Publications by authors named "Alex Hlavaty"
Detection and Evaluation of Drug-associated Pulmonary Arterial Hypertension.
Am J Respir Crit Care Med
June 2025
Objectives: To describe the priors and decision thresholds in phase 2 and 3 randomized controlled trials (RCTs) evaluating drug efficacy using Bayesian methods.
Study Design And Setting: A systematic review of phase 2 and 3 RCTs evaluating drug efficacy through Bayesian inference was conducted across the MEDLINE, EMBASE, and Cochrane databases, with no date restrictions until September 2022. The type of prior used for the analysis of the primary endpoint and its characteristics (type and parameters of the distribution, justification, and sensitivity analysis), the use of a posterior probability decision threshold defined a priori, and its value, were extracted.
Background: Trastuzumab emtansine has been recently suspected to be associated with the development of pulmonary arterial hypertension (PAH).
Research Question: Is there an association between trastuzumab, trastuzumab emtansine, or trastuzumab deruxtecan and the development of PAH?
Study Design And Methods: Characteristics of incident PAH cases treated with trastuzumab, trastuzumab emtansine, or trastuzumab deruxtecan were analyzed from the French Pulmonary Hypertension Registry, the VIGIAPATH program, concurrently with a pharmacovigilance disproportionality analysis using the World Health Organization pharmacovigilance database using a broad definition of pulmonary hypertension (PH) and a narrow definition of PAH. A signal of disproportionate reporting was deemed significant if the lower boundary of the 95% credibility interval of the information component (IC) was superior to 0.
Development and validation of a code-based algorithm using in-hospital medical records to identify patients with pulmonary arterial hypertension in a French healthcare database.
ERJ Open Res
July 2024
Introduction: Pulmonary arterial hypertension (PAH) is a rare and severe disease for which most of the evidence about prognostic factors, evolution and treatment efficacy comes from cohorts, registries and clinical trials. We therefore aimed to develop and validate a new PAH identification algorithm that can be used in the French healthcare database "Système National des Données de Santé (SNDS)".
Methods: We developed and validated the algorithm using the Grenoble Alpes University Hospital medical charts.
Background: Pulmonary arterial hypertension (PAH) has been described in patients treated with proteasome inhibitors (PIs). Our objective was to evaluate the association between PIs and PAH.
Methods: Characteristics of incident PAH cases previously treated with carfilzomib or bortezomib were analysed from the French pulmonary hypertension registry and the VIGIAPATH programme from 2004 to 2023, concurrently with a pharmacovigilance disproportionality analysis using the World Health Organization (WHO) global database (VigiBase) and a meta-analysis of randomised controlled trials.
Article Synopsis
- The study aimed to assess if drug safety profiles and toxicity are heightened during the Christmas season by analyzing adverse events from the WHO database over a six-year period.
- Researchers reviewed 4,999,459 case reports from five countries with Christmas traditions, finding that 91 adverse events were significantly more frequent during this festive period.
- Notably, increases in adverse events related to drugs like oxycodone and fentanyl were linked to psychiatric disorders and drug dependence, suggesting a seasonal impact on drug safety.
Article Synopsis
- Observational studies indicate that many patients switching from TNF-α inhibitor reference products to biosimilars stop treatment due to adverse effects, prompting a need to analyze these adverse events.
- The study extracted data from the WHO pharmacovigilance database, focusing on cases of "Product substitution issue," categorizing adverse events reported in over 1% of cases, and applying statistical analysis to understand patterns.
- Results show 2543 cases and 6807 adverse events were reported, with injection-site reactions being the most common (37%), while various other disorders also emerged, highlighting the differences in reported adverse events based on reporting sources and the type of TNF-α inhibitor used.*
Unlabelled: Since the 1960s, several drugs have been linked to the onset or aggravation of pulmonary arterial hypertension (PAH): dasatinib, some amphetamine-like appetite suppressants (aminorex, fenfluramine, dexfenfluramine, benfluorex) and recreational drugs (methamphetamine). Moreover, in numerous cases, the implication of other drugs with PAH have been suggested, but the precise identification of iatrogenic aetiologies of PAH is challenging given the scarcity of this disease and the potential long latency period between drug intake and PAH onset. In this context, we used the World Health Organization's pharmacovigilance database, VigiBase, to generate new hypotheses about drug associated PAH.
View Article and Find Full Text PDFOn March 16, 2020, the French Society of Pharmacology and Therapeutics put online a national Question and Answer (Q&A) website, https://sfpt-fr.org/covid19 on the proper use of drugs during the COVID-19 pandemic. The working group 'Drugs and COVID-19' was composed of a scientific council, an editorial team, and experts in the field.
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