-
European Journal of Clinical... Oct 2022Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring... (Review)
Review
PURPOSE
Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring emergency department visits. In addition to conventional strategies for SAEs (inhaled β-agonists, anticholinergics, and systemic corticosteroids), another pharmacological option is represented by ketamine. We performed a systematic review to explore the role of ketamine in refractory SAEs.
METHODS
We performed a systematic search on PubMed and EMBASE up to August 12th, 2021. We selected prospective studies only, and outcomes of interest were oxygenation/respiratory parameters, clinical status, need for invasive ventilation and effects on weaning.
RESULTS
We included a total of seven studies, five being randomized controlled trials (RCTs, population range 44-92 patients). The two small prospective studies (n = 10 and n = 11) did not have a control group. Four studies focused on adults, and three enrolled a pediatric population. We found a large heterogeneity regarding sample size, age and gender distribution, inclusion criteria (different severity scores, if any) and ketamine dosing (bolus and/or continuous infusion). Of the five RCTs, three compared ketamine to placebo, while one used fentanyl and the other aminophylline. The outcomes evaluated by the included studies were highly variable. Despite paucity of data and large heterogeneity, an overview of the included studies suggests absence of clear benefit produced by ketamine in patients with refractory SAE, and some signals towards side effects.
CONCLUSION
Our systematic review does not support the use of ketamine in refractory SAE. A limited number of prospective studies with large heterogeneity was found. Well-designed multicenter RCTs are desirable.
Topics: Adrenal Cortex Hormones; Adult; Aminophylline; Anti-Asthmatic Agents; Asthma; Child; Cholinergic Antagonists; Fentanyl; Humans; Ketamine; Multicenter Studies as Topic; Prospective Studies
PubMed: 36008492
DOI: 10.1007/s00228-022-03374-3 -
Rare Heterogeneous Adverse Events Associated with mRNA-Based COVID-19 Vaccines: A Systematic Review.Medicines (Basel, Switzerland) Aug 2022Since the successful development, approval, and administration of vaccines against SARS-CoV-2, the causative agent of COVID-19, there have been reports in the published... (Review)
Review
Since the successful development, approval, and administration of vaccines against SARS-CoV-2, the causative agent of COVID-19, there have been reports in the published literature, passive surveillance systems, and other pharmacovigilance platforms of a broad spectrum of adverse events following COVID-19 vaccination. A comprehensive review of the more serious adverse events associated with the Pfizer-BioNTech and Moderna mRNA vaccines is warranted, given the massive number of vaccine doses administered worldwide and the novel mechanism of action of these mRNA vaccines in the healthcare industry. A systematic review of the literature was conducted to identify relevant studies that have reported mRNA COVID-19 vaccine-related adverse events. Serious and severe adverse events following mRNA COVID-19 vaccinations are rare. While a definitive causal relationship was not established in most cases, important adverse events associated with post-vaccination included rare and non-fatal myocarditis and pericarditis in younger vaccine recipients, thrombocytopenia, neurological effects such as seizures and orofacial events, skin reactions, and allergic hypersensitivities. As a relatively new set of vaccines already administered to billions of people, COVID-19 mRNA-based vaccines are generally safe and efficacious. Further studies on long-term adverse events and other unpredictable reactions in close proximity to mRNA vaccination are required.
PubMed: 36005648
DOI: 10.3390/medicines9080043 -
Research in Social & Administrative... Jan 2023Regulatory medicines risk communications aim to prevent patient harm through the dissemination of safety information to healthcare professionals (HCPs), patients, and... (Review)
Review
BACKGROUND
Regulatory medicines risk communications aim to prevent patient harm through the dissemination of safety information to healthcare professionals (HCPs), patients, and the public. Evidence suggests that in addition to implementing the required changes, HCPs also respond to these communications through unintended and unwarranted actions and behaviours such as stopping medicine courses unnecessarily, and blanket actions spilling over to unintended patients' populations. Misunderstanding and mis-implementation of medicines risk communications could jeopardise patients' safety and clinical outcomes. Therefore, it is important to understand the determinants that affect HCPs responses to medicines risk communications. This systematic review aims to identify the factors that affect the implementation of risk communications by healthcare professionals.
METHODS
Fifteen databases, including EMBASE, PubMed, Scopus, Web of science, CINAHL PLUS were searched in April-May 2018, and the search was updated again in June 2021 to identify studies reporting on factors influencing HCPs' uptake of medicine risk alerts. We used keywords such as risk communication, safety update, and safety regulation. Studies were excluded if they did not involve pharmacovigilance or patient safety alerts; or if they only focused on measuring HCPs' practice after alerts; or evaluating the effectiveness of risk minimisation measures without reporting on factors affecting HCPs' actions. Studies relating to occupational hazards, case reports, interventional studies, and studies not involving HCPs were also excluded. The Mixed Method Appraisal Tool (MMAT) was used to assess the quality of the included studies. A Narrative synthesis approach was undertaken using thematic analysis and concept mapping, followed by a critical reflection of the synthesis.
RESULTS
Twenty-eight studies met our criteria and were included in the synthesis. We identified four themes summarising the factors influencing HCPs' implementation of risk communications. These include HCPs: knowledge of medicine alerts; perceptions of alerts; attitudes, and concerns regarding medicine alerts; and the self-reported impact of these alerts. Our concept mapping exercise identified key interactions between different stakeholders, and these interactions determine HCPs' implementation of medicine risk communications. These stakeholders comprise of alert developers, including the sources and senders of safety information, and the receivers of safety information including health care institutions, HCPs, patients and their carers.
CONCLUSIONS
Healthcare professionals are crucial to translating risk communication messages into clinical practice. However, if they have inadequate information about the content of the alert, and have inaccurate perceptions about the alert, they may not implement the required clinical changes as intended. Communication of medicine risk alerts does not always translate into improved patient care, due to a complex interaction between stakeholders involved in the creation and implementation of these alerts. These complex interactions should be the subject of future research efforts to understand the alert-implementation trajectory and identify the mediators for change and interventions to improve implementation.
Topics: Humans; Health Personnel; Communication; Caregivers; Delivery of Health Care; Patient Safety
PubMed: 35989221
DOI: 10.1016/j.sapharm.2022.07.003 -
BMC Public Health Aug 2022Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that...
BACKGROUND
Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies.
METHODS
We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021.
RESULTS
We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables.
CONCLUSIONS
Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond.
Topics: Cost of Illness; Disabled Persons; Europe; Global Burden of Disease; Humans; Quality-Adjusted Life Years
PubMed: 35978333
DOI: 10.1186/s12889-022-13925-z -
International Journal of Environmental... Jul 2022Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is... (Meta-Analysis)
Meta-Analysis
Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis.
Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is limited. This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30−10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17−32.35), mucositis (RR 3.18; 95% CI 1.52−6.65), hypomagnesemia (RR 20.10; 95% CI 5.92−68.21), and dehydration (RR 2.81; 95% CI 1.03−7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.
Topics: Antineoplastic Agents; Bevacizumab; Cetuximab; Colorectal Neoplasms; Humans; Network Meta-Analysis; Panitumumab
PubMed: 35954563
DOI: 10.3390/ijerph19159196 -
Frontiers in Pediatrics 2022Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that has proven efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL)....
BACKGROUND
Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that has proven efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Despite its efficacy, it has also been associated with the development of potentially serious adverse events such as the cytokine release syndrome (CRS) and neurologic events. The present meta-analysis aimed to assess the safety profile of blinatumomab in terms of serious adverse events, CRS, and neurologic events (such as seizure and encephalopathy) in pediatric patients with B-cell ALL.
METHODS AND FINDINGS
A systematic review was conducted in Pubmed up to December 10, 2021 to retain pediatric clinical trials on blinatumomab. A random effect meta-analysis approach was used. This study followed the PRISMA statement. Four out of the 255 initial references were selected, of which 2 were phase 1/2 clinical trials and 2 phase 3 clinical trials. Blinatumomab was associated with a lower risk of serious adverse events (Risk ratio RR, 0.56; 95% CI, 0.32-0.99), febrile neutropenia (RR, 0.13; 95% CI, 0.06-0.26), infection (RR, 0.40; 95% CI, 0.29-0.56), and grade ≥ 3 adverse events (RR, 0.79; 95% CI, 0.67-0.93) compared to chemotherapy. No difference in the risk of CRS (RR, 8.37; 95% CI, 0.27-260.97) and seizure (RR, 6.43; 95% CI, 0.79-53.08) was observed between groups, while for encephalopathy a higher risk was associated with blinatumomab compared to chemotherapy (RR, 8.90; 95% CI, 1.08-73.29).
CONCLUSION
Our data support the good safety profile of bliantumomab in treating pediatric patients with B-ALL.
PubMed: 35935358
DOI: 10.3389/fped.2022.929122 -
The World Allergy Organization Journal Jul 2022The change from prescription to over-the-counter (OTC) status of oral antihistamines may raise concerns about drug safety due to the possibility of misuse/abuse. In most... (Review)
Review
BACKGROUND
The change from prescription to over-the-counter (OTC) status of oral antihistamines may raise concerns about drug safety due to the possibility of misuse/abuse. In most European countries, oral antihistamines are available without prescription, whereas in Italy, only <10-tablet packs are available OTC.
OBJECTIVES
To evaluate the safety profile of fexofenadine after OTC switch in Italy in a real-world setting, and to compare its safety profile to that of other European countries where larger pack sizes are available. To compare the safety of fexofenadine, cetirizine, and loratadine in Italy. To examine safety/efficacy across Europe with a systematic review.
METHODS
This case-by-case analysis used the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) to extract data of the adverse events (AEs) related to fexofenadine, loratadine and cetirizine in Italy January 2010-June 2020. The year 2016 was taken as the index date (removal of prescription requirement) for evaluation of the reporting trend of AEs of fexofenadine in Italy and make a comparison pre/post-OTC switch. A comparison of AEs with other European countries where fexofenadine is sold OTC in large packs >20 tablets (Belgium, Portugal, Switzerland, Finland, Hungary) was made. The rate at which an AE related to oral antihistamines occurred was estimated by calculation of the reporting rate (number of cases/[defined daily dose/1000 inhabitants per day]) on the basis of IQVIA sales data using the Italian Institute of Statistics database. A systematic review of the literature was also performed.
RESULTS
There were 3760 reports of AEs with a suspected association with fexofenadine; of these, eight were reported from Italy. There was a slightly increasing trend per year, in line with a general reporting trend of other drugs. In European countries where fexofenadine is available, the impact of OTC switch on AE reporting activity was negligible: from 2016, the reporting rate increased slightly and then normalized at 3.01, an incidence value similar to that recorded before the OTC switch (3.7 in 2015). Of 22 studies included in the systematic review, 18 (82%) positively evaluated the OTC use of oral antihistamines, confirming an acceptable safety/tolerability profile.
CONCLUSION
There was no difference in number of AEs reported for fexofenadine pre/post-OTC switch, indicating a similar safety profile. Spontaneous reporting systems are a valuable source of real-world data and support the OTC provision of oral antihistamines in Europe and fexofenadine in Italy, in addition to supporting the use of larger pack sizes in Italy.
PubMed: 35833202
DOI: 10.1016/j.waojou.2022.100658 -
Drug Safety Jul 2022Traditional, complementary and alternative medicine (TCAM) refers to a broad range of health practices and products typically not part of the 'conventional medicine'...
INTRODUCTION
Traditional, complementary and alternative medicine (TCAM) refers to a broad range of health practices and products typically not part of the 'conventional medicine' system, and its use is substantial among the general population. TCAM products and therapies may be used in addition to, or instead of, conventional medicine approaches, and some have been associated with adverse reactions or other harms.
OBJECTIVES
The aims of this systematic review were to identify and examine recently published national studies globally on the prevalence of TCAM use in the general population, to review the research methods used in these studies and to propose best practices for future studies exploring prevalence of use of TCAM.
METHODS
MEDLINE, Embase, CINAHL, PsycINFO and AMED were searched to identify relevant studies published since 2010. Articles/reports describing the prevalence of TCAM use in a national study among the general population were included. The quality of included studies was assessed using a risk of bias tool developed by Hoy et al. Relevant data were extracted and summarised.
RESULTS
Forty studies from 14 countries, comprising 21 national surveys and one cross-national survey, were included. Studies explored the use of TCAM products (e.g. herbal medicines), TCAM practitioners/therapies, or both. Included studies used different TCAM definitions, prevalence time frames and data collection tools, methods and analyses, thereby limiting comparability across studies. The reported prevalence of use of TCAM (products and/or practitioners/therapies) over the previous 12 months was 24-71.3%.
CONCLUSION
The reported prevalence of use of TCAM (products and/or practitioners/therapies) is high, but may underestimate use. Published prevalence data varied considerably, at least in part because studies utilise different data collection tools, methods and operational definitions, limiting cross-study comparisons and study reproducibility. For best practice, comprehensive, detailed data on TCAM exposures are needed, and studies should report an operational definition (including the context of TCAM use, products/practices/therapies included and excluded), publish survey questions and describe the data-coding criteria and analysis approach used.
Topics: Complementary Therapies; Humans; Prevalence; Reproducibility of Results; Surveys and Questionnaires
PubMed: 35788539
DOI: 10.1007/s40264-022-01189-w -
Drugs & Aging Aug 2022Frailty is highly prevalent in heart failure populations and a major risk factor for adverse drug reactions (ADRs) and adverse drug events (ADEs). This review aimed to...
INTRODUCTION
Frailty is highly prevalent in heart failure populations and a major risk factor for adverse drug reactions (ADRs) and adverse drug events (ADEs). This review aimed to describe the prevalence, causality and severity of ADRs or ADEs from heart failure medications among frail compared with non-frail older adults.
METHODS
A systematic search of CENTRAL, MEDLINE, Embase, Ageline, CINAHL, International Pharmaceutical Abstracts, PsychInfo, Scopus, registries and citations prior to 18 May 2021 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. Risk of bias and quality of evidence were assessed. Eligible studies included randomised controlled trials (RCTs) and observational studies of people diagnosed with heart failure, aged ≥ 65 years, with frailty defined by an objective measurement, and reported ADRs/ADEs from/with heart failure medications.
RESULTS
Two reviewers screened 2419 articles; interrater reliability kappa = 0.88. Three observational studies (n = 2596), a secondary analysis of two RCTs (n = 2098) and two cohort studies (n = 498) were included in a narrative synthesis. Frail patients in randomised trials of sacubitril/valsartan, aliskiren, or enalapril had twice the risk of mortality (hazard ratio [HR] 2.09, 1.62-2.71) and hospitalisations (HR 1.82, 1.37-2.41) compared with robust patients, which may reflect responsiveness to medications and/or factors unrelated to medication use. Hospitalisations from falls, tiredness and nausea were probably attributable to digoxin and possibly preventable according to the Naranjo and Hallas scales, respectively.
CONCLUSION
The potential harms from heart failure medications in frail older people are poorly studied and understood. Clinical trials and pharmacovigilance studies should include frailty as a covariate to inform medication optimisation for this vulnerable and growing population.
REGISTRATION
Prospero registration number: CRD 42021253762.
Topics: Aged; Aminobutyrates; Biphenyl Compounds; Drug-Related Side Effects and Adverse Reactions; Frailty; Heart Failure; Humans; Pharmaceutical Preparations; Prevalence
PubMed: 35761118
DOI: 10.1007/s40266-022-00957-8 -
Frontiers in Pharmacology 2022to characterize pediatric cases of antibiotic-associated neutropenia through a multidisciplinary approach, focusing on the temporal association between the wide...
to characterize pediatric cases of antibiotic-associated neutropenia through a multidisciplinary approach, focusing on the temporal association between the wide spectrum of treatment options and the occurrence of this relatively uncommon but potentially clinically relevant adverse event. we carried out a pharmacoepidemiological analysis based on the FDA Adverse Event Reporting System (FAERS) database, a retrospective chart review and a systematic review of the literature, focusing on the time to onset (TTO) of this side effect, in the pediatric clinical setting. A total of 281 antibiotic-related neutropenia events, involving 11 categories of antibiotics, were included in the time to onset analysis. The median TTO ranged from 4 to 60 days after the start of the therapy. A shorter median TTO was found from the retrospective chart review [16 patients: median days (25th-75th percentiles) = 4 (3-5)], compared to 15 (9-18) vs. 10 (6-18) for literature (224 patients) and FAERS (41 cases), respectively. The Anatomical Therapeutic Chemical classes, J01X, J01F, J01E and J04A, and the median TTOs retrieved from more than one source revealed high accordance ( > 0.05), with J01X causing neutropenia in less than a week and J01F/J01E/J04A in more than 10 days. Antibiotics were discontinued in nearly 34% of cases. In FDA Adverse Event Reporting System reports, half of the patients experiencing neutropenia were hospitalized. Whereas antibiotic associated neutropenia is benign in the majority of cases, yet it should not be neglected as, even if rarely, it may put children at higher risk of clinical consequences. Clinicians' awareness of antibiotic-associated neutropenia and its mode of presentation contributes to the continuous process of monitoring safety of antibiotics.
PubMed: 35721197
DOI: 10.3389/fphar.2022.877932