Comment Samuel devint prophète: Analyse du récit de 1 Samuel 3 dans son contexte

Le récit de 1 S 3 raconte comment une nuit Yhwh essaya à plusieurs reprises de se révéler au jeune Samuel, alors serviteur au sanctuaire de Silo. Instruit par son maître Éli, le garçon put finalement répondre à Yhwh. Il devint alors récepteur d'un message divin. Yhwh annonce un événement effrayant qui va « faire tinter les oreilles de quiconque en entendra parler ». Au matin, Samuel rapporte la parole divine à Éli, son maître. À la fin du récit le lecteur apprend que Yhwh continue de se évéler à Samuel. Voilà en résumé comment, selon le récit de 1 S 3, Samuel devint prophète. Ce chapitre est interprété par les chercheurs de manières très différentes. On peut néanmoins discerner deux tendances d'interprétation : a) 1 S 3 serait composé selon un certain genre littéraire : il s'agirait d'un « récit de vocation », voire d'un « récit de rêve d'incubation » ou encore d'un « récit de théophanie onirique ». b) Le récit 1 S 3 a des liens forts avec le récit de 1 S 1-2, récit d'ouverture des livres de Samuel qui rapporte comment Samuel a été dédié au sanctuaire de Silo par sa mère Anne et comment et dans quelles circonstances il a grandi au sanctuaire. Étant donné ces liens, certains chercheurs estiment que les deux récits, à un moment donné, ont été réunis en une seule narration portant sur la naissance de Samuel et sa jeunesse au sanctuaire de Silo. Cette narration de 1 S 1-3 aurait été à l'origine indépendante des récits suivants (1 S 4-6) qui forment une entité autonome en commun avec 2 S 6, le soi-disant « récit de l'arche ». Le présent article présentera et discutera ces propositions en dialogue avec des idées d'autres chercheurs ainsi que des suggestions personnelles. J'aborderai donc la question du genre du récit, et celle de la relation avec les récits qui l'encadrent. Pour cette seconde question il sera important d'examiner de très près l'oracle de Yhwh se trouvant au coeur du récit (v. 11-14) et de poser la question de l'événement qu'il vise. À la fin de la contribution les questions concernant le milieu et l'âge du récit seront abordées.

In vivo measurement of tissue oxygenation by time-resolved luminescence spectroscopy: advantageous properties of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate.

Measuring tissue oxygenation in vivo is of interest in fundamental biological as well as medical applications. One minimally invasive approach to assess the oxygen partial pressure in tissue (pO2) is to measure the oxygen-dependent luminescence lifetime of molecular probes. The relation between tissue pO2 and the probes' luminescence lifetime is governed by the Stern-Volmer equation. Unfortunately, virtually all oxygen-sensitive probes based on this principle induce some degree of phototoxicity. For that reason, we studied the oxygen sensitivity and phototoxicity of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate [Ru(Phen)] using a dedicated optical fiber-based, time-resolved spectrometer in the chicken embryo chorioallantoic membrane. We demonstrated that, after intravenous injection, Ru(Phen)'s luminescence lifetime presents an easily detectable pO2 dependence at a low drug dose (1 mg∕kg) and low fluence (120 mJ∕cm2 at 470 nm). The phototoxic threshold was found to be at 10 J∕cm2 with the same wavelength and drug dose, i.e., about two orders of magnitude larger than the fluence necessary to perform a pO2 measurement. Finally, an illustrative application of this pO2 measurement approach in a hypoxic tumor environment is presented.

Quality Assessment of Cardiac Magnetic Resonance Images at 1.5/3.0 T: Description and Validation of Standardized Criteria

PURPOSE: Cardiovascular magnetic resonance (CMR) has become a robust and important diagnostic imaging modality in cardiovascular medicine. However,insufficient image quality may compromise its diagnostic accuracy. No standardized criteria are available to assess the quality of CMR studies. We aimed todescribe and validate standardized criteria to evaluate the quality of CMR studies including: a) cine steady-state free precession, b) delayed gadoliniumenhancement, and c) adenosine stress first-pass perfusion. These criteria will serve for the assessment of the image quality in the setting of the Euro-CMR registry.METHOD AND MATERIALS: First, a total of 45 quality criteria were defined (35 qualitative criteria with a score from 0-3, and 10 quantitative criteria). Thequalitative score ranged from 0 to 105. The lower the qualitative score, the better the quality. The quantitative criteria were based on the absolute signal intensity (delayed enhancement) and on the signal increase (perfusion) of the anterior/posterior left ventricular wall after gadolinium injection. These criteria were then applied in 30 patients scanned with a 1.5T system and in 15 patients scanned with a 3.0T system. The examinations were jointly interpreted by 3 CMR experts and 1 study nurse. In these 45 patients the correlation between the results of the quality assessment obtained by the different readers was calculated.RESULTS: On the 1.5T machine, the mean quality score was 3.5. The mean difference between each pair of observers was 0.2 (5.7%) with a mean standarddeviation of 1.4. On the 3.0T machine, the mean quality score was 4.4. The mean difference between each pair of onservers was 0.3 (6.4%) with a meanstandard deviation of 1.6. The quantitative quality assessments between observers were well correlated for the 1.5T machine: R was between 0.78 and 0.99 (pCONCLUSION: The described criteria for the assessment of CMR image quality are robust and have a low inter-observer variability, especially on 1.5T systems.CLINICAL RELEVANCE/APPLICATION: These criteria will allow the standardization of CMR examinations. They will help to improve the overall quality ofexaminations and the comparison between clinical studies.

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42.

HIV-1 coreceptor usage and CXCR4-specific viral load predict clinical disease progression during combination antiretroviral therapy

Background: Although combination antiretroviral therapy (cART) dramatically reduces rates of AIDS and death, a minority of patients experience clinical disease progression during treatment. <p>Objective: To investigate whether detection of CXCR4(X4)-specific strains or quantification of X4-specific HIV-1 load predict clinical outcome. Methods: From the Swiss HIV Cohort Study, 96 participants who initiated cART yet subsequently progressed to AIDS or death were compared with 84 contemporaneous, treated nonprogressors. A sensitive heteroduplex tracking assay was developed to quantify plasma X4 and CCR5 variants and resolve HIV-1 load into coreceptor-specific components. Measurements were analyzed as cofactors of progression in multivariable Cox models adjusted for concurrent CD4 cell count and total viral load, applying inverse probability weights to adjust for sampling bias. Results: Patients with X4 variants at baseline displayed reduced CD4 cell responses compared with those without X4 strains (40 versus 82 cells/mu l; P= 0.012). The adjusted multivariable hazard ratio (HR) for clinical progression was 4.8 [95% confidence interval (Cl) 2.3-10.0] for those demonstrating X4 strains at baseline. The X4-specific HIV-1 load was a similarly independent predictor, with HR values of 3.7(95%Cl, 1.2-11.3) and 5.9 (95% Cl, 2.2-15.0) for baseline loads of 2.2-4.3 and > 4.3 log(10)copies/ml, respectively, compared with < 2.2 log(10)copies/ml. Conclusions: HIV-1 coreceptor usage and X4-specific viral loads strongly predicted disease progression during cART, independent of and in addition to CD4 cell count or total viral load. Detection and quantification of X4 strains promise to be clinically useful biomarkers to guide patient management and study HIV-1 pathogenesis.

Improved HIV-1 RNA quantitation by COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 using a novel dual-target approach.

BACKGROUND: HIV-1 RNA viral load is a key parameter for reliable treatment monitoring of HIV-1 infection. Accurate HIV-1 RNA quantitation can be impaired by primer and probe sequence polymorphisms as a result of tremendous genetic diversity and ongoing evolution of HIV-1. A novel dual HIV-1 target amplification approach was realized in the quantitative COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 (HIV-1 TaqMan test v2.0) to cope with the high genetic diversity of the virus. OBJECTIVES AND STUDY DESIGN: The performance of the new assay was evaluated for sensitivity, dynamic range, precision, subtype inclusivity, diagnostic and analytical specificity, interfering substances, and correlation with the COBAS AmpliPrep/COBAS TaqMan HIV-1 (HIV-1 TaqMan test v1.0) predecessor test in patients specimens. RESULTS: The new assay demonstrated a sensitivity of 20 copies/mL, a linear measuring range of 20-10,000,000 copies/mL, with a lower limit of quantitation of 20 copies/mL. HIV-1 Group M subtypes and HIV-1 Group O were quantified within +/-0.3 log(10) of the assigned titers. Specificity was 100% in 660 tested specimens, no cross reactivity was found for 15 pathogens nor any interference for endogenous substances or 29 drugs. Good comparability with the predecessor assay was demonstrated in 82 positive patient samples. In selected clinical samples 35/66 specimens were found underquantitated in the predecessor assay; all were quantitated correctly in the new assay. CONCLUSIONS: The dual-target approach for the HIV-1 TaqMan test v2.0 enables superior HIV-1 Group M subtype coverage including HIV-1 Group O detection. Correct quantitation of specimens underquantitated in the HIV-1 TaqMan test v1.0 test was demonstrated.

Decreased Probability of Initial Pain Cessation in Classic Trigeminal Neuralgia Treated With Gamma Knife Surgery in Case of Previous Microvascular Decompression: A Prospective Series of 45 Patients With >1 Year of Follow-up.

BACKGROUND: Microvascular decompression (MVD) is the reference technique for pharmacoresistant trigeminal neuralgia (TN). OBJECTIVE: To establish whether the safety and efficacy of Gamma Knife surgery for recurrent TN are influenced by prior MVD. METHODS: Between July 1992 and November 2010, 54 of 737 patients (45 of 497 with >1 year of follow-up) had a history of MVD (approximately half also with previous ablative procedure) and were operated on with Gamma Knife surgery for TN in the Timone University Hospital. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range, 3.9-11.9 mm) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range, 70-90 Gy) was delivered. RESULTS: The median follow-up time was 39.5 months (range, 14.1-144.6 months). Thirty-five patients (77.8%) were initially pain free in a median time of 14 days (range, 0-180 days), much lower compared with our global population of classic TN (P = .01). Their actuarial probabilities of remaining pain-free without medication at 3, 5, 7, and 10 years were 66.5%, 59.1%, 59.1%, and 44.3%. The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable until 12 years (median, 8 months). CONCLUSION: Patients with previous MVD showed a significantly lower probability of initial pain cessation compared with our global population with classic TN (P = .01). The toxicity was low (only 9.1% hypoesthesia); furthermore, no patient reported bothersome hypoesthesia. However, the probability of maintaining pain relief without medication was 44.3% at 10 years, similar to our global series of classic TN (P = .85). ABBREVIATIONS: BNI, Barrow Neurological InstituteCI, confidence intervalCTN, classic trigeminal neuralgiaGKS, Gamma Knife surgeryHR, hazard ratioMVD, microvascular decompressionTN, trigeminal neuralgia.

Fulvestrant with or without selumetinib, a MEK 1/2 inhibitor, in breast cancer progressing after aromatase inhibitor therapy: A multicentre randomised placebo-controlled double-blind phase II trial, SAKK 21/08.

BACKGROUND: Second line endocrine therapy has limited antitumour activity. Fulvestrant inhibits and downregulates the oestrogen receptor. The mitogen-activated protein kinase (MAPK) pathway is one of the major cascades involved in resistance to endocrine therapy. We assessed the efficacy and safety of fulvestrant with selumetinib, a MEK 1/2 inhibitor, in advanced stage breast cancer progressing after aromatase inhibitor (AI). PATIENTS AND METHODS: This randomised phase II trial included postmenopausal patients with endocrine-sensitive breast cancer. They were ramdomised to fulvestrant combined with selumetinib or placebo. The primary endpoint was disease control rate (DCR) in the experimental arm. ClinicalTrials.gov Indentifier: NCT01160718. RESULTS: Following the planned interim efficacy analysis, recruitment was interrupted after the inclusion of 46 patients (23 in each arm), because the selumetinib-fulvestrant arm did not reach the pre-specified DCR. DCR was 23% (95% confidence interval (CI) 8-45%) in the selumetinib arm and 50% (95% CI 27-75%) in the placebo arm. Median progression-free survival was 3.7months (95% CI 1.9-5.8) in the selumetinib arm and 5.6months (95% CI 3.4-13.6) in the placebo arm. Median time to treatment failure was 5.1 (95% CI 2.3-6.7) and 5.6 (95% CI 3.4-10.2) months, respectively. The most frequent treatment-related adverse events observed in the selumetinib-fulvestrant arm were skin disorders, fatigue, nausea/vomiting, oedema, diarrhoea, mouth disorders and muscle disorders. CONCLUSIONS: The addition of selumetinib to fulvestrant did not show improving patients' outcome and was poorly tolerated at the recommended monotherapy dose. Selumetinib may have deteriorated the efficacy of the endocrine therapy in some patients.

Genotype 3 is associated with rapid histological progression in chronic HCV infection

While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of the present study was to assess independent predictors for fibrosis progression. Methods: We identified 1540 patients from the Swiss Hepatitis C Cohort database with at least one liver biopsy prior to antiviral treatment. Factors associated with fibrosis stage, steatosis and histological activity were assessed in univariate and multivariate regression models. Fibrosis progression rate per year was calculated in a subgroup of 1263 patients, in whom risk factors were assessed by cumulative incidence curves, logistic and linear regression models. Results: Independent risk factors for rapid fibrosis progression included male sex (OR = 1.66, 95% CI 1.25-2.21, P <0.001), age at infection (OR = 1.08, 95% CI 1.06-1.10, P <0.001), histological activity (OR = 2.14, 95% CI 1.61-2.85, P <0.001) and genotype 3 (OR = 1.97, 95% CI 1.43-2.72, P <0.001). Genotype 2 was associated with slow progression (OR = 0.51, 95% CI 0.30-0.89, P = 0.02), but this observation may be due to the decreased prevalence of genotype 2 over the last decades, leading to an overrepresentation of subjects with genotype 2 with a slow progression rate. Conclusion: This study shows a significant association of genotype 3 with accelerated fibrosis. While assessing risk factors for fibrosis progression, the changing epidemiology of HCV genotypes over time needs to be taken into account.

Should we await IFN-free regimens to treat HCV genotype 1 treatment-naive patients? A cost-effectiveness analysis (ANRS 95141).

BACKGROUND & AIMS: In treatment-naive patients mono-infected with genotype 1 chronic HCV, treatments with telaprevir/boceprevir (TVR/BOC)-based triple therapy are standard-of-care. However, more efficacious direct-acting antivirals (IFN-based new DAAs) are available and interferon-free (IFN-free) regimens are imminent (2015). METHODS: A mathematical model estimated quality-adjusted life years, cost and incremental cost-effectiveness ratios of (i) IFN-based new DAAs vs. TVR/BOC-based triple therapy; and (ii) IFN-based new DAAs initiation strategies, given that IFN-free regimens are imminent. The sustained virological response in F3-4/F0-2 was 71/89% with IFN-based new DAAs, 85/95% with IFN-free regimens, vs. 64/80% with TVR/BOC-based triple therapy. Serious adverse events leading to discontinuation were taken as: 0-0.6% with IFN-based new DAAs, 0% with IFN-free regimens, vs. 1-10% with TVR/BOC-based triple therapy. Costs were euro60,000 for 12weeks of IFN-based new DAAs and two times higher for IFN-free regimens. RESULTS: Treatment with IFN-based new DAAs when fibrosis stage &#10878;F2 is cost-effective compared to TVR/BOC-based triple therapy (euro37,900/QALY gained), but not at F0-1 (euro103,500/QALY gained). Awaiting the IFN-free regimens is more effective, except in F4 patients, but not cost-effective compared to IFN-based new DAAs. If we decrease the cost of IFN-free regimens close to that of IFN-based new DAAs, then awaiting the IFN-free regimen becomes cost-effective. CONCLUSIONS: Treatment with IFN-based new DAAs at stage &#10878;F2 is both effective and cost-effective compared to TVR/BOC triple therapy. Awaiting IFN-free regimens and then treating regardless of fibrosis is more efficacious, except in F4 patients; however, the cost-effectiveness of this strategy is highly dependent on its cost.

n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia.

BACKGROUND: The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown. METHODS: In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here. RESULTS: During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P=0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P=0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P=0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups. CONCLUSIONS: Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

Localization of HLA-A2.1-restricted T cell epitopes in the circumsporozoite protein of Plasmodium falciparum.

Localization of human MHC class I-restricted T cell epitopes in the circumsporozoite (CS) protein of the human parasite Plasmodium falciparum is an important objective in the development of antimalarial vaccines. To this purpose, we synthesized a series of overlapping synthetic 20-mer peptides, spanning the entire sequence of the 7G8 CS molecule except for the central repeat B cell domain. The P.f.CS peptides were first tested for their ability to bind to the human MHC class I HLA-A2.1 molecule on T2, a human cell line. Subsequently, the use of a series of shorter peptide analogues allowed us to determine the optimal A2.1 binding sequence present in several of the 20-mers. Binding P.f.CS peptides were further tested for their capacity to activate PBL from HLA-A2.1+ immune donors living in a malaria-endemic area. Specific IFN-gamma production was detected in the supernatant of cultures of PBL from exposed individuals. Cytotoxic T cell lines and clones were derived from the PBL of one responder, and their activity was shown to be HLA-A2.1-restricted and specific for the peptide 334-342 of the CS protein. In addition, double transgenic HLA-A2.1 x human beta 2-microglobulin mice were immunized with peptide 1-10 of the CS protein. T cells derived from immune lymph nodes displayed a peptide-specific HLA-A2.1-restricted cytolytic activity after one in vitro stimulation.

Measurement of immunoreactive angiotensin-(1-7) heptapeptide in human blood.

BACKGROUND: The renal enzyme renin cleaves from the hepatic alpha(2)-globulin angiotensinogen angiotensin-(1-10) decapeptide [Ang-(1-10)], which is further metabolized to smaller peptides that help maintain cardiovascular homeostasis. The Ang-(1-7) heptapeptide has been reported to have several physiological effects, including natriuresis, diuresis, vasodilation, and release of vasopressin and prostaglandins. METHODS: To investigate Ang-(1-7) in clinical settings, we developed a method to measure immunoreactive (ir-) Ang-(1-7) in 2 mL of human blood and to estimate plasma concentrations by correcting for the hematocrit. A sensitive and specific antiserum against Ang-(1-7) was raised in a rabbit. Human blood was collected in the presence of an inhibitor mixture including a renin inhibitor to prevent peptide generation in vitro. Ang-(1-7) was extracted into ethanol and purified on phenylsilylsilica. The peptide was quantified by radioimmunoassay. Increasing doses of Ang-(1-7) were infused into volunteers, and plasma concentrations of the peptide were measured. RESULTS: The detection limit for plasma ir-Ang-(1-7) was 1 pmol/L. CVs for high and low blood concentrations were 4% and 20%, respectively, and between-assay CVs were 8% and 13%, respectively. Reference values for human plasma concentrations of ir-Ang-(1-7) were 1.0-9.5 pmol/L (median, 4.7 pmol/L) and increased linearly during infusion of increasing doses of Ang-(1-7). CONCLUSIONS: Reliable measurement of plasma ir-Ang-(1-7) is achieved with efficient inhibition of enzymes that generate or metabolize Ang-(1-7) after blood sampling, extraction in ethanol, and purification on phenylsilylsilica, and by use of a specific antiserum.

Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV cohort study.

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/μL decrease̴1;=̴1;1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR̴1;=̴1;1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use̴1;=̴1;0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer.

Insertion dans les soins après une première hospitalisation dans un secteur pour psychose [Linkage to care after first hospitalisation for psychosis]

BACKGROUND: First hospitalisation for a psychotic episode causes intense distress to patients and families, but offers an opportunity to make a diagnosis and start treatment. However, linkage to outpatient psychiatric care remains a notoriously difficult step for young psychotic patients, who frequently interrupt treatment after hospitalisation. Persistence of symptoms, and untreated psychosis may therefore remain a problem despite hospitalisation and proper diagnosis. With persisting psychotic symptoms, numerous complications may arise: breakdown in relationships, loss of family and social support, loss of employment or study interruption, denial of disease, depression, suicide, substance abuse and violence. Understanding mechanisms that might promote linkage to outpatient psychiatric care is therefore a critical issue, especially in early intervention in psychotic disorders. OBJECTIVE: To study which factors hinder or promote linkage of young psychotic patients to outpatient psychiatric care after a first hospitalisation, in the absence of a vertically integrated program for early psychosis. Method. File audit study of all patients aged 18 to 30 who were admitted for the first time to the psychiatric University Hospital of Lausanne in the year 2000. For statistical analysis, chi2 tests were used for categorical variables and t-test for dimensional variables; p<0.05 was considered as statistically significant. RESULTS: 230 patients aged 18 to 30 were admitted to the Lausanne University psychiatric hospital for the first time during the year 2000, 52 of them with a diagnosis of psychosis (23%). Patients with psychosis were mostly male (83%) when compared with non-psychosis patients (49%). Furthermore, they had (1) 10 days longer mean duration of stay (24 vs 14 days), (2) a higher rate of compulsory admissions (53% vs 22%) and (3) were more often hospitalised by a psychiatrist rather than by a general practitioner (83% vs 53%). Other socio-demographic and clinical features at admission were similar in the two groups. Among the 52 psychotic patients, 10 did not stay in the catchment area for subsequent treatment. Among the 42 psychotic patients who remained in the catchment area after discharge, 20 (48%) did not attend the scheduled or rescheduled outpatient appointment. None of the socio demographic characteristics were associated with attendance to outpatient appointments. On the other hand, voluntary admission and suicidal ideation before admission were significantly related to attending the initial appointment. Moreover, some elements of treatment seemed to be associated with higher likelihood to attend outpatient treatment: (1) provision of information to the patient regarding diagnosis, (2) discussion about the treatment plan between in- and outpatient staff, (3) involvement of outpatient team during hospitalisation, and (4) elaboration of concrete strategies to face basic needs, organise daily activities or education and reach for help in case of need. CONCLUSION: As in other studies, half of the patients admitted for a first psychotic episode failed to link to outpatient psychiatric care. Our study suggests that treatment rather than patient's characteristics play a critical role in this phenomenon. Development of a partnership and involvement of patients in the decision process, provision of good information regarding the illness, clear definition of the treatment plan, development of concrete strategies to cope with the illness and its potential complications, and involvement of the outpatient treating team already during hospitalisation, all came out as critical strategies to facilitate adherence to outpatient care. While the current rate of disengagement after admission is highly concerning, our finding are encouraging since they constitute strategies that can easily be implemented. An open approach to psychosis, the development of partnership with patients and a better coordination between inpatient and outpatient teams should therefore be among the targets of early intervention programs. These observations might help setting up priorities when conceptualising new programs and facilitate the implementation of services that facilitate engagement of patients in treatment during the critical initial phase of psychotic disorders.