The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.

We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.

The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.

Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.

We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.

This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.

Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).

Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.

This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.

Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).

For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.

La prise en charge optimale du sepsis grave dans les départements d'urgence a connu une évolution rapide. Le but des présentes lignes directrices est de revoir pour le bénéfice des médecins d'urgence canadiens les principes clés qui régissent la prise en charge du sepsis grave en se fondant sur un système de classification fondé sur des preuves.

Ce sont les membres du comité de l'ACMU pour les soins critiques, ou comité C4 (pour CAEP Critical Care Interest Group) qui ont déterminé les secteurs clés de la prise en charge des patients atteints de sepsis. Chaque membre du C4 avait pour tâche de répondre à une question qui lui avait été assignée après avoir fait un survol de la littérature établie selon le système de classification Oxford, après quoi, chaque secteur faisait l'objet d'une seconde révision par un autre membre du C4. D'autres experts de l'extérieur ont procédé à un troisième examen et les modifications ont été déterminées par voie de consensus. La classification reposait sur des publications révisées par des pairs uniquement, et là où les preuves étaient insuffisantes pour répondre à une question importante, le groupe a proposé un «point pratique».

Le projet a débuté en 2005 et a pris fin en décembre 2007. Les secteurs clés qui ont été passés en revue incluent la définition du terme sepsis, l'utilisation des interventions effractives, la réanimation liquidienne, l'utilisation d'agents vasopresseurs/inotropes, l'importance des prélèvements pour culture aux départements d'urgence, l'antibiothérapie et le contrôle des sources. Parmi les autres secteurs examinés, mentionnons l'utilisation des corticostéroïdes, la protéine C activée, les transfusions et la ventilation mécanique.

La prise en charge précoce du sepsis dans les départements d'urgence est extrêmement importante pour améliorer le pronostic des patients. L'énoncé de position du C4 sur le sepsis fournit un cadre de travail afin d'améliorer les soins prodigués à cette population de patients dans les départements d'urgence.

Optimal management of severe sepsis in the ED has evolved rapidly. The purpose of these guidelines is to review key management principles for Canadian emergency physicians, utilizing an evidence-based grading system.

Key areas in the management of septic patents were determined by members of the CAEP Critical Care Interest Group (C4). Members of C4 were assigned a question to be answered after literature review, based on the Oxford grading system. After completion, each section underwent a secondary review by another member of C4. A tertiary review was conducted by additional external experts, and modifications were determined by consensus. Grading was based on peer-reviewed publications only, and where evidence was insufficient to address an important topic, a “practice point” was provided based on group opinion.

The project was initiated in 2005 and completed in December 2007. Key areas which were reviewed include the definition of sepsis, the use of invasive procedures, fluid resuscitation, vasopressor/inotrope use, the importance of culture acquisition in the ED, antimicrobial therapy and source control. Other areas reviewed included the use of corticosteroids, activated protein C, transfusions and mechanical ventilation.

Early sepsis management in the ED is paramount for optimal patient outcomes. The CAEP Critical Care Interest Group Sepsis Position Statement provides a framework to improve the ED care of this patient population.