Trauma-related mortality of patients with severe psychiatric disorders: population-based study from the French national hospital database.

BACKGROUND: Most research on mortality in people with severe psychiatric disorders has focused on natural causes of death. Little is known about trauma-related mortality, although bipolar disorder and schizophrenia have been associated with increased risk of self-administered injury and road accidents. AIMS: To determine if 30-day in-patient mortality from traumatic injury was increased in people with bipolar disorder and schizophrenia compared with those without psychiatric disorders. METHOD: A French national 2016 database of 144 058 hospital admissions for trauma was explored. Patients with bipolar disorder and schizophrenia were selected and matched with mentally healthy controls in a 1:3 ratio according to age, gender, social deprivation and region of residence. We collected the following data: sociodemographic characteristics, comorbidities, trauma severity characteristics and trauma circumstances. Study outcome was 30-day in-patient mortality. RESULTS: The study included 1059 people with bipolar disorder, 1575 people with schizophrenia and their respective controls (n = 3177 and n = 4725). The 30-day mortality was 5.7% in bipolar disorder, 5.1% in schizophrenia and 3.3 and 3.8% in the controls, respectively. Only bipolar disorder was associated with increased mortality in univariate analyses. This association remained significant after adjustment for sociodemographic characteristics and comorbidities but not after adjustment for trauma severity. Self-administered injuries were associated with increased mortality independent of the presence of a psychiatric diagnosis. CONCLUSIONS: Patients with bipolar disorder are at higher risk of 30-day mortality, probably through increased trauma severity. A self-administered injury is predictive of a poor survival prognosis regardless of psychiatric diagnosis.

Methylphenidate: Gender trends in adult and pediatric populations over a 7year period.

OBJECTIVE: Methylphenidate (MPH) is a prescription-stimulant medication which is authorized in France for two indications: attention-deficit hyperactivity disorder in children (aged≥6years) and narcolepsy in cases where modafinil is ineffective (for children and adults). MPH use has increased worldwide in the past 2 decades in children and adults. Different pharmacoepidemiological Europeans studies have described MPH patterns of use. To our knowledge, few pharmacoepidemiological studies have described MPH patterns of use in France. METHODS: In this context, we have performed a study on regional reimbursement database (PACA-Corse area, covering approximately 4 millions inhabitants). The first part of the study analyzed the evolution of MPH users characteristic's yearly (grouped by age and gender) over a 7year period (2005-2011). In order to better characterize patterns of MPH use in adults, a specific analyze has been performed in the second part on MPH adult users in 2011 with a gender descriptive approach. RESULTS: During the 7year period, MPH dispensing grew from 0.28 to 0.68 patient per 1000. The proportion of adult patients rose from 14.8 to 25.7% (P<0.0001), with patients mainly aged 35-49years old. Gender differences in MPH users were noted between adults and children: the proportion of girls was less important in children than in adult (in 2011, 20.7% of girls among children vs 44.9% among adults). Moreover, the proportion of girls among children increased between 2005 to 2011 (15.1% of girls in 2005 versus 20.7% in 2011). Among adults, women were prescribed more antidepressants (41.5% versus 28.2%, P=0.003) and less opiate maintenance treatments (22.4% versus 31.9%, P=0.03) than men. Finally, 11% of men and 16.4% of women were over 50years old. CONCLUSION: MPH prescription greatly increased over7years, especially in adults. Moreover, in this population, patterns of MPH use differed with gender specificities. Such findings may increase clinical attention on monitoring MPH use in adults.

Patterns of Methylphenidate Use and Assessment of Its Abuse among the General Population and Individuals with Drug Dependence.

PURPOSE: The aim of this study was to describe the extent of methylphenidate (MPH) abuse and characterize its patterns by following several cases involving intravenous administration of crushed MPH tablets. METHODS: First, a drug reimbursement database (covering 4 million inhabitants) was explored to assess the magnitude of MPH abuse among the general population, and second, a specific study based on individuals with drug dependence was performed to describe abusers' characteristics (n = 64), patterns of abuse and clinical implications. RESULTS: From 2005 to 2011, the number of patients who were dispensed MPH at least once increased by 166%. The patients with 'deviant' patterns of MPH consumption were mainly male adults with opiate maintenance treatment reimbursements. MPH abusers had precarious living conditions. Half of them consumed MPH daily by intravenous route and reported amphetamine-like effects (cardiovascular events, weight loss, psychiatric adverse events). CONCLUSION: Given the increase of MPH use, it is important to warn the scientific community about possible MPH abuse, especially in individuals with drug dependence. This study has facilitated public health intervention and dissemination of information related to MPH abuse among health care professionals at local and national levels.

Triptans use and overuse: A pharmacoepidemiology study from the French health insurance system database covering 4.1 million people.

INTRODUCTION: The objective of this study was to estimate and to characterize the actual patterns of triptan use and overuse in France using a drug reimbursement database. METHODS: We included all people covered by the French General Health Insurance System (GHIS) from the Provence-Alpes-Côte-d'Azur (PACA) and Corsica administrative areas who had at least one dispensed dose of triptans between May 2010 and December 2011. All dispensed doses of triptans, migraine prophylactic treatment and psychotropic medications were extracted from the GHIS database. Triptan overuse was defined as triptan use >20 defined daily doses (DDD) per month on a regular basis for more than three consecutive months. Risk of overuse was assessed using logistic regression adjusted for gender and age. RESULTS: We included 99,540 patients who had at least one prescription of a triptan over the 20 months of the study. Among them, 2243 patients (2.3%) were identified as overusers and received 20.2% of the total DDD prescribed. Twelve percent of overusers and 6.9% of non-overusers were aged more than 65 years (OR: 1.81). Overusers did not have a greater number of prescribers and pharmacists than non-overusers. They were more frequently prescribed a prophylactic medication for migraine treatment (56.8% vs 35.9%, OR: 2.36), benzodiazepines (69.9% vs 54.7%, OR: 1.93) and antidepressants (49.4% vs 30.2%, OR: 2.33). CONCLUSIONS: This work suggests that triptan overuse may be due to insufficient prescriber awareness of appropriate prescribing. The off-label prescription of triptans among the elderly necessitates investigating their cardiovascular risk profile in this sub-group.

What strategy should France implement for H2020?

The initiation of Horizon 2020--the European Union's 8th Framework Programme for Research and Innovation, allotted a budget of 79 billion euros--provides an opportunity to review France's participation in previous Framework Programmes. Indeed, French participation does not match either its scientific importance or its financial investment. While France contributed 16.5 to 17% of the EU's 7th Framework Programme research budget, its return through the funding of coordinated projects in which French teams are participating stands at around 12.5 to 13%, a shortfall of 600 million euros. Although the situation depends on the type of activity, French participation in clinical research appears to be smaller than that of its neighbours, with fewer responses to European calls for proposals. While France has many assets, which include the assured funding of clinical research, structured thematic networks and the initiation of major national programmes, it suffers from the dilution of resources due to France's regional development policy, the lack of multidisciplinarity and the ignorance of both the medical and scientific community and the institutions to which they belong as to how Horizon 2020 actually works. We propose three types of strategy to encourage proposals for coordinated clinical research projects or projects involving French teams, and to help in the drawing up of applications: Broaden the vision of our children, students and colleagues, helping them to adapt to the globalisation of knowledge throughout their educational and professional lives. Recognise the value of European actions to influence the European landscape and change mentalities. Help and support project initiators by pooling skills within a limited number of expert centres designed to assist them in their funding application. • Broaden the vision of our children, students and colleagues, helping them to adapt to the globalisation of knowledge throughout their educational and professional lives. • Recognise the value of European actions to influence the European landscape and change mentalities. • Help and support project initiators by pooling skills within a limited number of expert centres designed to assist them in their funding application.

Information and communication on risks related to medications and proper use of medications for healthcare professionals and the general public: precautionary principle, risk management, communication during and in the absence of crisis situations.

Recent drug crises have highlighted the complexity, benefits and risks of medication communication. The difficulty of this communication is due to the diversity of the sources of information and the target audience, the credibility of spokespersons, the difficulty to communicate on scientific uncertainties and the precautionary principle, which is influenced by variable perceptions and tolerances of the risk. Globally, there is a lack of training in risk management with a tendency of modern society to refuse even the slightest risk. Communication on medications is subject to regulatory or legal requirements, often uses tools and messages that are not adapted to the target audience and is often based on a poor knowledge of communication techniques. In order to improve this situation, the available information must be coordinated by reinforcing the unique medication information website and by coordinating communication between authorities by means of a single spokesperson. A particular effort must be made in the field of training in the proper use and risk of medications for both the general population and patients but also for healthcare professionals, by setting up a unified academic on-line teaching platform for continuing medical education on medications and their proper use.

Pattern of infections in French and migrant homeless hospitalised at Marseille infectious disease units, France: A retrospective study, 2017-2018.

BACKGROUND: No research has been conducted on the clinical characteristics and outcomes of homeless patients (HP) hospitalized in Infectious Disease Units (IDU). METHODS: We conducted a retrospective survey among 98 HP and 98 non-HP admitted between 2017 and 2018 in several IDUs in Marseille, France. RESULTS: HP were more likely to be migrant, to report frequent alcohol consumption or illicit drug use, and to present with respiratory symptoms at admission compared to controls. The most common final diagnoses in HP were respiratory tract infections (other than pulmonary tuberculosis [PTB], 35.7%), sexually transmitted infections (20.4%), cutaneous and mucosal infections (19.4%) and tuberculosis (12.2%). Sexually transmitted infections and ectoparasite infestations were significantly more frequent in HP compared to controls. One HP died from pleural effusion as a complication of PTB. The surviving HP had a longer length of stay (LOS, average 11.6 ± 13.6 days, p < 0.0001) than controls; independent factors of increased LOS were tobacco use (p = 0.009), tuberculosis infection (p < 0.0001), urinary tract infection (p = 0.018) and bacteraemia (p = 0.018). After hospital discharge, attendance at subsequent planned consultations was significantly lower in HP (0.72 ± 1.25 times/persons) compared to controls (2.03 ± 2.2). CONCLUSIONS: We suggest that HP present specific demographic characteristics and patterns of infectious diseases compared to other patients and therefore require adapted management.

Impact of an awareness of the doctors treating on the decrease of the prescriptions of antipsychotics in the demented residents in Ehpad.

BACKGROUND: Despite the context of several national warnings, antipsychotics drugs are commonly used to treat behavioural and psychological symptoms in dementia (BPSD). AIM: To observe a decrease of antipsychotic drug prescription, in old NH (nursing homes) residents with dementia, after an awareness of their general practitioner. METHODS: Observational, prospective, multicenter study. The study population corresponds to NH residents with dementia, and antipsychotic drug consumption, in nursing homes volunteered to participate. Awareness-raising is carried out through information documents. The evaluation criteria is the proportion of residents under antipsychotics after sensitization. RESULTS: out of the 30 nursing homes included, 26.7% of the patients were prescribed at least one antipsychotic and 15% were both demented and under antipsychotics. A total of 317 residents with dementia and antipsychotics were included 15% of the total NH population. Psychotropic drug co-prescriptions was very frequent 43.2% also used benzodiazepines, 37.2% anxiolytics and 33.1% antidepressants. Agitation, aggressiveness, opposition to care and wandering were the most commonly BPSD encountered. After a first sensitization, we obtained a 15.5% decrease of antipsychotic prescriptions. CONCLUSION: A personalized sensitization towards GP allowed a reduction of antipsychotic drugs prescription in NH residents with dementia and BPSD.

Antidepressant adherence patterns in older patients: use of a clustering method on a prescription database.

According to the World Health Organization, depression will become the second most important cause of disability worldwide by 2020. Our objective was to identify patterns of adherence to antidepressant treatments in older patients using several indicators of adherence and to characterize these patterns in terms of medication exposure. We conducted a retrospective cohort study using the French National Health Insurance reimbursement database. Incident antidepressant users aged more than 65 were included from July 1, 2010, to June 30, 2011, and followed up for 18 months. Antidepressant and other psychotropic drugs (opioids, benzodiazepines, antipsychotics, anti-epileptics) were recorded. Adherence to antidepressant treatment was assessed by several measures including proportion of days covered, discontinuation periods, persistence of treatment, and doses dispensed. Patients were classified according to their adherence patterns using a mixed clustering method. We identified five groups according to antidepressant adherence. One group (n = 7505, 26.9%) was fully adherent with regard to guidelines on antidepressant use. Two patterns of nonadherent users were identified: irregular but persistent users (n = 5131, 18.4%) and regular but nonpersistent users (n = 9037, 32.4%). Serotonin reuptake inhibitors were the most frequently dispensed antidepressant class (70.6%), followed by other antidepressants (43.3%, mainly serotonin-norepinephrine reuptake inhibitors and tianeptine) and tricyclic antidepressants (TCAs) (13.4%). Nonadherent users more frequently had a dispensing of TCA, opioid, and anti-epileptic medication than adherent users. Health policies to improve adherence to antidepressant treatment may require better training of physicians and pharmacists, insisting on the important role of the continuation period of antidepressant treatment.

Increased serum levels of fractalkine and mobilisation of CD34+CD45- endothelial progenitor cells in systemic sclerosis.

BACKGROUND: The disruption of endothelial homeostasis is a major determinant in the pathogenesis of systemic sclerosis (SSc) and is reflected by soluble and cellular markers of activation, injury and repair. We aimed to provide a combined assessment of endothelial markers to delineate specific profiles associated with SSc disease and its severity. METHODS: We conducted an observational, single-centre study comprising 45 patients with SSc and 41 healthy control subjects. Flow cytometry was used to quantify circulating endothelial microparticles (EMPs) and CD34+ progenitor cell subsets. Colony-forming unit-endothelial cells (CFU-ECs) were counted by culture assay. Circulating endothelial cells were enumerated using anti-CD146-based immunomagnetic separation. Blood levels of endothelin-1, vascular endothelial growth factor (VEGF) and soluble fractalkine (s-Fractalkine) were evaluated by enzyme-linked immunosorbent assay. Disease-associated markers were identified using univariate, correlation and multivariate analyses. RESULTS: Enhanced numbers of EMPs, CFU-ECs and non-haematopoietic CD34+CD45- endothelial progenitor cells (EPCs) were observed in patients with SSc. Patients with SSc also displayed higher serum levels of VEGF, endothelin-1 and s-Fractalkine. s-Fractalkine levels positively correlated with CD34+CD45- EPC numbers. EMPs, s-Fractalkine and endothelin-1 were independent factors associated with SSc. Patients with high CD34+CD45- EPC numbers had lower forced vital capacity values. Elevated s-Fractalkine levels were associated with disease severity, a higher frequency of pulmonary fibrosis and altered carbon monoxide diffusion. CONCLUSIONS: This study identifies the mobilisation of CD34+CD45- EPCs and high levels of s-Fractalkine as specific features of SSc-associated vascular activation and disease severity. This signature may provide novel insights linking endothelial inflammation and defective repair processes in the pathogenesis of SSc.

Fetal megacystis: etiologies, management, and outcome according to the trimester.

OBJECTIVE: To describe the diagnostic criteria and outcome of fetal megacystis according to the gestational age at diagnosis. METHODS: A 7-year retrospective study was carried out from 2004 to 2011, including cases of megacystis referred to 2 prenatal fetal medicine units. The following data were collected and analyzed: maternal age, term at diagnosis (gestational weeks), ultrasonographic and magnetic resonance imaging data, karyotype, decision of the multidisciplinary prenatal team, fetopathology in cases of termination of pregnancy or fetal death, final diagnosis at birth after ultrasonography and voiding cystourethrography, and medical and surgical follow-up. RESULTS: Of the 69 fetuses included in this study, 82.6% were males; 26 were diagnosed during the first trimester, 21 during the second, and 22 during the third. During the first trimester, the main etiologies were urethral occlusions and prune-belly syndrome with poor fetal prognosis. Nineteen pregnancies (69%) were terminated for medical reasons including the association with other malformations, poor evolution, or miscarriage. Only 4 children were born alive. The main etiologies of megacystis discovered during the second and third trimesters were vesicoureteral reflux and urethral occlusion. Twenty of 22 fetuses (91%) were born alive when the fetal megacystis was discovered after 27 weeks of gestation. CONCLUSION: Antenatal discovery of megacystis is a complex and challenging prognostic situation. The prognosis depends on the gestational age at discovery. Megacystis is not always associated with obstruction. In a newborn with megacystis, bladder outlet obstruction has to be excluded. Optimal counseling of the involved parents requires a multidisciplinary approach.

OPPIDUM surveillance program: 20 years of information on drug abuse in France.

It is important to assess drug abuse liability in 'real life' using different surveillance systems. Some are based on specific population surveys, such as individuals with drug abuse or dependence, or under opiate maintenance treatment, because this population is very familiar with drugs and is more likely to divert or abuse them. In France, an original surveillance system based on this specific population and called 'Observation of illegal drugs and misuse of psychotropic medications (OPPIDUM) survey' was set up in 1990 as the first of its kind. The aim of this article is to describe this precursor of French drug abuse surveillance using different examples, to demonstrate its ability to effectively give health authorities and physicians interesting data on drug abuse. OPPIDUM is an annual, cross-sectional survey that anonymously collects information on abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. From 1990 to 2010, a total of 50,734 patients were included with descriptions of 102,631 psychoactive substance consumptions. These data have outlined emergent behaviors such as the misuse of buprenorphine by intravenous or nasal administration. It has contributed to assess abuse liability of emergent drugs such as clonazepam or methylphenidate. This surveillance system was also able to detect the decrease of flunitrazepam abuse following implementation of regulatory measures. OPPIDUM's twenty years of experience clearly demonstrate that collection of valid and useful data on drug abuse is possible and can provide helpful information for physicians and health authorities.

Obstetric outcome of women with in vitro fertilization pregnancies hospitalized for ovarian hyperstimulation syndrome: a case-control study.

OBJECTIVE: To evaluate the obstetric outcome of women with IVF pregnancies hospitalized for ovarian hyperstimulation syndrome (OHSS). DESIGN: A case-control study. SETTING: Department of Obstetrics-Gynecology and Reproductive Medicine. PATIENT(S): All IVF patients hospitalized for OHSS with a positive pregnancy test matched to an IVF pregnancy control group who did not develop OHSS. INTERVENTION(S): Retrospective study of all clinical and laboratory data. MAIN OUTCOME MEASURE(S): OHSS morbidity, early pregnancy outcome, and obstetric complications. RESULT(S): The incidence of OHSS requiring hospitalization was 1.14% among 3,504 IVF cycles. Forty patients (31 singletons, 8 twins, and 1 triplet) hospitalized for severe OHSS with a mean duration of hospitalization of 10.2 ± 7.2 days were compared with a control group of 80 IVF pregnancies (48 singletons, 15 twins, and 2 triplets). Early OHSS occurred in 22.5% of patients, and late OHSS in the remaining 77.5% patients. In the OHSS group, 10% had thromboembolic complications. The miscarriage rate was similar for the OHSS group and the control IVF group (17.5% vs. 16%). Concerning ongoing clinical pregnancies, pregnancy-induced hypertension (PIH) and preterm labor were significantly higher in the OHSS group (respectively, 21.2% vs. 9.2% and 36% vs. 10.7%). In the subgroup of singletons, PIH was significantly higher for OHSS pregnancies than for controls. CONCLUSION(S): Pregnancies after IVF and OHSS are associated with a greater risk of adverse obstetric outcome.