Jules Desmeules

Geneva University Hospitals · Clinical pharmacology and toxicology, Multidisciplinary pain center

Introduction Following the contraindication of codeine use in children, an increase in the use of tramadol has been observed in pain management protocols. However, tramadol PK/PD are also influenced by CYP2D6 activity. Genotyping and phenotyping are available to assess CYP2D6 activity and guide tramadol dosing. In adults, a correlation between pupi...

Following the contraindication of codeine use in children, increasing use of tramadol has been observed in pain management protocols. However, tramadol’s pharmacokinetics (PK) and pharmacodynamics are influenced by cytochrome P450 (CYP)2D6 activity, similarly to codeine. Previous studies in adults have demonstrated a correlation between pupillary r...

In cognitive-behavioral group therapy, the therapeutic alliance with the psychotherapists and between the patients in the group, allows patients to develop coping strategies. These include cognitive and behavioral efforts aimed to control, reduce or tolerate specific demands, whether internal or external, experienced as threatening, exhausting or e...

Introduction The use of massage therapy has received increased attention in the treatment of chronic pain. However, barriers can hinder its use in nursing care. This study uses a qualitative methodology to explore professionals’ experiences regarding touch massage (TM) and identify barriers and facilitators for the implementation of this interventi...

Variation in genes involved in the absorption, distribution, metabolism, and excretion of drugs (ADME) can influence individual response to therapeutic treatment. Study of ADME genetic diversity in human populations has led to evolutionary hypotheses of adaptation to distinct chemical environments. Population differentiation in measured drug metabo...

Opioid use and associated morbidity and mortality have increased in several countries during the past 20 years. We performed a study whose objective was to assess the frequency and causes of opioid‐related emergency division (ED) visits in an adult tertiary Swiss University Hospital over 9 weeks in 2018. We primarily assessed opioid‐related adverse...

Context The management of behavioral symptoms and rigidity in patients with dementia constitutes a significant challenge. Short-term studies suggest an interest in the use of medical cannabis, but long-term data are lacking. Objectives The objective of this study was to investigate the feasibility and long-term safety of administering tetrahydroca...

During the latest pandemic, the RECOVERY study showed the benefits of dexamethasone (DEX) use in COVID‐19 patients. Obesity has been proven to be an independent risk factor for severe forms of infection, but little information is available in the literature regarding DEX dose adjustment according to body weight. We conducted a prospective, observat...

While morphine is the gold standard treatment for severe nociceptive pain in children, hydromorphone is increasingly prescribed in this population. This review aims to assess available knowledge about hydromorphone and explore the evidence for its safe and effective prescription in children. Hydromorphone is an opioid analgesic similar to morphine...

The suitability of the endogenous 6‐hydroxymelatonin/melatonin urinary metabolic ratio as a surrogate for the paraxanthine/caffeine ratio to predict cytochrome P450 1A2 (CYP1A2) activity was assessed in this study. Twelve healthy volunteers completed four study sessions spread over 1 month (including overnight urine collection with first morning vo...

Background: Dexamethasone is widely used for the prevention of postoperative nausea and vomiting (PONV) but little is known about its efficacy for the treatment of established PONV. Objective: To test the antiemetic efficacy of intravenous dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia...

Background and Purpose Individualized assessment of cytochrome P450 2D6 (CYP2D6) activity is usually performed through phenotyping following administration of a probe drug to measure the enzyme's activity. To avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non‐burdensome tools for real‐...

Pharmacokinetic variability is a major source of differences in drug response and can be due to genetic variants and/or drug-drug interactions. Cytochromes P450 are among the most studied enzymes from a pharmacokinetic point of view. Their activity can be measured by phenotyping, and/or predicted by genotyping. Depending on the presence of drugs an...

We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately...

Background: Polypharmacy and inappropriate prescription are frequent in vulnerable and multi-morbid populations. Adults with intellectual disability (ID) are at risk of being polymedicated because they often present with multiple comorbidities and challenging behaviors. Aim: The objective of this study was thus to evaluate the prevalence of potenti...

Tapentadol shares with tramadol a mixed mechanism of action. It has no identified analgesically active metabolite and is not significantly metabolised by CYP450, thus overcoming some limitations of tramadol, including potential for pharmacokinetic drug-drug interactions and inter-individual variability due to genetic polymorphisms of CYP450. It is...

Decentration and cognitive restructuring are used in cognitive-behavioural therapy (CBT) with patients suffering from chronic pain and are reinforced by group work. They can also be useful to the general practitioner. Clinical vignettes summarize the role of group CBT in identifying realistic and meaningful activities. They stress decentration and...

In this study, we assessed the potential use of the 1β-hydroxy-deoxycholic acid (1β-OH-DCA) to deoxycholic acid (DCA) urinary metabolic ratio (UMR) as a CYP3A metric in ten male healthy volunteers. Midazolam (MDZ) 1 mg was administered orally at three sessions: alone (control session), after pre-treatment with fluvoxamine 50 mg (12 h and 2 h prior...

Background and Purpose: Individualized assessment of the activity of cytochrome P450 2D6 (CYP2D6), a highly variable drug-metabolizing enzyme, is performed through phenotyping during which a probe drug is administered to measure the enzyme’s activity. In order to avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe...

Objectives: Adults with an intellectual disability (AWID) are often polymedicated because of somatic and psychiatric health problems. Besides, they may display challenging behaviours, leading to off-label prescription of psychotropic drugs, without efficacy and with numerous adverse effects. In this context, a prescription/deprescription tool (Too...

Background Chronic pain is a significant risk factor for suicidal ideation (SI) and suicidal behavior (SB), including a 20%-40% prevalence rate of SI, a prevalence between 5% and 14% of suicide attempts, and a doubled risk of death by suicide in patients with chronic pain compared to controls. In most studies, associations between chronic pain and...

This retrospective study evaluates the link between an adverse drug reaction (ADR) or a non-response to treatment and cytochromes P450 (CYP), P-glycoprotein (P-gp) or catechol-O-methyltransferase (COMT) activity in patients taking analgesic drugs for chronic pain. Patients referred to a pain center for an ADR or a non-response to an analgesic drug...

BACKGROUND Chronic pain is a significant risk factor for suicidal ideation (SI) and suicidal behavior (SB), including a 20-40% prevalence rate of SI, a prevalence between 5-14% of suicidal attempts (SA), and a doubled risk of death by suicide in patients with chronic pain compared to controls. In most studies, associations between chronic pain and...

Tolerance and hyperalgesia associated with chronic exposure to morphine are major limitations in the clinical management of chronic pain. At a cellular level, neuronal signaling can in part account for these undesired side effects, but unknown mechanisms mediated by central nervous system glial cells are likely also involved. Here we applied data-i...

Introduction and Objective Cytochrome P450 enzymes are the major drug-metabolizing enzymes in humans and the importance of drug transport proteins, in particular P-glycoprotein, in the variability of drug response has also been highlighted. Activity of cytochrome P450 enzymes and P-glycoprotein can vary widely between individuals and genotyping and...

Cardiovascular disease (CVD) is the leading cause of mortality worldwide in both sexes. Despite considerable progress in better understanding the patterns of disease in women, they are still often undertreated and benefit less from evidence-based treatment. Hypertension is a key contributor to CVD and is also one of the most potent risk factors for...

The antihyperalgesic and sedative effects of the α2‐subunit preferring GABAA positive allosteric modulator (GAM), N‐desmethyl‐clobazam (NDMC), 20 and 60 mg, were assessed in a randomized, placebo and active‐controlled (clonazepam 1,5 mg), 4‐way crossover study, in healthy volunteers, using the ultraviolet B‐induced experimental pain model. Single (...

Devant faire face quotidiennement aux problèmes de prescription chez les adultes présentant une déficience intellectuelle en contexte hospitalier et étant fréquemment confrontés à la question de la prescription d’un antalgique, nous avons mené une réflexion sur les spécificités à prendre en compte dans cette population sur la base des données de la...

Background and objective: Having to deal on a daily routine with prescriptions in adults with intellectual disability (ID), we systematically reviewed the literature on the specificities of pain interventions in that population, focusing on medication and trying to gather practical information on appropriate pain treatments. Given the scarcity of...

Background: Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low-dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, six and 12 months after major lower back surgery. Methods: In this single-centre randomized trial, 80 patients received intravenous ketamin...

The activity of drug-metabolizing enzymes (DME) shows high inter- and intra-individual variability. Genetic polymorphisms, exposure to drugs, and environmental toxins are known to significantly alter DME expression. In addition, the activity of these enzymes is highly age-dependent due to maturation processes that occur during development. Currentl...

Drug metabolic enzymes and transporters are responsible for an important variability in drug disposition. The cocktail approach is a sound strategy for the simultaneous evaluation of several enzyme and transporter activities for a personalized dosage of medications. Recently, we have demonstrated the reliability of the Geneva cocktail, combining th...

Background Identifying patients at high risk of hospital preventable readmission is an essential step towards selecting those who might benefit from specific transitional interventions. Objective Derive and validate a predictive risk score for potentially avoidable readmission (PAR) based on analysis of readmissions, with a focus on medication. D...

The aim of this work was to predict the extent of Cytochrome P450 2D6 (CYP2D6)‐mediated drug–drug interactions (DDIs) in different CYP2D6 genotypes using physiologically‐based pharmacokinetic (PBPK) modeling. Following the development of a new duloxetine model and optimization of a paroxetine model, the effect of genetic polymorphisms on CYP2D6‐med...

Cognitive and behavioral techniques (CBT) are used in the approach of chronic pain, based on the assumption that pain and disability are not (only) influenced by somatic issues but also by psychosocial factors. CBT aim to improving quality of life while targeting disability. Psychoeducation, activity-centered and cognitive techniques are central, d...

Drug response is subject to an important within- and between-individual variability owing, mainly, to pharmacokinetic and pharmacodynamic factors. Pharmacokinetics includes metabolism by cytochrome P450 (CYP450), major enzymes of phase I reactions that are responsible for the biotransformation of around 60% of the currently approved drugs. CYP450 a...

Les interventions de massage permettent de diminuer les sensations liées à la douleur et surtout d’améliorer la qualité de vie des personnes confrontées à une douleur chronique. Un effet bénéfique est également relevé auprès des soignants et de l’entourage. Entre 2013 et 2017, des séances de Toucher-massage® ont été prodiguées par des infirmières f...

Background Rebound cholinergic syndrome is a rare, but well known unwanted phenomenon occurring after abrupt clozapine discontinuation. There have been previous reported cases of cholinergic rebound in the literature; however, these reports described cholinergic rebound following cessation of high doses of clozapine in patients diagnosed with schiz...

Acute nociceptive pain management in children is a major public health concern. Effective and safe pain treatment is essential, but safety data cannot be simply extrapolated from adults to children due to pharmacokinetic and pharmacodynamic specificities. In addition, the frequent absence of child‐specific data, the difficulty to assess drug tolera...

Cytochrome P450 (CYP) 2D6 metabolizes a wide range of xenobiotics and is characterized by a huge inter‐individual variability. A recent clinical study highlighted differential magnitude of CYP inhibition as a function of CYP2D6 genotype. The aim of this study was to investigate the effect of CYP2D6 genotype on the inhibition of dextromethorphan O‐d...

Résumé Le syndrome du grêle court (SGC) se caractérise par la présence d’un intestin grêle fonctionnel dont la longueur est inférieure à 200 cm. L’absorption des médicaments ayant principalement lieu par un processus de diffusion passive, elle peut être influencée par la surface d’absorption. Ainsi en cas de SGC, des doses plus élevées ou une admin...

Pain management in ambulatory care regularly requires the prescription of opioids. These drugs allow adequate analgesia achievement in many patients, but inefficiency and/or intolerable side effects may limit their use. Factors related to physiological particularities, comorbidities and comedication, as well as difficulties related to drug intake a...

Drug pharmacokinetics (PK) is influenced by multiple intrinsic and extrinsic factors, among which concomitant medications are responsible for drug–drug interactions (DDIs) that may have a clinical relevance, resulting in adverse drug reactions or reduced efficacy. The addition of intrinsic factors affecting cytochromes P450 (CYPs) activity and/or e...

Objective: Drug-metabolizing enzymes (DMEs), such as cytochrome P450 (CYP) enzymes, and transporters have emerged as major determinants of variability in drug metabolism and response. This study investigated the association between CYP and P-glycoprotein activities and plasma antidepressant concentration in an outpatient clinical setting. Secondar...

New pharmaceutical drug development requires more than a billion dollars and can take 12 years of research effort. New chemical entities or NCEs can be dropped from development for many reasons during this process, two major reasons being efficacy and toxicity. Lapatinib was approved in 2007 by FDA as an orally active drug against breast cancer. Wh...

Background It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and cos...

Objectives Potentially inappropriate medication (PIM) occurs frequently and is a well-known risk factor for adverse drug events, but its incidence is underestimated in internal medicine. The objective of this study was to develop an electronic prescription-screening checklist to assist residents and young healthcare professionals in PIM detection....

The aim of this qualitative study was to explore patients' representations regarding generics in patients suffering from non-specific disabling chronic musculoskeletal pain, as these patients are confronted with the issue of the prescription and/or substitution of original formulations with generics. Patients' representations suggest that they migh...

Cytochrome P450 (CYP) activity can be assessed using a 'cocktail' phenotyping approach. Recently, we have developed a cocktail (Geneva cocktail) which combines the use of low-dose probes with a low-invasiveness dried blood spots (DBS) sampling technique and a single analytical method for the phenotyping of six major CYP isoforms. We have previously...

Pharmacogenomics is a relatively recent yet rapidly expanding field of study examining how genetic variations influence responses to drugs. Antithrombotic drugs include the anticoagulant and antiplatelet compounds widely prescribed for the treatment and prevention of cardiovascular diseases. However, there is a large variability in response to anti...

Purpose: Peripheral neuropathy is a frequent vincristine-induced adverse effect. Vincristine is a substrate of P-glycoprotein and is metabolized by the cytochrome P-450 (CYP) 3A5 and 3A4 isoforms, with CYP3A5 contributing to 75% of the intrinsic clearance of vincristine. Alterations in the function of these proteins may lead to an increase in vinc...

Background: Safe and effective vaccines against Ebola could prevent or control outbreaks. The safe use of replication-competent vaccines requires a careful dose-selection process. We report the first safety and immunogenicity results in volunteers receiving 3 × 10(5) plaque-forming units (pfu) of the recombinant vesicular stomatitis virus-based ca...

Objective: Parallel to an ever stronger advocacy for the use of generics, various sources of information report concerns regarding substitution. The literature indicates that information regarding substitution is not univocal. The aim of this qualitative study was to explore patients' representations regarding generics in patients suffering from n...

Chronic kidney disease has been identified as an independent cardiovascular risk factor. The morbidity and mortality due to cardiovascular disease are higher among chronic kidney disease patients when compared with patients with normal kidney function. Although P2Y12 inhibitors (eg. clopidogrel) are associated with increased survival rates after a...