[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.

The Angers CT Score is a Risk Factor for the Failure of the Conservative Management of Adhesive Small Bowel Obstruction: A Prospective Observational Multicentric Study.

BACKGROUND: Identifying the 30% of adhesive small bowel obstructions (aSBO) for which conservative management will require surgery is essential. The association between the previously described radiological score and failure of the conservative management of aSBO remains to be confirmed in a large prospective multicentric cohort. Our aim was to assess the risk factors of failure of the conservative management of aSBO considering the radiological score. MATERIAL AND METHODS: This prospective observational study took place in 15 French centers over 3 months. Consecutive patients experiencing aSBO with no early surgery were included. The six radiological features from the Angers radiological computed tomography (CT) score were noted (beak sign, closed loop, focal or diffuse intraperitoneal liquid, focal or diffuse mesenteric haziness, focal or diffuse mesenteric liquid, and diameter of the most dilated small bowel loop > 40 mm). RESULTS: Two hundred and seventy nine patients with aSBO were screened. Sixty patients (21.5%) underwent early surgery, and 219 (78.5%) had primary conservative management. In the end, 218 patients were included in the analysis of the risk factors for conservative treatment failure. Among them, 162 (74.3%) had had successful management while for 56 (25.7%) management had failed. In multivariate analysis, a history of surgery was not a significant risk factor for the failure of conservative treatment (OR = 0.11; 95%CI = 0-1.23). A previous episode of aSBO was protective against the failure of conservative treatment (OR = 0.36; 95%CI = 0.15-0.85) and an Angers CT score ≥ 5 as the only individual risk factor (OR = 2.39; 95%CI = 1.01-5.69). CONCLUSION: The radiological score of aSBO is a promising tool in improving the management of aSBO patients. A first episode of aSBO and/or a radiological score ≥5 should lead physicians to consider early surgical management.

Hydromorphone Prescription for Pain in Children-What Place in Clinical Practice?

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 structurally and in its pharmacokinetic and pharmacodynamic properties but 5-7 times more potent. Pediatric pharmacokinetic and pharmacodynamic data on hydromorphone are sorely lacking; they are non-existent in children younger than 6 months of age and for oral administration. The current data do not support any advantage of hydromorphone over morphine, both in terms of efficacy and safety in children. Morphine should remain the treatment of choice for moderate and severe nociceptive pain in children and hydromorphone should be reserved as alternative treatment. Because of the important difference in potency, all strategies should be taken to avoid inadvertent administration of hydromorphone when morphine is intended.

[When the discontinuation of psychotropic drugs is necessary: clinical manifestations and therapeutic approach]. / Quand la discontinuation des psychotropes s'impose : manifestations cliniques et approche thérapeutique.

The reduction or suspension of psychotropic treatment may be necessary for various medical reasons. This can have serious consequences for patients, including clinical manifestations, both physical and psychological. These manifestations, which are often unpleasant, can compromise care during hospitalization and undermine the therapeutic alliance. Their early detection, readjustment of treatment, when necessary, as well as regular communication with the patient and among specialists are important tips to take into account from caregivers.

La diminution ou mise en suspens d'un traitement psychotrope peut être imposée par des raisons médicales diverses. Cela peut avoir d'importantes conséquences pour les patients, notamment des manifestations cliniques, tant physiques que psychologiques. Elles sont souvent désagréables, peuvent compromettre l'adhésion aux soins lors d'une hospitalisation et mettre à mal le lien thérapeutique. Leur détection précoce, le réajustement du traitement quand nécessaire, ainsi que la communication régulière avec le patient et entre spécialistes sont des éléments importants à prendre en compte lors de ces prises en charge.

Gabapentinoids: The rise of a new misuse epidemics?

Gabapentinoids and opioids have in common that they are used in medicine in the treatment of pain, and by addicts in recreational use. In recent years, in the context of the "opioid epidemics", gabapentinoids, which had a reputation for low risk of abuse, have been increasingly prescribed. This was accompanied by increasingly frequent abuses, the patients most at risk being those suffering from opiate addiction. However, gabapentinoids increase the risks associated with opioids or other sedatives, due to a synergy of central depressant effects. This leads to reconsider the framework of their prescription and the management of chronic pain.

CYP450 Genotype-Phenotype Concordance Using the Geneva Micrococktail in a Clinical Setting.

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 and/or diseases that can affect their in vivo activity, both approaches can be complementary. In 2014, the Geneva cocktail using dried blood spots was validated in healthy volunteers for CYP450 phenotyping. Since its clinical implementation, it has been used in approximately 500 patients in various clinical situations. Our study aims to report the concordance between CYP450 genotype and phenotype in real-life patients. The prospectively collected data from patients who were genotyped and/or phenotyped between January 2014 and December 2020 were reviewed. A total of 537 patients were genotyped and/or phenotyped for CYP450 during this period, and 241 underwent simultaneous genotyping and phenotyping allowing for genotype/phenotype concordance assessment. Genotyping correctly predicted poor metabolizer phenotypes for most CYPs isoenzymes studied, whereas agreement was more variable for intermediate, normal, and ultrarapid metabolizers. Discrepancies between the phenotype predicted on the basis of genotyping and the measured phenotype were not always explained by concurrent medication (phenotypic switch). Therefore genotyping and phenotyping tests are complementary approaches when aiming to individualize drug therapy. In the 537 patients, the majority of clinical situations were observed with analgesic/anesthetic drugs (n = 187), followed by antidepressants (n = 153), antineoplastics (n = 97), and immunosuppressants (n = 93). Inefficacy (or low drug levels) and adverse drug reaction (or high drug levels) were the main reasons for testing. Genotype and/or phenotype results explained or at least contributed to the clinical event in 44% of cases.

Antibiomania: a case report of clarithromycin and amoxicillin-clavulanic acid induced manic episodes separately.

BACKGROUND: Antibiomania is a rare but recognized side effect with yet unclear definite pathogenesis although multiple hypotheses have been proposed. The novelty of this case is the suspected pharmacodynamic drug-drug interaction between clarithromycin and amoxicillin-clavulanic acid. CASE PRESENTATION: We present the occurrence of a brief manic episode concerning a 50-year-old man with no psychiatric history, first started on amoxicillin-clavulanic acid therapy and then switched to clarithromycin for left basal pneumonia. Shortly after the antibiotic prescription, he presented psychiatric symptomatology (logorrhea, elevated mood, irritability, increase in physical activity and delusions). The antibiotic was stopped and the patient received lorazepam (2.5 mg p.o.) to treat psychomotor agitation. Approximately 12 h after clarithromycin cessation, amelioration was already observed, supporting the diagnosis of a clarithromycin-induced manic episode. Amoxicillin-clavulanic acid was then reintroduced because of the pneumonia and psychiatric symptoms reemerged. This second antibiotic was also stopped, and 1 week later, the patient was symptom-free. CONCLUSION: The emergence of psychiatric side effects related to antibiotherapy, which is a common treatment, can greatly impact a patient's quality of life. Early recognition and intervention could substantially influence the administered medical care and recovery. Moreover, given the widespread use of antibiotics including in combination, we thought our case report might be clinically useful as a clinical reminder relevant to the use of antibiotic combinations.

Prevalence of Polypharmacy and Inappropriate Medication in Adults With Intellectual Disabilities in a Hospital Setting in Switzerland.

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 potentially inappropriate medications (PIM) and polypharmacy in a hospital unit dedicated to adults with ID. Methods: A 10-month prospective observational study took place at a hospital unit specializing in the care of adults with ID in Geneva, Switzerland. Once a week, health and prescription data were collected and screened for PIM according to preset definitions. Results: Fourteen patients consented to participate, leading to 20 hospitalization events assessed during the study. Hospitalizations lasted 12.8 weeks on average. ID severities ranged from mild to profound, all degrees of severity being equally represented. One hundred percent of the patients were polymedicated (defined as five drugs or more prescribed simultaneously). A mean number of 9.4 drugs were prescribed per week, including 5.3 psychotropic drugs. The number of prescribed drugs remained stable throughout the hospitalizations. Antipsychotics were the most prescribed drug class (19% of all prescribed drugs), followed by benzodiazepines (13%) and laxatives (12%). A total of 114 PIM were recorded with an average of 5.7 PIM per hospitalization. Conclusions: This study showed that polypharmacy and inappropriate prescription are very common in adults with ID, even though the literature and expert positions advocate for deprescription in these patients. Specific prescribing and deprescribing guidelines are needed for that specific population.

[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.

[About the use of ketamine in emergency psychiatric settings]. / À propos de l'utilisation du traitement de la kétamine aux urgences psychiatriques.

Ketamine and its S-enantiomer, esketamine, have shown to be promising molecules for use in psychiatry. Widely investigated for the treatment of drug-resistant depression, they could be used in emergency conditions, due to their rapid onset of action, in two main conditions : 1) psychomotor agitation, and 2) acute suicidal ideation and behavior (suicidal crisis). In particular, intranasal administration offers a non-invasive, safe and very easy to administer option. An effect begins a few hours to a day after intake and lasts for about a week. These molecules present an innovative option for the future and their specific use in psychiatric emergencies.

La kétamine et son énantiomère S, l'eskétamine, se sont révélés être des molécules prometteuses pour leur utilisation en psychiatrie. Largement étudiées pour le traitement de la dépression pharmacorésistante, elles pourraient être utilisées dans des conditions d'urgence et, grâce à leur rapidité d'action, dans deux situations : 1) l'agitation psychomotrice, et 2) l'idéation et le comportement suicidaire aigus (crise suicidaire). En particulier, l'administration par voie intranasale offre une option non invasive, sûre et facile à utiliser. On observe un effet quelques heures à un jour après la prise, qui perdure pendant environ une semaine. Ces molécules représentent une option innovatrice pour le futur et pour une utilisation spécifique aux urgences psychiatriques.

TOP-ID: a Delphi technique-guided development of a prescription and deprescription tool for adults with intellectual disabilities.

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 (Tool for Optimising Prescription in Intellectual Disability/TOP-ID) was developed to improve the care of AWID. This paper describes how TOP-ID was designed. DESIGN: Four-step consensus-based process involving a review of the literature, eight semistructured interviews and a two-round Delphi process. SETTING: Seventeen general practices and university and general hospitals from Belgium, France and Switzerland. PARTICIPANTS: Eighteen French-speaking physicians from different domains of expertise participated in the Delphi process. PRIMARY AND SECONDARY OUTCOME MEASURES: For the Delphi iteration process, consensus was defined as at least a 65% agreement between the experts. RESULTS: Two rounds were needed for the Delphi process. Eighty-one items of the tool were submitted to 18 out of 35 recruited French-speaking experts during the first round. Sixty-nine per cent of the items reached a rate of agreement of 65% or more in that round. Thirteen questions were reformulated and resubmitted for the second Delphi iteration round. All of the statements reached a rate of agreement of 65% or more in the second round. CONCLUSION: TOP-ID is the first prescription-deprescription tool developed specifically for AWIDs in French. It is intended to help prescribers document patient care in order to reduce prescription errors and to improve safety. The next steps of the project include the development of an electronic version of TOP-ID and a utility study.

Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study.

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 between January 2005 and November 2014 were included. The genotype and/or phenotype was obtained for assessment of the CYPs, P-gp or COMT activities. The relation between the event and the result of the genotype and/or phenotype was evaluated using a semi-quantitative scale. Our analysis included 243 individual genotypic and/or phenotypic explorations. Genotypes/phenotypes were mainly assessed because of an ADR (n = 145, 59.7%), and the majority of clinical situations were observed with prodrug opioids (n = 148, 60.9%). The probability of a link between an ADR or a non-response and the genotypic/phenotypic status of the patient was evaluated as intermediate to high in 40% and 28.2% of all cases, respectively. The drugs in which the probability of an association was the strongest were the prodrug opioids, with an intermediate to high link in 45.6% of the cases for occurrence of ADRs and 36.0% of the cases for non-response. This study shows that the genotypic and phenotypic approach is useful to understand ADRs or therapeutic resistance to a usual therapeutic dosage, and can be part of the evaluation of chronic pain patients.

[Drug management of behavioral disorders in people with developmental and intellectual disability]. / Gestion médicamenteuse des troubles du comportement de la personne en situation de handicap mental.

Behavioral disorders in people with developmental and intellectual disability are frequent but their management is rarely taught. This article is to help primary physicians prescribe drug treatment. We will also discuss the key elements of two of the most commonly used classes of drugs, taking into account the patient's co-morbidities, contraindications and the main side effects.

Les troubles du comportement chez la personne en situation de handicap mental sont fréquents, mais leur prise en charge est peu enseignée aux médecins de premier recours. Cet article a pour objectif d'aider à la prescription d'un traitement médicamenteux. Nous discutons des éléments clés des deux classes de médicaments les plus utilisés, en tenant compte des comorbidités du patient, des contre-indications et des principaux effets secondaires.

[Why using antidepressants in chronic pain†? Practical prescription recommendations]. / Antidépresseurs dans la douleur chronique†: pourquoi les utiliser, comment les prescrire en pratique†?

The use over the last 50 years of antidepressants having both serotonergic and noradrenergic properties, as the first line for the management of neuropathic pain or chronic pain syndromes, is based on a twofold rationale: on the one hand, a plausible analgesic mechanism of action independent of the effect on mood, on the other hand, efficacy data in humans and animals. Their prescription should be part of a multimodal approach to pain. The dose to reach the analgesic effect, which on average occurs within four weeks after the initiation of treatment, is sometimes lower than the dose required to achieve the antidepressant effect. The choice of antidepressant will rely on the profile of adverse effects and other expected secondary benefits in the case of comorbidities.

L'utilisation depuis 50 ans d'antidépresseurs ayant à la fois une action sérotoninergique et noradrénergique comme première ligne pour la prise en charge de douleurs neuropathiques ou de syndromes douloureux chroniques est basée sur les deux raisons suivantes : d'une part, un mécanisme d'action antalgique plausible et indépendant de l'effet thymique, d'autre part, des données d'efficacité chez l'humain et l'animal. Leur prescription doit s'inscrire dans une approche multimodale de la douleur. La dose nécessaire pour atteindre l'effet antalgique, qui survient en moyenne dans les 4 semaines après l'introduction du traitement, est parfois moins importante que celle qui permet d'obtenir l'effet antidépresseur. Le choix de la molécule se fera en fonction du profil d'effets indésirables et d'autres bénéfices secondaires éventuels attendus.

GABAergic modulation of secondary hyperalgesia: A randomized controlled 4-way crossover trial with the α2-subunit preferring GABA positive allosteric modulator, N-desmethyl-clobazam in healthy volunteers.

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 (20, 40, 60 mg) and repeated doses (20 mg over 15 days) of NDMC pharmacokinetics were evaluated. Thirty-two subjects participated in the study. Primary outcome parameter was maximal change in the area of cutaneous UVB irradiation-induced secondary hyperalgesia (ASH). ASH decreased under all treatments. Mean (SD) relative change was 79 (22)%, 83 (24)%, 77 (30)% and 92 (16)% for placebo, NDMC20, NDMC60 and clonazepam, respectively. Neither absolute change nor relative change in ASH was significantly different between NDMC60 and placebo (mean difference = 2.3 cm2 [95% CI 4.0-8.5], p = .462 and 0.4% [-11.9 to 12.6], p = .952, respectively). An overall treatment effect was found on level of sedation. Compared to placebo, sedation was higher under clonazepam (mean difference = 39 mm [30-49] on a visual analogue scale, p < .001) while NDMC was free of sedative effect. NDMC pharmacokinetics after single doses showed poor absorption, but was linear. Steady-state plasma concentrations of NDMC20 were attained within 14 days, with low between-subjects variability. Mean steady-state concentration (CS-S , SD) reached 209 (22) ng/ml. NDMC absence of sedative effect and its overall well-characterized safety coming from years of utilization as a metabolite from clobazam, raise the prospect of dose escalating trials in patients to quantify its clinical utility. SIGNIFICANCE: This article, presenting the Phase I data of the new antihyperalgesic compound, α2-subunit GABAA positive allosteric modulator, N-desmethyl-clobazam (NDMC) is exploring the modulation of a new target in the treatment of neuropathic pain. Based on these results and on its preclinical properties NDMC would qualify as a good tool compound to seek confirmation of the clinical utility of selective GABA allosteric modulators in neuropathic pain patients.

Pain interventions in adults with intellectual disability: A scoping review and pharmacological considerations.

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 the literature on the topic, we also discussed the pharmacological considerations to be taken into account when prescribing analgesic drugs in that vulnerable population. DATABASES AND DATA TREATMENT: Articles on pain and ID were searched in the Medline and Google scholar electronic databases using the key words "Intellectual Disability," "Developmental Disability" and specific keywords for pharmacological and non-pharmacological pain interventions. Preset outcomes about pharmacological treatment specificity, efficacy and safety were then collected. RESULTS: One hundred and fifty-two articles were found and 16 were retained based on our inclusion and exclusion criteria. Of the 16 articles, five were topical reviews. Among the 11 remaining articles, five discussed pharmacological interventions, four considered non-pharmacological interventions and two discussed both. As anticipated, the literature matching our specific outcomes about the pharmacological treatment of pain was scarce and for the most part not designed to answer the questions of specificity, efficacy and safety of pain treatment in adults with ID. CONCLUSION: The specificity of analgesic treatments in adults with ID is a totally unexplored domain. In the absence of clinical guidelines, pharmacological facts-such as inter-individual variability in drug response, pharmacokinetic and pharmacodynamic interactions, frequent co-morbidities and ease of administration-must be systematically integrated, when prescribing in the population of adults with ID. SIGNIFICANCE: This review synthesizes the state of research on pain interventions in adults with ID and is one of the rare articles addressing the specificities of analgesic prescriptions in this population.

[Suicidal crisis and suicide prevention†: psychopharmacological aspects]. / Crise suicidaire et prévention du suicide†: aspects psychopharmacologiques.

Suicide is a common cause of death in Switzerland. It often occurs during a period of crisis marked by a disruption of the subject's intrapsychic, interpersonal or social balance. The management of this crisis is crucial and essentially psychotherapeutic. Drug therapy may be necessary for the management of acute symptoms or for the prevention of long-term suicidal risk. Benzodiazepines and atypical antipsychotics are often used for acute symptoms such as anxiety or sleep disorders while other molecules are recognized in reducing long-term suicidal risk. Some disorders, such as borderline personality disorder, account for more frequent suicidal behaviors. The pharmacological management of these specific situations is discussed.

Le suicide est une cause de mortalité fréquente en Suisse. Il survient souvent durant une période de crise marquée par une perturbation de l'équilibre intrapsychique, interpersonnel ou social du sujet. La prise en charge de cette crise est cruciale et essentiellement psychothérapeutique. Un traitement médicamenteux peut s'avérer nécessaire pour la gestion des symptômes aigus ou la prévention du risque suicidaire à long terme. Les benzodiazépines et les antipsychotiques atypiques sont souvent utilisés pour les symptômes aigus comme l'anxiété ou les troubles du sommeil. D'autres molécules sont reconnues dans la diminution du risque suicidaire à long terme. Certains troubles, comme le trouble borderline, rendent compte de comportements suicidaires plus fréquents. La prise en charge pharmacologique de ces situations spécifiques est discutée.

Cannabinoids and COVID-19.

Since the endocannabinoid system is involved in immune function, the effect of cannabinoid intake on infectious conditions is questioned for several years and is of particular interest in the COVID 19 pandemia. Some data suggest that the immunomodulatory effect of cannabinoids may affect the course and severity of SARS-CoV-2 infection. Given the large number of cannabinoids consumers in the community, this commentary presents the current knowledge on the potential impact of cannabinoids and endocannabinoids on bacterial and viral infection courses namely SARS-CoV-2 disease. Practical recommendations, which can be drawn from the literature, are given.

Natural history of liver adenomatosis: A long-term observational study.

BACKGROUND & AIMS: Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs. METHODS: We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies. RESULTS: Forty patients (36 female) were included with a median follow-up of 10.6 (1.9-26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9-55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A-mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up. CONCLUSIONS: The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients. LAY SUMMARY: Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up.

Ability to pay for medication: a clustering analysis of 1404 patients with the Patient Financial Eligibility Tool.

Aim: The study was conducted to understand how key determinants of the Patient Financial Eligibility Tool (PFET), a previously validated tool for assessing patients' ability to contribute to their medication costs, vary across countries. Materials & methods: A clustering analysis was conducted on economic data from 1404 patients from Thailand (n = 947), the UAE (n = 347) and Mexico (n = 110). Results: The analysis identified seven patient clusters, including globally wealthy or poor patients (14%/48%) and those with only selectively increased PFET economic indicators (38%), and revealed country-specific differences in the correlation between PFET metrics and patients' overall economic status. Conclusion: The PFET is a versatile tool that can be adapted to each country's economic context to assess patients' ability to contribute to their medication costs.