Intervention précoce dans les troubles psychotiques: quel rôle pour les praticiens de premier recours [Early intervention in psychotic disorders: which role for primary care practitioners?]

The development of early intervention in psychotic disorders has allowed a more optimistic approach and the development of more adapted and more efficient treatments. Primary care practitioners are often the first professional contact for patients developing psychosis, but diagnostic difficulties and patients' reluctance to engage in treatment are often an obstacle to private practice treatment. It is therefore important to provide more information to primary care practitioners on specific characteristics of these disorders and about locally available treatment structures in order to allow them to suspect this relatively rare diagnosis, facilitate the collaboration with flexible and accessible specialist services, that ideally should provide home treatment, and to improve prognosis.

Chondrodysplasia and Abnormal Joint Development Associated with Mutations in IMPAD1, Encoding the Golgi-Resident Nucleotide Phosphatase, gPAPP.

We used whole-exome sequencing to study three individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism. Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, a Golgi-resident nucleotide phosphatase that hydrolyzes phosphoadenosine phosphate (PAP), the byproduct of sulfotransferase reactions, to AMP. The mutations affected residues in or adjacent to the phosphatase active site and are predicted to impair enzyme activity. A fourth unrelated patient was subsequently found to be homozygous for a premature termination codon in IMPAD1. Impad1 inactivation in mice has previously been shown to produce chondrodysplasia with abnormal joint formation and impaired proteoglycan sulfation. The human chondrodysplasia associated with gPAPP deficiency joins a growing number of skeletoarticular conditions associated with defective synthesis of sulfated proteoglycans, highlighting the importance of proteoglycans in the development of skeletal elements and joints.

Methicillin-susceptible Staphylococcus aureus clonal complex 398: high prevalence and geographical heterogeneity in bone and joint infection and nasal carriage.

The prevalence of clonal complex (CC) 398 methicillin-susceptible Staphylococcus aureus (MSSA) was unexpectedly high among bone and joint infections (BJIs) and nasal-colonizing isolates in France, with surprising geographical heterogeneity. With none of the major, most-known staphylococcal virulence genes, MSSA CC398 BJI was associated with lower biological inflammatory syndrome and lower treatment failure rates.

A higher mutational burden in females supports a "female protective model" in neurodevelopmental disorders.

Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a "female protective model." We investigated the molecular basis of this sex-based difference in liability and demonstrated an excess of deleterious autosomal copy-number variants (CNVs) in females compared to males (odds ratio [OR] = 1.46, p = 8 × 10(-10)) in a cohort of 15,585 probands ascertained for NDs. In an independent autism spectrum disorder (ASD) cohort of 762 families, we found a 3-fold increase in deleterious autosomal CNVs (p = 7 × 10(-4)) and an excess of private deleterious single-nucleotide variants (SNVs) in female compared to male probands (OR = 1.34, p = 0.03). We also showed that the deleteriousness of autosomal SNVs was significantly higher in female probands (p = 0.0006). A similar bias was observed in parents of probands ascertained for NDs. Deleterious CNVs (>400 kb) were maternally inherited more often (up to 64%, p = 10(-15)) than small CNVs < 400 kb (OR = 1.45, p = 0.0003). In the ASD cohort, increased maternal transmission was also observed for deleterious CNVs and SNVs. Although ASD females showed higher mutational burden and lower cognition, the excess mutational burden remained, even after adjustment for those cognitive differences. These results strongly suggest that females have an increased etiological burden unlinked to rare deleterious variants on the X chromosome. Carefully phenotyped and genotyped cohorts will be required for identifying the symptoms, which show gender-specific liability to mutational burden.

Stent graft exclusion of a ruptured mycotic popliteal pseudoaneurysm complicating sternoclavicular joint infection.

A mycotic pseudoaneurysm of the popliteal artery is usually a consequence of septic embolization and often a result of bacterial endocarditis. Conventional treatment is surgical and avoids the placement of foreign material in infected sites. Here we report our treatment of a 59-year-old man who presented with a rupture of a mycotic pseudoaneurysm of the popliteal artery due to septic embolism from sternoclavicular infectious arthritis. Radiological investigations are included. This is the first documented case of septic arthritis complicated by a rupture of a mycotic popliteal false aneurysm and treated using an endovascular procedure. Combining endovascular stent grafts with evacuation of the joint abscess and antibiotic therapy can offer a safe alternative for frail and unstable patients.

Sleep structure and cardiometabolic disorders in the general population : the Hypnolaus study

Objectives: Previous studies using subjective assessments have reported associations between sleep quantity and quality and cardiometabolic disorders, but little is known regarding the associ-ations with objective sleep characteristics. The purpose of this study was to evaluate the association between objective sleep measure sand metabolic syndrome (MS), hypertension, diabetes and obesity. Methods: 2162 subjects (51.2% women, mean age 58,11.1) from the general population were evaluated for hypertension,diabetes, overweight/obesity and MS, and underwent a full polysom-nography (PSG). PSG measured variables included: Total sleep time(TST), percentage and time spent in slow wave sleep (SWS) and in rapid eye movement (REM) sleep, sleep efficiency and arousal index(ArI) Results: In univariate analyses, MS was associated with decreased TST, SWS, REM sleep, sleep efficiency and increased ArI. After adjustment for age, gender, smoking, alcohol, physical activity, drugsthat affect sleep and depression, the ArI remained significantly higher, but the difference disappeared in subjects without significant sleep disordered breathing (SDB). Differences in sleep structure were also found according to the presence or absence of hypertension, diabetes and overweight/obesity in univariate analysis. However, these differences were attenuated after multivariate adjustment and after excluding subjects with significant SDB. Conclusions: In this population-based sample we found significant associations between sleep structure and MS, hypertension, diabetes and obesity. However, these associations were cancelled after multivariate adjustment. We conclude that normal variations in sleep contribute little if any to MS and associated disorders.

Direct magnetic resonance arthrography of the wrist with axial traction: A feasibility study to assess joint cartilage.

PURPOSE: To assess the impact of axial traction during acquisition of direct magnetic resonance (MR) arthrography of the wrist with regard to joint space width and amount of contrast material between the opposing cartilage surfaces. MATERIALS AND METHODS: Fifteen consecutive patients (12 male, mean age 38.1 years) were included in this Institutional Review Board-approved prospective study. Three-compartment wrist MR arthrographies were performed between October and December 2009 on a 3 T unit using a fat-suppressed T1-weighted isotropic high-resolution volumetric interpolated breathhold examination (VIBE) sequence in the coronal plane, with and without axial traction (3 kg). Two radiologists measured radiocarpal (radioscaphoid, radiolunate) and midcarpal (lunocapitate, hamatolunate) joint space widths, with and without traction, and assessed the amount of contrast material between the opposing cartilage surfaces using a three-point scale: 0 = absence, 1 = partial, 2 = complete. RESULTS: With traction, joint space width increased significantly at the radioscaphoid (Delta = 0.78 mm, P < 0.01), radiolunate (Delta = 0.18 mm, P < 0.01), and lunocapitate (Delta = 0.45 mm, P < 0.01) spaces, and both observers detected significantly more contrast material between the cartilage surfaces. At the hamatolunate space, the differences in joint space width (Delta = 0.14 mm, P = 0.54) and amount of contrast material were not significant. CONCLUSION: Direct wrist MR arthrography with axial traction of 3 kg increases joint space width at the radiocarpal and lunocapitate spaces, and prompts better coverage of the articular cartilage by the contrast material. J. Magn. Reson. Imaging 2011;. (c) 2011 Wiley-Liss, Inc.

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.

A measure of the intensity of response to alcohol to screen for alcohol use disorders in primary care.

Alcohol-dependent subjects tend to report lower level of response to alcohol (LR) in the years before the disorder developed, compared to control subjects. The Self-Rating of the Effects of alcohol (SRE) score is a quick and valid retrospective estimate of LR. This study examined the associations between alcohol abuse or dependence and early experience of alcohol as measured on retrospective SRE score (relating to the first five times alcohol was imbibed), and the presence of alcohol abuse or dependence, in patients attending primary care. Higher Early SRE score (i.e. greater early tolerance of alcohol) was obtained in patients with an alcohol-related diagnosis than in patients without those diagnoses. Using a cut-off of 2 on the Early SRE score, the Early SRE score could discriminate between patients with and without an alcohol diagnosis with moderate to high sensitivity (84%) and modest specificity (57%).

The value of 'positive' clinical signs for weakness, sensory and gait disorders in conversion disorder: a systematic and narrative review.

Experts in the field of conversion disorder have suggested for the upcoming DSM-V edition to put less weight on the associated psychological factors and to emphasise the role of clinical findings. Indeed, a critical step in reaching a diagnosis of conversion disorder is careful bedside neurological examination, aimed at excluding organic signs and identifying 'positive' signs suggestive of a functional disorder. These positive signs are well known to all trained neurologists but their validity is still not established. The aim of this study is to provide current evidence regarding their sensitivity and specificity. We conducted a systematic search on motor, sensory and gait functional signs in Embase, Medline, PsycINfo from 1965 to June 2012. Studies in English, German or French reporting objective data on more than 10 participants in a controlled design were included in a systematic review. Other relevant signs are discussed in a narrative review. Eleven controlled studies (out of 147 eligible articles) describing 14 signs (7 motor, 5 sensory, 2 gait) reported low sensitivity of 8-100% but high specificity of 92-100%. Studies were evidence class III, only two had a blinded design and none reported on inter-rater reliability of the signs. Clinical signs for functional neurological symptoms are numerous but only 14 have been validated; overall they have low sensitivity but high specificity and their use should thus be recommended, especially with the introduction of the new DSM-V criteria.