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International Immunopharmacology Mar 2024Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are used for a variety of cancers and are associated with a...
INTRODUCTION
Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are used for a variety of cancers and are associated with a risk of developing immune-related adverse events, most commonly dermatitis, colitis, hepatitis, and pneumonitis. Immune-mediated hematologic toxicities have been reported, but are less well-described in the literature. Immune thrombocytopenia (ITP) is a rare autoimmune, hematologic adverse event that has been reported with PD-1/PD-L1 inhibitors.
METHODS
We performed a retrospective observational analysis of the United States Food and Drug Administration Adverse Event Reporting System (FAERS) data. We searched for cases of ITP reported with exposure to PD-1/PD-L1 inhibitors from initial FDA approval for each agent to September 30, 2022. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). Oxaliplatin was used as a positive control for sensitivity analysis as it is an anticancer therapy that has been associated with drug-induced ITP. A systematic review of the PubMed database was also conducted to identify published cases of PD-1/PD-L1 inhibitor-induced ITP.
RESULTS
There were 329 reports of ITP with ICIs in the FAERS database that were reviewed for a disproportionality signal, including atezolizumab (n = 27), durvalumab (n = 17), nivolumab (n = 160), and pembrolizumab (n = 125). The ROR was significant for atezolizumab (ROR 5.39, 95 % CI 3.69-7.87), avelumab (ROR 10.32, 95 % CI 4.91-21.69), durvalumab (ROR 7.91, 95 % CI 4.91-12.75), nivolumab (ROR 9.76, 95 % CI 8.34-11.43), and pembrolizumab (ROR 12.6, 95 % CI 10.55-15.06). In our systematic review, we summated 57 cases of ICI-induced ITP. Nivolumab and pembrolizumab had the most reported cases of ITP in the literature. Most cases reported (53 %) included ITP-directed therapies beyond corticosteroids for the management of ICI-induced ITP.
CONCLUSION
There is a significant reporting signal of ITP with several ICI agents. Clinicians should be aware of and monitor for signs of this potentially serious adverse event.
Topics: United States; Humans; Nivolumab; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Purpura, Thrombocytopenic, Idiopathic; Pharmacovigilance; Retrospective Studies; Drug-Related Side Effects and Adverse Reactions; Thrombocytopenia
PubMed: 38359661
DOI: 10.1016/j.intimp.2024.111606 -
Journal of Biomedical Informatics Mar 2024An adverse drug event (ADE) is any unfavorable effect that occurs due to the use of a drug. Extracting ADEs from unstructured clinical notes is essential to biomedical... (Review)
Review
BACKGROUND
An adverse drug event (ADE) is any unfavorable effect that occurs due to the use of a drug. Extracting ADEs from unstructured clinical notes is essential to biomedical text extraction research because it helps with pharmacovigilance and patient medication studies.
OBJECTIVE
From the considerable amount of clinical narrative text, natural language processing (NLP) researchers have developed methods for extracting ADEs and their related attributes. This work presents a systematic review of current methods.
METHODOLOGY
Two biomedical databases have been searched from June 2022 until December 2023 for relevant publications regarding this review, namely the databases PubMed and Medline. Similarly, we searched the multi-disciplinary databases IEEE Xplore, Scopus, ScienceDirect, and the ACL Anthology. We adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines and recommendations for reporting systematic reviews in conducting this review. Initially, we obtained 5,537 articles from the search results from the various databases between 2015 and 2023. Based on predefined inclusion and exclusion criteria for article selection, 100 publications have undergone full-text review, of which we consider 82 for our analysis.
RESULTS
We determined the general pattern for extracting ADEs from clinical notes, with named entity recognition (NER) and relation extraction (RE) being the dual tasks considered. Researchers that tackled both NER and RE simultaneously have approached ADE extraction as a "pipeline extraction" problem (n = 22), as a "joint task extraction" problem (n = 7), and as a "multi-task learning" problem (n = 6), while others have tackled only NER (n = 27) or RE (n = 20). We further grouped the reviews based on the approaches for data extraction, namely rule-based (n = 8), machine learning (n = 11), deep learning (n = 32), comparison of two or more approaches (n = 11), hybrid (n = 12) and large language models (n = 8). The most used datasets are MADE 1.0, TAC 2017 and n2c2 2018.
CONCLUSION
Extracting ADEs is crucial, especially for pharmacovigilance studies and patient medications. This survey showcases advances in ADE extraction research, approaches, datasets, and state-of-the-art performance in them. Challenges and future research directions are highlighted. We hope this review will guide researchers in gaining background knowledge and developing more innovative ways to address the challenges.
Topics: Humans; Machine Learning; Pharmacovigilance; Drug-Related Side Effects and Adverse Reactions; Natural Language Processing; PubMed
PubMed: 38331081
DOI: 10.1016/j.jbi.2024.104603 -
Health Economics Review Feb 2024Adverse drug events (ADEs) are not only a safety and quality of care issue for patients, but also an economic issue with significant costs. Because they often occur... (Review)
Review
BACKGROUND
Adverse drug events (ADEs) are not only a safety and quality of care issue for patients, but also an economic issue with significant costs. Because they often occur during hospital stays, it is necessary to accurately quantify the costs of ADEs. This review aimed to investigate the methods to calculate these costs, and to characterize their nature.
METHODS
A systematic literature review was conducted to identify methods used to assess the cost of ADEs on Medline, Web of Science and Google Scholar. Original articles published from 2017 to 2022 in English and French were included. Economic evaluations were included if they concerned inpatients.
RESULTS
From 127 studies screened, 20 studies were analyzed. There was a high heterogeneity in nature of costs, methods used, values obtained, and time horizon chosen. A small number of studies considered non-medical (10%), indirect (20%) and opportunity costs (5%). Ten different methods for assessing the cost of ADEs have been reported and nine studies did not explain how they obtained their values.
CONCLUSIONS
There is no consensus in the literature on how to assess the costs of ADEs, due to the heterogeneity of contexts and the choice of different economic perspectives. Our study adds a well-deserved overview of the existing literature that can be a solid lead for future studies and method implementation.
TRIAL REGISTRATION
PROSPERO registration CRD42023413071.
PubMed: 38329561
DOI: 10.1186/s13561-024-00481-y -
Thrombosis and Haemostasis Apr 2024For the treatment of von Willebrand disease (VWD), von Willebrand factor (VWF) concentrates can be used in on-demand, long-term prophylaxis, and surgical prophylaxis...
BACKGROUND
For the treatment of von Willebrand disease (VWD), von Willebrand factor (VWF) concentrates can be used in on-demand, long-term prophylaxis, and surgical prophylaxis regimens.
METHODS
This systematic literature review was conducted to evaluate the efficacy, consumption, and safety of plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Voncento/Biostate) for the treatment of patients with any inherited VWD type. An electronic search was conducted in MEDLINE and Cochrane Library databases on VWD therapies. All retrieved publications were assessed against predefined inclusion/exclusion criteria following the Cochrane group recommendations. Associated pharmacovigilance data were collected across the same time period.
RESULTS
Eleven publications from eight study cohorts were identified for data retrieval. All were from multicenter studies and included both pediatric and adult patients. Eight publications included evaluations of the efficacy of pdVWF/FVIII for on-demand treatment, eight included long-term prophylactic treatment, and eight included surgical prophylaxis. Treatment protocols and VWF administration methods differed between studies, as did safety evaluations. The clinical response was rated as excellent/good for on-demand treatment in 66 to 100% of nonsurgical bleeds, 89 to 100% in the treatment of breakthrough bleeds during long-term prophylaxis treatment, and hemostatic efficacy in surgical procedures was 75 to 100%. Pharmacovigilance data confirmed a low incidence of adverse events in treated patients.
CONCLUSION
This review provides a comprehensive summary of studies that evaluated the use of pdVWF/FVIII in VWD demonstrating the long-term effectiveness and safety of this pdVWF/FVIII across all ages, types of VWD, and treatment settings.
PubMed: 38272065
DOI: 10.1055/a-2253-9701 -
Health Science Reports Dec 2023The reliability of interferon-gamma-release-assays (IGRAs) for tuberculosis (TB) testing in coronavirus disease 2019 (COVID-19) patients is unknown. This study aimed to...
BACKGROUND AND AIMS
The reliability of interferon-gamma-release-assays (IGRAs) for tuberculosis (TB) testing in coronavirus disease 2019 (COVID-19) patients is unknown. This study aimed to systematically review the prevalence of indeterminate TB-IGRA following SARS-CoV-2 infection or vaccination and to review associated factors.
METHODS
This systematic literature review was guided according to the PRISMA guidelines by searching PubMed, Scopus, Web of Science, Clinicalkey, and Cochrane Library. Studies reporting results of TB-IGRA tests (QuantiFERON [QFT]-TB, T-SPOT.TB) in COVID-19 patients or vaccines were included. The random effects model was used to assess the prevalence of indeterminate IGRA results. Heterogeneity was evaluated using the and 95% predictive interval.
RESULTS
Of the 273 citations screened, 12 articles were included in the final analysis including a total of 2107 patients. The overall pooled effect size proportion of indeterminate QFT-TB results, estimated in eight studies using the QFT-TB Plus assay, was 0.26 (95% CI: 0.205-0.324, = 0.158). The mean true effect size was 0.26 (95% predictive interval: [0.110-0.500]). A subgroup analysis was not undertaken due to the small number of studies. Indeterminate QFT-TB rates were associated with COVID-19 severity, steroid treatment, inflammation-related parameters, neutrophilia, and lymphopenia.
CONCLUSION
Indeterminate QFT-TB results in COVID-19 patients occur in almost one-quarter of tests performed. Further studies are needed to assess associated factors.
PubMed: 38130328
DOI: 10.1002/hsr2.1695 -
Kidney360 Jan 2024There is dramatic global variability in the prevalence of ESKD. Higher health care spending in each country is associated with increased delivery of care for ESKD.
KEY POINTS
There is dramatic global variability in the prevalence of ESKD. Higher health care spending in each country is associated with increased delivery of care for ESKD.
BACKGROUND
Approaches to treating ESKD may vary internationally on the basis of the availability of care and other factors. We performed a systematic review to understand the international variability in ESKD epidemiology, management, and outcomes.
METHODS
We systematically searched PubMed for population-based studies of CKD and ESKD epidemiology and management. Population-level data from 23 predesignated nations were eligible for inclusion if they pertained to people receiving dialysis or kidney transplant for ESKD. When available, government websites were used to identify and extract data from relevant kidney registries. Measures gathered included those related to the prevalence and mortality of ESKD; the availability of nephrologists; health care expenditures; and use of erythropoietin-stimulating agents.
RESULTS
We obtained data from the United States; seven nations in Eastern Europe; four each in Western Europe, Latin America, and Africa; and three in Asia. The documented prevalence of ESKD per million population varied from a high of 3600 (Malaysia) to a low of 67 (Senegal). The annual mortality associated with ESKD varied from 31% (Ethiopia and Senegal) to 10% (the United Kingdom). Nephrologist availability per million population varied from 40 (Japan) to <1 (South Africa) and was associated with health care expenditures.
CONCLUSIONS
The delivery of kidney care related to ESKD varies widely among countries. Higher health care spending is associated with increased delivery of kidney care. However, in part because documentation of kidney disease varies widely, it is difficult to determine how outcomes related to ESKD may vary across nations.
Topics: Humans; Kidney Failure, Chronic; Disease Progression
PubMed: 38055708
DOI: 10.34067/KID.0000000000000335 -
Research in Veterinary Science Jan 2024This article aims to perform a comparative systematic review of regulations in veterinary medicine between the years 2016 to 2023. It explores the complex web of... (Review)
Review
This article aims to perform a comparative systematic review of regulations in veterinary medicine between the years 2016 to 2023. It explores the complex web of veterinary medicine regulations in various agencies and the nations, including USA (United States of America), EU (European Union), UK (United Kingdom), Japan, Australia, and India. Current article provides the comparative study on the veterinary regulations of different countries, including acts, directives, and drug approval processes. Such as, the specific legislation is needed to address zoonotic diseases. The strategic and regulated stockpiling of the veterinary drugs especially in chronic veterinary disease outbreak. It is essential to develop the dedicated Veterinary Pharmacopoeia for the regulated standardization of the raw materials as well as the formulations. Veterinary medical device is a field which is highly unregulated. There is a need to have regulations for the same. It is important to have dedicated veterinary pharmacovigilance centers which help in improving quality of medications to the livestock farms. After comparing the regulations of different countries. We observed that there is the absence of the zoonotic diseases and pharma stockpiling in every country. There is also an absence of the dedicated veterinary pharmacopoeia in every country. USA and Australia have the veterinary medical device regulation which is not there in other countries. Around the globe only Australia has the dedicated pharmacovigilance center. Including these recommendations into regulatory framework enhances the quality and safety of veterinary medicine. The current article adds a valuable resource for policymakers, veterinarians, and stakeholders in the field of animal health care.
Topics: Animals; Humans; Animal Husbandry; European Union; Japan; United States; Veterinarians; Zoonoses
PubMed: 38016218
DOI: 10.1016/j.rvsc.2023.105101 -
Expert Opinion on Drug Safety Jun 2024The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications. (Meta-Analysis)
Meta-Analysis
Risk of pancreatitis and pancreatic carcinoma for anti-diabetic medications: findings from real-world safety data analysis and systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications.
RESEARCH DESIGN AND METHODS
A retrospective case/non-case study was conducted by using spontaneous reports on pancreatic events for anti-diabetic medications from the FDA Adverse Event Reporting System (FAERS) and VigiBase. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were calculated by a disproportionality analysis. Furthermore, PubMed, Google Scholar, Scopus, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) on anti-diabetic drugs with pancreatic outcomes.
RESULTS
The FAERS data analysis found strong signals on incretin mimetics causing pancreatic events, with sitagliptin having the highest risk [PRR = 24.2, lower bound (LB) ROR = 24.4, IC = 4.4 for pancreatitis, and PRR = 15.4, LB ROR = 14.9, IC = 3.8 for pancreatic carcinoma]. Empagliflozin was the most pancreatitis-risk sodium-glucose co-transporter-2 inhibitor [PRR = 4.0, LB ROR = 3.5, IC = 1.8]. VigiBase reiterated these findings and identified some new signals for novel anti-diabetics. Meta-analysis revealed that the incidence of pancreatitis and pancreatic carcinoma with anti-diabetic medications was insignificant. However, compared to the placebo/active comparator, gliptins had a higher risk of acute pancreatitis (OR 1.44; 95% CI 1.03, 2.01; = 0.03).
CONCLUSION
Evidence from the post-marketing safety data analysis identified a strong association between incretin mimetics and pancreatic events. Fewer events in RCTs may justify insignificant meta-analysis results.
Topics: Humans; Pancreatic Neoplasms; Pancreatitis; Randomized Controlled Trials as Topic; Hypoglycemic Agents; Adverse Drug Reaction Reporting Systems; Retrospective Studies; Risk; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37986140
DOI: 10.1080/14740338.2023.2284992 -
Schizophrenia Research Jun 2024The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
BACKGROUND
The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
METHODS
Cases of clozapine-associated pericarditis and pancreatitis in children were studied using searches in: 1) PubMed (June 16, 2023), and 2) the World Health Organization's pharmacovigilance database (June 1, 2022), VigiBase. VigiBase uses a logarithmic measure of disproportionality called the information component (IC).
RESULTS
The PubMed search yielded 3 clozapine-associated pericarditis cases, 1 pancreatitis case and 1 with both. VigiBase provided a significant clozapine-associated pericarditis IC = 3.6 with an IC = 2.9 (only 3 cases were expected while 22 were observed). VigiBase provided a significant clozapine-associated pancreatitis IC = 2.2 with an IC = 1.4 (only 3 cases were expected while 16 were observed). In VigiBase clozapine-associated pericarditis and pericardial effusion in youth looked similar and on a continuum with myocarditis, as myocarditis, pericarditis and pancreatitis appeared to occur mainly during clozapine titration. Combining PubMed and VigiBase we identified: 1) 29 cases of at least possible clozapine-associated pericarditis/pericardial effusion (6 probable and 23 possible) including 7 cases with and 22 without myocarditis, and 2) 17 cases of clozapine-associated pancreatitis (1 definite and 16 possible). Two of the pancreatitis cases occurred during overdoses. No fatal outcomes were found in any clozapine-associated pericarditis and pancreatitis cases.
CONCLUSIONS
Despite the lack of attention in the literature to clozapine-associated pericarditis and pancreatitis, results demonstrate that they can happen in youth, particularly during titration. Pericarditis and pancreatitis appear to be forms of clozapine-associated inflammation during dose titration.
Topics: Humans; Pancreatitis; Clozapine; Pericarditis; Pharmacovigilance; Adolescent; Child; Antipsychotic Agents; Databases, Factual; Male; Female; Pericardial Effusion
PubMed: 37981478
DOI: 10.1016/j.schres.2023.10.027 -
Research in Social & Administrative... Feb 2024Adverse drug reactions (ADRs) are known to cause hospitalisation, longer hospital stays, as well as higher healthcare costs and mortality. Unrecognised ADRs are... (Review)
Review
Understanding factors influencing the implementation of medicine risk communications by healthcare professionals in clinical practice: a systematic review using the Theoretical Domains Framework.
BACKGROUND
Adverse drug reactions (ADRs) are known to cause hospitalisation, longer hospital stays, as well as higher healthcare costs and mortality. Unrecognised ADRs are anticipated throughout the medicine lifecycle as, before the medicine reaches the market, clinical trials are conducted for a short period on a limited number of people, who might underrepresent the actual population. After the medicine reaches the market, emergent information that could affect its benefit-to-risk balance is usually shared by regulatory agencies and pharmaceutical companies through medicine risk communications. Medicines risk communications aim to prevent harm to patients by targeting their behaviour, knowledge, and attitudes, as well as those of health care professionals (HCPs). Despite their important role in translating these communications into their clinical practice, HCPs do not always adhere to the recommendations provided in risk communications. Measurement of medicine risk communications' effectiveness does not necessarily guarantee their implementation, cost-effectiveness, or transferability in real-world situations. To enhance the impact of drug regulatory interventions, implementation science has been encouraged. However, implementation science was not previously used to identify factors affecting HCPs' implementation of medicines risk communications. A recently widely used framework is the Theoretical Domain Framework (TDF). In this systematic review, the TDF was employed to categorise a range of different factors that could affect HCPs' implementation of medicine risk communications within their clinical contexts.
METHODS
The search strategy involved a set of predefined search terms and fifteen databases, such as EMBASE, PubMed, Web of Science and CINAHL PLUS. Searches were conducted from April to May 2018 and updated in June 2021 using PubMed, Scopus, and CINAHL PLUS. A second reviewer independently conducted the screening process of the initial search. The total number of records screened was 10,475. A study was included if it reported any factors influencing HCPs' uptake of medicine risk communications. Only studies with English or Arabic abstracts were included. Those studies that did not include pharmacovigilance-related medicine risk communications were excluded. Additionally, studies only assessing HCPs' practice or evaluating the effectiveness of risk minimisation measures were excluded. Likewise, studies related to occupational hazards, case reports, interventional studies, and studies not involving HCPs were excluded. In case the published information was insufficient to decide whether to include or exclude a study, the authors were contacted. Furthermore, the authors of seven eligible abstracts were contacted for full-text articles. The mixed method appraisal tool (MMAT) was used to evaluate the quality of the included studies. All included studies were assessed by one reviewer, and a total of 16 studies were assessed by two reviewers independently. Disagreements were resolved through discussion. Using thematic analysis and concept mapping, a narrative synthesis was performed, followed by a critical reflection on the synthesis process. This review presents the results of the concept mapping, which involved matching the identified factors to the TDF.
RESULTS
A total of 28 studies were included. Eleven domains influenced HCPs' implementation of medicine risk communications. A large number of studies included factors related to the "Knowledge" domain (n = 23), followed by "Beliefs about Consequences" (n = 13), "Memory, Attention and Decision Processes" (n = 12) and "Environmental Context and Resources" domains (n = 12). Seven studies reported "social influences" and six studies included factors relating to "Goals", followed by four studies involving factors related to "Social/Professional Role and Identity". Underrepresented domains included "Emotion" (n = 2), "Beliefs about Capabilities" (n = 2), "Behavioural Regulation" (n = 1), and "Reinforcement" (n = 1). On the other hand, none of the identified factors were related to the "Skills", "Optimism", or "Intentions" domains. Except for "Beliefs about Consequences", most studies contributing to the other three most commonly reported domains ("Knowledge"; "Environmental Context and Resources"; and "Memory, Attention and Decision Processes") scored low (1 or 2 out of 5) on the MMAT quality assessment. Moreover, the same number of studies (n = 5) contributing to the "Beliefs about Consequences" domain had low (1 or 2 out of 5), and intermediate (3 out of 5) scores on the MMAT.
CONCLUSION
Medicines risk communications are important tools for disseminating information that may influence the benefit-to-risk balance of medicines. Even though HCPs are required to implement the recommendations of these communications, they do not always adhere to them. Using the TDF enabled the categorization of the range of factors that affect whether or not HCPs implement the recommendations provided in a medicine risk communication. However, most of these factors relate to four domains only ("Knowledge"; "Beliefs about Consequences"; "Memory, Attention and Decision Processes"; and "Environmental Context and Resources"). Additionally, most of the studies contributing to three of these four domains were of low quality. Future research should focus on using implementation science to identify target behaviours for actionable medicine risk communications. Regulators should use such science to develop cost-effective strategies for improving the implementation of medicines risk communication by HCPs.
Topics: Humans; Health Personnel; Communication; Risk Assessment; Delivery of Health Care
PubMed: 37978010
DOI: 10.1016/j.sapharm.2023.10.004