were high in 25% of patients following BNT162b2 and CoronaVac. All patients required antihistamines and 4 cases required intravenous betametasone. The median time to symptom resolution was 3 days but urticaria rapidly reccured throughout the entire body inspite the regular use of full dose of antihistamine. Intradermal test for the vaccine excipient as well as the offended Covid-19 vaccine was carried out in 5 patients, and were negative in all of them.Currently, all patients still has the pruritic rash daily. Conclusion(s): These cutaneous reactions seem to be particularly prolonged despite the use of symptomatic drugs, as compared with of drug induced-urticaria. Consequently, careful monitoring of urticaria over an extended period of time is needed.

The perspective of clinical pharmacologist: what is the safety of complex polypharmacy in hospitalized COVID-19 patients?

Introduction: For today, in order to improve the prognosis of COVID-19 treatment outcome, the most urgent task is the rational and safe use of medicines in case of required polypharmacy. Aim(s): To assess the safety of provided complex pharmacotherapy in hospitalized COVID-19 patients. Method(s): Single-center retrospective study of medical records of 590 COVID-19 patients hospitalized during 08.2021-10.2021. The information concerning drug prescriptions from patients' medication's charts was collected and processed using descriptive statistics. Result(s): The frequency of different medication groups' prescriptions with certain drugs is presented in Figure 1. The median number of concurrent prescribed drugs stood at 6(3;9). Notably, coadministration of glucocorticoids and anticoagulants along with antibiotics and antifungals increases the risks of hepatonephrotoxicity and GI bleeding. Conclusion(s): Analysis showed that complex pharmacotherapy of COVID-19 patients was provided according to the protocols. Nevertheless, from the point of view of clinical pharmacology, the combination of the above-mentioned drugs groups may increase the risk of side effects. Therefore, even standard treatment requires monitoring of the patient's clinical condition and laboratory parameters to increase the medication safety of personalized complex polypharmacy. (Figure Presented).

Antidepressant Advisor (ADeSS): a decision support system for antidepressant treatment for depression in UK primary care - a feasibility study.

OBJECTIVES: To develop and probe the first computerised decision-support tool to provide antidepressant treatment guidance to general practitioners (GPs) in UK primary care. DESIGN: A parallel group, cluster-randomised controlled feasibility trial, where individual participants were blind to treatment allocation. SETTING: South London NHS GP practices. PARTICIPANTS: Ten practices and eighteen patients with treatment-resistant current major depressive disorder. INTERVENTIONS: Practices were randomised to two treatment arms: (a) treatment-as-usual, (b) computerised decision support tool. RESULTS: Ten GP practices participated in the trial, which was within our target range (8-20). However, practice and patient recruitment were slower than anticipated and only 18 of 86 intended patients were recruited. This was due to fewer than expected patients being eligible for the study, as well as disruption resulting from the COVID-19 pandemic. Only one patient was lost to follow-up. There were no serious or medically important adverse events during the trial. GPs in the decision tool arm indicated moderate support for the tool. A minority of patients fully engaged with the mobile app-based tracking of symptoms, medication adherence and side effects. CONCLUSIONS: Overall, feasibility was not shown in the current study and the following modifications would be needed to attempt to overcome the limitations found: (a) inclusion of patients who have only tried one Selective Serotonin Reuptake Inhibitor, rather than two, to improve recruitment and pragmatic relevance of the study; (b) approaching community pharmacists to implement tool recommendations rather than GPs; (c) further funding to directly interface between the decision support tool and self-reported symptom app; (d) increasing the geographic reach by not requiring detailed diagnostic assessments and replacing this with supported remote self-report. TRIAL REGISTRATION NUMBER: NCT03628027.

Colchicine and high-intensity rosuvastatin in the treatment of non-critically ill patients hospitalised with COVID-19: a randomised clinical trial.

OBJECTIVE: To evaluate the effect of colchicine and high-intensity rosuvastatin in addition to standard of care on the progression of COVID-19 disease in hospitalised patients. DESIGN: A pragmatic, open-label, multicentre, randomised controlled trial conducted from October 2020 to September 2021. Follow-up was conducted at 30 and 60 days. The electronic medical record was used at all stages of the trial including screening, enrolment, randomisation, event ascertainment and follow-up. SETTING: Four centres in the Yale New Haven Health System. PARTICIPANTS: Non-critically ill hospitalised patients with COVID-19. INTERVENTIONS: Patients were randomised 1:1 to either colchicine plus high-intensity rosuvastatin in addition to standard of care versus standard of care alone. Assigned treatment was continued for the duration of index hospitalisation or 30 days, whichever was shorter. PRIMARY AND SECONDARY OUTCOME MEASURES: The prespecified primary endpoint was progression to severe COVID-19 disease (new high-flow or non-invasive ventilation, mechanical ventilation, need for vasopressors, renal replacement therapy or extracorporeal membrane oxygenation, or death) or arterial/venous thromboembolic events (ischaemic stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism) evaluated at 30 days. RESULTS: Among the 250 patients randomised in this trial (125 to each arm), the median age was 61 years, 44% were women, 15% were Black and 26% were Hispanic/Latino. As part of the standard of care, patients received remdesivir (87%), dexamethasone (92%), tocilizumab (18%), baricitinib (2%), prophylactic/therapeutic anticoagulation (98%) and aspirin (91%). The trial was terminated early by the data and safety monitoring board for futility. No patients were lost to follow-up due to electronic medical record follow-up. There was no significant difference in the primary endpoint at 30 days between the active arm and standard of care arm (15.2% vs 8.8%, respectively, p=0.17). CONCLUSIONS: In this small, open-label, randomised trial of non-critically ill hospitalised patients with COVID-19, the combination of colchicine and rosuvastatin in addition to standard of care did not appear to reduce the risk of progression of COVID-19 disease or thromboembolic events, although the trial was underpowered due to a lower-than-expected event rate. The trial leveraged the power of electronic medical records for efficiency and improved follow-up and demonstrates the utility of incorporating electronic medical records into future trials. TRIAL REGISTRATION: NCT04472611.

Assessing medication use patterns in patients hospitalised with COVID-19: a retrospective study.

OBJECTIVE: To describe patterns of medication use-that is, dexamethasone; remdesivir; and tocilizumab-in the management of patients hospitalised with COVID-19. DESIGN AND SETTING: Retrospective observational study, using routinely collected, linked electronic data from clinical practice in Scotland. Data on drug exposure in secondary care has been obtained from the Hospital Electronic Prescribing and Medicines Administration System. PARTICIPANTS: Patients being treated with the drugs of interest and hospitalised for COVID-19 between 1 March 2020 and 10 November 2021. OUTCOMES: Identification of patients subject to the treatments of interest; summary of patients' baseline characteristics; description of medication use patterns and treatment episodes. Analyses were descriptive in nature. RESULTS: Overall, 4063 patients matching the inclusion criteria were identified in Scotland, with a median (IQR) age of 64 years (52-76). Among all patients, 81.4% (n=3307) and 17.8% (n=725) were treated with one or two medicines, respectively; dexamethasone monotherapy accounted for the majority (n=3094, 76.2%) followed by dexamethasone in combination with tocilizumab (n=530, 13.0%). Treatment patterns were variable over time but roughly followed the waves of COVID-19 infections; however, the different drugs were used to varying degrees during the study period.The median (IQR) treatment duration differed by medicine: dexamethasone 5 days (2-9); remdesivir 5 days (2-5); and tocilizumab 1 day (1-1). The overall median (IQR) length of hospital stay among all patients included in the study cohort was 9 days (5-17); 24.7% of patients died in hospital. CONCLUSION: The use of adjuvant medicines in patients hospitalised with COVID-19 appears in line with evolving evidence and changing treatment guidelines. In-hospital electronic prescribing systems are a valuable source of information, providing detailed patient-level data on in-hospital drug use.

Remdesivir.

Remdesivir, marketed under the brand name Veklury, is an antiviral drug with a broad spectrum of activity. There were various countries where the use of Remdesivir for the treatment of COVID-19 was authorized during the pandemic. Remdesivir was first designed to treat hepatitis C, but it was later tested for Ebola virus sickness and Marburg virus infections. Remdesivir is a prodrug designed to facilitate the intracellular transport of GS-441524 monophosphate and its subsequent biotransformation into GS-441524 triphosphate, a ribonucleotide analogue inhibitor of viral RNA polymerase. The objective of this chapter is to provide a comprehensive review of Remdesivir (GS-5734), including its nomenclature, physiochemical properties, preparation methods, identification procedures, numerous qualitative and quantitative analytical techniques, ADME profiles, and pharmacological effects. In addition, the chapter provides a variety of chromatographic and spectroscopic techniques for separating brimonidine from other drugs in combination formulations.

Drug-drug interaction between dexamethasone and direct-acting oral anticoagulants: a nested case-control study in the National COVID Cohort Collaborative (N3C).

OBJECTIVE: The goal of this work is to evaluate if there is an increase in the risk of thromboembolic events (TEEs) due to concomitant exposure to dexamethasone and apixaban or rivaroxaban. Direct oral anticoagulants (DOACs), as well as corticosteroid dexamethasone, are commonly used to treat individuals hospitalised with COVID-19. Dexamethasone induces cytochrome P450-3A4 enzyme that also metabolises DOACs apixaban and rivaroxaban. This raises a concern about possible interaction between dexamethasone and DOACs that may reduce the efficacy of the DOACs and result in an increased risk of TEE. DESIGN: We used nested case-control study design. SETTING: This study was conducted in the National COVID Cohort Collaborative (N3C), the largest electronic health records repository for COVID-19 in the USA. PARTICIPANTS: Study participants were adults over 18 years who were exposed to a DOAC for 10 or more consecutive days. Exposure to dexamethasone was at least 5 or more consecutive days. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary exposure variable was concomitant exposure to dexamethasone for 5 or more days after exposure to either rivaroxaban or apixaban for 5 or more consecutive days. We used McNemar's Χ2 test and adjusted logistic regression to evaluate association between concomitant use of dexamethasone with either apixaban or rivaroxaban. RESULTS: McNemar's Χ2 test did not find a discernible association of TEE in patients concomitantly exposed to dexamethasone and a DOAC (χ2=0.5, df=1, p=0.48). In addition, a conditional logistic regression model did not find an increase in the risk of TEE (adjusted OR 1.15, 95% CI 0.32 to 4.18). CONCLUSION: This nested case-control study did not find evidence of an association between concomitant exposure to dexamethasone and a DOAC with an increase in risk of TEE. Due to small sample size, an association cannot be completely ruled out.

HOW TO DEAL WITH HEALTHCARE WORKERS ALLERGIC TO COVID-19 MRNA VACCINE

The Occupational Risk and Prevention Service is notified the case of a 37-year-old nurse who reported watery rhinorrhea and generalized itching 10-15 minutes after first dose of the vaccine produced by BioNTech/Pfizer's administration. She presents: facial erythema, maxillary wheal and normal constants. How should the Occupational Risk and Prevention Service should deal with a health worker who suffers an allergic reaction to the mRNA vaccine against COVID-19? This clinical case draws attention to common preventive measures such as vaccination, but also to others such as collaboration between different hospital services, management and diagnosis by Allergology, follow-up by the Occupational Risk and Prevention Service and notification of adverse vaccine effects by Clinical Pharmacology. Coordination between these services is essential for the correct management of workers affected by adverse reactions to the first vaccine dose against COVID-19, being the workers able to be vaccinated and protected. Copyright © 2022, Accion Medica S.A. All rights reserved.

Signal Detection by Disproportionality Analysis in the Monitoring of COVID-19 Vaccine Safety in Switzerland

Introduction: Initial knowledge on the COVID-19 vaccines' safety from randomised clinical trials was limited and concerned mostly common adverse events related to vaccine immunogenicity occurring rapidly after vaccination [1,2]. Since these vaccines have been approved and used in large scale, the Swiss Agency for Therapeutic Products Swissmedic has been conducting an intensive surveillance activity on their safety, based on the collection and analysis of spontaneous reports from healthcare professionals and patients. Objective(s): Signal detection in spontaneous reports associated with COVID-19 vaccines first relies on a case-by-case analysis by clinically qualified assessors who take into account detailed information provided by reporters. However, with the number of reports increasing, the clinical review could benefit from the use of statistical methods for signal detection, such as disproportionality analysis [3]. Method(s): In light of this, the Institute of Pharmacological Sciences of Southern Switzerland, in close collaboration with Swissmedic, set up and routinely perform a signal detection activity by disproportionality analysis in VigiBase, the global database of the World Health Organization (WHO) Programme for International Drug Monitoring, using spontaneous reports originating from Switzerland and concerning adverse events following immunization (AEFIs) associated with the Moderna (Spikevax) and Pfizer/BioNTech (Comirnaty) COVID-19 vaccines. These included the measurement of the reporting odds ratios (RORs) for COVID-19 vaccine/AEFI combinations meeting two predefined statistical signal detection criteria, namely a minimum of 5 reports concerning a COVID-19 vaccine/AEFI combination and a ROR lower limit of the 95% confidence interval>1. Excluding AEFIs either already labelled in the Swiss information for healthcare professionals, or already debated internationally, a panel of pharmacovigilance and clinical pharmacology experts are examining and discussing findings on novel and unexpected COVID-19 vaccine/ AEFI combinations, in order to promptly detect potential safety signals that could warrant further investigation. Result(s): Since the start of the signal detection activity in August 2021, an early signal of disproportionate reporting in VigiBase for paraesthesia with the Moderna (Spikevax) vaccine was detected in Switzerland. This occurred a few months before the same signal was assessed and validated by the European Medicines Agency, which ultimately added paraesthesia to the European summary of product characteristics for the Moderna (Spikevax) vaccine [4]. Conclusion(s): Disproportionality analysis has some limitations such as lack of information about incidence rate of the adverse event in the population, and the existence of reporting biases. Nevertheless, continued research on newly identified safety signals can provide valuable information to support public health, guide regulatory decisions and design specific follow-up confirmatory studies.

Dose optimisation and scarce resource allocation: two sides of the same coin.

OBJECTIVE: A deep understanding of the relationship between a scarce drug's dose and clinical response is necessary to appropriately distribute a supply-constrained drug along these lines. SUMMARY OF KEY DATA: The vast majority of drug development and repurposing during the COVID-19 pandemic - an event that has made clear the ever-present scarcity in healthcare systems -has been ignorant of scarcity and dose optimisation's ability to help address it. CONCLUSIONS: Future pandemic clinical trials systems should obtain dose optimisation data, as these appear necessary to enable appropriate scarce resource allocation according to societal values.

CEFAZOLIN-INDUCED COAGULOPATHY

SESSION TITLE: Critical Thinking SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Cephalosporins have been known to cause hypo-prothrombinemia and prothrombin prolongation (1). The proposed mechanism of this coagulopathy is secondary to a N-methylthiotetrazole side chain interfering with vitamin-k metabolism (1). Current literature supporting the association between cefazolin and hypo-prothombinemia have only been reported through case reports. As cefazolin is a commonly used antibiotic, it is important that healthcare professionals are aware of its potential bleeding risk. We present a case of a 72 year old female with cefazolin-induced hypo-prothrombinemia. CASE PRESENTATION: A malnourished 72-year old female with a past medical history of recent methicillin-susceptible Staphyloccocus aureus (MSSA) bacteremia and COVID-19 pneumonia presented to the emergency department from a skilled nursing facility (SNF) due to shortness of breath. The patient was previously discharged to SNF to complete a 14 day course of IV cefazolin due to her MSSA bacteremia. On admission, vital signs were significant for a respiratory rate of 22 and a pulse oximetry reading of 78% on room air. Laboratory findings were significant for an elevated prothrombin time of >100 seconds, an INR >15, and a D-dimer of 42,344 ng/mlL. A computed tomography angiography (CTA) of the chest revealed a small segmental pulmonary embolus in the right lower lobe of the lung. The patient was started on a heparin drip, placed on a non-rebreather mask, and admitted to the ICU for closer monitoring. Infectious disease was consulted and cefazolin was discontinued. Due to the patient's risk of bleeding her heparin drip was stopped. It was decided not to reverse the patient's coagulopathy with vitamin K as there were no signs of an acute bleed in the setting of an acute pulmonary embolus. The patient was started on nafcillin in place of cefazolin. Four days after discontinuation of cefazolin, the patient's INR had trended down from >15 to 1.6 and she was started on Lovenox 1mg/kg for the treatment of her acute PE. DISCUSSION: Due to the timing of the discontinuation of cefazolin and the correction of the hypo-prothrombinemia, a clear association between the two can be made. It has been proposed that cefazolin's side chain, heterocyclic thiol, 2-methyl-1,3,4-thiadiazole-5-thiol (MTD), causes a similar reaction that other cephalosporins have on the metabolism of Vitamin K (2). This altered Vitamin K metabolism was also likely exacerbated due to the patient's malnourishment and likely depleted vitamin k reserves (2). CONCLUSIONS: Although rare, this case demonstrates the need for clinicians to be aware of the potential bleeding risk associated with cephalosporins and cefazolin in particular. In the future, routine monitoring of PT/INR levels may be recommended when initiating cephalosporins. Reference #1: Park GH, Kim S, Kim MS, Yu YM, Kim GH, Lee JS, Lee E. The Association Between Cephalosporin and Hypoprothrombinemia: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2019 Oct 16;16(20):3937 Reference #2: Shearer, M. J., Bechtold, H., Andrassy, K., Koderisch, J., McCarthy, P. T., Trenk, D., Jähnchen, E., & Ritz, E. (1988). Mechanism of cephalosporin-induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status. Journal of clinical pharmacology, 28(1), 88–95 DISCLOSURES: no disclosure on file for John Abernathy;No relevant relationships by Ethan Goldberg No relevant relationships by Renee Miu No relevant relationships by Luis Osorio no disclosure on file for Satesh Saroop;no disclosure on file for Oliver Sevilla;no disclosure on file for Kristen Zubel;

Utilizing clinical pharmacology in the drug repurposing arena: a look into COVID-19.

INTRODUCTION: Drug repurposing represented an important contribution in the management of COVID-19, becoming the first line of defense to mitigate the effects of the new coronavirus. In a brief time, drug repurposing (DR) provided potentially effective and already available drugs for COVID-19, while specific therapies against SARS-CoV-2 and/or vaccines were developing. Identifying repurposed drugs requires a multidisciplinary approach, where clinical pharmacology represents the missing piece of the puzzle. AREAS COVERED: Nowadays, clinical pharmacology is recognized as a discipline at the core of translational science, whose activities lead to the identification of the right drug for the right patient. In the context of the COVID-19 pandemic, its role in drug development and therapy choice has been decisive and itself repositioned. In this review, we tried to highlight the important role of clinical pharmacology in the identification and evaluation of possible repurposed drugs for COVID-19. EXPERT OPINION: We believe that clinical pharmacology had an important role in identifying patient-oriented therapy during the COVID-19 pandemic. In this context, DR was just one of the challenges for clinical pharmacology, which proved that this discipline is ready to respond to future threats.

Pharmacokinetic considerations to optimize clinical outcomes for COVID-19 drugs.

The development of clinically effective drugs that could complement existing vaccines is urgently needed to reduce the morbidity and mortality associated with COVID-19. Drug-metabolizing enzymes, membrane-associated drug transporters, and inflammatory responses can partly determine the safety and efficacy of COVID-19 drugs by controlling their concentrations in both the systemic circulation and in peripheral tissues. It is still unknown how these factors affect how well COVID-19 drugs work in the clinic. We explore how drug metabolism and transport, as well as SARS-CoV-2-associated inflammatory response at disease target sites, may affect the clinical outcomes of COVID-19 drugs. In addition, we provide expert opinion on potential strategies for overcoming the clinical pharmacology and pathophysiological obstacles to improve COVID-19 drug effectiveness.

ERN-EUROBLOODNET EUROPEAN REGISTRY OF PATIENTS AFFECTED BY RED BLOOD CELL DISORDERS AND COVID-19

Background: Patients with red blood cell disorders (RBCD), are likely to be at increased risk of complications from SARS-Co-2 (Coid-19), but eidence in this population is scarce due to its low frequency and heterogeneous distribution. Aims: ERN-EuroBloodNet, the European Reference Network in rare hematological disorders, established a European registry to determine the impact of COVID-19 on RBCD patients and identify risk factors predicting seere outcomes. Methods: The ERN-EuroBloodNet registry was established in March 2020 by VHIR based on Redcap software in accordance with the Regulation (EU) 2016/679 on personal data. The local Research Ethics Committee confirmed that the exceptional case of the pandemic justifies the waier of informed consent. Eligible patients had confirmed RBCD and COVID-19. Data collected included demographics, diagnosis, comorbidities, treatments, and COVID-19 symptoms and management. For analysis of COVID-19 seerity, two groups were established 1) Mild: asymptomatic or mild symptoms without clinical pneumonia and 2) Seere: pneumonia requiring oxygen/respiratory support and/or admission to intensie care unit. Continuous ariables were compared using the Wilcoxon rank-sum test or Kruskall Wallis test, while categorical ariables were analyzed using the Chi-square test or Fisher's Exact test. Releant factors influencing disease or seerity were examined by the logistic regression adjusted for age. Results: As of February 25, 2022, 42 medical centers from 10 EU countries had registered 428 patients: 212 Sickle cell disease (SCD), 186 Thalassemia major and intermedia (THAL). The mean age of SCD was lower (22y) than of THAL (39.4y). Splenectomy and comorbidities were higher in THAL (51.4% and 61,3%) than in SCD (16,3% and 46,8%) (p<0.001, p=0.004). Age and BMI correlated with COVID-19 seerity, as described in the general population (p=0.003, p<0.001). Fig 1 shows age distribution and COVID-19 seerity by disease seerity groups. The mean age for seere COVID-19 was lower in patients with seere SCD (SS/SB0 s SC/SB+: 23y s 67.5y) and THAL (major s intermedia: 43.5 s 51.3y) (p<0.001). Potential risk factors such as eleated ferritin, current chelation or history of splenectomy did not confer additional risk for deeloping seere COVID-19 in any patient group. Only diabetes as a comorbidity correlated with seerity grade in SCD (p=0.01) and hypertension in THAL (p=0.009). While seere COVID-19 infection in SCD was associated with both ACS (p<0.001) and kidney failure requiring treatment (p<0.001), this was not predicted by a history of preious ACS or kidney disease in steady state. Oerall, 14,6% RBC patients needed oxygen/respiratory support, 4% were admitted to ICU with an oerall mortality rate of 1%, much lower than reported in other similar cohorts. Hospital Son Espases, Palma de Mallorca, Spain;54 Clinical Pharmacology Serice, Hospital Uniersitari Vall d'Hebron, Barcelona, Spain;55 Vall d'Hebron Institut de Recerca, Barcelona, Spain;56 Diision of Hematology and Oncology, Department of Internal Medicine, American Uniersity of Beirut Medical Center, Beirut, Lebanon;57 UOC Pediatric Hematology Oncology, Uniersity of Padoa, Padoa, Italy;58 Department of Haematology, Oxford Uniersity Hospitals NHS Foundation Trust, Oxford, United Kingdom;59 Translational Research in Child and Adolescent Cancer, Vall d'Hebron Institut de Recerca, Barcelona, Spain Background: Patients with red blood cell disorders (RBCD), are likely to be at increased risk of complications from SARS-Co-2 (Coid-19), but eidence in this population is scarce due to its low frequency and heterogeneous distribution. Aims: ERN-EuroBloodNet, the European Reference Network in rare hematological disorders, established a European registry to determine the impact of COVID-19 on RBCD patients and identify risk factors predicting seere outcomes. Methods: The ERN-EuroBloodNet registry was established in March 2020 by VHIR based on Redcap software in accordance with the Regulation (EU) 2016/679 on personal data. The local Research Ethics Committee confirm d that the exceptional case of the pandemic justifies the waier of informed consent. Eligible patients had confirmed RBCD and COVID-19. Data collected included demographics, diagnosis, comorbidities, treatments, and COVID-19 symptoms and management. For analysis of COVID-19 seerity, two groups were established 1) Mild: asymptomatic or mild symptoms without clinical pneumonia and 2) Seere: pneumonia requiring oxygen/respiratory support and/or admission to intensie care unit. Continuous ariables were compared using the Wilcoxon rank-sum test or Kruskall Wallis test, while categorical ariables were analyzed using the Chi-square test or Fisher's Exact test. Releant factors influencing disease or seerity were examined by the logistic regression adjusted for age. Results: As of February 25, 2022, 42 medical centers from 10 EU countries had registered 428 patients: 212 Sickle cell disease (SCD), 186 Thalassemia major and intermedia (THAL). The mean age of SCD was lower (22y) than of THAL (39.4y). Splenectomy and comorbidities were higher in THAL (51.4% and 61,3%) than in SCD (16,3% and 46,8%) (p<0.001, p=0.004). Age and BMI correlated with COVID-19 seerity, as described in the general population (p=0.003, p<0.001). Fig 1 shows age distribution and COVID-19 seerity by disease seerity groups. The mean age for seere COVID-19 was lower in patients with seere SCD (SS/SB0 s SC/SB+: 23y s 67.5y) and THAL (major s intermedia: 43.5 s 51.3y) (p<0.001). Potential risk factors such as eleated ferritin, current chelation or history of splenectomy did not confer additional risk for deeloping seere COVID-19 in any patient group. Only diabetes as a comorbidity correlated with seerity grade in SCD (p=0.01) and hypertension in THAL (p=0.009). While seere COVID-19 infection in SCD was associated with both ACS (p<0.001) and kidney failure requiring treatment (p<0.001), this was not predicted by a history of preious ACS or kidney disease in steady state. Oerall, 14,6% RBC patients needed oxygen/respiratory support, 4% were admitted to ICU with an oerall mortality rate of 1%, much lower than reported in other similar cohorts. Summary/Conclusion: Results obtained so far show that seere COVID-19 occurs at younger ages in more aggressie forms of SCD and THAL. Current preentie approaches focus on age oer disease seerity. Our data highlights the risk of seere COVID-19 infection in some young patients, particularly those with SS/SB0 SCD, suggesting that immunization should be considered in this pediatric group as well. Results between similar sized cohorts of RBCD patients ary between each other and those presented here, highlighting the importance of collecting all of these small cohorts together to ensure adequate statistical power so that definitie risk factors can be reliably identified and used to guide management of patients with these rare disorders in the light of the ongoing pandemic. (Figure Presented).

Highlights

Cell Resistance to Ebola and Coronaviruses

American Society for Clinical Pharmacology and Therapeutics - 123rd Annual Meeting. Virtual - March 16-18, 2022

The 2022 American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting held virtually, with "Disruptive innovation" as the motto, offered attendees an outstanding scientific program focused on clinical pharmacology, translational medicine, drug discovery and drug development. It is the most important event for scientists involved in clinical pharmacology and translational medicine. The ASCPT conference offers scientists from different professional scopes and around the world the perfect opportunity to discuss emerging science. It focuses on improving the understanding and use of existing drug therapies and developing safer and more effective treatments for the future. Oral and poster presentations were available for participants during the running of the conference to accommodate the different time zones. Presentations covered the latest research with the option to ask questions after each presentation via a chat function. Discussion boards were available to provide networking opportunities for virtual attendees.

EVALUATING THE EFFICIENCY OF SPENDING ON ANTIMICROBIAL THERAPY IN THE PULMONOLOGY DEPARTMENT OF A MULTIDISCIPLINARY HOSPITAL IN A PANDEMIC SETTING

Introduction: Antimicrobial resistance is recognized as one of the top 10 threats to public health.Due to recent circumstanceswith the 2019 Covid pandemic worldwide, the urgency of monitoring antibiotic consumption and rational use of medications has increased. According to WHO recommendations, countries should aim to increase the proportion of Access group antibiotics consumption to 60% and higher in AWaRe classification system (Access,Watch and Reserve). The ABC/VEN analysis (80%, 15%, 5% of spending) is the simplest and most relevant method for evaluating the effectiveness of antibiotic therapy expenditures. Objectives: Evaluating the cost-effectiveness of antibiotic therapy in the Department of Pulmonology. Methods: ABC/VEN analysis was performed with data on antibiotic costs in the pulmonology department (30 beds) of a multidisciplinary regional hospital (844 beds in total) with 1 full-time clinical pharmacologist for no clinical pharmacy or pharmacology service. To analyze antibiotic consumption patterns according to the AWaRe 2021 classification, we used data on the number of antibiotics procured. Results: The results of the antibiotics spending analysis from 2019-2021 showed that all antibiotics from the most costly group A (80% of total spending) are in the Watch group (J01DH Carbapenems - Ertapenem, Doripenem, Meropenem;J01MA Fluoroquinolones - Levofloxacin;J01DD Third-generation-cephalosporins - Ceftazidime, Ceftriaxone and J01DE Fourth-generation-cephalosporins: Cefepime). Meanwhile, there has been an increase in the share of spending on the most consumed group of antibiotics, J01DH Carbapenems, from 42.9% in 2019 to 62.8% by 2021. On the contrary, there is downward trend in spending on the third-generation-cephalosporins which was 35.6% in 2019 and only 6.7% by 2021. Assessment of antibiotic prescription patterns in the pulmonology department based on classification AWaRe 2021 and WHO Model List of Essential Medicines (EML) 2021 (22nd edition) revealed a negative trend in the use of the most costly group (A) of antibiotics with a low level of evidence of efficiency or safety in pulmonology: Doripenem, Ertapenem, Levofloxacin, Cefepime. However, there is a positive result in the work of the clinical pharmacology service - the drugs mentioned above were moved into group B (medium-cost) by 2021, except for Cefepim, which was not purchased at all. Conclusion: Despite the positive trend in antibiotic consumption patterns (transfer of antibiotics with efficiency proof from gr A to gr B), current antibiotic therapy in the pulmonology department needs comprehensive optimization of approach to rational antibiotic use, strengthening pharmaceutical care by implementing a clinical pharmacy service that will conduct regular systematic evaluation and contribute to the pharmacoeconomic expediency of antibiotic therapy. Suchmeasures lead to an improvement of the quality of medical care for the population and reduce the cost of this nosology, which proves that there is a need for a comprehensive detailed analysis.