Relapses of Immune Thrombocytopenia after the Second and Booster Doses of BNT162b2 Vaccine.

We present here a 65-year-old male patient known for immune thrombocytopenic purpura (ITP) and fluctuating platelet count who experienced a severe exacerbation of thrombocytopenia following BNT162b2 COVID-19 vaccination. One month after the second dose, he presented petechiae and asthenia with isolated thrombocytopenia (platelet count: 3 × 109/L). He recovered after a 4-day course of intravenous corticosteroid treatment and intravenous immunoglobulin therapy. Eight months later, his platelet count was within the normal range, and he received a booster dose of vaccine after premedication with prednisone. Eight days later, his platelet count dropped to 29 × 109/L, but he remained asymptomatic. He received a rescue treatment with prednisone followed by rituximab over 4 weeks, allowing progressive improvement. Our case suggests a strong association between COVID-19 vaccination and the exacerbation of ITP.

[Therapeutic alliance and cognitive behavioral group therapy]. / Alliance thérapeutique et thérapie cognitivo-comportementale de groupe.

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 exceeding the patient's resources. This adaptive mechanism lowers the intensity of anxiety, favors control of fear and reinforces the motivation and energy invested in the process of change. We describe the importance of therapeutic alliance in group therapy with patients suffering from chronic pain. These processes will be illustrated with clinical vignettes.

Lors de thérapie cognitivo-comportementale de groupe, l'alliance thérapeutique, avec les psychothérapeutes et entre les patients, permet à ces derniers de développer leurs capacités de coping, c'est-à-dire l'ensemble des efforts cognitifs et comportementaux destinés à maîtriser, réduire ou tolérer des demandes spécifiques internes et/ou externes, vécues par le sujet comme menaçantes, épuisantes ou dépassant ses ressources. Cette alliance fonctionne en tant que mécanisme adaptatif permettant de diminuer l'intensité de l'anxiété, favoriser le contrôle des peurs et renforcer la motivation et l'énergie investies dans le processus de changement. Nous décrivons l'importance de cette alliance thérapeutique dans le processus groupal réunissant des thérapeutes et des patients souffrant de douleurs chroniques. Ces mouvements seront illustrés par des vignettes cliniques.

Deep proteomics and phosphoproteomics reveal novel biological pathways perturbed by morphine, morphine-3-glucuronide and morphine-6-glucuronide in human astrocytes.

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-independent acquisition mass spectrometry to perform a deep proteome and phosphoproteome analysis of how human astrocytes responds to opioid stimulation. We unveil time- and dose-dependent effects induced by morphine and its major active metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide that converging on activation of mitogen-activated protein kinase and mammalian target of rapamycin signaling pathways. We also find that especially longer exposure to M3G leads to significant dysregulation of biological pathways linked to extracellular matrix organization, antigen presentation, cell adhesion, and glutamate homeostasis, which are crucial for neuron- and leukocyte-astrocyte interactions.

Dexamethasone for the treatment of established postoperative nausea and vomiting: A randomised dose finding trial.

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 and to determine whether there is dose-responsiveness. DESIGN: The DexPonv trial is a multicentre, placebo-controlled, randomised, double-blind, dose-finding study. Inclusion of patients was between September 2012 and November 2017. Follow-up for PONV symptoms was for 24 h. Thirty days postoperatively, patients were contacted by study nurses for any information on postoperative bleeding and infection. SETTING: Four public hospitals in Switzerland. PATIENTS: A total of 803 adults scheduled for elective surgery without any antiemetic prophylaxis signed the consent form; 714 were included. Among those, 319 had PONV and 281 patients were eventually randomised (intention to treat population and safety set). The per protocol set consisted of 260 patients. INTERVENTIONS: Patients with PONV symptoms (including retching) were randomised to a single intravenous dose of dexamethasone 3, 6 or 12 mg or matching placebo. MAIN OUTCOME MEASURES: The primary endpoint was the absence of further nausea or vomiting (including retching), within 24 h after administration of the study drug. RESULTS: Dexamethasone was ineffective during the first 24 h, whatever the dosage, compared to placebo, even when the model was adjusted for known risk factors (P = 0.170). There were no differences in the time to treatment failure or the quality of sleep during the first night. There was a positive correlation between the dose of dexamethasone and blood glucose concentrations (P < 0.001), but not with bleeding risk, wound infections or other adverse effects. CONCLUSION: This randomised trial failed to show anti-emetic efficacy of any of the tested intravenous regimens of dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia. TRIAL REGISTRATION: clinicaltrials.gov (NCT01975727).

[Monoaminergic opioids: which one should we choose?] / Opioïdes monoaminergiques : lequel choisir ?

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 likely to expose less to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) and more to opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. As a conclusion, tapentadol represents an additional analgesic which some patients may benefit from after careful examination of their clinical situation, comorbidities and comedications.

Le tapentadol partage avec le tramadol un mode d'action mixte. Il n'a pas de métabolite actif identifié et n'est pas significativement métabolisé par le cytochrome P450 (CYP450), ce qui lui permet de contourner certaines limites du tramadol (interactions pharmacocinétiques, variabilité due aux polymorphismes génétiques du CYP450). Il expose potentiellement moins aux effets indésirables sérotoninergiques (nausées, vomissements, hypoglycémie) et davantage aux effets opioïdergiques (constipation, dépression respiratoire, abus) que le tramadol. Le niveau de preuve des données disponibles sur l'efficacité du tramadol et du tapentadol dans les douleurs chroniques est globalement faible. Le tapentadol représente un antalgique supplémentaire dont certains patients peuvent bénéficier après un examen attentif de leurs comorbidités, de leurs comédications et de la situation clinique.

[Activity, decentration and cognitive restructuring in cognitive-behavioural therapy - practice-based aspects]. / Activité, décentration et restructuration cognitive dans la thérapie cognitivocomportementale - Éléments pour la pratique clinique.

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 cognitive restructuring as key therapeutic tools in group CBT. Using them with patients suffering from chronic pain is complex and challenging when it comes to allow the patients to overcome the impossibility to function 'as before' while figuring out how to cope 'as for now'.

La décentration et la restructuration cognitive sont utilisées dans les thérapies cognitivocomportementales (TCC) chez les patients souffrant de douleurs chroniques et sont renforcées par le travail en groupe. Elles peuvent également être utilisées par les praticiens dans leurs cabinets. Des vignettes cliniques résument leur rôle dans l'identification d'activités réalistes et significatives et posent la décentration et la restructuration cognitive en tant qu'outils d'intérêt pour la TCC de groupe. Leur utilisation avec des patients douloureux chroniques peut permettre aux patients de surmonter l'impossibilité à faire « comme avant ¼ pour s'imaginer parvenir à gérer « comme maintenant ¼.

Toward precision medicine in pediatric population using cytochrome P450 phenotyping approaches and physiologically based pharmacokinetic modeling.

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. Currently, there is a vast choice of phenotyping methods in adults using exogenous probes to characterize the activity of these enzymes. However, this can hardly be applied to children since it requires the intake of non-therapeutic xenobiotics. In addition, sampling may be challenging in the pediatric population for a variety of reasons: limited volume (e.g., blood), inappropriate sampling methods for age (e.g., urine), and metric requiring invasive or multiple blood samples. This review covers the main existing methods that can be used in the pediatric population to determine DME activity, with a particular focus on cytochrome P450 enzymes. Less invasive tools are described, including phenotyping using endogenous probes. Finally, the potential of pediatric model-informed precision dosing using physiologically based pharmacokinetic modeling is discussed.

Comparing Dried Blood Spots and Plasma Concentrations for Busulfan Therapeutic Drug Monitoring in Children.

BACKGROUND: Busulfan (Bu) is one of the conditioning regimen components for pediatric hematopoietic stem cell transplantation. Bu therapeutic drug monitoring (TDM) is essential for a successful treatment outcome and toxicity evasion. Dried blood spot (DBS) sampling is a rapid and simple method for Bu TDM, compared with conventional plasma sampling. This study evaluated the feasibility of using the DBS method for Bu TDM. The hematocrit (Hct) and conditioning day were also examined for their impact on the DBS method's performance. METHODS: Venous blood collected from 6 healthy volunteers was diluted, using their plasma into 4 samples of varying Hct values. Each sample was spiked with Bu calibrators (300, 600, and 1400 ng/mL), prepared using DBS and dried plasma spot (DPS) sampling and analyzed using a validated liquid-chromatography tandem-mass spectrometry method. Clinical blood samples (n = 153) from pediatric patients (n = 15) treated with Bu (mainly from doses 1, 2, 5, and 9) were used to prepare paired volumetric DBS and DPS samples. A Bland-Altman plot and Deming regression were used to define the agreement between the paired DBS and DPS measurements. Passing-Bablok regression analyses investigated the effects of Hct and conditioning day on the linearity between both methods. RESULTS: In vitro analyses showed good agreement between DBS and DPS measurements, with a mean difference of -5.4% and a 95% confidence interval on the limits of agreement of -15.3% to 4.6%. Clinical samples showed good correlation (Pearson correlation coefficient = 0.96; slope = 1.00) between the DBS and DPS methods. The DBS method met the clinical acceptance limits for clinical samples, with a bias <±20%. Bland-Altman plots showed good agreement, with only 5.8% of paired measurements exceeding the limits of agreement (±1.96 SD), although within its 95% confidence interval. Hct observations ranged from 21.7% to 34.7% and did not affect Bu concentrations measured from DBS in either the in vitro or in vivo studies. CONCLUSIONS: These results show that DBS is a useful method for Bu TDM, provided samples are analyzed on the collection day. DBS sampling offers advantages over traditional plasma sampling in infants and younger children because only small volumes of blood are required.

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.).

A case report of cholinergic rebound syndrome following abrupt low-dose clozapine discontinuation in a patient with type I bipolar affective disorder.

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 schizophrenia. Here, we report a case of rebound cholinergic syndrome and catatonia in a male patient three days after abrupt discontinuation of 50 mg of clozapine prescribed for type I bipolar affective disorder. CASE PRESENTATION: A 66-year old male of Spanish origin, treated for type I bipolar affective disorder for 15 years and for Crohn disease, was brought to the emergency department because of a sudden onset of mutism, dysphagia and trismus. He was described catatonic and presented hypertension, tachycardia and tachypnea. His body temperature was normal and the laboratory tests were unremarkable at presentation. A head CT and an EEG were in the normal range. While reviewing his history, it appeared the he was on clozapine 50 mg a day, first introduced 2 months ago, during a previous hospitalization for a manic episode resistant to other mood stabilizers. For an unknown reason, the patient's psychiatrist stopped clozapine three days before the admission and replaced it by risperidone 5 mg and quetiapine 200 mg daily. A cholinergic rebound syndrome was then evoked. The patient's ability to speak recovered dramatically and fast after the intravenous administration of 2.5 mg of biperiden supporting the diagnosis. Risperidone and quetiapine were also stopped. The patient fully recovered in 20 days after the reintroduction of 50 mg of clozapine and 2.5 mg of biperiden daily. CONCLUSIONS: This case report underscores that cholinergic rebound syndrome may occur in patients suffering from bipolar affective disorders, being on clozapine as a mood stabilizer. The low dose clozapine does not preclude severe manifestations of the phenomenon. Progressive tapering should therefore be adopted in any case.

[Why propose cognitive-behavioural therapy for chronic pain patients†?] / Pourquoi proposer la thérapie cognitivo-comportementale dans les douleurs chroniques ?

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, drawing on the identification of an activity that is not only important and meaningful for the patient but also realistic. This should allow the patient to overcome the impossibility to function «â€…as before ¼ while figuring out how to cope «â€…as for now ¼. The ways to explore possible alternative options during the group therapy is presented and discussed.

Les techniques cognitives et comportementales (TCC) sont utilisées dans l'approche des douleurs chroniques, sur la base du postulat que douleur et handicap ne sont pas (uniquement) influencés par la pathologie somatique, mais aussi par des facteurs psychosociaux. Les TCC visent à l'amélioration de la qualité de vie, au-travers d'une réduction du handicap. La dimension psychoéducative, les techniques centrées sur l'activité et les techniques cognitives y tiennent une place centrale, reposant sur le choix d'une activité importante et qui fasse du sens pour le patient, autour d'objectifs réalistes, et qui permettent au patient de dépasser l'impossibilité de faire «â€…comme avant ¼ pour imaginer des façons de faire «â€…comme maintenant ¼. La manière dont l'exploration du champ des possibles est abordée au fil des séances est présentée et discutée.

Prediction of drug-drug interactions using physiologically-based pharmacokinetic models of CYP450 modulators included in Simcyp software.

In recent years, physiologically based PharmacoKinetic (PBPK) modeling has received growing interest as a useful tool for the assessment of drug pharmacokinetics. It has been demonstrated to be informative and helpful to quantify the modification in drug exposure due to specific physio-pathological conditions, age, genetic polymorphisms, ethnicity and particularly drug-drug interactions (DDIs). In this paper, the prediction success of DDIs involving various cytochrome P450 isoenzyme (CYP) modulators namely ketoconazole (a competitive inhibitor of CYP3A), itraconazole (a competitive inhibitor of CYP3A), clarithromycin (a mechanism-based inhibitor of CYP3A), quinidine (a competitive inhibitor of CYP2D6), paroxetine (a mechanism-based inhibitor of CYP2D6), ciprofloxacin (a competitive inhibitor of CYP1A2), fluconazole (a competitive inhibitor of CYP2C9/2C19) and rifampicin (an inducer of CYP3A) were assessed using Simcyp® software. The aim of this report was to establish confidence in each CYP-specific modulator file so they can be used in the future for the prediction of DDIs involving new victim compounds. Our evaluation of these PBPK models suggested that they can be successfully used to evaluate DDIs in untested scenarios. The only noticeable exception concerned a quinidine inhibitor model that requires further improvement. Additionally, other important aspects such as model validation criteria were discussed.

[Opioids prescription in the vulnerable populations : the children and the elderly. Practical guidelines]. / Prescription des opioïdes chez les patients vulnérables : les enfants et les personnes âgées. Recommandations pratiques.

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 and pain assessment, make children and the elderly more vulnerable to variability in opioid response and problems of safety and efficacy profile. The purpose of this article is to remain the specificities of these two populations and to propose recommendations for the good use of opioids for ambulatory care.

La prise en charge de la douleur en médecine de ville nécessite régulièrement le recours à la prescription d'opioïdes. Une antalgie adéquate est obtenue chez de nombreux patients, mais une inefficacité et/ou des effets indésirables intolérables peuvent limiter leur utilisation. Les facteurs liés aux particularités physiologiques, aux comorbidités et aux comédications, les difficultés liées à la prise médicamenteuse et l'évaluation de la douleur, rendent l'enfant et le sujet âgé plus vulnérables à la variabilité de réponse aux opioïdes et aux problèmes de sécurité et d'efficacité. Le présent article a pour but de rappeler les spécificités de ces deux populations aux extrêmes de l'âge et de proposer des recommandations de bon usage des opioïdes pour la médecine ambulatoire.

[Acute pain management in opioid-maintained patients]. / Gestion de la douleur aiguë chez les patients sous traitements de substitution aux opioïdes.

Treatment of acute nociceptive pain in patients with opioid substitution therapy (OST) is an actual topic. The clinical features of this population, as pain sensibility, and the pharmacological features of OST, require an individualized care which must be adjusted to the patient's pain and the OST used. This article offers a summary of the main possible pharmacological strategies by highlighting the features of pain in these patients and removing the barriers to an effective management. Generally, the OST is kept and a multimodal analgesia is added according to the intensity of the pain. Multimodal analgesia includes non pharmacological measures, non opioid drugs and/or opioid drugs which must be chosen according to the OST. Collaboration between different health professionals provides an effective management of pain in order to protect this vulnerable population from the negative health consequences of an insufficiently relieved pain.

La prise en charge de la douleur nociceptive aiguë chez les patients sous traitements basés sur la substitution (TBS) de la dépendance aux opioïdes représente un enjeu thérapeutique majeur. Les particularités cliniques de ces patients, notamment une sensibilité exacerbée à la douleur, tout comme les particularités pharmacologiques des TBS, imposent une prise en charge individualisée et adaptée au patient, à sa douleur et au TBS employé. Cet article, après avoir souligné les spécificités de la douleur chez ces patients et levé les barrières à une prise en charge efficace, propose une synthèse des stratégies thérapeutiques pharmacologiques possibles. D'une manière générale, le principe est de maintenir le TBS et d'y associer une analgésie multimodale adaptée à l'intensité de la douleur et incluant des mesures non médicamenteuses, des antalgiques non opioïdes et/ou opioïdes si nécessaire, en sélectionnant adéquatement le type d'opioïde selon le TBS. Une prise en charge efficace implique, en outre, une collaboration entre les différents professionnels de santé impliqués dans le suivi de ces patients, et reste fondamentale afin de protéger cette population vulnérable des conséquences sanitaires négatives liées à une douleur insuffisamment soulagée.

Screening for genotypic and phenotypic variations in CYP450 activity in patients with therapeutic problems in a psychiatric setting, a retrospective study.

OBJECTIVES: This retrospective study aimed to assess to what extent an adverse drug reaction (ADR), an abnormal therapeutic drug monitoring (TDM) or a non-response, was attributable to an abnormal cytochrome P450 activity in a psychiatric setting. METHOD: We collected the results of investigations performed in these situations related to psychotropic drugs between January 2005 and November 2014. Activities of different cytochrome P450 were assessed by genotyping and/or phenotyping. Two experienced clinical pharmacologists assessed independently the possible association between the event and the results of the investigations. RESULTS: One hundred and thirty eight clinical or biological situations had a complete assessment of all major metabolic pathways of the target drug. A majority of clinical or biological situations were observed with antidepressants (n=93, 67.4%), followed by antipsychotics (n=28, 20.3%), benzodiazepines and hypnotics (n=13, 9.4%), and psychostimulants (n=4, 2.9%). Genotype and/or phenotype determination was mainly performed because of ADRs (n=68, 49.3%) or non-response (n=46, 33.3%). Inter-rate reliability of the scoring system between the pharmacologists was excellent (kappa=0.94). The probability of an association between ADR, TDM or non-response and metabolic status was rated as intermediate to high in 34.7% of all cases, with proportions of 30.4% and 36.7%, for non-response and ADR respectively. CONCLUSION: When indicated by clinical pharmacologists, ADR, TDM or non-response may be attributable to a variation of the metabolic status with an intermediate to high probability in 34.7% of patients, based on the congruent assessment made by two clinical pharmacologists. Further studies assessing the clinical relevance of prospective explorations and clarifying the appropriate method according to the clinical context are needed.

[It is not only about cost ... when it comes to generic medication]. / Le coût, ce n'est pas tout ... à propos des médicaments génériques.

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 might be confident in taking a generic medication: when the generic medication is prescribed by the physician and each prescription is discussed, i.e., the patient is prescribed the generic version of a given medication and not a generic medication. Economic arguments are not sufficient to accept substitution. Negative representations require attention and need be considered.

A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients.

BACKGROUND: GNbAC1 is an immunoglobulin (IgG4) humanised monoclonal antibody against multiple sclerosis-associated retrovirus (MSRV)-Env, a protein of endogenous retroviral origin, expressed in multiple sclerosis (MS) lesions, which is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation. OBJECTIVE: This is a randomised, double-blind placebo-controlled dose-escalation study followed by a six-month open-label phase to test GNbAC1 in MS patients. The primary objective was to assess GNbAC1 safety in MS patients, and the other objectives were pharmacokinetic and pharmacodynamic assessments. METHODS: Ten MS patients were randomised into two cohorts to receive a single intravenous infusion of GNbAC1/placebo at doses of 2 or 6 mg/kg. Then all patients received five infusions of GNbAC1 at 2 or 6 mg/kg at four-week intervals in an open-label setting. Safety, brain magnetic resonance imaging (MRI), pharmacokinetics, immunogenicity, cytokines and MSRV RNA expression were studied. RESULTS: All patients completed the study. GNbAC1 was well tolerated in all patients. GNbAC1 pharmacokinetics is dose-linear with mean elimination half-life of 27-37 d. Anti-GNbAC1 antibodies were not detected. Cytokine analysis did not indicate an adverse effect. MSRV-transcripts showed a decline after the start of treatment. Nine patients had stable brain lesions at MRI. CONCLUSION: The safety, pharmacokinetic profile, and pharmacodynamic responses to GNbAC1 are favourable in MS patients over a six-month treatment period.

Assessing the affective load in the narratives of women suffering from fibromyalgia: the clinicians' appraisal.

OBJECTIVE: Fibromyalgia is characterized by chronic widespread pain and various associated symptoms, including psychological distress. This study presents a secondary analysis of the interviews of patients with fibromyalgia to appraise the affective load of the patient narratives as assessed by independent clinicians. SETTING AND PARTICIPANTS: Three clinicians, an internist, a psychiatrist and a psychologist, who were experienced in chronic pain reviewed the interview transcripts of 56 women eliciting their views regarding fibromyalgia onset. A Clinical Global Impression (CGI) scale was used (0 = no affective load to 5 = maximum affective load) to provide a subjective appraisal of the intensity of the affective impact, as suggested in the transcripts and from the clinician perspectives. RESULTS: The mean affective load was 3.6 (SD = ±1), indicating the perception of a high affective load in the clinicians. Values indicating a high or very high affective load (≥4 points on the CGI scale) were more frequent than those in the lower range [23 narratives (41%) vs. 3 (5%)]. The inter-rater agreement of the affective load of the narratives was high (K > 0.85). These results of the clinician perspectives parallel those of the patient narratives, emphasizing disruptive circumstances, psychological distress and hopelessness surrounding symptom onset. CONCLUSION: The affective load in the narratives of these patients with fibromyalgia was high and had a negative undertone when considered from the clinicians' perspective. This study highlights the importance of considering the affective resonance in the context of therapeutic relationships that are often emotionally laden and highly challenging for the clinician.

[Prescription of antidepressants in the treatment of pain: role of pharmacogenetics]. / Prescription d'antidépresseurs dans le traitement de la douleur: rôle de la pharmacogénétique.

Antidepressants, mainly tricyclic and non-selective reuptake inhibitors of serotonin antidepressants, are part of the treatment of chronic pain. The management is complicated by a large interindividual variability of efficacy and tolerance. Important part of this variability is associated with nucleotide polymorphisms of genes encoding enzymes involved in the pharmacokinetics and pharmacodynamics of these molecules. Identification of these genetic variants could to predict clinical consequences and allowed individualized adjustments in medication or dosage. This article presents the current knowledge on the influence of genetics on the efficacy and adverse effects of antidepressants used in chronic pain treatment.

[Clinical pharmacology of medical cannabinoids in chronic pain]. / Cannabinoïdes médicaux dans les douleurs chroniques: aspects pharmacologiques.

In Switzerland, medical cannabinoids can be prescribed under compassionate use after special authorization in justified indications such as refractory pain. Evidence of efficacy in pain is limited and the clinical benefit seems to be modest. Their drug-drug interactions (DDI) profile is poorly documented. Cytochromes P450 (CYP) 2C9 and 3A4 are involved in the metabolism of tetrahydrocannabinol and cannabidiol, which implies possible DDI with CYP450 inhibitor and inducer, such as anticonvulsivants and HIV protease inhibitors, which may be prescribed in patients with neuropathic pain.