Proton pump inhibitors: Understanding the associated risks and benefits of long-term use.

PURPOSE: Proton pump inhibitors (PPIs) are widely prescribed medications. Various adverse clinical effects of PPIs have been reported in the literature, particularly over the past decade. The purpose of this article is to review published data primarily describing adverse effects associated with PPI use and to help clinicians determine which patients may still benefit from therapy despite safety concerns. SUMMARY: Associations between PPIs and the following have been described: bone fracture, acute and chronic kidney disease, gastrointestinal infections, deficiencies in vitamin B12 and magnesium, and coronavirus disease 2019 and respiratory infections. For inclusion in this review, studies must have evaluated potential adverse events associated with PPIs as a primary or secondary objective. Increased risks of bone fracture, acute and chronic kidney disease, gastrointestinal infections, and magnesium deficiency were consistently reported, albeit mostly in studies involving low-quality data (case-control and/or observational studies) and subject to bias. In the only pertinent randomized controlled trial to date, chronic pantoprazole use was associated with a greater risk of enteric infections relative to placebo use; there was no significant between-group difference in any other adverse event evaluated. PPIs continue to be recommended by the American College of Gastroenterology as a first-line treatment for management of gastroesophageal reflux disease and in the acute period following upper gastrointestinal and ulcer bleeding. CONCLUSION: Higher-quality data is needed to better understand PPI-associated risks of the adverse effects listed above. Until then, clinicians may consider greater vigilance with PPI use; however, the data does not demonstrate a need for wide adoption of de-escalation strategies solely out of safety concerns.

Myocarditis following Coronavirus vaccination

Introduction: Myocarditis is an adverse reaction discovered after the marketing of SARS-CoV-2 mRNA vaccines. Nevertheless, this effect is not mentioned as an adverse reaction in the summary of product characteristics of other types of vaccines against this disease. Objective(s): In this work, we aim to present the cases of myocarditis after vaccination against COVID-19 reported to the national Tunisian centre of pharmacovigilance. Method(s): We present the cases of myocarditis reported after the COVID-19 vaccination. All cases are diagnosed according to Brighton's case definition of myocarditis. The vaccines causality assessment was estimated by the French imputability updated method of Begaud et al. Result(s): We included five patients. The sex ratio (M/F) was 4. The mean age was 30 years. All patients had no notable cardiovascular history and did not report any significant past medical history. The onset of symptoms was two days post-vaccination in three patients. The predominant reported symptoms are chest pain and dyspnea in the five cases. Cardiac magnetic resonance imaging (MRI) confirmed the myocarditis diagnosis in four patients (not performed for one patient). All cases were classified as definitive cases according to the Brighton case definition of myocarditis. No patient required hospitalization in a cardiac intensive care unit. All the patients recovered from acute myocarditis within a few days. Conclusion(s): Reported cases of myocarditis post-COVID-19 vaccination in our population are rare, not severe, and have a quick favorable outcome.Copyright © 2022

Uygulamada Hidroksiklorokin Kullanımına Veda Öncesi: COVID-19'lu Çocuklarda Hidroksiklorokin Tedavisine Ílişkin Güvenlik Verilerimizin Değerlendirilmesi

Objective: This study aimed to evaluate the adverse effects of hydroxychloroquine (HCQ) in children with COVID-19. Material and Methods: This study was conducted between MarchAugust 2020 at a referral tertiary hospital for pediatric infectious diseases in the Aegean Region of Turkey. All hospitalized children with COVID-19 who were received HCQ include in this study. An electrocardiogram (ECG) was performed prior to the initiation of HCQ and at certain times (first and 24th hours of HCQ administration and two hours after the final dose of HCQ) during treatment. Adverse effects associated with HCQ were evaluated during the hospitalization and also the first and second months after discharge. Results: A total of 62 children with COVID-19 who administered HCQ treatment were evaluated. Of these, 35 (56.5%) were girls and 27 (43.5%) were boys. The mean age 13.7 ± 3.0 years (range 6.0 to 18.0 years). Prior to the admission, none of the patients had arrhythmia, cardiovascular disease, or any cardiotoxic drugs usage. There was no abnormality on the baseline and following ECGs during the treatment with HCQ. Thirteen patients had nausea (20.9%) and 10 patients (17.7%) had mild abdominal pain. None of the patients had no arrhythmia. Conclusion: No cardiac side effects were observed in our patients. However, it is not possible to give a general statement on the safety data of HCQ therapy without any randomized controlled large-scale studies.

The Influence of the Rapid Increase in the Number of Adverse Event Reports for COVID-19 Vaccine on the Disproportionality Analysis Using JADER.

BACKGROUND/AIM: The COVID-19 prophylactic vaccine for the prevention of coronavirus infection was approved in Japan on February 14, 2021. Adverse event reports for the vaccine were collected from the Japan Adverse Drug Event Relief (JADER) database, similar to those for drugs. Reported odds ratios (RORs) and proportional reporting ratios (PRRs) are commonly used in disproportionality analysis to detect safety signals. Therefore, adverse event reports from the vaccinated population may affect the detection of safety signals for the registered drugs. This study determined the impact of adverse event reports on the detection of safety signals for a COVID-19 prophylactic vaccine by analyzing the JADER database using disproportionality analysis. PATIENTS AND METHODS: We extracted data from the JADER dataset, in which the COVID-19 vaccine was reported as a suspected drug, and selected the top 10 adverse events in terms of the number of reports. We then extracted the top 30 drugs by the amount of information in the selected 10 adverse events and compared the changes in the number of signal detections with and without the COVID-19 vaccine report data. RESULTS: The total number of adverse events reported in the JADER database during the study period was 2,002,564. Of the total number of reports, 85,489 (4.3%) reported adverse events related to the COVID-19 vaccine. Of the top 30 drugs reported in the 10 selected adverse events, the ROR and PRR were found to be lower with the inclusion of COVID-19 vaccine data than without. Detection by ROR excluded 23 out of 245 drugs, and detection by PRR excluded 34 out of 204 drugs. CONCLUSION: The rapid increase in the number of adverse event reports for the COVID-19 vaccine in JADER may affect the detection of safety signals by disproportionality analysis.

Myocarditis following Coronavirus vaccination

Introduction Myocarditis is an adverse reaction discovered after the marketing of SARS-CoV-2 mRNA vaccines. Nevertheless, this effect is not mentioned as an adverse reaction in the summary of product characteristics of other types of vaccines against this disease. Objective In this work, we aim to present the cases of myocarditis after vaccination against COVID-19 reported to the national Tunisian centre of pharmacovigilance. Method We present the cases of myocarditis reported after the COVID-19 vaccination. All cases are diagnosed according to Brighton's case definition of myocarditis. The vaccines causality assessment was estimated by the French imputability updated method of Bégaud et al. Results We included five patients. The sex ratio (M/F) was 4. The mean age was 30 years. All patients had no notable cardiovascular history and did not report any significant past medical history. The onset of symptoms was two days post-vaccination in three patients. The predominant reported symptoms are chest pain and dyspnea in the five cases. Cardiac magnetic resonance imaging (MRI) confirmed the myocarditis diagnosis in four patients (not performed for one patient). All cases were classified as definitive cases according to the Brighton case definition of myocarditis. No patient required hospitalization in a cardiac intensive care unit. All the patients recovered from acute myocarditis within a few days. Conclusion Reported cases of myocarditis post-COVID-19 vaccination in our population are rare, not severe, and have a quick favorable outcome.

Elevated NETs and Calprotectin Levels after ChAdOx1 nCoV-19 Vaccination Correlate with the Severity of Side Effects.

ChAdOx1 nCoV-19 vaccination has been associated with the rare side effect; vaccine-induced immune thrombotic thrombocytopenia (VITT). The mechanism of thrombosis in VITT is associated with high levels of neutrophil extracellular traps (NETs). The present study examines whether key markers for NETosis, such as H3-NETs and calprotectin, as well as syndecan-1 for endotheliopathy, can be used as prognostic factors to predict the severity of complications associated with ChAdOx1 vaccination. Five patients with VITT, 10 with prolonged symptoms and cutaneous hemorrhages but without VITT, and 15 with only brief and mild symptoms after the vaccination were examined. Levels of H3-NETs and calprotectin in the vaccinated individuals were markedly increased in VITT patients compared to vaccinees with milder vaccination-associated symptoms, and a strong correlation (r ≥ 0.745, p < 0.001) was found with severity of vaccination side effects. Syndecan-1 levels were also positively correlated (r = 0.590, p < 0.001) in vaccinees to side effects after ChAdOx1 nCoV-19 vaccination. We hypothesize that the inflammatory markers NETs and calprotectin may be used as confirmatory tests in diagnosing VITT.

Immunisation: ‘if you were me, what would you do?’

The article informs about James works on an inpatient mental health ward and although we have been vaccinating healthcare staff since January 2020, and history of allergies or anaphylaxis and experience people who have allergies are safest having the AstraZeneca vaccine.

Influence of the Coronavirus Disease 2019 Vaccine on Drug Therapy for Urological Cancer.

BACKGROUND/AIM: We investigated whether coronavirus disease 2019 (COVID-19) vaccination and its adverse events would cause cancer treatment of patients with urological cancer to be postponed or changed. PATIENTS AND METHODS: We collected COVID-19 vaccination information including adverse events from the medical records of 214 patients with urological cancer receiving cancer drug therapy. RESULTS: The cancer types were renal cancer in 40 cases (18.7%), upper urinary tract cancer in 10 cases (4.7%), bladder cancer in 21 cases (9.8%), prostate cancer in 140 cases (65.4%), and others in 3 cases (1.4%). Of the 214 patients, 178 (83.2%) had received the second dose of the vaccine. Out of 180 vaccinated patients, some adverse events were observed in 69 (38.3%). Vaccination rates for males and females were 85.4% (169/198) and 68.8% (11/16), respectively, and were not significantly different (p=0.081). The incidence of adverse events was significantly higher in females [72.7% (8/11)] than in males [36.1% (61/169)]; p=0.015. Treatment was modified in 11 vaccinated patients; postponed or changed at the discretion of the attending physician in 8 cases, skipped at the discretion of the patient in 1 case, and postponed due to side effects of the immune checkpoint inhibitor in 1 case. Treatment for one patient with upper urinary tract cancer on pembrolizumab was postponed for three weeks due to adverse events of the vaccine. CONCLUSION: Only 0.6% of the adverse events of the vaccine required postponement of treatment, suggesting that vaccination is safe even during cancer drug therapy.

Variation in Expression of Cytochrome P450 3A Isoforms and Toxicological Effects: Endo- and Exogenous Substances as Regulatory Factors and Substrates.

The CYP3A subfamily, which includes isoforms CYP3A4, CYP3A5, and CYP3A7 in humans, plays important roles in the metabolism of various endogenous and exogenous substances. Gene and protein expression of CYP3A4, CYP3A5, and CYP3A7 show large inter-individual differences, which are caused by many endogenous and exogenous factors. Inter-individual differences can cause negative outcomes, such as adverse drug events and disease development. Therefore, it is important to understand the variations in CYP3A expression caused by endo- and exogenous factors, as well as the variation in the metabolism and kinetics of endo- and exogenous substrates. In this review, we summarize the factors regulating CYP3A expression, such as bile acids, hormones, microRNA, inflammatory cytokines, drugs, environmental chemicals, and dietary factors. In addition, variations in CYP3A expression under pathological conditions, such as coronavirus disease 2019 and liver diseases, are described as examples of the physiological effects of endogenous factors. We also summarize endogenous and exogenous substrates metabolized by CYP3A isoforms, such as cholesterol, bile acids, hormones, arachidonic acid, vitamin D, and drugs. The relationship between the changes in the kinetics of these substrates and the toxicological effects in our bodies are discussed. The usefulness of these substrates and metabolites as endogenous biomarkers for CYP3A activity is also discussed. Notably, we focused on discrimination between CYP3A4, CYP3A5, and CYP3A7 to understand inter-individual differences in CYP3A expression and function.

Assessment of adverse events associated with remdesivir use for coronavirus disease 2019 using real-world data.

Background: Remdesivir has been used for treating patients with moderate to severe coronavirus disease 2019 (COVID-19) although there is conflicting evidence regarding its usefulness. Data regarding its safety largely come from the clinical trials conducted to support its emergency use authorization (EUA). This study aimed to identify the adverse events of remdesivir with disproportionately high reporting using real-world data.Research design and methods: The adverse event reports submitted to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) by health-care professionals for drugs that have received EUA or approved for the treatment of COVID-19 in the US were studied. Adisproportionality analysis was performed to determine adverse events more frequently reported with remdesivir compared with other COVID-19 drugs in the database.Results: Elevated liver enzymes, acute kidney injury, raised blood creatinine levels, bradycardia, cardiac arrest, and death had disproportionately higher reporting with remdesivir as asuspect drug compared with other drugs. There is no significant difference in the reporting of these events based on patient sex or age.Conclusions: Our study confirms the drug label information regarding liver enzyme elevation. The renal and cardiac safety signals identified necessitate reevaluation for potential drug-labeling changes.

Tocilizumab in COVID-19: a study of adverse drug events reported in the WHO database.

BACKGROUND: Elevated inflammatory cytokines in Coronavirus disease 2019 (COVID-19) affect the lungs leading to pneumonitis with a poor prognosis. Tocilizumab, a type of humanized monoclonal antibody antagonizing interleukin-6 receptors, is currently utilized to treat COVID-19. The present study reviews tocilizumab adverse drug events (ADEs) reported in the World Health Organization (WHO) pharmacovigilance database. RESEARCH DESIGN AND METHODS: All suspected ADEs associated with tocilizumab between April to August 2020 were analyzed based on COVID-19 patients' demographic and clinical variables, and severity of involvement of organ system. RESULTS: A total of 1005 ADEs were reported among 513 recipients. The majority of the ADEs (46.26%) were reported from 18-64 years, were males and reported spontaneously. Around 80%, 20%, and 64% were serious, fatal, and administered intravenously, respectively. 'Injury, Poisoning, and Procedural Complications' remain as highest (35%) among categorized ADEs. Neutropenia, hypofibrinogenemia were common hematological ADEs. The above 64 years was found to have significantly lower odds than of below 45 years. In comparison, those in the European Region have substantially higher odds compared to the Region of Americas. CONCLUSION: Neutropenia, superinfections, reactivation of latent infections, hepatitis, and cardiac abnormalities were common ADEs observed that necessitate proper monitoring and reporting.

Guiding axes for drug safety management of pharmacovigilance centres during the COVID-19 era.

The COVID-19 pandemic presents several challenges to the organisation and workflow of pharmacovigilance centres as a result of the massive increase in reports, the need for quick detection, processing and reporting of safety issues and the management of these within the context of lack of complete information on the disease. Pharmacovigilance centres permanently monitor the safety profile of medicines, ensuring risk management to evaluate the benefit-risk relationship. However, traditional pharmacovigilance approaches of spontaneous reporting, are not suitable in the context of a pandemic; the scientific community and regulators need information on a near real-time point. The aim of this commentary is to suggest six interrelated multidimensional guiding axes for drug safety management by pharmacovigilance centres during the COVID-19 pandemic. This working plan can increase knowledge on COVID-19 and associated therapeutic approaches, support decisions by the regulatory authorities, oppose fake news and promote more efficient public health protection.

A pharmacist-driven Food and Drug Administration incident surveillance and response program for compounded drugs.

PURPOSE: To provide an overview of compounding under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act, and to describe the pharmacist's role within the US Food and Drug Administration's (FDA's) Compounding Incidents Program, whose efforts are aimed at protecting the public against poor-quality compounded drugs through surveillance, review and response to adverse events and complaints. SUMMARY: Compounded drugs may serve an important medical need for patients who cannot be treated with medications approved by FDA; however, compounded drugs are not approved by FDA and are not subject to premarket review for safety, efficacy, or manufacturing quality; thus, they may pose safety risks to patients. Prompt reporting of adverse events or complaints related to compounding is important in identifying these risks and implementing safeguards to protect the public. FDA's Compounding Incidents Program consists of a team of pharmacists dedicated to the surveillance and review of adverse events and complaints and follow-up actions related to safety risks associated with compounded drugs. Pharmacists are a vital component of FDA's Compounding Incidents Program, utilizing their clinical skill set and regulatory knowledge to review and act on safety issues that affect public health. CONCLUSION: As FDA continues to expand the Compounding Incidents Program and its efforts to protect the public against poor-quality compounded drugs, we encourage the continued submission of adverse event reports by healthcare professionals and consumers to FDA's MedWatch reporting system in addition to adverse event reporting compliance by outsourcing facilities.