-
PloS One 2017Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. (Review)
Review
INTRODUCTION
Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined.
AIM
The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia.
METHODS
A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia.
RESULTS
The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR.
CONCLUSION
Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.
Topics: Antipsychotic Agents; Computational Biology; Genetic Predisposition to Disease; Humans; Pneumonia
PubMed: 29077727
DOI: 10.1371/journal.pone.0187034 -
Journal of Virus Eradication Sep 2023Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the... (Review)
Review
INTRODUCTION
Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the effects of LRAs in human intervention studies.
METHODS
A literature search was performed using medical databases focusing on studies with adults living with HIV-1 receiving LRAs. Eligibility criteria required participants from prospective clinical studies, a studied compound hypothesised as LRA, and reactivation or tolerability assessments. Relevant demographical data, LRA reactivation capacity, reservoir size, and adverse events were extracted. A study quality assessment with analysis of bias was performed by RoB 2 and ROBINS-I tools. The primary endpoints were HIV-1 reservoir reactivation after LRA treatment quantified by cell-associated unspliced HIV-1 RNA, and LRA tolerability defined by adverse events. Secondary outcomes were reservoir size and the effect of LRAs on analytical treatment interruption (ATI) duration.
RESULTS
After excluding duplicates, 5182 publications were screened. In total 45 publications fulfilled eligibility criteria including 26 intervention studies and 16 randomised trials. The risk of bias was evaluated as high. Chromatin modulators were the main investigated LRA class in 24 studies. Participants were mostly males (90.1%). Where reported, HIV-1 subtype B was most frequently observed. Reactivation after LRA treatment occurred in 78% of studies and was observed with nearly all chromatin modulators. When measured, reactivation mostly occurred within 24 h after treatment initiation. Combination LRA strategies have been infrequently studied and were without synergistic reactivation. Adverse events, where reported, were mostly low grade, yet occurred frequently. Seven studies had individuals who discontinued LRAs for related adverse events. The reservoir size was assessed by HIV-1 DNA in 80% of studies. A small decrease in reservoir was observed in three studies on immune checkpoint inhibitors and the histone deacetylase inhibitors romidepsin and chidamide. No clear effect of LRAs on ATI duration was observed.
CONCLUSION
This systematic review provides a summary of the reactivation of LRAs used in current clinical trials whilst highlighting the importance of pharmacovigilance. Highly heterogeneous study designs and underrepresentation of relevant patient groups are to be considered when interpreting these results. The observed reactivation did not lead to cure or a significant reduction in the size of the reservoir. Finding more effective LRAs by including well-designed studies are needed to define the required reactivation level to reduce the HIV-1 reservoir.
PubMed: 37663575
DOI: 10.1016/j.jve.2023.100342 -
ClinicoEconomics and Outcomes Research... 2016The growing evidence of the increased frequency and severity of adverse drug events (ADEs), besides the negative impact on patient's health status, indicates that costs... (Review)
Review
INTRODUCTION
The growing evidence of the increased frequency and severity of adverse drug events (ADEs), besides the negative impact on patient's health status, indicates that costs due to ADEs may be steadily rising. Observational studies are an important tool in pharmacovigilance. Despite these studies being more susceptible to bias than experimental designs, they are more competent in assessing ADEs and their associated costs.
OBJECTIVE
To identify and characterize the best available evidence on ADE-associated costs.
METHODS
MEDLINE, Cochrane Library, and Embase were searched from 1995 to 2015. Observational studies were included. The methodological quality of selected studies was assessed by Cochrane Collaboration tool for experimental and observational studies. Studies were classified according to the setting analyzed in "ambulatory", "hospital", or both. Costs were classified as "direct" and "indirect". Data were analyzed using descriptive statistics. The total incremental cost per patient with ADE was estimated.
RESULTS
Twenty-nine (94%) longitudinal observational studies and two (7%) cross-sectional studies were included. Twenty-three (74%) studies were assessed with the highest methodological quality score. The studies were mainly conducted in the US (61%). Twenty (65%) studies evaluated any therapeutic group. Twenty (65%) studies estimated costs of ADEs leading to or prolonging hospitalization. The "direct costs" were evaluated in all studies, whereas only two (7%) also estimated the "indirect costs". The "direct costs" in ambulatory ranged from €702.21 to €40,273.08, and the in hospital from €943.40 to €7,192.36.
DISCUSSION
Methodological heterogeneities were identified among the included studies, such as design, type of ADEs, suspected drugs, and type and structure of costs. Despite such discrepancies, the financial burden associated with ADE costs was found to be high. In the light of the present findings, validated methods to measure ADE-associated costs need future research efforts.
PubMed: 27601925
DOI: 10.2147/CEOR.S115689 -
Scientific Reports May 2021Previous studies have drawn causal associations between fluoroquinolone use and collagen pathologies including tendon rupture and retinopathy. This... (Meta-Analysis)
Meta-Analysis
Previous studies have drawn causal associations between fluoroquinolone use and collagen pathologies including tendon rupture and retinopathy. This meta-analysisattempted to assess the association between fluoroquinolone use and the risk of aortic dissection or aortic aneurysm. A systematic search was performed on Medline, EMBASE, and the Cochrane library. 9 studies were included in final analysis. Primary random-effects meta-analysis of 7 studies, excluding 2 pharmacovigilance studies demonstrated statistically increased odds of aortic dissection (OR, 2.38; 95% CI, 1.71-3.32) aortic aneurysm (OR, 1.98; 95% CI, 1.59-2.48), and aortic aneurysm or dissection (OR, 1.47; 95% CI, 1.13-1.89; I = 72%) with current use of fluoroquinolones compared to their nonuser counterparts. Based on the "number needed-to-harm" analysis, 7246 (95% CI: 4329 to 14,085) patients would need to be treated with fluoroquinolones for a duration of at least three days in order for one additional patient to be harmed, assuming a population baseline incidence of aortic dissection and aneurysm rupture to be 10 per 100,000 patient-years. With strong statistical association, these findings suggest a causal relationship, warranting future research to elucidate the pathophysiological and mechanistic plausibility of this association. These findings however, should not cease prescription of fluoroquinolones, especially when clinically indicated.
Topics: Aortic Dissection; Aortic Aneurysm; Fluoroquinolones; Humans; Incidence; Pharmacovigilance; Risk
PubMed: 34040146
DOI: 10.1038/s41598-021-90692-8 -
Wiener Klinische Wochenschrift Mar 2021Signal management is considered an important activity in pharmacovigilance and should be performed using any available source of data, including scientific literature....
BACKGROUND
Signal management is considered an important activity in pharmacovigilance and should be performed using any available source of data, including scientific literature. The main aim of this study was to assess the role of scientific literature in both indexed and unindexed journals and compare the relevance of both in the signal management process.
METHODS
The study was a retrospective analysis of safety data. For the purposes of the study, drugs for which safety signals were evaluated by European Medicine Agency (EMA) were chosen. A match analysis of data collected in the EudraVigilance (EV) database with data from bibliographic databases such as MEDLINE, Embase or EBSCO (International Pharmaceutical Abstracts, IPA and the Allied and the Complementary Medicine Database, AMED) was performed.
RESULTS
A total of 73 drug event associations (DEA) and 4160 individual case safety reports (ICSRs) were analyzed. About 33% of ICSRs were created based on scientific literature. A total of 1196 ICSRs were submitted to the EV database based on journals indexed in global bibliographic databases Embase (86.00%) or MEDLINE (81.96%) or EBSCO (IPA or AMED, 0.66%).
CONCLUSION
This study underlines the importance of scientific literature for the signal management process in addition to other data sources. Most literature ICSRs from this analysis were created based on scientific journals indexed in bibliographic databases; therefore, it can be concluded that a systematic review of bibliographic databases, such as Embase or MEDLINE is highly relevant for the signal management process.
Topics: Databases, Factual; Humans; Information Storage and Retrieval; Pharmaceutical Preparations; Pharmacovigilance; Retrospective Studies
PubMed: 32458200
DOI: 10.1007/s00508-020-01677-y -
International Journal of Clinical... Aug 2023Only 5-10% of all adverse drug reactions (ADRs) are reported. Mechanisms to support patient and public reporting offer numerous advantages to health care systems... (Review)
Review
BACKGROUND
Only 5-10% of all adverse drug reactions (ADRs) are reported. Mechanisms to support patient and public reporting offer numerous advantages to health care systems including increasing reporting rate. Theory-informed insights into the factors implicated in patient and public underreporting are likely to offer valuable opportunity for the development of effective reporting-interventions and optimization of existing systems.
AIM
To collate, summarize and synthesize the reported behavioral determinants using the theoretical domains framework (TDF), that influence patient and public reporting of ADRs.
METHOD
Cochrane, CINAHL, Web of science, EMBASE and PubMed were systematically searched on October 25th, 2021. Studies assessing the factors influencing public or patients reporting of ADRs were included. Full-text screening, data extraction and quality appraisal were performed independently by two authors. Extracted factors were mapped to TDF.
RESULTS
26 studies were included conducted in 14 countries across five continents. Knowledge, social/professional role and identity, beliefs about consequences, and environmental context and resources, appeared to be the most significant TDF domains that influenced patient and public behaviors regarding ADR reporting.
CONCLUSION
Studies included in this review were deemed of low risk of bias and allowed for identification of key behavioural determinants, which may be mapped to evidence-based behavioral change strategies that facilitate intervention development to enhance rates of ADR reporting. Aligning strategies should focus on education, training and further involvement from regulatory bodies and government support to establish mechanisms, which facilitate feedback and follow-ups on submitted reports.
Topics: Humans; Adverse Drug Reaction Reporting Systems; Drug-Related Side Effects and Adverse Reactions; Patients; Government; Pharmacovigilance
PubMed: 37247158
DOI: 10.1007/s11096-023-01591-z -
Frontiers in Pediatrics 2021Cyproheptadine is a first-generation H1-antihistamine drug first that was distributed in the 1960s. While its orexigenic effect was observed early, cyproheptadine is...
Cyproheptadine is a first-generation H1-antihistamine drug first that was distributed in the 1960s. While its orexigenic effect was observed early, cyproheptadine is not yet authorized for this indication in all countries today. There is an increasing medical interest and demand for the orexigenic effect of cyproheptadine, especially in children with poor appetite. As cyproheptadine might be evaluated in future clinical trials, we wanted to assess its safety profile. Using the French national pharmacovigilance database, we retrospectively analyzed all pediatric and adult reports of adverse effects of cyproheptadine recorded since its first distribution in France. Next, we performed a systematic review of the literature of cyproheptadine adverse effects. Since 1985, 93 adverse effects were reported in the French pharmacovigilance database (adults 81.7%, children 18.3%); these were mainly neurological symptoms ( = 38, adults 71%, children 28.9%), and hepatic complications ( = 15, adults 86.7%, children 13.3%). In the literature, the most frequent adverse effect reported was drowsiness in adults or children, and five case reports noted liver complications in adults. We estimated the frequency of hepatic adverse effects at 0.27 to 1.4/1000, regardless of age. Cyproheptadine can be considered a safe drug. Mild neurological effects appear to be frequent, and hepatotoxicity is uncommon to rare. Randomized controlled trials are needed to evaluate the safety and efficacy of cyproheptadine before authorization for appetite stimulation, especially in young children as studies at this age are lacking. Possible hepatic complications should be monitored, as very rare cases of liver failure have been reported.
PubMed: 34676184
DOI: 10.3389/fped.2021.712413 -
Frontiers in Pharmacology 2019Drug Safety (DS) is a domain with significant public health and social impact. Knowledge Engineering (KE) is the Computer Science discipline elaborating on methods and...
Drug Safety (DS) is a domain with significant public health and social impact. Knowledge Engineering (KE) is the Computer Science discipline elaborating on methods and tools for developing "knowledge-intensive" systems, depending on a conceptual "knowledge" schema and some kind of "reasoning" process. The present systematic and mapping review aims to investigate KE-based approaches employed for DS and highlight the introduced added value as well as trends and possible gaps in the domain. Journal articles published between 2006 and 2017 were retrieved from PubMed/MEDLINE and Web of Science® (873 in total) and filtered based on a comprehensive set of inclusion/exclusion criteria. The 80 finally selected articles were reviewed on full-text, while the mapping process relied on a set of concrete criteria (concerning specific KE and DS core activities, special DS topics, employed data sources, reference ontologies/terminologies, and computational methods, etc.). The analysis results are publicly available as online interactive analytics graphs. The review clearly depicted increased use of KE approaches for DS. The collected data illustrate the use of KE for various DS aspects, such as Adverse Drug Event (ADE) information collection, detection, and assessment. Moreover, the quantified analysis of using KE for the respective DS core activities highlighted room for intensifying research on KE for ADE monitoring, prevention and reporting. Finally, the assessed use of the various data sources for DS special topics demonstrated extensive use of dominant data sources for DS surveillance, i.e., Spontaneous Reporting Systems, but also increasing interest in the use of emerging data sources, e.g., observational healthcare databases, biochemical/genetic databases, and social media. Various exemplar applications were identified with promising results, e.g., improvement in Adverse Drug Reaction (ADR) prediction, detection of drug interactions, and novel ADE profiles related with specific mechanisms of action, etc. Nevertheless, since the reviewed studies mostly concerned proof-of-concept implementations, more intense research is required to increase the maturity level that is necessary for KE approaches to reach routine DS practice. In conclusion, we argue that efficiently addressing DS data analytics and management challenges requires the introduction of high-throughput KE-based methods for effective knowledge discovery and management, resulting ultimately, in the establishment of a continuous learning DS system.
PubMed: 31156424
DOI: 10.3389/fphar.2019.00415 -
BioDrugs : Clinical Immunotherapeutics,... Oct 2020Tumour necrosis factor (TNF)-α inhibitors have been widely used for the treatment of moderate-to-severe inflammatory bowel disease (IBD). TNFα also plays an important... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tumour necrosis factor (TNF)-α inhibitors have been widely used for the treatment of moderate-to-severe inflammatory bowel disease (IBD). TNFα also plays an important role in the regulation of weight homeostasis and metabolism and has been linked to variations in anthropometric responses. This relationship in patients with IBD has yet to be determined.
OBJECTIVES
Our objective was to evaluate the effects of TNFα inhibitors on changes in anthropometric measures in both adults and children with IBD through a systematic review and meta-analysis.
METHODS
Multiple database searches identified studies involving children and adults with IBD and treated with TNFα inhibitors and reporting at least one primary outcome measure. Where possible, data were combined for meta-analysis. The primary outcomes included weight, body mass index (BMI), waist circumference, height, height/velocity, and fat and lean mass. Secondary outcomes included surrogate markers of disease activity. A random-effects model was used to estimate the standardised mean difference (SMD).
RESULTS
In total, 23 cohort studies (total 1167 participants) met the inclusion criteria. Meta-analysis was performed on 13 of these studies. In children, 6-29.3 months of anti-TNFα therapy had a small but statistically significant effect on weight (SMD 0.31; 95% confidence interval [CI] 0.12-0.49; P = 0.001) with a mean gain in z score of 0.30 (standard error [SE] 0.12). In adults, 2-22.4 months of treatment had a moderate effect on BMI (SMD 0.72; 95% CI 0.17-1.26; P = 0.010; mean gain 1.23 kg/m; SE 0.21). A small but statistically significant increase in BMI z score was found in children (SMD 0.28; 95% CI 0.03-0.53; P = 0.026; mean change 0.31 ± standard deviation [SD] 0.14) after 12-29.3 months of therapy. A meta-analysis of four studies found a negligible but statistically significant increase in height (SMD 0.16; 95% CI 0.06-0.26; P = 0.002; mean change 0.17 z score [SE 0.05]). A negligible effect on fat mass (SMD 0.24; 95% CI -0.19-0.66; P = 0.272) was found in a meta-analysis of five studies. Of note, despite the high heterogeneity among the studies that addressed the issue, these results were also consistently supported by findings from studies not included in the meta-analysis and reviewed in the systematic review. Unfortunately, a lack of data meant we were unable to perform moderator analysis on observed heterogeneity.
CONCLUSION
Anti-TNFα treatment appears to be associated with an increase in body weight, BMI, and other anthropometric parameters. Given the differing courses of IBD between children and adults, this association should be considered before initiating biologics for undernourished, overweight, and obese patients. Registration: PROSPERO registration number CRD42020163079.
Topics: Adult; Child; Humans; Inflammatory Bowel Diseases
PubMed: 32940873
DOI: 10.1007/s40259-020-00444-9 -
Frontiers in Public Health 2023To perform a systematic review on the use of Artificial Intelligence (AI) techniques for predicting COVID-19 hospitalization and mortality using primary and secondary...
AIM
To perform a systematic review on the use of Artificial Intelligence (AI) techniques for predicting COVID-19 hospitalization and mortality using primary and secondary data sources.
STUDY ELIGIBILITY CRITERIA
Cohort, clinical trials, meta-analyses, and observational studies investigating COVID-19 hospitalization or mortality using artificial intelligence techniques were eligible. Articles without a full text available in the English language were excluded.
DATA SOURCES
Articles recorded in Ovid MEDLINE from 01/01/2019 to 22/08/2022 were screened.
DATA EXTRACTION
We extracted information on data sources, AI models, and epidemiological aspects of retrieved studies.
BIAS ASSESSMENT
A bias assessment of AI models was done using PROBAST.
PARTICIPANTS
Patients tested positive for COVID-19.
RESULTS
We included 39 studies related to AI-based prediction of hospitalization and death related to COVID-19. The articles were published in the period 2019-2022, and mostly used Random Forest as the model with the best performance. AI models were trained using cohorts of individuals sampled from populations of European and non-European countries, mostly with cohort sample size <5,000. Data collection generally included information on demographics, clinical records, laboratory results, and pharmacological treatments (i.e., high-dimensional datasets). In most studies, the models were internally validated with cross-validation, but the majority of studies lacked external validation and calibration. Covariates were not prioritized using ensemble approaches in most of the studies, however, models still showed moderately good performances with Area under the Receiver operating characteristic Curve (AUC) values >0.7. According to the assessment with PROBAST, all models had a high risk of bias and/or concern regarding applicability.
CONCLUSIONS
A broad range of AI techniques have been used to predict COVID-19 hospitalization and mortality. The studies reported good prediction performance of AI models, however, high risk of bias and/or concern regarding applicability were detected.
Topics: Humans; Artificial Intelligence; COVID-19; Hospitalization; Language; ROC Curve
PubMed: 37408750
DOI: 10.3389/fpubh.2023.1183725