[Sentinel program: Example of suicide prevention for an agricultural population in Switzerland]. / Programme sentinelle : exemple de prévention du suicide auprès d'une population agricole en Suisse.

OBJECTIVES: In the field of suicide prevention, the identification of risk groups is important, as is the training of front-line workers, to raise awareness of suicide issues. Agricultural workers represent a group at high risk of suicidal behavior due to various factors (low income of farmers, work related to climatic conditions, social isolation, poor access to primary care). The main objective of this article is to present the implementation of prevention training in suicide prevention for a population of agricultural workers in two cantons of French-speaking Switzerland (Vaud and Neuchâtel) which represent a population of about 980,000 inhabitants. The second objective is to identify the experiences of the participants in this training and their expectations. METHODS: Suicide prevention training sessions are organized in collaboration with public health departments, agriculture departments and suicide prevention professionals. Each session is led by four trainers experienced in suicide prevention and belonging to the "Groupement Romand Prévention du Suicide" (GRPS) which manages the training and other training modules on this topic in French-speaking Switzerland. The GRPS guarantees the content of the training as well as the updating of scientific knowledge. The training model is based on a concept that alternates between brief theoretical contributions, exchanges between participants in plenary sessions and role playing in small groups. The training has two main objectives: on the one hand to work on the participants' representations of suicide and to modify their posture by training "sentinels", i.e. "peers" who can establish a link between suffering individuals and the available support resources. On the other hand, to give key messages: dare to talk about the suicidal question and to not remain alone with this. RESULTS: Between December 2016 and May 2018, nine sessions were held in the two cantons of Vaud and Neuchâtel with a total of 220 participants. The sessions took place in agricultural schools or buildings related to agriculture. Invited to express themselves on the theme of suicide as well as on the concept of training, agricultural workers all verbalized the importance of this issue and were often very moved when the subject was discussed. The topics addressed by the participants were the taboo aspect of the subject, the difficulty of talking about it and the need to be able to address the subject (breaking the isolation). Participants also highlighted the need for peers to act as relays for help. CONCLUSIONS: The sessions were highly appreciated by the organizers concerned, particularly by the public health and agricultural departments. Participants expressed their satisfaction at the opportunity to express their views on this subject, regretting that such initiatives are all too rare. Although studies highlight the difficulty of emotional expression in the agricultural field, we observed on the contrary a great facility of the participants to express their emotions in relation to the suicidal theme. We have highlighted that the issue of suicide in this population is linked to several causal factors, as is the suicidal issue more broadly. Factors specific to this population emerged from the sessions, including working conditions and difficulties related to the family environment of farmers. There is a need to strengthen suicide prevention with training programs among the agricultural population. We also note the major importance of improving access to mental health care which is often very deficient in rural areas.

Gold-based nanospheres and nanorods particles used as theranostic agents: An in vitro and in vivo toxicology studies.

The adverse effect of gold-based nanoparticles is still an open question since it depends on several factors as shape, surface charge or route of administration. In this study, we investigated the influence of shape and human serum albumin (HSA) coating on the adverse effects of spherical (AuNP) and nanorods (AuNR) gold-based particles. F C3H (fibroblast) and HTC (hepatocellular carcinoma) cell lines both from liver were exposed to 25, 75 and 125 µg mL-1, which correspond to 109 NP mL-1. For in vivo studies, Wistar rats received these materials by oral administration in doses of 10 µg kg-1 or 40 µg kg-1. Systemic toxicity was verified after 24 h and 48 h by morphological analysis, blood parameters and myeloperoxidase enzyme activity. Our results revealed that HSA corona does not influence totally the pathway of interactions between AuNP and AuNR. In vitro results evidenced that AuNP can decrease in at least 50% viability of F C3H and cell adhesion of HTC, but corona significantly overcomes these effects. No differences between shape or corona were observed in function of cell lines. In vivo studies showed that 40 µg kg-1 of AuNP-HSA caused an enhancement of the myeloperoxidase response indicating inflammatory processes. An increase from 40% to 80% on alkaline phosphatase levels were found for all groups. Our findings suggested that gold-based particles coated or not with HSA do not cause expressive adverse effects on in vitro or in vivo systems, and their oral administration cannot cause a systemic effect in the experimental conditions used here.

[Study of algorithms to identify schizophrenia in the SNIIRAM database conducted by the REDSIAM network]. / Étude des algorithmes de repérage de la schizophrénie dans le Sniiram par le réseau REDSIAM.

BACKGROUND: The aim of the REDSIAM network is to foster communication between users of French medico-administrative databases and to validate and promote analysis methods suitable for the data. Within this network, the working group "Mental and behavioral disorders" took an interest in algorithms to identify adult schizophrenia in the SNIIRAM database and inventoried identification criteria for patients with schizophrenia in these databases. METHODS: The methodology was based on interviews with nine experts in schizophrenia concerning the procedures they use to identify patients with schizophrenia disorders in databases. The interviews were based on a questionnaire and conducted by telephone. RESULTS: The synthesis of the interviews showed that the SNIIRAM contains various tables which allow coders to identify patients suffering from schizophrenia: chronic disease status, drugs and hospitalizations. Taken separately, these criteria were not sufficient to recognize patients with schizophrenia, an algorithm should be based on all of them. Apparently, only one-third of people living with schizophrenia benefit from the longstanding disease status. Not all patients are hospitalized, and coding for diagnoses at the hospitalization, notably for short stays in medicine, surgery or obstetrics departments, is not exhaustive. As for treatment with antipsychotics, it is not specific enough as such treatments are also prescribed to patients with bipolar disorders, or even other disorders. It seems appropriate to combine these complementary criteria, while keeping in mind out-patient care (every year 80,000 patients are seen exclusively in an outpatient setting), even if these data are difficult to link with other information. Finally, the experts made three propositions for selection algorithms of patients with schizophrenia. CONCLUSION: Patients with schizophrenia can be relatively accurately identified using SNIIRAM data. Different combinations of the selected criteria must be used depending on the objectives and they must be related to an appropriate length of time.

Community-acquired Clostridium difficile infections.

OBJECTIVE: To describe the management and treatment of community-acquired C. difficile infections (CDI) and to evaluate family physicians' (FP) knowledge and practice. PATIENTS AND METHODS: Observational study from December 2013 to June 2014. All community-acquired CDI case patients diagnosed in the community or at the University Hospital of Nantes were prospectively included. A questionnaire was mailed to 150 FPs of the area of Nantes. RESULTS: A total of 27 community-acquired CDI case patients were included (incidence: 7.7 case patients/100,000 inhabitants). Mean age was higher among case patients diagnosed at hospital (69years) compared with those diagnosed in the community (44years). Fifteen patients were treated at home (55%) and 22 received a first-line treatment with metronidazole. Only one patient did not receive any prior antibiotic treatment. Amoxicillin-clavulanic acid was mainly prescribed (68%) for respiratory and ENT infections (40%). Twenty-three patients were cured on Day 7 and three had complications (two deaths). Thirty-one of 47 FPs reported to have already managed CDI patients. Twenty-two FPs reported to usually treat patients with uncomplicated CDI at home, 21 to refer patients to a specialist, and three to hospital. Forty-one FPs reported to prescribe a CD toxin test only after recent antibiotic exposure and 30 when patients are at risk of CDI. CONCLUSION: The incidence and impact of community-acquired CDIs may be underestimated and the unjustified use of antibiotics may promote their emergence. FPs are not used to treat CDIs as more than 50% prefer referring patients to hospital or to a specialist.

Opioid maintenance therapy in Switzerland: an overview of the Swiss IMPROVE study.

BACKGROUND/AIMS: Switzerland's drug policy model has always been unique and progressive, but there is a need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and access to treatment. To obtain a "real-world" view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires. METHODS: IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians' offices or OMT treatment centres. RESULTS: A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians. CONCLUSION: The subset of IMPROVE data presented gives a present-day, real-life overview of the OMT landscape in Switzerland. It represents a valuable resource for policy makers, key opinion leaders and drug addiction researchers and will be a useful basis for improving the current Swiss OMT model.

[Addiction]. / Addictions.

What's new in addiction medicine in 2012? The news are presented according three axes: first, in the field of neuroscience, the process of extinction of addiction memories. Then in the clinical field, a reflexion is reported on how to treat addiction in psychiatric hospitals. At last, in the area of teaching, an e-learning development with a virtual patient shows a great interest in addiction psychiatry.

[Addiction]. / Dépendances.

The news in addiction medicine for 2011 include new knowledges coming from the neurosciences, but also new clinical concepts, as the role of hospital addiction units in an integrated network of care. The issue of cocaine vaccination is discussed from an ethical point of view. Finally, the integration of mindfulness techniques is introduced as a useful approach in the treatment of the addictions.

[Addiction]. / Dépendances.

The news in addiction medicine for 2010 include somatic, neuroscientific as well as psychotherapeutic aspects. First are considered the risks of cardiac arythmy with methadone as long as the racemate form is prescribed in Switzerland. Then the neurosciences bring their usual novelties in the field of the addictions, this year in relational neuroscience and in the relationship between trauma and addiction. At last a contribution bridges the notion of low threshold treatment with the psychodynamic approach.

ß-Arrestin2 influences the response to methadone in opioid-dependent patients.

ß-Arrestin2 (ARRB2) is a component of the G-protein-coupled receptor complex and is involved in µ-opioid and dopamine D(2) receptor signaling, two central processes in methadone signal transduction. We analyzed 238 patients in methadone maintenance treatment (MMT) and identified a haplotype block (rs34230287, rs3786047, rs1045280 and rs2036657) spanning almost the entire ARRB2 locus. Although none of these single nucleotide polymorphisms (SNPs) leads to a change in amino-acid sequence, we found that for all the SNPs analyzed, with exception of rs34230287, homozygosity for the variant allele confers a nonresponding phenotype (n=73; rs1045280C and rs2036657G: OR=3.1, 95% CI=1.5-6.3, P=0.004; rs3786047A: OR=2.5, 95% CI=1.2-5.1, P=0.02) also illustrated by a 12-fold shorter period of negative urine screening (P=0.01). The ARRB2 genotype may thus contribute to the interindividual variability in the response to MMT and help to predict response to treatment.

Microarray analysis of genes with impaired insulin regulation in the skeletal muscle of type 2 diabetic patients indicates the involvement of basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2).

AIMS/HYPOTHESIS: One of the major processes by which insulin exerts its multiple biological actions is through gene expression regulation. Thus, the identification of transcription factors affected by insulin in target tissues represents an important challenge. The aim of the present study was to gain a greater insight into this issue through the identification of transcription factor genes with insulin-regulated expression in human skeletal muscle. METHODS: Using microarray analysis, we defined the sets of genes modulated during a 3 h hyperinsulinaemic-euglycaemic clamp (2 mU min(-1) kg(-1)) in the skeletal muscle of insulin-sensitive control volunteers and in moderately obese insulin-resistant type 2 diabetic patients. RESULTS: Of the 1,529 and 1,499 genes regulated during the clamp in control and diabetic volunteers, respectively, we identified 30 transcription factors with impaired insulin-regulation in type 2 diabetic patients. Analysis of the promoters of the genes encoding these factors revealed a possible contribution of the transcriptional repressor basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2), insulin regulation of which is strongly altered in the muscle of diabetic patients. Gene ontology analysis of BHLHB2 target genes, identified after BHLHB2 overexpression in human primary myotubes, demonstrated that about 10% of the genes regulated in vivo during hyperinsulinaemia are potentially under the control of this repressor. The data also suggested that BHLHB2 is situated at the crossroads of a complex transcriptional network that is able to modulate major metabolic and biological pathways in skeletal muscle, including the regulation of a cluster of genes involved in muscle development and contraction. CONCLUSIONS/INTERPRETATION: We have identified BHLHB2 as a potential novel mediator of insulin transcriptional action in human skeletal muscle.

[Addiction]. / Dépendances.

The highlights 2008 in the addiction field are correlated to the progress of psychiatric neurosciences. Clarifications are also necessary towards the psychiatric comorbidities (schizophrenia) with the addictions. Then, useful considerations are given for the prescription of substitution treatment among HIV patients under tritherapy.

[Mental retardation and psychiatry]. / Handicap mental et psychiatrie.

In the canton de Vaud (Switzerland) the psychiatric units devoted to mental retardation have been suppressed during the deinstitutionalization process in the 1970/80s. However, the use of psychiatric hospitalizations has increased these last years. This increase is accompanied by an interdiction of seclusion and restraint outside of the specialized psychiatric unit. A unit of liaison psychiatry has been created as an alternative to psychiatric hospitalization and to assist directly the staff of specialized institutions for people with mental retardation or the family of the patient. The article describes the challenges of liaison psychiatry in this field and the potential benefits of research for the psychiatry of mental retardation.

[Addiction]. / Dépendances.

This year review emphasizes four aspects coming from addiction psychiatry: 1. Initiation and maintenance of cannabis use. 2. Methadone and heart toxicity. 3. Suicidal behaviour in gambling. 4. Treatment of addictive disorders via internet: present and future perspectives.

Inter-informant agreement and prevalence estimates for substance use disorders: direct interview versus family history method.

OBJECTIVES: Family studies typically use multiple sources of information on each individual including direct interviews and family history information. The aims of the present study were to: (1) assess agreement for diagnoses of specific substance use disorders between direct interviews and the family history method; (2) compare prevalence estimates according to the two methods; (3) test strategies to approximate prevalence estimates according to family history reports to those based on direct interviews; (4) determine covariates of inter-informant agreement; and (5) identify covariates that affect the likelihood of reporting disorders by informants. METHODS: Analyses were based on family study data which included 1621 distinct informant (first-degree relatives and spouses) - index subject pairs. RESULTS: Our main findings were: (1) inter-informant agreement was fair to good for all substance disorders, except for alcohol abuse; (2) the family history method underestimated the prevalence of drug but not alcohol use disorders; (3) lowering diagnostic thresholds for drug disorders and combining multiple family histories increased the accuracy of prevalence estimates for these disorders according to the family history method; (4) female sex of index subjects was associated with higher agreement for nearly all disorders; and (5) informants who themselves had a history of the same substance use disorder were more likely to report this disorder in their relatives, which entails the risk of overestimation of the size of familial aggregation. CONCLUSION: Our findings have important implications for the best-estimate procedure applied in family studies.

[Addiction]. / Dépendances.

This year review emphasizes three aspects coming from addiction psychiatry: 1. Psychosis and cannabis: a motivational approach. 2. Connection between addiction services and psychiatric wards. 3. Use of antiepileptic agents in addiction medicine.

Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers.

Methadone inhibits the cardiac potassium channel hERG and can cause a prolonged QT interval. Methadone is chiral but its therapeutic activity is mainly due to (R)-methadone. Whole-cell patch-clamp experiments using cells expressing hERG showed that (S)-methadone blocked the hERG current 3.5-fold more potently than (R)-methadone (IC50s (half-maximal inhibitory concentrations) at 37 degrees C: 2 and 7 microM). As CYP2B6 slow metabolizer (SM) status results in a reduced ability to metabolize (S)-methadone, electrocardiograms, CYP2B6 genotypes, and (R)- and (S)-methadone plasma concentrations were obtained for 179 patients receiving (R,S)-methadone. The mean heart-rate-corrected QT (QTc) was higher in CYP2B6 SMs (*6/*6 genotype; 439+/-25 ms; n=11) than in extensive metabolizers (non *6/*6; 421+/-25 ms; n=168; P=0.017). CYP2B6 SM status was associated with an increased risk of prolonged QTc (odds ratio=4.5, 95% confidence interval=1.2-17.7; P=0.03). This study reports the first genetic factor implicated in methadone metabolism that may increase the risk of cardiac arrhythmias and sudden death. This risk could be reduced by the administration of (R)-methadone.

Learning the structure of correlated synaptic subgroups using stable and competitive spike-timing-dependent plasticity.

Synaptic plasticity must be both competitive and stable if ongoing learning of the structure of neural inputs is to occur. In this paper, a wide class of spike-timing-dependent plasticity (STDP) models is identified that have both of these desirable properties in the case in which the input consists of subgroups of synapses that are correlated within the subgroup through the occurrence of simultaneous input spikes. The process of synaptic structure formation is studied, illustrating one particular class of these models. When the learning rate is small, multiple alternative synaptic structures are possible given the same inputs, with the outcome depending on the initial weight configuration. For large learning rates, the synaptic structure does not stabilize, resulting in neurons without consistent response properties. For learning rates in between, a unique and stable synaptic structure typically forms. When this synaptic structure exhibits a bimodal distribution, the neuron will respond selectively to one or more of the subgroups. The robustness with which this selectivity develops during learning is largely determined by the ratio of the subgroup correlation strength to the number of subgroups. The fraction of potentiated subgroups is primarily determined by the balance between potentiation and depression.

[Addictions]. / Dépendances.

This year reviews on the addictions emphasizes five aspects, on a bio-psycho-social perspective: (1) The relationship between methadone and cardiotoxicity. (2) The introduction of Eye Movement Desensibilization and Reprocessing (EMDR). (3) The apparition of a possible specific pharmacotherapy for excessive gambling. (4) A better knowledge of the relationship between cannabis and psychoses. (5) Resistance to treatment in the doctor-patient relationship.

Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomised clinical trial.

BACKGROUND: While detoxification under anaesthesia accelerates the detoxification procedure, there is a lack of randomised clinical trials evaluating its effectiveness compared to traditional detoxification procedures, and a lack of data on long-term abstinence. METHODS: Prospective randomised clinical trial. Analysis by intention to treat and per protocol. SETTING: Specialised substance abuse unit in a psychiatric teaching hospital and an intensive care unit of a general hospital. PARTICIPANTS: Seventy patients with opiate mono-dependence requesting detoxification: 36 randomised to RODA (treatment as allocated received by 26) and 34 randomised to classical clonidine detoxification (treatment as allocated received by 21). MAIN OUTCOME MEASURES: Successful detoxification, safety and self-reported abstinence at 3, 6 and 12 months after detoxification. RESULTS: Socio-demographics were similar in both groups at baseline. No complications were reported during or after anaesthesia. According to the intention to treat analysis, 28/36 (78%) RODA patients and 21/34 (62%) of the clonidine group successfully completed the detoxification process (p=0.14). In the intention to treat analysis, 30% of RODA patients were abstinent after 3 months compared to 14% in the clonidine group (p=0.11). No difference was found at 6 and 12 months (both groups showed less than 5% abstinence after 12 months). The per-protocol analysis showed similar results with no statistical differences either for ASI mean scores or for the SF36 questionnaire. CONCLUSION: Although the detoxification success rate and abstinence after 3 months were slightly better for the RODA procedure compared to clonidine treatment, these differences were not statistically significant and disappeared completely after 6 and 12 months.