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Background and aims Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. First-line medications consist of drugs that act by counteracting dopamine deficiency in the basal ganglia. Unfortunately, iatrogenic impulsive-compulsive behaviors (ICBs) can occur in up to 20% of PD patients over the course of their illness. ICBs must be considered multifactorial disorders that reflect the interactions of the medication with an individual's vulnerability and the underlying neurobiology of PD. We aimed to explore the predictive genetic, psychopathological and neurological factors involved in the development of ICBs in PD patients by building a complete model of individual vulnerability. Methods The PARKADD study was a case/non-case study. A total of 225 patients were enrolled (“ICB” group, N = 75; “no ICB” group, N = 150), and 163 agreed to provide saliva samples for genetic analysis. Sociodemographic, neurological and psychiatric characteristics were assessed, and genotyping for the characterization of polymorphisms related to dopaminergic and opioid systems was performed. Results Factors associated with “ICBs” were younger age of PD onset, personal history of ICB prior to PD onset and higher scores on the urgency and sensation seeking facets of impulsivity. No gene variant was significantly associated, but the association with the opioid receptor mu 1 (OPRM1) rs1799971 polymorphism was close to significance. Discussion and conclusions The influence of gene-environment interactions probably exists, and additional studies are needed to decipher the possible role of the opioid system in the development of ICBs in PD patients.

EMONO is an equimolar mixture of oxygen and nitrous oxide and is considered a reference for dental care in children. Completion of dental treatment has usually been used as a criterion to assess EMONO treatment. However, patient-reported outcomes are needed because i) we treat vulnerable subjects, and ii) effects felt can impact dental care prognosis. The aim of this study was to describe the patients’ feelings during EMONO sedation for dental care, especially anxiolytic and analgesic effects. We conducted a national prospective observational multicentric study between September 2018 and June 2020 in 13 French university hospitals. Participants were children between 3 and 15 years of age requiring dental care under EMONO. We assessed i) the prevalence of complete achievement of therapeutic effects (analgesia and anxiolysis) and ii) associated factors using a mixed effects logistic regression. In total, 677 children were analyzed. Anxiolysis and analgesia were experienced by a large majority of patients (86.5% and 79.0%, respectively, and 73% for both effects experienced). Several factors were associated with complete achievement of therapeutic effects: the presence of expected effects (no loss of judgment and slight decrease in level of consciousness), the absence of agitation and distress, a positive perception of EMONO using the VAS and race. Our study characterized the patients who best benefit from the therapeutic effects (anxiolysis and analgesia) expected by EMONO during dental treatment. It is reassuring to observe that most sociodemographic characteristics and medical history do not seem to influence the effectiveness of care.

Purpose Patient autonomy is a key concept in medical ethics, which consists of recognizing each person as a free individual capable of judging and determining for himself or herself. The objectives of this study were to describe digestive cancer patients’ desire for autonomy in therapeutic decision-making and to identify variables associated with these preferences. Methods An observational prospective study in a French university cancer center has been conducted. Patients completed two questionnaires to qualify and quantify their desire for autonomy in therapeutic decision-making: the Control Preference Scale (CPS) and the Autonomy Preference Index (API), which is composed of the Decision Making (DM) score and the Information Seeking (IS) score. Associations between these scores and socio-demographic data, disease-related data, coping strategies (Brief-COPE), physical (QLQ-C30) and psychological (HADS) quality of life were tested. Results One-hundred fifteen patients returned the questionnaires. The majority of patients reported a passive (49.1%) or a collaborative (43.0%) CPS status. The mean DM score was 51.5. Variables associated with decision-making preferences were occupational status and time since diagnosis. Conclusion The identification of variables associated with patients' preferences for autonomy and participation in decision-making can help make clinicians aware of patients' needs and wishes. However, it can only be determined by interviewing the patient individually.

Background Rapid-onset paralytic agents are recommended to achieve muscle relaxation and facilitate tracheal intubation during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents. However, opioids are frequently used in this setting. The study’s objective is to demonstrate the non-inferiority of remifentanil compared to rapid-onset paralytic agents, in association with an hypnotic drug, for tracheal intubation in patients undergoing procedure under general anesthesia and at risk of pulmonary aspiration of gastric contents. Methods The REMICRUSH (Remifentanil for Rapid Sequence Induction of Anaesthesia) study is a multicenter, single-blinded, non-inferiority randomized controlled trial comparing remifentanil (3 to 4 μg/kg) with rapid-onset paralytic agents (succinylcholine or rocuronium 1 mg/kg) for rapid sequence induction in 1150 adult surgical patients requiring tracheal intubation during general anesthesia. Enrolment started in October 2019 in 15 French anesthesia units. The expected date of the final follow-up is October 2021. The primary outcome is the proportion of successful tracheal intubation without major complications. A non-inferiority margin of 7% was chosen. Analyses of the intent-to-treat and per-protocol populations are planned. Discussion The REMICRUSH trial protocol has been approved by the ethics committee of The Comité de Protection des Personnes Sud-Ouest et Outre-Mer II and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The REMICRUSH trial is the first randomized controlled trial powered to investigate whether remifentanil with hypnotics is non-inferior to rapid-onset paralytic agents with hypnotic in rapid sequence induction of anesthesia for full stomach patients considering successful tracheal intubation without major complication. Trial registration ClinicalTrials.gov NCT03960801. Registered on May 23, 2019.

International audience; OBJECTIVES: Benzodiazepines and non-benzodiazepine hypnotics (or Z-drugs) (BZD/Z) are widely prescribed for older patients despite major side effects and risks when chronically used. The patient's understanding of the treatment is one of the keys to good adherence. The purpose of the study was to assess the knowledge of BZD/Z treatment among older people who were taking BZD/Z for the long term by studying the concordance between the declared reason for taking BZD/Z and its indication. METHODS: This was a cross-sectional, pharmacoepidemiologic ancillary of a national study. Data were collected through a semi-structured interview. All patients from the main study were included. "Good knowledge" was considered when patients gave an indication for each BZD/Z that was similar to its marketing authorization. Univariate and multivariate analyses were carried out to adequately determine profiles and characterize associations. RESULTS: More than half of the patients (61.6%) had a good knowledge regarding their treatment. The presence of a psychiatric disorder, a mean duration of BZD/Z use of less than 120\,months, a desire to stop treatment, educational status, and number and type of BZD/Z used were significantly associated (P\

In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency decreed the implementation of secure prescription pads in April, 2017. The objective of this study was to characterize the impact of this regulatory change on the patterns of zolpidem use.We included patients with at least one reimbursement for zolpidem before and/or after the regulatory change using a sample of the French health insurance database. For each period, we identified profiles of users using a latent class analysis (LCA).In total, 15,550 zolpidem users were identified before the measure and 8,301 after the measure. We identified the same three profiles of zolpidem users before and after the measure: non-problematic users (the most prevalent), users whose drug prescriptions suggest psychiatric disorder and potential problematic users. The profile of potential problematic users was similar after the regulatory change but represented a lower absolute number of patients.In conclusion, the regulatory change had a positive impact on the patterns of zolpidem use, but the impact should be reevaluated, because withdrawal can take a long time, especially in long-term users.The study was registered at www.clinicaltrials.gov under the reference number NCT03584542.

Transfusion is a specific cause of acute kidney injury (AKI) after cardiac surgery. Whether there is an association between the composition of blood products and the onset of AKI is unknown. The present study suggests that the transfusion of packed red blood cells containing a high amount of myeloid-related protein 14 (MRP_14) could increase the incidence of AKI after cardiac surgery. In a mouse model, MRP_14 increased the influx of neutrophils in the kidney after ischemia-reperfusion and their ability to damage tubular cells. Higher concentrations of MRP_14 were found in packed red blood cells from female donors or prepared by whole blood filtration.

Benzodiazepines (BZDs) and related drugs (Z-drugs) are mainly taken chronically, and older people are much more likely to take them on a chronic basis despite recommendations. Withdrawal symptoms could be an obstacle to stopping BZD/Z-drug administration. The main objective of this study is to estimate the prevalence of withdrawal symptoms in patients aged 65 years and older who have experience a stop of BZD/Z-drug. The secondary objectives are to describe the withdrawal symptoms and identify factors associated. This ancillary study was based on a national observational study in patients with chronic BZD/Z-drug consumption. Patients who made at least one BZD/Z-drug stop experience were selected. Withdrawal symptoms are described, and a logistic regression was carried out to identify the variables most associated with withdrawal symptoms. In total, 697 patients were selected: 78% experienced at least one withdrawal symptom after a stop administering BZDs or Z-drugs; most of the withdrawal symptoms were psychological disorders. Our study identifies a specific population experiencing withdrawal symptoms and who cannot stop administering BZD/Z-drug. We assume that withdrawal symptoms in patients with chronic use play an essential role in the nonstop use of BZD/Z-drugs.

AIMS In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency (ANSM) decreed in April 2017 the implementation of secure prescription pads. The objective of this study was to evaluate the impact of this regulatory measure on the prescription of zolpidem and other sedative medications (zopiclone, benzodiazepines and antihistamines) in long-term users of zolpidem and associated factors. METHODS We performed a historical cohort study using data from the Generalist Sample of Beneficiaries (EGB). All patients aged over 18 years old who were long-term users (at least 3 months) before the measure were enacted. We analysed the reimbursement trajectories of zolpidem, zopiclone, benzodiazepines and antihistamines (hydroxyzine and alimemazine) up to 2 years after the measure using a state sequence analysis. RESULTS Overall, 2502 patients were analysed. A four-cluster typology was identified: continuation of zolpidem (n = 1044, 42%), discontinuation of sedative medications (n = 766, 31%), change to zopiclone (n = 537, 21%) and change to hypnotic benzodiazepines (n = 155, 6%). The most frequently prescribed hypnotic benzodiazepine was lormetazepam. We identified age, sex, treatment for psychiatric or addictive disorder and volume of zolpidem use before the measure as factors associated with different reimbursement trajectories after the regulatory change. CONCLUSION The regulatory change for zolpidem prescriptions reduced exposure to zolpidem among long-term users and also had a broad impact on prescriptions of other sedative medications. Switching to other medications that also present a potential risk of abuse or dependence should be carefully monitored.

Objective To assess the effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery. Design Phase III, randomised, double blind, placebo controlled trial. Setting 34 centres in France, December 2017 to March 2019. Participants 1222 adults (>50 years) requiring major non-cardiac surgery with an expected duration of more than 90 minutes. The anticipated time frame for recruitment was 24 months. Interventions Participants were randomised to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Randomisation was stratified on the two prespecified criteria of cancer and thoracic procedure. Main outcomes measures The primary outcome was a composite of postoperative complications or all cause mortality within 14 days after surgery, assessed in the modified intention-to-treat population (at least one treatment administered). Results Of the 1222 participants who underwent randomisation, 1184 (96.9%) were included in the modified intention-to-treat population. 14 days after surgery, 101 of 595 participants (17.0%) in the dexamethasone group and 117 of 589 (19.9%) in the placebo group had complications or died (adjusted odds ratio 0.81, 95% confidence interval 0.60 to 1.08; P=0.15). In the stratum of participants who underwent non-thoracic surgery (n=1038), the primary outcome occurred in 69 of 520 participants (13.3%) in the dexamethasone group and 93 of 518 (18%) in the placebo group (adjusted odds ratio 0.70, 0.50 to 0.99). Adverse events were reported in 288 of 613 participants (47.0%) in the dexamethasone group and 296 of 609 (48.6%) in the placebo group (P=0.46). Conclusions Dexamethasone was not found to significantly reduce the incidence of complications and death in patients 14 days after major non-cardiac surgery. The 95% confidence interval for the main result was, however, wide and suggests the possibility of important clinical effectiveness. Trial registration ClinicalTrials.gov NCT03218553 .

Background We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). Methods This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. Results Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38–56%) in the intervention group and 42% (IQR, 25–53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5–14 days) in the control group and 9 days (IQR, 5–20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69–2.01; P = .10). Conclusions The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. Clinical Trials Registration NCT03348579.

Benzodiazepines and Z-drugs, zolpidem and zopiclone, (BZD/Z) are used longer than recommended in the elderly population. However, to date, very few attempts have been made to evaluate dependence on BDZ/Z among the elderly population. We conducted a national multicentric observational prospective study aimed at evaluating the prevalence of and risk factors for dependence among elderly adults. Patients aged 65 or older who were treated with BZD/Z for at least 3 months were evaluated through clinical interviews that conformed to official Diagnostic and Statistical Manual of Mental Disorders (DSM) dependence criteria. Among the 1,024 patients included in the survey, 442 of 976 (45.3%) met the dependence criteria. In the multivariate logistic regression model, dependent patients were categorized as follows: younger (odds ratio (OR) = 0.97), living mostly alone (OR = 1.45), showing psychiatric problems (OR = 2.22), having additional treatments (other than BZD/Z; OR = 1.37), having long-lasting treatment (OR = 1.04), exhibiting significant relationship difficulties (OR = 1.96), committing transgressional behaviors to procure BZD/Z (OR = 2.70), and wanting to stop their consumption of BZD/Z (OR = 7.60). A latent class analysis, which was applied to sort out subgroups within dependent patients, identified two profiles according to the prevalence of dependence items: profile 1 (73%), "withdrawal syndrome when BZD/Z is stopped" (100%) and "previous unsuccessful attempts to stop consumption" (82%); and profile 2 (27%), "tolerance" (76%) and "intake in larger amounts or over a longer period than intended" (86%). BZD/Z dependence is frequent in the elderly population, and among dependent patients, we found two profiles corresponding to positive and negative conditioning of the psychoactive effects of BZD/Z. This study is registered as NCT01920581.

Introduction Ces dernieres annees, le zolpidem a ete le medicament hypnotique le plus prescrit en France et a egalement fait l’objet de multiples rapports de mesusage, d’abus et de dependance. Devant ces risques, les medecins ont ete informes en janvier 2017 qu’a partir d’avril 2017 la prescription du zolpidem devait obligatoirement etre realisee sur ordonnance securisee. L’etude ZORRO (ZOlpidem et Renforcement de la Reglementation des Ordonnances) a ete mise en place pour evaluer l’impact global du changement reglementaire a partir d’une analyse de donnees de l’Assurance maladie et a partir d’une etude de terrain. L’objectif de l’etude presentee ici etait d’evaluer l’impact de la mesure sur le type de consommation du zolpidem a partir de donnees de remboursement de soins. Materiel et methodes Nous avons inclus tous les patients ayant au moins un remboursement de zolpidem avant et/ou apres le changement reglementaire a partir de l’Echantillon generaliste de beneficiaires (EGB). A partir des donnees de remboursement de soins, nous avons construit differents indicateurs afin de caracteriser le type de consommation tels que : la duree de traitement, le nomadisme medical, le nomadisme pharmaceutique, la surconsommation, la coprescription d’autres medicaments hypnotiques ou anxiolytiques, la prescription par un psychiatre, la presence d’une comorbidite psychiatrique. Une analyse en classes latentes a ete realisee chez les consommateurs reguliers de zolpidem (au moins deux delivrances dans chaque periode d’etude) avant et apres la reglementation pour identifier des profils de consommation. Resultats Au total, 15 550 consommateurs de zolpidem ont ete analyses avant la mise en place de la mesure et 8301 apres. Globalement, les habitudes de prescription ont evolue apres la reforme : moins de prescriptions par patient (nombre de patients avec au moins deux delivrances quasiment divise par deux) et moins de prescriptions concomitantes d’autres medicaments hypnotiques ou anxiolytiques. Chez les patients qui consommaient sur les deux periodes, nous avons egalement observe une diminution de la frequence de nomadisme pharmaceutique (2,1 % a 1,6 %), nomadisme medical (1,1 a 0,7 %) et surconsommation (24,2 % a 20,1 %). Parmi les patients ayant au moins deux delivrances de zolpidem, nous avons identifie les 3 memes profils de consommateurs de zolpidem avant et apres la reforme : – les consommateurs non problematiques (70–73 %), – les consommateurs avec une comorbidite psychiatrique associee (25–28 %), – les consommateurs potentiellement problematiques (2 %) (frequence elevee de nomadisme pharmaceutique, nomadisme medical et surconsommation). Le profil de consommateurs potentiellement problematiques, bien que toujours present apres la reforme, representait un nombre absolu de patients moins important apres la reforme. Conclusion En conclusion, le renforcement de la reglementation de prescription du zolpidem a eu un impact positif sur la consommation du zolpidem. Cet impact devra neanmoins etre reevalue avec plus de recul car l’arret ou la diminution de la consommation de zolpidem peuvent etre longs, specifiquement chez les utilisateurs chroniques.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Craniotomy for brain tumor displays significant morbidity and mortality, and no score is available to discriminate high-risk patients. Our objective was to validate a prediction score for postoperative neurosurgical complications in this setting. Methods Creation of a score in a learning cohort from a prospective specific database of 1,094 patients undergoing elective brain tumor craniotomy in one center from 2008 to 2012. The validation cohort was validated in a prospective multicenter independent cohort of 830 patients from 2013 to 2015 in six university hospitals in France. The primary outcome variable was postoperative neurologic complications requiring in–intensive care unit management (intracranial hypertension, intracranial bleeding, status epilepticus, respiratory failure, impaired consciousness, unexpected motor deficit). The least absolute shrinkage and selection operator method was used for potential risk factor selection with logistic regression. Results Severe complications occurred in 125 (11.4%) and 90 (10.8%) patients in the learning and validation cohorts, respectively. The independent risk factors for severe complications were related to the patient (Glasgow Coma Score before surgery at or below 14, history of brain tumor surgery), tumor characteristics (greatest diameter, cerebral midline shift at least 3 mm), and perioperative management (transfusion of blood products, maximum and minimal systolic arterial pressure, duration of surgery). The positive predictive value of the score at or below 3% was 12.1%, and the negative predictive value was 100% in the learning cohort. In–intensive care unit mortality was observed in eight (0.7%) and six (0.7%) patients in the learning and validation cohorts, respectively. Conclusions The validation of prediction scores is the first step toward on-demand intensive care unit admission. Further research is needed to improve the score’s performance before routine use.

International audience; INTRODUCTION: In France, an addictovigilance network is responsible for evaluating drug dependence, by drawing on pharmacoepidemiological studies, clinical studies and by assessing healthcare professionals' reports on problematic consumption. METHODS: The aim of this study was to determine whether zolpidem and zopiclone have different dependence profiles, based on healthcare professionals' reports, and to identify various consumer dependence profiles among zolpidem users and among zopiclone users. Dependence in reports was assessed using the EGAP scale; a scale developed using the DSM diagnostic dependence criteria. RESULTS: The comparison of dependence profiles for zolpidem and zopiclone showed differences both in total EGAP score and EGAP item positivity. The descriptive analysis showed that EGAP scores were higher for zolpidem than for zopiclone, suggesting more severe problematic consumption with zolpidem. For zolpidem 2 subpopulations of consumers were identified, with one subpopulation's consumption being more severe than the other, with a significantly higher total EGAP score and more harmful consequences. No subpopulation was highlighted for zopiclone. CONCLUSION: These results were in favour of a higher prevalence of physical and compulsive signs of dependence and of harmful consequences of dependence, with zolpidem than with zopiclone.

Many studies were conducted to assess the benefit/risk ratio of EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide) in France before it was authorized for use outside the hospital setting in 2009. The main objective of this project is to evaluate the effects sought and felt by children when EMONO is used in paediatric dentistry. The secondary objectives are to (i) evaluate the appreciation of EMONO by the children, (ii) characterize children who experience both analgesia and anxiolysis, (iii) evaluate children’s appetite for EMONO and characterize children with a high appetite and (iv) evaluate the impact of the difference in practice among the French dental service university hospitals on anxiety. The maintenance of a framework for the safe use of this drug, whose place in dental care is fundamental, is essential. Twelve of the 16 French dental service university hospitals agreed to participate in this study. MEOPAeDent is an observational, descriptive, transversal study that aims to evaluate the effects sought and felt by children when EMONO is used in paediatric dentistry. Subjects requiring dental care under EMONO are recruited by 12 French dental service university hospitals. Patients aged from 3 to 15 years are recruited for the study when they visit a dental service of a French university hospital requiring dental care under EMONO. The investigator collects the necessary data from the child’s medical records, from his own observations and from questions posed to the child and his/her parents. A survey is completed at the first and final sessions of dental care under EMONO. This study will provide an evaluation of the effects of EMONO on the French paediatric population in need of dental care as well as evaluate the appetite for the use of this substance. The results will first be used to provide additional data that is essential to monitor the use of a product with an authorization to use it outside of hospitals from 2009 in France, confirm its safety for use and justify its framework of application. ClinicalTrials.gov ID: NCT03453411 registered 2 March 2018.

IntroductionAlthough preoxygenation and airway management respond to precise algorithms, difficult intubation (DI) remains a daily challenge in intensive care units and in the operating rooms because of its frequent complications, including hypoxaemia. To prevent desaturation during DI, high-flow oxygenation by nasal cannula (HFNC) could prove beneficial. Indeed, contrary to standard preoxygenation device, it can be held in place throughout the intubation trying to perform apnoeic oxygenation during DI. Hence, recent guidelines recommend HFNC during DI, but its relevance has never been evaluated in this setting in a large randomised study until now.Methods and analysisThe PREOPTIDAM trial is a prospective, single-centre, randomised, controlled study in Nantes University Hospital. In anticipated DI, we hypothesised that HFNC can decrease the incidence of desaturation ≤94% or face mask ventilation from 16% to 4% compared with standard device. Using a two-sided t-test with a first species risk of 5% and 80% power, a total of 186 patients will be included. Using a computer-generated randomisation, with a 1:1 allocation ratio, patients will be randomised to HFNC or face mask preoxygenation. Randomisation will be stratified on intubation sequence: Rapid sequence intubation or awake fibreoptic intubation. The primary objective is to determine whether HFNC is more efficient than standard oxygenation techniques to prevent desaturation ≤94% or face mask ventilation during DI. Intent-to-treat and per-protocol analysis are planned for the primary outcome.Ethics and disseminationThe study project has been approved by an independent ethics committee. Written informed consent will be obtained before study inclusion. Participant recruitment begins in September 2018. Results will be submitted to international peer-reviewed medical journals.Trial registration numberNCT03604120.

Importance Fluid therapy is an important component of care for patients with traumatic brain injury, but whether it modulates clinical outcomes remains unclear. Objective To determine whether continuous infusion of hypertonic saline solution improves neurological outcome at 6 months in patients with traumatic brain injury. Design, Setting, and Participants Multicenter randomized clinical trial conducted in 9 intensive care units in France, including 370 patients with moderate to severe traumatic brain injury who were recruited from October 2017 to August 2019. Follow-up was completed in February 2020. Interventions Adult patients with moderate to severe traumatic brain injury were randomly assigned to receive continuous infusion of 20% hypertonic saline solution plus standard care (n = 185) or standard care alone (controls; n = 185). The 20% hypertonic saline solution was administered for 48 hours or longer if patients remained at risk of intracranial hypertension. Main Outcomes and Measures The primary outcome was Extended Glasgow Outcome Scale (GOS-E) score (range, 1-8, with lower scores indicating worse functional outcome) at 6 months, obtained centrally by blinded assessors and analyzed with ordinal logistic regression adjusted for prespecified prognostic factors (with a common odds ratio [OR] >1.0 favoring intervention). There were 12 secondary outcomes measured at multiple time points, including development of intracranial hypertension and 6-month mortality. Results Among 370 patients who were randomized (median age, 44 [interquartile range, 27-59] years; 77 [20.2%] women), 359 (97%) completed the trial. The adjusted common OR for the GOS-E score at 6 months was 1.02 (95% CI, 0.71-1.47;P = .92). Of the 12 secondary outcomes, 10 were not significantly different. Intracranial hypertension developed in 62 (33.7%) patients in the intervention group and 66 (36.3%) patients in the control group (absolute difference, −2.6% [95% CI, −12.3% to 7.2%]; OR, 0.80 [95% CI, 0.51-1.26]). There was no significant difference in 6-month mortality (29 [15.9%] in the intervention group vs 37 [20.8%] in the control group; absolute difference, −4.9% [95% CI, −12.8% to 3.1%]; hazard ratio, 0.79 [95% CI, 0.48-1.28]). Conclusions and Relevance Among patients with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline compared with standard care did not result in a significantly better neurological status at 6 months. However, confidence intervals for the findings were wide, and the study may have had limited power to detect a clinically important difference. Trial Registration ClinicalTrials.gov Identifier:NCT03143751

Introduction Le zolpidem est un des medicaments hypnotiques les plus prescrits en France et son potentiel d’abus et de dependance a ete montre dans plusieurs etudes. En janvier 2017, une information a ete communiquee aux medecins sur l’obligation a partir d’avril 2017 de prescription du zolpidem sur ordonnance securisee. L’etude ZORRO (ZOlpidem et Renforcement de la Reglementation des Ordonnances) a ete mise en place afin d’evaluer l’impact de ce changement reglementaire a partir de l’analyse de donnees de l’Assurance maladie et a partir d’une etude de terrain. L’etude presentee ici est une partie de l’etude de terrain dont l’objectif etait d’evaluer la perception du changement reglementaire et l’impact sur la prescription de medicaments hypnotiques en medecine generale. Methodes Une etude descriptive a ete realisee parmi des medecins generalistes tires au sort. Les donnees ont ete recueillies a partir d’un questionnaire evaluant la perception du changement reglementaire, la strategie therapeutique pour les patients deja traites par zolpidem (et si cette strategie dependait de caracteristiques individuelles du patient) et les criteres pris en compte pour un eventuel choix de remplacement du zolpidem par un autre medicament. Resultats Au total, 206 medecins generalistes ont ete inclus. Les principaux resultats etaient que plus de la moitie des medecins generalistes (55 %) ont rapporte avoir percu le changement reglementaire comme une contrainte supplementaire pour la prescription. Cependant, une majorite de medecins (61 %) ont egalement declare considerer le changement comme une aide pour proposer/justifier un arret du zolpidem ou des hypnotiques en general. La strategie therapeutique la plus frequemment rapportee etait le remplacement du zolpidem par un autre medicament hypnotique (36 %). Cependant, la poursuite du traitement par zolpidem etait egalement frequemment citee (27 %). Les principaux criteres pour le choix d’un medicament de remplacement etaient les parametres pharmacocinetiques (50 %) et l’indication d’hypnotique (37 %). Discussion Le changement reglementaire a ete percu par les medecins generalistes comme une contrainte supplementaire pour la prescription mais aussi comme un levier pour initier un arret du zolpidem. Un impact sur la strategie therapeutique des medecins a egalement ete mis en evidence.

Introduction Ces dernieres annees, le zolpidem a ete le medicament hypnotique le plus prescrit en France et a egalement fait l’objet de multiples rapports de mesusage, d’abus et de dependance. Devant ces risques, les medecins ont ete informes en janvier 2017 qu’a partir d’avril 2017 la prescription du zolpidem devait obligatoirement etre realisee sur ordonnance securisee. L’etude ZORRO (ZOlpidem et Renforcement de la Reglementation des Ordonnances) a ete mise en place pour evaluer l’impact global du changement reglementaire a partir d’une analyse de donnees de l’Assurance maladie et a partir d’une etude de terrain. L’objectif de l’etude presentee ici etait d’evaluer l’impact de la mesure sur la prescription des medicaments sedatifs par l’analyse de trajectoires de traitement et d’etudier les facteurs associes a ces trajectoires a partir de donnees de l’Assurance maladie. Methodes Nous avons realise une etude de cohorte historique a partir des donnees de l’echantillon generaliste de beneficiaires (EGB, echantillon permanent du systeme national des donnees de sante [SNDS]). Tous les patients consideres comme consommateurs chroniques de zolpidem avant la mesure (au moins un remboursement pour du zolpidem dans les 3 mois consecutifs : octobre, novembre et decembre 2016) ont ete inclus dans l’etude. Nous avons etudie les remboursements de zolpidem, zopiclone, benzodiazepines et antihistaminiques jusqu’a 2 ans apres la mesure (de janvier 2017 a decembre 2018). Une analyse de sequences a ete realisee a partir du package R TraMineR et les clusters de sequences ont ete identifies a partir d’une classification ascendante hierarchique. Resultats Au total, 2502 trajectoires de traitement ont ete analysees. Quatre clusters de trajectoires de traitement ont ete mis en evidence : poursuite du zolpidem (42 %), arret des traitements hypnotiques/sedatifs (31 %), remplacement par de la zopiclone (21 %) et remplacement par des benzodiazepines hypnotiques (6 %). La benzodiazepine hypnotique la plus frequemment prescrite etait le lormetazepam. Des facteurs individuels ont ete identifies comme associes a ces clusters (âge et sexe). Discussion Le changement reglementaire a eu un impact important sur la prescription du zolpidem mais aussi plus largement sur la prescription des medicaments hypnotiques/sedatifs en general.

Importance Unhealthy alcohol use can lead to agitation in the intensive care unit (ICU). Objective To assess whether high-dose baclofen reduces agitation-related events compared with placebo in patients with unhealthy alcohol use receiving mechanical ventilation. Design, settings, and participants This phase 3, double-blind, placebo-controlled, randomized clinical trial conducted in 18 ICUs in France recruited adults receiving mechanical ventilation who met criteria for unhealthy alcohol use. Patients were enrolled from June 2016 to February 2018; the last follow-up was in May 2019. Interventions Baclofen (n = 159), adjusted from 50 to 150 mg per day based on estimated glomerular filtration rate, or placebo (n = 155) during mechanical ventilation up to a maximum of 15 days before gradual dose reduction over 3 to 6 days. Main outcomes and measures The primary end point was the percentage of patients with at least 1 agitation-related event over the treatment period. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and 28-day mortality. Results Among 314 patients who were randomized (mean age, 57 years; 60 [17.2%] women), 313 (99.7%) completed the trial. There was a statistically significant decrease in the percentage of patients who experienced at least 1 agitation-related event in the baclofen group vs the placebo group (31 [19.7%] vs 46 [29.7%]; difference, -9.93% [95% CI, -19.45% to -0.42%]; adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]). Of 18 prespecified secondary end points, 14 were not significantly different. Compared with the placebo group, the baclofen group had a significantly longer median length of mechanical ventilation (9 vs 8 days; difference, 2.00 [95% CI, 0.00-3.00]; hazard ratio [HR] for extubation, 0.76 [95% CI, 0.60-0.97]) and stay in the ICU (14 vs 11 days; difference, 2.00 [95% CI, 0.00-4.00]; HR for discharge, 0.70 [95% CI, 0.54-0.90]). At 28 days, there was no significant difference in mortality in the baclofen vs placebo group (25.3% vs 21.6%; adjusted odds ratio, 1.24 [95% CI, 0.72-2.13]). Delayed awakening (no eye opening at 72 hours after cessation of sedatives and analgesics) occurred in 14 patients (8.9%) in the baclofen group vs 3 (1.9%) in the placebo group. Conclusions and relevance Among patients with unhealthy alcohol use receiving mechanical ventilation, treatment with high-dose baclofen, compared with placebo, resulted in a statistically significant reduction in agitation-related events. However, considering the modest effect and the totality of findings for the secondary end points and adverse events, further research is needed to determine the possible role of baclofen in this setting and to potentially optimize dosing. Trial registration ClinicalTrials.gov Identifier: NCT02723383.

Background: Non-invasive ventilation (NIV) is the gold standard for preoxygenation in obese patients. In this population, high-flow nasal cannulae (HFNC) before and during intubation extends apnoea time without desaturation, possibly through apnoeic oxygenation. No randomised study comparing HFNC with NIV is available. Methods: The PREOPTIPOP study is a randomised, single-centre, open-labelled, controlled trial including obese patients requiring intubation before scheduled surgery. Patients were randomised to receive preoxygenation by HFNC or NIV. HFNC was maintained throughout intubation whereas NIV was removed to perform laryngoscopy. The study was designed to assess the superiority of HNFC. The primary outcome was the lowest level of end-tidal oxygen concentration (EtO2) within two minutes after intubation. Secondary outcomes included drop in pulse oximetry and complications related to intubation. Main findings: A total of 100 patients were randomised. The intent-to-treat analysis found median [IQR] lowest EtO2 of 76% [66-82] for HFNC and 88% [82-90] for NIV (mean difference -12·1 [-15·1 to -8·5], p

WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Craniotomy for brain tumor displays significant morbidity and mortality, and no score is available to discriminate high-risk patients. Our objective was to validate a prediction score for postoperative neurosurgical complications in this setting.Creation of a score in a learning cohort from a prospective specific database of 1,094 patients undergoing elective brain tumor craniotomy in one center from 2008 to 2012. The validation cohort was validated in a prospective multicenter independent cohort of 830 patients from 2013 to 2015 in six university hospitals in France. The primary outcome variable was postoperative neurologic complications requiring in-intensive care unit management (intracranial hypertension, intracranial bleeding, status epilepticus, respiratory failure, impaired consciousness, unexpected motor deficit). The least absolute shrinkage and selection operator method was used for potential risk factor selection with logistic regression.Severe complications occurred in 125 (11.4%) and 90 (10.8%) patients in the learning and validation cohorts, respectively. The independent risk factors for severe complications were related to the patient (Glasgow Coma Score before surgery at or below 14, history of brain tumor surgery), tumor characteristics (greatest diameter, cerebral midline shift at least 3 mm), and perioperative management (transfusion of blood products, maximum and minimal systolic arterial pressure, duration of surgery). The positive predictive value of the score at or below 3% was 12.1%, and the negative predictive value was 100% in the learning cohort. In-intensive care unit mortality was observed in eight (0.7%) and six (0.7%) patients in the learning and validation cohorts, respectively.The validation of prediction scores is the first step toward on-demand intensive care unit admission. Further research is needed to improve the score's performance before routine use.

International audience; INTRODUCTION: Acute respiratory distress syndrome often requires invasive mechanical ventilation, with both mortality and mechanical ventilation duration as outcomes of interest. The concept of ventilator-free days has been proposed as an outcome combining these two outcomes. Here we analyzed the construction of the ventilator-free day outcome and provided a hypothetical scenario to alert physicians that such an outcome can lead to misleading interpretations. METHODS: We proposed the isoventilator-free day curve concept and, using an analytical development, illustrated how a median ventilator-free day value can actually result from very different combinations of death rates and mechanical ventilation durations. We also used a hypothetical example to compare the Student t test, Wilcoxon rank-sum test, and Gray test (which accounts for death as a competing event with extubation) in comparing exposition to mechanical ventilation. RESULTS: A median ventilator-free day value of 10 days may mean that 10% of the patients died while survivors were ventilated during a median of 14 days or that 40% died while survivors were ventilated during a median of 5 days. Changing the time horizon affected the Student t test but not the Wilcoxon rank-sum result. The Gray test was more relevant than both the Student t test and Wilcoxon rank-sum test in identifying differences in groups showing highly different mechanical ventilation duration, despite equal median ventilator-free days. This approach was also illustrated using real data. CONCLUSIONS: Use of ventilator-free days as an outcome appears to have many drawbacks. Suitable methods of analyzing time to extubation should be preferred.

We assessed outcomes in brain-injured patients after implementation of a multi-faceted approach to reduce respiratory complications in intensive care units. Prospective nationwide before–after trial. Consecutive adults with acute brain injury requiring mechanical ventilation for ≥24 h in 20 French intensive care units (ICUs) were included. The management of invasive ventilation in brain-injured patients admitted between 1 July 2013 and 31 October 2013 (4 months) was monitored and analysed. After the baseline period (1 November 2013–31 December 2013), ventilator settings and decision to extubate were selected as targets to hasten weaning from invasive ventilation. During the intervention period, low tidal volume (≤7 ml/kg), moderate positive end-expiratory pressure (PEEP, 6–8 cm H2O) and an early extubation protocol were recommended. The primary endpoint was the number of days free of invasive ventilation at day 90. Comparisons were performed between the two periods and between the compliant and non-compliant groups. A total of 744 patients from 20 ICUs were included (391 pre-intervention; 353 intervention). No difference in the number of invasive ventilation-free days at day 90 was observed between the two periods [71 (0–80) vs. 67 (0–80) days; P = 0.746]. Compliance with the complete set of recommendations increased from 8 (2%) to 52 (15%) patients after the intervention (P

Introduction A l’ere de la medecine 4P, les patients peuvent participer a leur prise en charge a l’aide notamment d’outils pronostiques. Le groupe TRIPOD a publie en 2015 des recommandations pour l’elaboration de ces outils pronostiques. Leur developpement doit s’appuyer sur une selection de predicteurs combines dans une approche multivariee a partir d’un echantillon d’apprentissage. Leur performances predictives (globales, discrimination ou/et calibration) doivent etre validees de maniere interne (« bootstrapping », « cross-validation », « splitting », etc.) et/ou de maniere externe (population independante). En reanimation neurologique (traumatismes crâniens severes (TC), accidents vasculaires cerebraux (AVC), etc.), le risque d’evolution vers un handicap severe, un etat vegetatif ou le deces est eleve. Chez ces patients jeunes, de nombreux outils pronostiques ont deja ete proposes afin d’objectiver le devenir et d’orienter le niveau des soins. Nous avons mene une revue systematique pour en evaluer la qualite methodologique et son evolution apres les recommandations du TRIPOD. Methodes Nous avons suivi les recommandations CHARMS pour les revues systematiques de scores predictifs. Nos criteres d’inclusion portaient sur les etudes developpant ou validant un modele pronostiquant la mortalite ou un critere de jugement de la recuperation neurologique de patients adultes atteints de TC ou AVC hemorragique en service de reanimation. Les bases de donnees consultees etaient Medline, Embase, Web of Science et Cochrane. Apres selection sur titres et abstracts, les articles eligibles etaient analyses en double lecture, en aveugle. Resultats Au total, 7341 references ont ete identifiees. Parmi les 367 eligibles sur titres et abstracts, nous en avons retenues 292. Parmi celles-la, 160 (55 %) ont ete exclues : 100 (63 %) etudiaient un marqueur seul sans volonte de developper un score multivarie, 60 (37 %) developpaient un score multivarie sans rapporter leurs performances pronostiques. Parmi les 132 etudes incluses, 52 etudes (40 %) developpaient un outil multivarie en ne presentant que les performances pronostiques apparentes (obtenues sur l’echantillon d’apprentissage) ; 25 (19 %) developpaient et validaient leur outil, dont 7 (25 %) rapportaient la performance globale (Brier score, R2), 20 (71 %) calculaient un AUC et 12 (43 %) presentaient une methode de calibration (graphique ou test statistique) ; 55 (42 %) etudes validaient en externe un outil deja existant, dont 5 (9 %) presentaient la performance globale, 52 (95 %) l’AUC et 31 (56 %) une methode de calibration. Conclusion Dans le contexte de la neuro-reanimation, seuls un tiers des articles publies suivent les bonnes pratiques d’elaboration d’un outil pronostique (developpement et validation), telles que le recommande le TRIPOD. On constate egalement une heterogeneite dans le rapport des indicateurs de performance, avec le rapport preferentiel de l’AUC qui n’est pas le meilleur indicateur de prediction individuelle. La publication de ces recommandations n’a pas permis l’amelioration des travaux publies, ce qui illustre un manque de rigueur ou une meconnaissance des approches methodologiques. Publiees dans des revues medicales, elles avaient pour objectif de democratiser les bonnes pratiques d’elaboration et d’usage des outils. Cet effort de dissemination doit etre poursuivi, ce d’autant plus que de nouvelles approches methodologiques continues a etre nouvellement proposees.

Mechanical ventilation is associated with morbidity in patients with brain injury.This study aims to assess the effectiveness of an extubation readiness bundle to decrease ventilator time in patients with brain injury.Before-after design in two intensive care units (ICUs) in one university hospital. Brain-injured patients ventilated more than 24 hours were evaluated during two phases (a 3-yr control phase followed by a 22-mo intervention phase). Bundle components were protective ventilation, early enteral nutrition, standardization of antibiotherapy for hospital-acquired pneumonia, and systematic approach to extubation. The primary endpoint was the duration of mechanical ventilation.A total of 299 and 200 patients, respectively, were analyzed in the control and the intervention phases of this before-after study. The intervention phase was associated with lower tidal volume (P0.01), higher positive end-expiratory pressure (P0.01), and higher enteral intake in the first 7 days (P = 0.01). The duration of mechanical ventilation was 14.9 ± 11.7 days in the control phase and 12.6 ± 10.3 days in the intervention phase (P = 0.02). The hazard ratio for extubation was 1.28 (95% confidence interval [CI], 1.04-1.57; P = 0.02) in the intervention phase. Adjusted hazard ratio was 1.40 (95% CI, 1.12-1.76; P0.01) in multivariate analysis and 1.34 (95% CI, 1.03-1.74; P = 0.02) in propensity score-adjusted analysis. ICU-free days at Day 90 increased from 50 ± 33 in the control phase to 57 ± 29 in the intervention phase (P0.01). Mortality at Day 90 was 28.4% in the control phase and 23.5% in the intervention phase (P = 0.22).The implementation of an evidence-based extubation readiness bundle was associated with a reduction in the duration of ventilation in patients with brain injury.

Zolpidem and zopiclone are two widely used non-benzodiazepine hypnotics whose usage seems to be associated to pharmacodependence. However, to our knowledge, there has as yet been no published epidemiological study which has compared their abuse or dependence potential. We used a pharmacoepidemiological approach to identify and characterise zolpidem and zopiclone users in real life situations. Regular users of zolpidem or zopiclone were identified in the database of a French regional health insurance organisation. A latent class analysis (LCA) was used to identify different subgroups of users of these two hypnotics. The study cohort comprised 25,168 patients who regularly used zolpidem and 21,860 who regularly used zopiclone. The results of the latent class analysis, which enables subgroups with similar patterns of response to be identified, revealed four clinical subtypes of users of zolpidem: non-problematic users, users with associations with hypnotics/anxiolytics or with associated mental disorders, and problematic users. Only three subgroups were identified for zopiclone, and LCA did not discriminate a special class of problematic users for this drug. Our analysis indicates that there is a subclass of zolpidem user suggestive of abuse; this was not the case for zopiclone. This methodology is very interesting because it allows analysis of databases and determination of a specific signature of drugs potentially leading to abuse or dependence.

Background Patients with brain injury are at high risk of extubation failure. Methods We conducted a prospective observational cohort study in four intensive care units of three university hospitals. The aim of the study was to create a score that could predict extubation success in patients with brain injury. Results A total of 437 consecutive patients with brain injury were included, and 338 patients (77.3%) displayed successful extubation. In the multivariate analysis, four features were associated with success the day of extubation: age less than 40 yr, visual pursuit, swallowing attempts, and a Glasgow coma score greater than 10. In the score, each item counted as one. A score of 3 or greater was associated with 90% extubation success. The area under the receiver–operator curve was 0.75 (95% CI, 0.69 to 0.81). After internal validation by bootstrap, the area under the receiver–operator curve was 0.73 (95% CI, 0.68 to 0.79). Extubation success was significantly associated with shorter duration of mechanical ventilation (11 [95% CI, 5 to 17 days] vs. 22 days [95% CI, 13 to 29 days]; P < 0.0001), shorter intensive care unit length of stay (15 [95% CI, 9 to 23 days] vs. 27 days [95% CI, 21 to 36 days]; P < 0.0001), and lower in-intensive care unit mortality (4 [1.2%] vs. 11 [11.1%]; P < 0.0001). Conclusions Our score exploring both airway functions and neurologic status may increase the probability of successful extubation in patients with severe brain injury.

IntroductionTraumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention and the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long-term outcomes of patients with TBI is uncertain. The aim of the COBI study (number clinicaltrial.gov 03143751, pre-results stage) is to assess the efficiency and the safety of continuous hyperosmolar therapy in patients with TBI.Methods and analysisThe COBI (COntinuous hyperosmolar therapy in traumatic Brain-Injured patients) trial is a multicentre, randomised, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalised in intensive care unit with a TBI (Glasgow Coma Scale ≤12 and abnormal brain CT scan) are randomised in the first 24 hours following trauma to standard care or continuous hyperosmolar therapy (20% NaCl) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to prevent ICH. The primary outcome is the score on the Extended Glasgow Outcome Scale at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common OR.Ethics and disseminationThe COBI trial protocol has been approved by the ethics committee of Paris Ile de France VIII and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The COBI trial is the first randomised controlled trial powered to investigate whether continuous hyperosmolar therapy in patients with TBI improve long-term recovery.Trial registration numberTrial registration number isNCT03143751.

Background The Hirschsprung’s disease Anorectal malformation QoL questionnaire (HAQL) is a disease-specific quality of life (QoL) questionnaire for patients with Hirschsprung’s disease (HD) or anorectal malformations (ARM). It was originally proposed in Dutch and is currently being translated into other languages to obtain an internationally standardized instrument. In this work we validate a French adaptation of the HAQL for adolescents and adults. Methods The questionnaires were translated into French and sent to patients aged 12 years and older, followed for HD or ARM at three French university hospitals. Questionnaires were sent to 147 adolescents and 188 adults. The psychometric properties of the questionnaires were analyzed in terms of reliability and validity. Results The original HAQL structure was not satisfactory. A new structure was proposed, while aiming to remain close to the original structure. The proposed structure has acceptable reliability and validity properties and reflects both physical, as well as psychosocial aspects. Conclusions A French version of the HAQL questionnaire for adults and adolescents is ready for use in France. In particular the score could discriminate between degrees of clinical status based on the Krickenbeck consensus, which can aid clinicians to inform patients about physical and psychosocial challenges they may expect. Electronic supplementary material The online version of this article (doi:10.1186/s12955-017-0599-7) contains supplementary material, which is available to authorized users.

Background: The links between attention deficit hyperactivity disorder (ADHD) and substance use disorders have been the subject of numerous papers. Few studies, however, have focused specifically on the relationship between ADHD and behavioural addictions. The aim of this study was to (i) examine the frequency of pathological and at-risk gamblers having a previous history of ADHD; (ii) give details of the characteristics of this association, and (iii) identify risk factors for a history of ADHD. Methods: 84 pathological and at-risk gamblers were assessed about socio-demographic, gambling and clinical characteristics. Results: Over 25% of the subjects had a history of ADHD. They were characterized as having more severe gambling problems and a higher level of gambling-related cognitions, a higher frequency of psychiatric comorbidities and an elevated risk of suicide. Finally, they differed in their level and type of impulsivity. Among pathological and at-risk gamblers, a high level of impulsivity, or a history of anxiety disorders, constitute risk factors for a comorbidity with ADHD. Conclusion: The association ‘ADHD-problem gambling’ therefore appears to be not only frequent, but also linked to factors that are known to worsen the prognosis. Researching this relationship is therefore important to adapt strategies for effective future therapy.