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Trigeminal neuralgia (TN) is a debilitating condition characterised by attacks of sharp, shooting, severe pain in the orofacial region. It can be triggered by activities of daily living such as eating, speaking, washing the face, shaving and brushing teeth. It therefore has a significant impact on a patient's social interaction, mood and well-being. Other causes for facial pain need to be effectively excluded prior to establishing a diagnosis of TN. It is important to establish a diagnosis promptly. Often patients can see many practitioners including their general dental practitioner, GP and various secondary referral practitioners before a diagnosis is made. This can add significantly to distress and delays treatment. This article describes the clinical features of TN, differential diagnosis, initial management options and presents guidance on referral to secondary care. [ABSTRACT FROM AUTHOR]

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted. [ABSTRACT FROM AUTHOR]

Large and rare copy number variants (CNVs) at several loci have been shown to increase risk for schizophrenia. Aiming to discover novel susceptibility CNV loci, we analyzed 6882 cases and 11 255 controls genotyped on Illumina arrays, most of which have not been used for this purpose before. We identified genes enriched for rare exonic CNVs among cases, and then attempted to replicate the findings in additional 14 568 cases and 15 274 controls. In a combined analysis of all samples, 12 distinct loci were enriched among cases with nominal levels of significance (P < 0.05); however, none would survive correction for multiple testing. These loci include recurrent deletions at 16p12.1, a locus previously associated with neurodevelopmental disorders (P = 0.0084 in the discovery sample and P = 0.023 in the replication sample). Other plausible candidates include non-recurrent deletions at the glutamate transporter gene SLC1A1, a CNV locus recently suggested to be involved in schizophrenia through linkage analysis, and duplications at 1p36.33 and CGNL1. A burden analysis of large (>500 kb), rare CNVs showed a 1.2% excess in cases after excluding known schizophrenia-associated loci, suggesting that additional susceptibility loci exist. However, even larger samples are required for their discovery.

Necrotizing fasciitis is a rare, severe, life-threatening soft tissue infection. Rapid progression and systemic illness are recognized features of the condition in which a high index of suspicion is essential to prompt early diagnosis and ensure a favourable outcome. Management necessitates immediate and aggressive surgical and antimicrobial treatment. This case report describes the rare presentation of facial necrotizing fasciitis with orbital involvement that required initial and subsequent widespread surgical resection within the first 24 h of admission, including unilateral enucleation of infected orbital contents. [ABSTRACT FROM AUTHOR]

An obituary for former Maryland Historical Society head librarian and U.S. Library of Congress manuscript archivist Karen A. Stuart is presented.

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts., Objective: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples., Design, Setting, and Participants: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G])., Main Outcomes and Measures: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition., Results: The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04)., Conclusions and Relevance: In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.

Identifying rare, highly penetrant risk mutations may be an important step in dissecting the molecular etiology of schizophrenia. We conducted a gene-based analysis of large (>100 kb), rare copy-number variants (CNVs) in the Wellcome Trust Case Control Consortium 2 (WTCCC2) schizophrenia sample of 1564 cases and 1748 controls all from Ireland, and further extended the analysis to include an additional 5196 UK controls. We found association with duplications at chr20p12.2 (P = 0.007) and evidence of replication in large independent European schizophrenia (P = 0.052) and UK bipolar disorder case-control cohorts (P = 0.047). A combined analysis of Irish/UK subjects including additional psychosis cases (schizophrenia and bipolar disorder) identified 22 carriers in 11 707 cases and 10 carriers in 21 204 controls [meta-analysis Cochran-Mantel-Haenszel P-value = 2 × 10(-4); odds ratio (OR) = 11.3, 95% CI = 3.7, ∞]. Nineteen of the 22 cases and 8 of the 10 controls carried duplications starting at 9.68 Mb with similar breakpoints across samples. By haplotype analysis and sequencing, we identified a tandem ~149 kb duplication overlapping the gene p21 Protein-Activated Kinase 7 (PAK7, also called PAK5) which was in linkage disequilibrium with local haplotypes (P = 2.5 × 10(-21)), indicative of a single ancestral duplication event. We confirmed the breakpoints in 8/8 carriers tested and found co-segregation of the duplication with illness in two additional family members of one of the affected probands. We demonstrate that PAK7 is developmentally co-expressed with another known psychosis risk gene (DISC1) suggesting a potential molecular mechanism involving aberrant synapse development and plasticity., (© The Author 2014. Published by Oxford University Press.)

Objectives: To evaluate the clinical effectiveness of group art therapy for people with schizophrenia and to test whether any benefits exceed those of an active control treatment., Design: Three arm, rater blinded, pragmatic, randomised controlled trial., Setting: Secondary care services across 15 sites in the United Kingdom., Participants: 417 people aged 18 or over, who had a diagnosis of schizophrenia and provided written informed consent to take part in the study., Interventions: Participants, stratified by site, were randomised to 12 months of weekly group art therapy plus standard care, 12 months of weekly activity groups plus standard care, or standard care alone. Art therapy and activity groups had up to eight members and lasted for 90 minutes. In art therapy, members were given access to a range of art materials and encouraged to use these to express themselves freely. Members of activity groups were offered various activities that did not involve use of art or craft materials and were encouraged to collectively select those they wanted to pursue., Main Outcome Measures: The primary outcomes were global functioning, measured using the global assessment of functioning scale, and mental health symptoms, measured using the positive and negative syndrome scale, 24 months after randomisation. Main secondary outcomes were levels of group attendance, social functioning, and satisfaction with care at 12 and 24 months., Results: 417 participants were assigned to either art therapy (n=140), activity groups (n=140), or standard care alone (n=137). Primary outcomes between the three study arms did not differ. The adjusted mean difference between art therapy and standard care at 24 months on the global assessment of functioning scale was -0.9 (95% confidence interval -3.8 to 2.1), and on the positive and negative syndrome scale was 0.7 (-3.1 to 4.6). Secondary outcomes did not differ between those referred to art therapy or those referred to standard care at 12 or 24 months., Conclusions: Referring people with established schizophrenia to group art therapy as delivered in this trial did not improve global functioning, mental health, or other health related outcomes., Trial Registration: Current Controlled Trials ISRCTN46150447.