Charles Khouri

• PharmD PhD
• Pharmacologist at Grenoble Alpes University Hospital & Univ. Grenoble Alpes

Pulmonary arterial hypertension (PAH) is a rare form of precapillary pulmonary hypertension. PAH may be idiopathic, heritable, associated, with features of pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis, or linked to drug and toxin exposure. Since the first identification of PAH cases associated with drugs and toxins mo...

Fear of side effects is the main motive for vaccine refusal. However, before the COVID-19 pandemic, little attention had been paid to the actual experience of adverse events and its relationship with vaccine hesitancy. This scoping review aimed to analyze the impact of VH on EAE and vice versa. We reviewed 55 articles. Most of the studies focused o...

Aims Low-density lipoprotein cholesterol (LDL-c) and non-high-density lipoprotein cholesterol (non-HDL-c) are prognostic factors of cardiovascular risk. However, their validity as trial-level surrogates for cardiovascular outcomes is debated. This study aimed to determine whether LDL-c and non-HDL-c are reliable surrogates for cardiovascular events...

Previous meta-epidemiological surveys have found considerable misinterpretation of results of disproportionality analyses. We aim to explore the relationship between the strength of causal statements used in title and abstract conclusions of pharmacovigilance disproportionality analyses and the strength of causal language used in citing studies. On...

Obstructive sleep apnoea (OSA) contributes to cerebrovascular diseases and cognitive decline. Preclinical studies support the deleterious impact on the brain of intermittent hypoxia (IH), one of the main components of OSA, but heterogeneity in rodent species and brain regions studied, or induced by IH paradigms, can challenge interpretation of the...

Disproportionality analyses are the most-commonly used study design used in the post-marketing phase to detect suspected adverse drug reactions in individual case safety reports. Recent years have witnessed an exponential increase in published articles on disproportionality analyses, thanks to publicly accessible databases. Unfortunately, this tren...

OBJECTIVE Multiregional trials are designed under the assumption that treatment effect applies to the entire target population, yet several factors may introduce geographic heterogeneity in treatment effect. We explored whether such variations exist in trials assessing the efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in major ca...

Introduction: Drug efficacy and effectiveness are assessed respectively through clinical trials and pharmaco-epidemiological studies. However, relative and absolute benefits of drugs are distinct measures that must be considered in relation to the baseline risk of disease incidence, complication or progression. On the other hand, adverse drug reac...

Background Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear. Objectives To assess the association between gemcitabine and PH. Methods We identified incident cases of precapillary PH confirmed by right hear...

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...

Disproportionality analyses using reports of suspected adverse drug reactions are the most commonly used quantitative methods for detecting safety signals in pharmacovigilance. However, their methods and results are generally poorly reported in published articles and existing guidelines do not capture the specific features of disproportionality ana...

In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correc...

Rationale Pulmonary arterial hypertension (PAH) has been described in patients treated with proteasome inhibitors (PI). Objectives To evaluate the association between PI and PAH. Methods Characteristics of incident PAH cases previously treated with Carfilzomib or Bortezomib were analyzed from the French PH Registry and the VIGIAPATH program from...

Observational studies that have reported an association between aspirin use in chronic obstructive pulmonary disease (COPD) with reductions in mortality and COPD exacerbations were shown to be affected by time-related biases. We assessed this association using a prevalent new-user study design that avoids these biases. We used the United Kingdom’s...

Purpose To report of a case of bilateral ocular hypotony associated with ciliary detachments and macula edema as an uncommon troublesome side-effect of pembrolizumab (an immune checkpoint inhibitor) treatment. Methods A 56-year-old man with a history of metastatic axillary melanoma (bone, lung, spleen and lymph node lesions) treated with pembroliz...

In refining drug safety signals, defining the object of study is crucial. While research has explored the effect of different event definitions, drug definition is often overlooked. The US FDA Adverse Event Reporting System (FAERS) records drug names as free text, necessitating mapping to active ingredients. Although pre-mapped databases exist, the...

Background Diabetic foot ulcers (DFUs) are a common complication of diabetes, associated with important morbidity. Appropriate animal models of DFUs may improve drug development, and subsequently the success rate of clinical trials. However, while many models have been proposed, they are extremely heterogeneous, and no standard has emerged. We thus...

The ATP-sensitive potassium channels (K ATP ) and their regulatory subunits, sulfonylurea receptor 1 (SUR1/Kir6.2) and SUR2/Kir6.1, contribute to the pathophysiology of pulmonary hypertension (PH). Loss-of-function pathogenic variants in the ABCC8 gene, which encodes for SUR1, have been associated with heritable pulmonary arterial hypertension. Con...

Introduction: Previous pre-clinical and pharmacovigilance disproportionality analyses highlighted a safety signal of cutaneous ulcer with bisphosphonate use. Therefore, our objective is to evaluate this risk and assess whether unmeasured confounding factors could explain this association. Methods: This study is a population-based cohort study fr...

Objectives: Measurement of digital perfusion, sometimes coupled with a cold challenge, has been widely used as an objective outcome in trials evaluating drug therapies in Raynaud's Phenomenon (RP), in addition to patient-reported outcomes or to establish the proof-of-concept in preliminary studies. However, whether digital perfusion is a valid sur...

Background and aim: Disproportionality analysis is traditionally used in spontaneous reporting systems to generate working hypotheses about potential adverse drug reactions: the so-called disproportionality signals. We aim to map the methods used by researchers to assess and increase the validity of their published disproportionality signals. Met...

Introduction: The FDA Adverse Event Reporting System (FAERS) receives drug names in various forms, including brand names, active ingredients, abbreviations, and misspellings, which creates challenges in nomenclature standardization. The lack of consensus on standardization strategies and of transparency hampers replicability and accuracy in conduct...

Background and objective: Observational studies have shown that a significant proportion of patients interchanging between tumor necrosis factor-α inhibitor biosimilars withdraws from the new treatment because of adverse effects. We aim to analyze adverse events related to interchanging from tumor necrosis factor-α (TNF-α) inhibitor reference prod...

Objectives: The literature on vaccine hesitancy has widely commented on the various factors leading some to feel particularly at risk of disease infection while others do not. But little attention has been paid to whether we also see such differences regarding people's assessment of their personal vulnerability towards vaccine adverse events (AEs)...

Introduction: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects o...

The objective of this study is to examine the potential association between drug use and adverse event reporting in France. Number of drug users and cases reported were extracted from the French Health Care Insurance database (Open Medic) and French pharmacovigilance database. We performed two separate mixed effect models (with drug used or reporti...

Background and aims: The current opioid epidemic in the USA began 20 years ago and has become the leading cause of accidental deaths in the country. This crisis prompted us to explore trends in opioid abuse and dependence worldwide. We sought to identify other countries at high-risk of opioid use disorders, using the World Health Organization's (W...

Introduction: Little is known about the impact of mandatory vaccination on people who are reluctant to be vaccinated, despite the potential importance in terms of public health policy. Objective: We aimed to explore the relationship between vaccine hesitancy and onset, severity and characteristics of self-reported adverse events. Methods: We u...

Background . Substantial placebo response has been observed in trials assessing treatments in Raynaud's Phenomenon (RP), which makes any treatment effect difficult to detect. However, whether this response is due to a real placebo effect or to other nonspecific effects, such as regression towards the mean (RTM), has not been explored. Our objective...

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 su...

Aim Intermittent hypoxia (IH) is considered to be a major contributor to obstructive sleep apnoea-related cardiovascular consequences. The present meta-analysis aimed to assess the effects of IH on cardiac remodelling, function and infarct size after myocardial ischaemia across different rodent species and IH severities. Methods and results Relevan...

Purpose: In patients with COPD, one of the leading indications for domiciliary non-invasive ventilation (NIV), a major paradigm shift has been observed over the past decade in the method for adjusting NIV settings, with the use of sufficient ventilatory support to achieve a significant reduction in PaCO2. Whether this approach may be relevant to o...

Background and objective: The concern surrounding the association between Guillain-Barré syndrome (GBS) and vaccination has increased with the widespread use of COVID-19 vaccines. The aim of this study was to assess the potential association of GBS with mRNA-based or adenovirus-vectored COVID-19 vaccines. Methods: Reports of GBS associated with...

Introduction A particularly high burden of sleep apnoea is reported in patients treated with cardiac implants such as pacemakers and defibrillators. Sleep apnoea diagnosis remains a complex procedure mainly based on sleep and respiratory indices captured by polysomnography (PSG) or respiratory polygraphy (PG). Objective We aimed to evaluate the pe...

Introduction: Cardiovascular adverse effects of COX-2 inhibitors are well described. Nevertheless, no study explored the cutaneous and vascular adverse effects of COX-2 inhibitors [1]. The aim of this study is to identify and quantify the risk of skin ulcer associated with COX-2 inhibitors in real world setting. Material and methods: A population-b...

Coronary microvascular dysfunction (CMVD) is common and associated with poorer outcomes in patients with ST Segment Elevation Myocardial Infarction (STEMI). The index of microcirculatory resistance (IMR) and the index of hyperemic microvascular resistance (HMR) are both invasive indexes of microvascular resistance proposed for the diagnosis of seve...

Objectives: While the World Health Organization has recommended preoperative washing with plain or antimicrobial soap for surgical site infection (SSI) prevention, it has not formulated recommendations on use of chlorhexidine gluconate (CHG)-impregnated cloths. The purpose of this systematic review was to evaluate the benefit of preoperative bathin...

The passe sanitaire increased levels of vaccination, but to a lower extent among the most vulnerable, and did not reduce vaccine hesitancy itself, showing the importance of outreach to underserved communities and the potential limits of mandatory vaccination policies.

Background Coronary microvascular dysfunction (CMVD) is common and associated with poorer outcomes in patients with ST Segment Elevation Myocardial Infarction (STEMI). The index of microcirculatory resistance (IMR) and the index of hyperemic microvascular resistance (HMR) are both invasive indexes of microvascular resistance proposed for the diagno...

Objective To provide a qualitative view and quantitative measure of sleep disturbances across and between early stages – clinical ultra high-risk and first episode – of psychotic and bipolar disorders. Methods Electronic databases (PubMed, Cochrane, Embase, PsychINFO) were searched up to March 2021 for studies comparing sleep measures between indi...

Background A particularly high burden of sleep apnoea is reported in patients treated with cardiac implants such as pacemakers and defibrillators. Sleep apnoea diagnosis remains a complex procedure mainly based on sleep and respiratory indices captured by polysomnography (PSG) or respiratory polygraphy (PG). Aim We aimed to evaluate the performanc...

Protein kinase inhibitors experienced their advent in the 2000s. Their market introduction made it possible to constitute the class of targeted therapies administered orally. This name was chosen to mark a break with conventional chemotherapy drugs, but it is important to stress that these are multi-target drugs with complex affinity profiles. Adve...

Erythromelalgia is a recurrent and paroxysmal syndrome characterized by the clinical triad of bilateral redness, heat, and paroxysmal burning pain, mostly localized on the feet. This disorder can be primary, as a consequence of mutations in the genes encoding the voltage gated sodium channels. It can also be secondary to an underlying disease or dr...

Obstructive Sleep Apnea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support the deleterious vascular impact of IH in rodents but an overall interpretation is challenging owing to heterogeneity in rodent species investigated and the severity and duration of IH...

Objective : To review and appraise methods and reporting characteristics of pharmacovigilance disproportionality analyses. Study Design and Setting : We randomly selected 100 disproportionality analyses indexed in Medline found during a systematic literature search. We then extracted and synthetized methodological and reporting characteristics usi...

We report the case of a 77-year-old man with Parkinson’s disease (PD) who experimented for the first time gout crisis after initiation of levodopa. Levodopa was withdrawn, colchicine and allopurinol were initiated to treat the gout crisis. Because of PD progression, levodopa was reintroduced, and the patient presented relapse of gout flare. To furt...

Objective: To systematically review and appraise misinterpretation of pharmacovigilance disproportionality analysis results in published studies. Study design and setting: We randomly selected 100 studies that performeddisproportionality analysesand indexed in Medline identified during a systematic literature search. Titles, abstracts and main t...

Background: A plethora of methods and models of disproportionality analyses for safety surveillance have been developed to date without consensus nor a gold standard, leading to methodological heterogeneity and substantial variability in results. We hypothesized that this variability is inversely correlated to the robustness of a signal of dispropo...

Few studies have simultaneously investigated the impact of inflammation and genetic polymorphisms of cytochromes P450 2C19 and 3A4 on voriconazole trough concentrations. We aimed to define the respective impact of inflammation and genetic polymorphisms on voriconazole exposure by performing individual data meta-analyses. A systematic literature rev...

Vancomycin is a tricyclic glycopeptide antibiotic produced from Streptococcus orientalis. There is much variation in the literature with regard to the recommended dose, dilution rate and type of infusion. Given the vesicant properties of vancomycin at supratherapeutic doses (>10mg/ml), tissue damage including blistering and necrosis have been repor...

This disproportionality analysis uses the World Health Organization pharmacovigilance database to explore the potential safety signal of facial paralysis after COVID-19 vaccination.

Background The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoven...