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Frontiers in Pediatrics 2023Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin... (Review)
Review
BACKGROUND
Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin receptor agonist, provides a hematologic improvement in adults with severe aplastic anemia (SAA) refractory to immunosuppressive therapy (IST). The association of ELT and IST was approved by the US Food and Drug Administration (FDA) for adults and children ≥2 years of age as a first-line treatment for SAA. However, the effects of ELT on pediatric patients with SAA remain controversial and limited.
METHODS AND FINDINGS
We conducted a systematic review of the most recent literature from Pubmed, Web of Science, and Embase, published up to 20th December 2022, in order to evaluate the available evidence on the efficacy and safety of ELT added to IST for the treatment of SAA in the pediatric population.
CONCLUSION
Eltrombopag added to the IST has shown a good safety profile, without manifestations of excessive toxic effects, although not all the results obtained from our studies support the addition of ELT to the IST in the first-line treatment of children with SAA.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42022325859.
PubMed: 37168802
DOI: 10.3389/fped.2023.1149718 -
International Journal of Gynecological... Aug 2023To evaluate the risk of interstitial lung disease associated with poly (ADP-ribose) polymerase inhibitors (PARPi) and characterize its clinical features.
Interstitial lung disease in patients treated with poly (ADP-ribose) polymerase inhibitors (PARPi): analysis of results from clinical trials and the FDA Adverse Events Reporting System database.
OBJECTIVE
To evaluate the risk of interstitial lung disease associated with poly (ADP-ribose) polymerase inhibitors (PARPi) and characterize its clinical features.
METHODS
We systematically reviewed phase III randomized clinical trials of interstitial lung disease related to PARPi and calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs). Pharmacovigilance studies were conducted by collecting cases of PARPi-related interstitial lung disease from the FDA Adverse Events Reporting System and assessing disproportionalities by reporting ORs and information components.
RESULTS
A total of five randomized clinical trials involving 2980 patients were included. Although PARPi showed a tendency to increase the risk of interstitial lung disease compared with controls, this difference was not significant (Peto OR: 4.92; 95% CI: 0.92 to 26.35). A total of 170 cases of interstitial lung disease related to PARPi were included, with a median latency of 99 days. PARPi had a significantly increased reporting of interstitial lung disease (reporting OR: 2.86; 95% CI: 2.46 to 3.33; information component (IC): 1.49; 95% CI: 1.28 to 1.74). Our sensitivity analyses showed strong robustness of the disproportionalities between PARPi as a class, olaparib, and interstitial lung disease. Some 91.9% of patients experienced discontinuation, 51.6% achieved remission, and no deaths were reported.
CONCLUSION
Our pharmacovigilance study suggested increased reporting of interstitial lung disease related to PARPi particularly olaparib.
Topics: Humans; Female; Poly(ADP-ribose) Polymerase Inhibitors; Ribose; Ovarian Neoplasms; Randomized Controlled Trials as Topic
PubMed: 37164363
DOI: 10.1136/ijgc-2022-004042 -
BMC Nephrology Apr 2023Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study.
METHODS
We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR).
RESULTS
A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78-2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24-1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01-1.65), diuretics (OR = 2.00, 95%CI 1.38-2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04-1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15-1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25-2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96-3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91-2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95-3.57), NSAIDs (ROR = 3.06, 95%CI 2.81-3.32) or diuretics (ROR = 2.82, 95%CI 2.50-3.19) were observed significant signals associated with AKI in ICIs-treated patients.
CONCLUSIONS
Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.
Topics: Humans; Retrospective Studies; Immune Checkpoint Inhibitors; Pharmacovigilance; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Risk Factors; Acute Kidney Injury; Diuretics; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37087434
DOI: 10.1186/s12882-023-03171-9 -
Biomarker Insights 2023The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years,... (Review)
Review
BACKGROUND
The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the use of biomarkers in pharmacovigilance and specifically in the monitoring and management of adverse drug reactions (ADRs).
OBJECTIVE
The objective of this manuscript is to identify the multiple uses of biomarkers in pharmacovigilance irrespective of the therapeutic area.
DESIGN
This is a systematic review of the literature.
DATA SOURCES AND METHODS
Embase and MEDLINE database searches were conducted for literature published between 2010-March 19, 2021. Scientific articles that described the potential use of biomarkers in pharmacovigilance in sufficient detail were reviewed. Papers that did not fulfill the United States Food and Drug Administration (US FDA) definition of a biomarker were excluded, which is based on the International Conference on Harmonisation (ICH)-E16 guidance.
RESULTS
Twenty-seven articles were identified for evaluation. Most articles involved predictive biomarkers (41%), followed by safety biomarkers (38%), pharmacodynamic/response biomarkers (14%), and diagnostic biomarkers (7%). Some articles described biomarkers that applied to multiple categories.
CONCLUSION
Various categories of biomarkers including safety, predictive, pharmacodynamic/response, and diagnostic biomarkers are being investigated for potential use in pharmacovigilance. The most frequent potential uses of biomarkers in pharmacovigilance in the literature were the prediction of the severity of an ADR, mortality, response, safety, and toxicity. The safety biomarkers identified were used to evaluate patient safety during dose escalation, identify patients who may benefit from further biomarker testing during treatment, and monitor ADRs.
PubMed: 37077840
DOI: 10.1177/11772719231164528 -
Vector Borne and Zoonotic Diseases... Apr 2023Lyme borreliosis (LB) is the most common tick-borne disease in Europe, but the burden of disease is incompletely described. We conducted a systematic review across...
Lyme borreliosis (LB) is the most common tick-borne disease in Europe, but the burden of disease is incompletely described. We conducted a systematic review across PubMed, EMBASE, and CABI Direct (Global Health) databases, from January 1, 2005, to November 20, 2020, of epidemiological studies reporting incidence of LB in Europe (PROSPERO, CRD42021236906). The systematic review yielded 61 unique articles describing LB incidence (national or subnational) in 25 European countries. Substantial heterogeneity in study designs, populations sampled, and case definitions restricted data comparability. The European Union Concerted Action on Lyme Borreliosis (EUCALB)-published standardized LB case definitions were used by only 13 (21%) of the 61 articles. There were 33 studies that provided national-level LB incidence estimates for 20 countries. Subnational LB incidence was available from an additional four countries (Italy, Lithuania, Norway, and Spain). The highest LB incidences (>100 cases per 100,000 population per year [PPY]) were reported in Belgium, Finland, the Netherlands, and Switzerland. Incidences were 20-40/100,000 PPY in the Czech Republic, Germany, Poland, and Scotland and <20/100,000 PPY in Belarus, Croatia, Denmark, France, Ireland, Portugal, Russia, Slovakia, Sweden, and the United Kingdom (England, Northern Ireland, and Wales); markedly higher incidences were observed at the subnational level (up to 464/100,000 PPY in specific local areas). Although countries in Northern (Finland) and Western (Belgium, the Netherlands, and Switzerland) Europe reported the highest LB incidences, high incidences also were reported in some Eastern European countries. There was substantial subnational variation in incidence, including high incidences in some areas of countries with low overall incidence. This review, complemented by the incidence surveillance article, provides a comprehensive view into LB disease burden across Europe that may guide future preventive and therapeutic strategies-including new strategies on the horizon.
Topics: Animals; Incidence; Lyme Disease; Europe; Tick-Borne Diseases; Belgium
PubMed: 37071407
DOI: 10.1089/vbz.2022.0070 -
Vector Borne and Zoonotic Diseases... Apr 2023Lyme borreliosis (LB) is the most common tick-borne disease in Europe. To inform European intervention strategies, including vaccines under development, we conducted a...
Lyme borreliosis (LB) is the most common tick-borne disease in Europe. To inform European intervention strategies, including vaccines under development, we conducted a systematic review for LB incidence. We searched publicly available surveillance data reporting LB incidence in Europe from 2005 to 2020. Population-based incidence was calculated as the number of reported LB cases per 100,000 population per year (PPY), and high LB risk areas (incidence >10/100,00 PPY for 3 consecutive years) were estimated. Estimates of LB incidence were available for 25 countries. There was marked heterogeneity in surveillance systems (passive vs. mandatory and sentinel sites vs. national), case definitions (clinical, laboratory, or both), and testing methods, limiting comparison across countries. Twenty-one countries (84%) had passive surveillance; four (Belgium, France, Germany, and Switzerland) used sentinel surveillance systems. Only four countries (Bulgaria, France, Poland, and Romania) used standardized case definitions recommended by European public health institutions. Among all surveillance systems and considering any case definition for the most recently available years, national LB incidences were highest in Estonia, Lithuania, Slovenia, and Switzerland (>100 cases/100,000 PPY), followed by France and Poland (40-80/100,000 PPY), and Finland and Latvia (20-40/100,000 PPY). Incidences were lowest in Belgium, Bulgaria, Croatia, England, Hungary, Ireland, Norway, Portugal, Romania, Russia, Scotland, and Serbia (<20/100,000 PPY). At the subnational level, highest LB incidences (>100/100,000 PPY) were observed in areas of Belgium, Czech Republic, France, Germany, and Poland. Overall, on average 128,888 cases are reported annually. An estimated 202/844 million (24%) persons in Europe reside in areas of high LB incidence and 202/469 million (43.2%) persons reside in areas of high LB incidence among countries with surveillance data. Our review showed substantial variability in reported LB incidence across and within European countries, with highest incidences reported from the Eastern, Northern (Baltic states and Nordic countries), and Western Europe surveillance systems. Standardization of surveillance systems, including wider implementation of common case definitions, is urgently needed to interpret the range of differences in LB incidence observed across European countries.
Topics: Animals; Incidence; Europe; Lyme Disease; Tick-Borne Diseases; Poland
PubMed: 37071405
DOI: 10.1089/vbz.2022.0071 -
Vector Borne and Zoonotic Diseases... Apr 2023Lyme borreliosis (LB), a tick bite-transmitted infection caused by () complex spirochetes, is the most common tickborne disease in Europe. Studies in European...
Lyme borreliosis (LB), a tick bite-transmitted infection caused by () complex spirochetes, is the most common tickborne disease in Europe. Studies in European countries have reported LB seroprevalence (prevalence of antibodies to infection) and diagnostic strategies used for testing. We conducted a systematic literature review to summarize contemporary LB seroprevalence in Europe. PubMed, Embase, and CABI Direct (Global Health) databases were searched from 2005 to 2020 to identify studies reporting LB seroprevalence in European countries. Reported single-tier and two-tier test results were summarized; algorithms (standard or modified) were used to interpret final test results from studies that used two-tier testing. The search yielded 61 articles from 22 European countries. Studies used a range of diagnostic testing methods and strategies (48% single-tier, 46% standard two-tier, and 6% modified two-tier). In 39 population-based studies, of which 14 were nationally representative, seroprevalence estimates ranged from 2.7% (Norway) to 20% (Finland). There was substantial heterogeneity among studies in terms of design, cohort types, periods sampled, sample sizes, and diagnostics, which limited cross-study comparisons. Nevertheless, among studies that reported seroprevalence in persons with greater exposure to ticks, LB seroprevalence was higher among these groups than in the general population (40.6% vs. 3.9%). Furthermore, among studies that used two-tier testing, general population LB seroprevalence was higher in Western Europe (13.6%) and Eastern Europe (11.1%) than in Northern Europe (4.2%) and Southern Europe (3.9%). Despite variations in LB seroprevalence between and within European subregions and countries, high seroprevalence was observed in certain geographic regions and particular risk groups, suggesting significant disease burden and supporting the need for improved, targeted public health interventions such as vaccination. Harmonized approaches to serologic testing and more nationally representative seroprevalence studies are needed to better understand the prevalence of infection in Europe.
Topics: Animals; Seroepidemiologic Studies; Lyme Disease; Europe; Borrelia burgdorferi; Borrelia burgdorferi Group; Ticks
PubMed: 37071401
DOI: 10.1089/vbz.2022.0069 -
International Journal of Environmental... Apr 2023Nowadays, the contamination caused by emerging pollutants is a global concern due to the lack of scientific evidence to demonstrate the risk or toxicity to humans due to...
Nowadays, the contamination caused by emerging pollutants is a global concern due to the lack of scientific evidence to demonstrate the risk or toxicity to humans due to the presence of pharmaceutical residues in the environment. This study aimed to identify and describe the disposal practices of unused and unwanted medications, as well as to analyze and identify the most frequent drugs determined on water bodies adjacent to the biggest urban population in Mexico. A two-phase study with an epidemiological and an ecological assessment was performed. The epidemiological phase was carried out with a descriptive cross-sectional study among citizens from Mexico City and the metropolitan area using an electronic survey applied to 719 subjects aimed to assess practices in which pharmaceutical products are disposed. The ecological phase included a review of scientific reports. The results show that nearly 83.5% of those surveyed use inappropriate practices for disposal medicines, the main ones are through the municipal dump or directly in the drain. The ecological approach was carried out by a systematic literature review of original reports published between 2013 to 2023; information about the class of drugs, active substance, environmental compartments, location, and concentration was extracted and presented. Fifty-one different types of pharmaceutical residues were detected in wastewater in Mexico City in the last decade. The results of this study can contribute to the application of public policies for waste management authorities to mitigate the socio-environmental risks due to the inappropriate disposal of medicines.
Topics: Humans; Medical Waste; Cross-Sectional Studies; Waste Management; Surveys and Questionnaires; Disease Susceptibility; Pharmaceutical Preparations; Refuse Disposal
PubMed: 37047980
DOI: 10.3390/ijerph20075366 -
Journal of Internal Medicine Jul 2023Although a few case reports have shown that immune checkpoint inhibitors (ICIs) are potential inducers of capillary leak syndrome (CLS), an incidental finding cannot be...
BACKGROUND
Although a few case reports have shown that immune checkpoint inhibitors (ICIs) are potential inducers of capillary leak syndrome (CLS), an incidental finding cannot be ruled out. The aim of this study was to describe the clinical characteristics of ICI-induced CLS through a systematic review and to assess a potential safety signal.
METHODS
Medline/PubMed, Embase, and Reactions Weekly were screened, and a global disproportionality study was performed using the World Health Organization pharmacovigilance database through January 15, 2023. A signal of disproportionate reporting was defined as a Bayesian information component (IC) with a 95% credibility interval (CrI) lower boundary that exceeds 0.
RESULTS
A total of 47 cases of ICI-associated CLS were included, 14 from the systematic review (of 61 screened articles) and 33 from VigiBase (of 34,058,481 reports of adverse drug reactions). The median time to CLS onset from the start of ICI was 12 weeks (interquartile range 8-49, n = 24). A total of 57% (8/14) of patients experienced an immune-related adverse event (irAE) before CLS. A fatal outcome was reported in 23% (7/31) of patients. A significant overreporting of CLS was found with ICIs compared with all other drugs (IC 2.4, 95% CrI from 1.8 to 2.8).
CONCLUSION
This study showed a significant signal of disproportionality reporting for ICI-induced CLS, characterized by a long time to onset, and compared with the idiopathic form of the disease with a less abrupt onset and a less consistent hemoconcentration pattern.
Topics: Humans; Immune Checkpoint Inhibitors; Pharmacovigilance; Capillary Leak Syndrome; Bayes Theorem; Antineoplastic Agents, Immunological; Retrospective Studies; Drug-Related Side Effects and Adverse Reactions
PubMed: 37038359
DOI: 10.1111/joim.13641 -
European Cardiology 2024Low-dose aspirin lowers cardiovascular event risk; dual-pathway inhibition (DPI) using low-dose aspirin with low-dose rivaroxaban may reduce this risk further. A... (Review)
Review
Dual-pathway Inhibition with Low-dose Aspirin and Rivaroxaban versus Aspirin Monotherapy in Patients with Coronary Artery Disease and Peripheral Artery Disease: Systematic Literature Review and Meta-analysis.
BACKGROUND
Low-dose aspirin lowers cardiovascular event risk; dual-pathway inhibition (DPI) using low-dose aspirin with low-dose rivaroxaban may reduce this risk further. A systematic literature review and meta-analysis compared the efficacy, safety and net clinical benefit (NCB) of DPI with aspirin.
METHODS
PubMed and Embase were searched for randomised controlled trials reporting clinical efficacy, safety and NCB of DPI compared with aspirin alone in patients with coronary artery disease (CAD) and/or peripheral artery disease. Six articles representing four trials were included.
RESULTS
DPI versus aspirin alone significantly reduced major adverse cardiovascular events (HR 0.77; 95% CI [0.69-0.87]; p<0.01), increased International Society on Thrombosis and Haemostasis major bleeding events (HR 1.67; 95% CI [1.37-2.02]; p<0.01) and resulted in a significant NCB (HR 0.79; 95% CI [0.70-0.90]; p<0.01).
CONCLUSION
These results underscore the potential benefit of DPI in patients with CAD, including those in the immediate post-acute coronary syndrome stage and with established CAD, as well as patients with peripheral artery disease.
PubMed: 38708371
DOI: 10.15420/ecr.2023.40