Haemodialysis patients are at risk of gram-positive bacteraemia and commonly require intravenous vancomycin. Intravenously administered vancomycin is primarily excreted by the kidney and exhibits complex pharmacokinetics in haemodialysis patients; achieving therapeutic levels can be challenging. An audit in our unit showed current practises of vancomycin administration resulted in a high proportion of sub-therapeutic levels. A new protocol was developed with fixed weight-based loading and subsequent dosing guided by pre-dialysis levels, target levels were 10-20mg/L. Its effectiveness was prospectively evaluated between 24th September 2012, and 8th February 2013. During this period 25 patients commenced vancomycin, 15 were included. In total, 112 vancomycin levels were taken, 94 (84%) were therapeutic, this was a significant improvement compared to previous practise (odds ratio 5.4, CI 3.1-9.4, p<0.0001). In conclusion, our study shows this protocol can consistently and reliably achieve therapeutic vancomycin levels.

The documentation of infection with meticillin-resistant Staphylococcus aureus (MRSA) on death certificates has been the subject of considerable public discussion. Using data from five tertiary referral hospitals in Ireland, we compared the documentation of MRSA and meticillin-susceptible S. aureus (MSSA) on death certificates in those patients who died in hospital within 30 days of having MRSA or MSSA isolated from blood cultures. A total of 133 patients had MRSA or MSSA isolated from blood cultures within 30 days of death during the study period. One patient was excluded as the death certificate information was not available; the other 132 patients were eligible for inclusion. MRSA and MSSA were isolated from blood cultures in 59 (44.4%) and 74 (55.6%) cases respectively. One patient was included as a case in both categories as both MRSA and MSSA were isolated from a blood culture. In 15 (25.4%) of the 59 MRSA cases, MRSA was documented on the death certificate. In nine (12.2%) of the 74 patients with MSSA cases, MSSA was documented on the death certificate. MRSA was more likely to be documented on the death certificate than MSSA (odds ratio: 2.46; 95% confidence interval: 1.01-6.01; P < 0.05). These findings indicate that there may be inconsistencies in the way organisms and infections are documented on death certificates in Ireland and that death certification data may underestimate the mortality related to certain organisms. In particular, there appears to be an overemphasis by certifiers on the documentation of MRSA compared with MSSA.

There remains uncertainty regarding any progressive nature of psychopathology and cognitive dysfunction in late-stage schizophrenia, and whether duration of initially untreated psychosis (DUP) might be associated with such 'progression'. This study examines longitudinally, over 3 years, the psychopathology and neuropsychology in 82 inpatients with DSM-IV schizophrenia, many of whom were admitted in the pre-neuroleptic era. Increase in executive dysfunction exceeded that in general cognitive impairment. Positive but not negative symptom severity decreased modestly; the primary predictor of negative symptom severity was DUP. On index assessment, psychopathology evidenced a three-factor structure; at follow-up, psychomotor poverty evidenced greater prominence and cohesion, and was on both occasions predicted primarily by DUP, while reality distortion was altered and disorganisation disassembled into alternative elements. It would appear that as years of chronic, refractory illness accrue, psychomotor poverty becomes more sharply delineated and dominant within the overall structure of psychopathology, and its prominence is predicted enduringly by DUP.

ResumenLa esquizofrenia se asocia con desarrolló neural alterado. Evaluamos los signos neurológicos menores (SNM) y las anomalías dermatoglíficas (recuento total de crestas a-b [RTCAB] y recuento total crestas digitales [RTCD]) en 15 pares de gemelos concordantes y dis-cordantes para esquizofrenia. Las diferencias intrapar en las puntuaciones tanto de SNL como de RTCAB fueron significativamente mayo-res en los pares discordantes comparado con los pares monocigóticos concordantes. No hubo diferencias significativas en las puntuaciones de SNM y RTCAB entre los sujetos con esquizofrenia y los co-gemelos sin la enfermedad. Sin embargo, los gemelos discordantes monocigóticos con esquizofrenia tenían recuentos de crestas a-b (RCAB) mayores en su mano derecha comparado con sus co-gemelos sin la enfermedad. Estos hallazgos indican que un acontecimiento ambiental no identificado que actúa entre las semanas 6 y 15 de la gestación afecta al desarrollo de los gemelos monocigóticos que continúan hasta desarrollar esquizofrenia, pero no tiene un efecto correspondiente en sus co-gemelos que no desarrollan la enfermedad. El efecto de este acontecimiento sobre los perfiles dermatoglíficos parece laterali-zado a la mano derecha en los gemelos afectados.

Schizophrenia is associated with altered neural development. We assessed neurological soft signs (NSS) and dermatoglyphic anomalies (total a-b ridge count (TABRC) and total finger ridge count) in 15 pairs of twins concordant and discordant for schizophrenia. Within-pair differences in both NSS and TABRC scores were significantly greater in discordant compared to concordant monozygotic pairs. There was no significant difference in NSS and TABRC scores between subjects with schizophrenia and their co-twins without the illness. However, monozygotic discordant twins with schizophrenia had higher ABRCs on their right hands compared to their co-twins without the illness. These findings suggest that an unidentified environmental event acting between weeks 6 and 15 of gestation affects the development of monozygotic twins who go on to develop schizophrenia but does not have a corresponding effect on their co-twins who do not develop the illness. The effect of such an event on dermatoglyphic profiles appears lateralised to the right hand in affected twins. (C) 2004 Elsevier SAS. All rights reserved.

Background: Finger and hand prints are formed during the late first and second trimester of foetal development, after which they remain unchanged. Their expression may be influenced by both genetic and environmental factors. Some studies have suggested that a reduced total finger ridge count (TFRC) and, in particular, a reduce total a–b ridge count (TABRC), may be associated with schizophrenia. Aim: To study these two variables in a large, ethnically homogenous sample and to compare our findings with those of other recent studies. Method: Finger and hand prints of 150 people with DSM-III-R schizophrenia were compared with those of 92 healthy controls. Results: Patients had a reduced mean TABRC (P=0.03) compared with controls. There was a significant (P=0.02) linear trend for lower TABRC and increasing incidence of schizophrenia (ORlineartrend=1.3; 95%CI1.1–1.7), implying a continuous increase in the risk for schizophrenia with reduction in TABRC. No significant difference between groups was observed for TFRC. Conclusion: These results provide further evidence that dermatoglyphic abnormalities exist in at least some patients with schizophrenia and that the a–b ridge count may be a marker of disruption, probably environmental, that occurs when the developing brain may also be particularly vulnerable to such insult. These findings support the concept that some cases of schizophrenia may be due to adverse intrauterine events.

We have performed genetic linkage analysis in 13 large multiply affected families, to test the hypothesis that there is extensive heterogeneity of linkage for genetic subtypes of schizophrenia. Our strategy consisted of selecting 13 kindreds containing multiple affected cases in three or more generations, an absence of bipolar affective disorder, and a single progenitor source of schizophrenia with unilineal transmission into the branch of the kindred sampled. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10-cM intervals across the whole genome. We observed LOD scores >3.0 at five distinct loci, either in the sample as a whole or within single families, strongly suggesting etiological heterogeneity. Heterogeneity LOD scores >3.0 in the sample as a whole were found at 1q33.2 (LOD score 3.2; P=.0003), 5q33.2 (LOD score 3.6; P=.0001), 8p22.1-22 (LOD score 3.6; P=.0001), and 11q21 (LOD score 3.1; P=.0004). LOD scores >3.0 within single pedigrees were found at 4q13-31 (LOD score 3.2; P=.0003) and at 11q23.3-24 (LOD score 3.2; P=.0003). A LOD score of 2.9 was also found at 20q12.1-11.23 within in a single family. The fact that other studies have also detected LOD scores >3.0 at 1q33.2, 5q33.2, 8p21-22 and 11q21 suggests that these regions do indeed harbor schizophrenia-susceptibility loci. We believe that the weight of evidence for linkage to the chromosome 1q22, 5q33.2, and 8p21-22 loci is now sufficient to justify intensive investigation of these regions by methods based on linkage disequilibrium. Such studies will soon allow the identification of mutations having a direct effect on susceptibility to schizophrenia.

This study assessed the prevalence of involuntary movements among older inpatients with severe schizophrenia, many of whom had experienced a lifetime of illness and its treatment, and examined their neuropsychological correlates. The subjects of this study were 128 inpatients with a DSM-IV diagnosis of schizophrenia. They were assessed using the Abnormal Involuntary Movement Scale, the Mini-Mental State Examination for general cognitive impairment and the Executive Interview for executive dyscontrol; additionally, their medical records were reviewed in detail for treatment histories. Prevalence of involuntary movements was examined and their clinical correlates determined in relation to topography of movement disorder using logistic regression. In schizophrenia, prevalence of involuntary movements was: age <65years, 63%; 65-75years, 80%; >75years, 93%. The primary correlate both of overall and of orofacial movements was poor executive function, whereas the primary correlate of limb-trunkal movements was poor general cognitive function. On approaching the limits of human longevity following a lifetime trajectory of illness and its treatment, essentially 'all' patients with schizophrenia appear inherently vulnerable to the emergence of involuntary movements in topographically specific association with cognitive deficits.

Timing of intervention with antipsychotic medication may influence long-term outcome in schizophrenia in a manner that is poorly understood. This study evaluated psychopathology, its factor structure, and cognitive dysfunction in older patients with chronic schizophrenia in relation to the intervals from onset of psychosis to initiation of treatment with antipsychotics, and from initiation of antipsychotic treatment to current assessments. The subjects were 129 patients with schizophrenia, many of whom became ill in the preneuroleptic era. Their current psychopathology was assessed using the Positive and Negative Syndrome Scale, and its factor structure examined using principal component analysis. Current general and executive cognitive function was evaluated using the Mini-Mental State Examination and the Executive Interview, respectively. Using multiple regression modelling, increasing duration of initially unmedicated psychosis, but not the much longer duration of subsequently treated illness, was the primary predictor of psychomotor poverty (negative symptoms) but not of reality distortion or disorganisation over the three domains of psychopathology resolved; duration of initially unmedicated psychosis marginally predicted the severity of general, but not of executive, cognitive dysfunction. Delayed intervention with antipsychotics appears associated with poorer long-term course in terms of increased severity of psychopathology in the psychomotor poverty domain.

In order to pursue equity in education, different directions have been taken by scholastic systems in most of the western countries (Origoni, 2007); the government of Cantone Ticino, established the principle of integration and equality of treatment for compulsory school, while it's, no longer pursued when it comes to the non-compulsory upper secondary school, where the objective is a multi- disciplinary formation, well balanced and coherent as condition for academic studies and to respond to society's needs (SKBF|CSRE, 2010). Still, the rate of scholastic failure in first year of upper secondary school in Ticino has increased from the 20% in 1997 to the 29% in 2010. A problem related to scholastic failure in first year persists, and the application of the principle of equity of results, success and achievements is questioned.The aim of the research is to understand reasons behind the growing rate of scholastic failure at first year of upper secondary school in Ticino.A mixed-methods research design (Teddlie & Tashakkori, 2009) has been implemented. A preliminary analysis of statistical data has been conducted; then, exploratory face-to-face interviews with schools principals (n=6) and teachers differentiated by subject matters and years of experience (n=32) have been administered. Afterwards, an extensive quantitative phase on the population of students has been designed. First results highlighted some peculiar dimensions related to failure and success in first year of secondary school. A cultural discontinuity between lower and upper secondary level has been detected, determined by a contraposition of basic assumption (inclusivity on one side and selectivity on the other) and the consequent lack of connection between teachers, programs, learning methods and evaluation.

La catatonie est un syndrome clinique fréquent et pourtant méconnu. Décrite précisément par le psychiatre allemand Karl Kahlbaum à la fin du xixe siècle, la catatonie a connu certains rebondissements nosologiques. Rattachée à la schizophrénie par Emil Kraepelin puis par Eugen Bleuler, il a fallu attendre le milieu du xixe siècle pour reconnaître des catatonies en lien avec d’autres étiologies, notamment des affections somatiques. Ce changement de paradigme a permis de redécouvrir ce syndrome, d’en dessiner une prise en charge et de tenter d’en comprendre l’origine. D’un point de vue diagnostique, nous verrons que quelques signes cardinaux peuvent être retenus : inhibition et rigidité, stéréotypies, agitation sans but, négativisme et ambivalence. Le traitement de la catatonie doit être double : soulager le symptôme, c’est-à-dire lever l’état catatonique, et traiter la cause. Parmi les traitements symptomatiques, certaines benzodiazépines (notamment le lorazépam) et le zolpidem sont efficaces dans la majeure partie des cas et constituent un test diagnostique. En cas d’échec, l’électroconvulsivothérapie reste le traitement de référence en seconde ligne. Concernant la cause de la catatonie, on distingue les affections psychiatriques : les troubles de l’humeur en premier lieu, la schizophrénie, mais aussi l’autisme et la catatonie périodique, et également de très nombreuses causes organiques parmi lesquelles nous soulignerons la place de l’encéphalite à anticorps anti-NMDAR (récepteur N-Méthyl-D-Aspartate du glutamate). Le traitement de la cause doit être entrepris au plus vite et parallèlement au traitement de l’état catatonique, à l’exception des neuroleptiques qui risquent d’aggraver la catatonie s’ils sont administrés trop tôt. La catatonie correspondrait au niveau cérébral à un dysfonctionnement des circuits impliqués dans le mouvement volontaire, en réaction à la peur, le plus souvent sous forme stuporeuse mais parfois sous forme furieuse. Le cortex orbitofrontal latéral, en défaut dans la catatonie, et porteur de récepteurs GABA-A, serait fortement impliqué dans cette réaction primitive qu’il a pour rôle d’inhiber par interaction avec le cortex orbitofrontal médian et l’amygdale.Catatonia is a frequent but unrecognized syndrome. Described in the late nineteenth century by the German psychiatrist Karl Kahlbaum, catatonia has experienced some nosological twists including the attachment to schizophrenia by Emil Kraepelin and Eugen Bleuler. It was not until the mid-nineteenth century that clinicians recognize catatonia related to other etiologies including somatic ones. This paradigm shift has helped to rediscover this syndrome, to find a treatment algorithm and try to understand its pathophysiology. From a diagnostic point of view, we will see that a few cardinal signs may be retained: inhibition and rigidity, stereotypies, aimless agitation, negativity and ambivalence. The treatment of catatonia must be twofold: to relieve the catatonic state, and to treat the cause. Among symptomatic treatments, some benzodiazepines (such as lorazepam) and zolpidem are generally very effective and provide a diagnostic test. If that fails, electroconvulsive therapy is the main second line treatment. Regarding the cause of catatonia, one should distinguish psychiatric disorders: mood disorders, schizophrenia, autism and periodic catatonia; and numerous organic causes among which we will highlight anti-NMDAR (N-Methyl-D-aspartate glutamate receptor) encephalitis. Treating the cause should be undertaken as quickly as possible in parallel with the treatment of the catatonic state, except for neuroleptics which may worsen catatonia if administered early. Catatonia corresponds to a dysfunction of the circuits involved in voluntary movement in response to fear, most often in the form of stupor but sometimes in a furious form. The lateral orbitofrontal cortex, in default in catatonia, and carrier of GABA-A receptors, would be heavily involved in this primitive reaction which it should inhibit by interaction with the median orbitofrontal cortex and the amygdala.

An autoimmune pathogeneses, at least in part, has been postulated for schizophrenia.Susceptibility to autoimmunity is strongly influenced by the genes clustered in the HLA region on chromosome 6, and linkage in a proportion of pedigrees has been reported in nearby markers.There is a negative association between schizophrenia and rheumatoid arthritis (RA), an autoimmune disease positively associated with HLA-DR4.Wright et al. (1996) postulated that there should therefore be a negative association between the DR4 allele and schizophrenia.In addition, a negative association between schizophrenia and DQB 1"0602 has been reported in American blacks (Nimgaonkar et al. 1993), and Chinese males (Zhang et al. 1994).We attempted to re-examine these findings in 229 familial schizophrenic probands and 248 unrelated controls at the DRB region, and 241 familial schizophrenic probands and 257 unrelated controls at the DQB region using the PCR-SSOP technique.The frequencies of DR4 in patients and controls was respectively 35.8 per cent vs. 35.8per cent, and the frequencies of DQBI*0602 in patients and controls was respectively 29.5 per cent vs. 27.6 per cent.These findings do not support the initial hypotheses.Some of the discrepancy may be due to study design in that the control frequencies in the Wright et al study were higher than in other samples from the region.It is also possible that the HLA association with schizophrenia is due to linkage disequilibrium with unidentified gene(s) within the HLA region which is less strong in the Irish population, particularly in the case of DQB 1"0602 as significant results were found.

Auditory verbal hallucinations (AVH) of schizophrenia are associated with a disrupted connectivity between frontal and temporoparietal language areas. We hypothesized that this dysconnectivity is underpinned by white matter abnormalities in the left arcuate fasciculus, the main fiber bundle connecting speech production and perception areas. We therefore investigated the relationship between AVH severity and the integrity of the arcuate fasciculus measured by diffusion tensor imaging (DTI) tractography in patients with schizophrenia.Thirty-eight patients with treatment-resistant schizophrenia were included: 26 presented with daily severe treatment-resistant AVH, 12 reported prominent negative symptoms and no AVH. Fractional anisotropy (FA) was measured along the length of the left and right anterior arcuate fasciculi and severity of AVH was assessed using P3 PANSS item.FA values were significantly higher in the left arcuate fasciculus in patients with AVH than in no AVH patients (F(1,35) = 3.86; p = 0.05). No difference was observed in the right arcuate fasciculus. There was a significant positive correlation between FA value in the left arcuate fasciculus and the severity of AVH (r = 0.36; p = 0.02). No correlation was observed between FA values and PANSS total score suggesting a specific relationship between AVH severity and the left arcuate fasciculus integrity.These results support the hypothesis of a relationship between left frontotemporal connectivity and AVH in patients with schizophrenia and suggest that whilst a disruption of frontotemporal connectivity might be present to ensure the emergence of AVH, more severe anatomical alterations may prevent the occurrence of AVH in patients with schizophrenia.

Background. Evidence suggests that schizophrenia may be a disorder with origins in early intrauterine mal-development. We have constructed a comprehensive anthropometric scale for the evaluation of dysmorphic features as an index of the nature and timing of developmental disturbance.Method. A detailed set of craniofacial and bodily measures was compiled and applied to 174 patients with schizophrenia and 80 matched control subjects.Results. Patients had significantly higher scores on this scale and displayed multiple anomalies of the craniofacial region with an overall narrowing and elongation of the mid-face and lower face. Twelve craniofacial anomalies independently distinguished patients from controls and these variables correctly classified 95% of patients and 80% of control subjects.Conclusions. This new scale, while procedurally more exacting than the Waldrop scale, more clearly defines the topography of anomalies previously suspected in individuals with schizophrenia. These findings constitute direct evidence for disturbed craniofacial development in schizophrenia and indicate origins in the foetal period during which the characteristic human facial pattern evolves in close association with brain differentiation.

Les infections des incisions au triangle de Scarpa sont particulierement redoutees en chirurgie vasculaire parce qu'elles peuvent compromettre les chances de succes d'une revascularisation sous-jacente. Plusieurs methodes de fermeture cutanee ont ete proposees a ce niveau. Notre travail a eu pour but de determiner prospectivement la relation entre la methode de fermeture cutanee et le risque d'infection locale. Cent quatorze malades consecutifs (70 hommes et 44 femmes) ont eu des interventions de revascularisation necessitant 173 incisions au triangle de Scarpa. Ces incisions ont ete randomisees en quatre groupes en fonction de la methode de fermeture cutanee (surjet intra-dermique au Maxon, points separes cutanes au nylon, surjet cutane au nylon ou agrafes) utilisee au-dessus d'une fermeture classique en deux plans de la voie d'abord. Quatorze malades (12 %) etaient diabetiques et 50 (44 %) operes pour troubles trophiques. Vingt-cinq pour cent des malades ont eu un pontage aorto-femoral et les autres 75 % un pontage sous-inguinal. Les malades ont fait l'objet d'un prelevement bacteriologique avant la fermeture de l'incision. La cicatrice a ete inspectee et cultivee a J3, J5, J7, J10 et J14. Nous avons defini comme infection la positivite des cultures. Une infection du triangle de Scarpa est survenue dans 3 % des cas, dont 0,6 % d'infections du greffon. Le type de fermeture cutanee n'a pas influence de facon significative le taux d'infection. Nous n'avons trouve aucune difference en fonction du type de fermeture cutanee choisi. Nous en concluons que le materiel de fermeture cutanee doit etre choisi en fonction de la preference du chirurgien et de considerations economiques