Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

Gastrointestinal symptoms and disorders related to COVID-19. Lessons learned from gastroenterologists

COVID-19 is mainly a respiratory illness caused by the SARS-CoV-2 but can also lead to GI symptoms. The primary host receptor which mediates the mechanism as SARS-CoV-2 enters the cell is the ACE2 receptor. Therefore, GI symptoms can be common in COVID-19, and in some cases, they are the first manifestation even before fever and respiratory symptoms. In addition, the liver function tests alteration often is related to a worse prognosis. The exact incidence of GI symptoms is a matter of debate. Moreover, wide variation concerning GI symptoms frequency exists, but the predominant ones seem to be diarrhea, anorexia, nausea, vomiting, and abdominal pain or discomfort.This review summarizes the most relevant findings of COVID-19 on the digestive system, including the liver, biliary tract, pancreas, the most common GI symptoms, and the atypical clinical GI manifestations.Copyright © 2022 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

General Surgery Resident Case Numbers During the Covid-19 Pandemic

Introduction: The COVID-19 pandemic has had widespread effects on the healthcare system. For trainees, one particular detriment has been the cancellation of elective operations, reducing clinical experience and procedural volumes. Measures instituted to combat the pandemic have resulted in decreased cancellation of elective cases to varying degrees. The aim of this study is to evaluate the ongoing effect of the pandemic on resident operative volume. Method(s): Operative case numbers of general surgical graduates in 2019, 2020, and 2021 were extracted from the Accreditation Council for Graduate Medical Education case logs. Data included mean total cases/graduate and means for individual case types. Data was considered by overall number of cases and cases performed as surgeon chief. Analysis of variance was employed to compare groups with p<0.05 considered significant. Result(s): Mean total major cases differed significantly among groups with reduced volume noted for 2020 graduates but no difference in volume between 2019 and 2021 graduates (1070.5+/-150 vs 1054.8+/-155 vs 1074.1+/-164, p=0.0041). This same pattern was noted for surgeon chief total cases (288.6+/-69 vs 264.4+/-67 vs 286.2+/-73, p<0.0001) as well as several major general surgery subcategories including cases involving the stomach, small intestine, large intestine, biliary system, among others. Conclusion(s): Despite continued reduction in and alteration of elective surgery practice, improved pandemic measures have allowed for increased surgical volume. This has translated to increased operative experience for graduating surgical trainees that are comparable to case numbers that preceded the pandemic. Ramifications for the 2020 graduating cohort as well subsequent cohorts require continued evaluation.

Chronic liver disease during a pandemic: preventive support for the combined phytopreparation Fumarta

The spread of SARS-CoV-2 virus among humanity has identified a number of new challenges in the field of medical science. In this regard, it is very important to understand the possible involvement of the liver in the infectious process, as well as the effect of this virus on liver function in its chronic pathology. The article pro-vides an overview of available sources of information regarding views on direct viral liver damage COVID-19, as well as the features of the course and prognosis of this infection in patients with chronic liver disease and cirrhosis. It was emphasized that chronic liver diseases are considered as a high risk factor for COVID-19 infec-tion, and are also predicted to be at an increased risk for the severe course of this infection with the development of complications. Substantial support to patients with chronic liver diseases during the COVID-19 pandemic can be provided by the Fumarta combination drug (Farmak), which includes fumarin alkaloid from the extract of dry herb of the fumaria officinalis and silymarin from the extract of dried fruit of milk thistle. This composition of the drug Fumarta allows normalizing the digestive disorders, which constantly accompany chronic liver disease. In the article, digestive disorders are considered from the point of view of biliary insufficiency, which occurs in virtually every chronic liver disease. Normalization of the formation of bile, its composition with the restoration of rheo-logical properties, improves not only general well-being of a patient, but also positively affects the restoration of the functional capabilities of the liver. The data on the study of each of the active components of the Fumarta drug are presented, which indicates the advisability of its use in this group of diseases. The healing properties of the Fumarta drug are stipulated by the optimal combination of the hepatoprotective effects of silymarin with the normalization of bile secretion and biliary motility by fumarin. The combination of hepatoprotective and choleretic activity complement and enhance the action of each other, which helps to optimize the functioning of the entire digestive system. Patients with liver disease in the context of the COVID-19 pandemic are recommended to take Fumarta drug, the components of which have a versatile positive effect in chronic liver diseases as preventive support. Approaches to pharmacotherapy of chronic liver diseases among the convalescents of COVID-19 are also being considered. In this regard, Fumarta may act as one of the optimal drugs for choosing a rehabilitation course for these patients. © M. B. Shcherbynin, Yu. M. Bondarenko, 2020.

What the Eye Cannot See: A Case of Persistent Altered Mental Status in a Patient With Cholestatic Liver Disease?

Introduction: Altered mental status (AMS) is a common symptom in patients with liver disease with a wide list of differential diagnoses. Knowledge of etiologies of AMS unique to patients with hepatic dysfunction is vital in order to help recognize, diagnose, and treat the underlying cause in a timely manner. Case Description/Methods: A 46-year-old man with a history of recent COVID infection was transferred to our hospital for further evaluation of acute liver injury and AMS. On arrival, his labs were notable for AST of 408 U/L, ALT of 620 U/L, ALP of 5942 U/L, TB of 11.0 mg/dL, and an INR of 1.1. His work-up included an MRCP that showed segmental biliary ductal dilation with associated restricted diffusion and peribiliary enhancement concerning for sclerosing cholangitis. ERCP revealed a 3cm biliary cast that was removed and noted diffuse rarefaction of ducts throughout the entire biliary tree. A liver biopsy revealed centrizonal cholestasis with portal-based bile ductular reaction and mild bile duct injury. Despite adequate treatment of suspected infection and hepatic encephalopathy, his AMS persisted. His basic metabolic panel (BMP) was notable for Na of 143 mEq/L. A send-out lipid panel that was obtained to work-up his dyslipidemia revealed a total cholesterol of 1018 mg/dL, triglycerides of 420mg/dL, and the presence of lipoprotein X. A venous blood gas (VBG) was obtained showing a Na of 157 mEq/L and serum osmolality was 322 mmol/kg, confirming true hypernatremia. He was slowly treated with hypotonic solutions with significant improvement in his mentation. On follow-up one year later, he has persistent cholestasis and is currently being considered for liver transplant. Discussion(s): The final diagnosis was COVID-related ischemic cholangitis and disappearing bile ducts with persistent cholangiopathy, presenting with severe cholestasis, accumulation of lipoprotein X, and pseudonormonatremia. When faced with severe cholestatic liver disease, clinicians should keep in mind the possibility of accumulation of lipoprotein X and its association with hyperviscosity and spurious electrolyte abnormalities. Clinicians should rely on obtaining blood gas analyses for accurate electrolyte measurement in such cholestatic patients as blood gas analyses utilize direct ion-sensitive electrodes (ISE) to measure electrolytes, whereas routine basic metabolic panels utilize indirect ISE that are liable to spurious results in the presence of hyperlipoproteinemia/lipoprotein X.

Prevalence of adverse drug reactions associated with emergency department visits and risk factors for hospitalization

Objective: Adverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. Method(s): Observational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Result(s): 10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 +/- 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47-7.13, p = 0.003, in Charlson comorbidity index 4-6;and aOR 20.07, 95% CI: 6.87-58.64, p = 0.000, in Charlson comorbidity index >= 10). Conclusion(s): The prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.Copyright © 2022 Sociedad Espanola de Farmacia Hospitalaria (S.E.F.H)

Gastrointestinal tract, liver, and pancreas affected by covid-19.

We reviewed literature about the effects of novel coronavirus disease COVID-19 on the digestive system. The review ses the pathogenesis, the natural history, and the frequency of gastrointestinal and hepatobiliary complications in patientCOVID-19. We briefly overviewed therapy for intestinal, liver, and pancreatic damage by COVID-19.Copyright © 2021, Media Sphera Publishing Group. All rights reserved.

Liver and COVID-19-Identifcation of early prognostic markers

COVID-19 is a systemic disease afecting the liver to a crucial extent. This study investigates the impact of COVID-19 on the liver and possible early prognostic markers for the development of secondary sclerosing cholangitis (SSC). This rising complication in critically ill patients, also occurs after a severe COVID-19 infection. Early prediction for SSC has not been sufciently investigated yet. 258 patients at intensive care unit (ICU) at the University Hospital of Regensburg were divided into groups depending on their medical history of preexisting liver diseases. Collected laboratory parameters during ICU comprised both baseline values, and worst values developed during hospitalization and were used to assess the rate of mortality between the different groups of patients. Development of SSC was evaluated against the baseline values. Preexisting liver disease increased mortality rate from 39.3 % to 52.6 %. In both groups, mortality correlated signifcantly with an increase in liver values during ICU stay. High baseline values of Bilirubin (P = .002) or INR (P = .018) also correlated with mortality independently of preexisting liver diseases. The risk of developing SSC increased with high liver enzymes and correlated signifcantly (P = .004) with high AP levels at admission. This study shows the high impact of COVID-19 on the liver and biliary system and possible complications in patients with and without preexisting liver diseases. Bilirubin and INR can be used as predictive factors regarding mortality. AP can be considered as an early predictor for development of SSC in patients with COVID-19 and could hint to optimized treatment strategies regarding ventilation and sedation.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection.

Long COVID is a novel syndrome characterizing new or persistent symptoms weeks after COVID-19 infection and involving multiple organ systems. This review summarizes the gastrointestinal and hepatobiliary sequelae of long COVID syndrome. It describes potential biomolecular mechanisms, prevalence, preventative measures, potential therapies, and health care and economic impact of long COVID syndrome, particularly of its gastrointestinal (GI) and hepatobiliary manifestations.

Diagnostic and Therapeutic Radiology of the GI Tract, Liver, and Pancreas in Patients with COVID.

Coronavirus disease 2019 (COVID-19) pulmonary involvement has been extensively reported in the literature. Current data highlight how COVID-19 is a systemic disease, affecting many other organs, including the gastrointestinal, hepatobiliary, and pancreatic organs. Recently, these organs have been investigated using imaging modalities of ultrasound and particularly computed tomography. Radiological findings of the gastrointestinal, hepatic, and pancreatic involvement in patients with COVID-19 are generally nonspecific but are nonetheless helpful to evaluate and manage COVID-19 patients with involvement of these organs.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.

It's not the shunt: an atypical cause of fever in an infant with hydrocephalus

Case Report:We present a 5-year-old male with two days of fever, cough, vomiting, and loose stools. His history is significant for premature birth (35 weeks gestational age) and shunted hydrocephalus. A ventriculoperitoneal (VP) shunt was placed 6 days prior to presentation. Parental report included episodes of post-tussive, nonbloody, non-bilious emesis, poor oral intake, tachypnea, and increased work of breathing. Physical examination demonstrated a dehydrated infant with sunken fontanelles. He had no notable rash, no lymphadenopathy, and clear conjunctiva. His VP shunt site appeared normal without swelling or erythema. Initial evaluation showed elevated inflammatory markers -ESR 51 and CRP 12.32 mg/dL. A viral respiratory PCR panel returned positive for coronavirus (not SARS-CoV-2). A head CT scan and shunt radiography series showed no abnormalities with his shunt. The following morning, Radiology reported an incidental retropharyngeal fluid collection on a re-read of the patient's initial CT scan. A neck CT was obtained and demonstrated a fluid pocket with secondary mass effect in addition to bilateral cervical lymphadenopathy. Screening blood cultures were negative. The patient remained febrile (tmax 103.6F) and developed a transaminitis (ALT 264.9, AST 654), elevated fibrinogen 476, elevated INR 1.4, and low albumin 2.1. Abdominal ultrasound showed a normal the liver and biliary tract. His transaminitis resolved without treatment. The next day, the patient developed lip erythema and conjunctival injection. An echocardiogram showed a dilated right coronary artery (z-score of 3.59) and his inflammatory markers (ESR 26, CRP 9.63) remained elevated. Treatment was initiated with IVIG and moderate-dose aspirin. The patient defervesced, and he remained afebrile for over 48 hours prior to discharge. A repeat echocardiogram 2 days later showed a slight reduction in coronary artery dilatation (z-score 3.39). Hewas discharged on lowdose aspirin, and followed up with cardiology as an outpatient. Kawasaki's Disease (KD) is most common in children from ages 1 to 4 years and is classically characterized by persistent fever with a constellation of symptoms including limbal sparing conjunctivitis, cervical lymphadenopathy, polymorphous rash, strawberry tongue, oral changes, and extremity changes. Our patient presented at a younger age with a concurrent diagnosis of coronavirus upper respiratory tract infection. His atypical hospital course and incidental finding of retropharyngeal edema and transaminitis increased the clinical suspicion for KD. His symptoms rapidly improved after administration of IVIG. Younger patients are at an increased risk for severe complications of KD including coronary aneurysm. KD has been shown in the literature to have an association with coronavirus infection as well as presentation with retropharyngeal edema. Clinicians should consider KD in their differential even if patients do not meet all criteria for diagnosis on initial presentation. Copyright © 2023 Southern Society for Clinical Investigation.

Living with liver disease in the era of COVID-19-the impact of the epidemic and the threat to high-risk populations.

The cardinal symptoms of severe acute respiratory syndrome coronavirus 2 infection as the pandemic began in 2020 were cough, fever, and dyspnea, thus characterizing the virus as a predominantly pulmonary disease. While it is apparent that many patients presenting acutely to the hospital with coronavirus disease 2019 (COVID-19) infection have complaints of respiratory symptoms, other vital organs and systems are also being affected. In fact, almost half of COVID-19 hospitalized patients were found to have evidence of some degree of liver injury. Incidence and severity of liver injury in patients with underlying liver disease were even greater. According to the Centers of Disease Control and Prevention, from August 1, 2020 to May 31, 2022 there have been a total of 4745738 COVID-19 hospital admissions. Considering the gravity of the COVID-19 pandemic and the incidence of liver injury in COVID-19 patients, it is imperative that we as clinicians understand the effects of the virus on the liver and conversely, the effect of underlying hepatobiliary conditions on the severity of the viral course itself. In this article, we review the spectrum of novel studies regarding COVID-19 induced liver injury, compiling data on the effects of the virus in various age and high-risk groups, especially those with preexisting liver disease, in order to obtain a comprehensive understanding of this disease process. We also provide an update of the impact of the new Omicron variant and the changing nature of COVID-19 pathogenesis.

Timing of endoscopic intervention in patients with cirrhosis with acute variceal haemorrhage (TEACH trial): protocol for a randomised clinical trial (RCT).

INTRODUCTION: Acute variceal haemorrhage (AVH) in patients with cirrhosis remains a topic of great interest. Although several guidelines recommend endoscopy within 24 hours after AVH, there is no consensus on the most appropriate time to perform this intervention. The purpose of this study is to identify whether urgent endoscopy (within 6 hours after gastroenterological consultation) is superior to non-urgent endoscopy (between 6 hours and 24 hours after gastroenterological consultation) in reducing the rebleeding rate of these patients. METHODS AND ANALYSIS: This is a single-centred, prospective, randomised clinical trial. Between March 2021 and December 2023, an estimated 400 patients will be randomised in a 1:1 ratio to receive endoscopic intervention either within 6 hours or between 6 and 24 hours after gastroenterological consultation. Randomisation will be conducted by permuted block randomisation, with stratification by age, systolic blood pressure and pulse rate. The primary efficacy endpoint is rebleeding within 42 days after control of AVH. The secondary efficacy endpoints mainly include all-cause mortality within 42 days after randomisation, persistent bleeding, length of hospitalisation, etc. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethical Committees of Jinling Hospital (authorised ethics no. DZQH-KYLL-21-01). This trial will provide valuable insights into the timing of endoscopic intervention for AVH in patients with cirrhosis. Furthermore, the trial results and conclusions could provide high-quality evidence to guide clinical research and treatment. TRIAL REGISTRATION NUMBER: NCT04786743.