A dismantling study of assertive outreach services: comparing activity and outcomes following replacement with the FACT model.

PURPOSE: Financial constraints and some disappointing research evaluations have seen English assertive outreach (AO) teams subject to remodelling, decommissioning and integration into standard care. We tested a specific alternative model of integrating the AO function from two AO teams into six standard community mental health teams (CMHT). The Flexible Assertive Community Treatment model (FACT) was adopted from the Netherlands (Van Veldhuizen, Commun Mental Health J 43(4):421-433, 2007; Bond and Drake, Commun Mental Health J 43(4):435-438, 2007). We aimed to demonstrate non-inferiority in clinical effectiveness and thereby show cost efficiencies associated with FACT. METHODS: Outcomes were compared in a mirror-image study of the 12 months periods pre- and post-service change with eligible individuals from the AO teams' caseloads (n = 112) acting as their own controls. We also conducted a cost-consequence analysis of the changes. Outcome data regarding admissions, use of crisis and home treatment, frequency of contact and DNA rate were extracted from the electronic patient record. RESULTS: The results show AO patients (n = 112) transferred to standard CMHTs with FACT had significantly fewer admissions and a halving of bed use (21 fewer admission and 2,394 fewer occupied bed days) whilst being in receipt of a less intensive service (2,979 fewer contacts). This was offset by significantly poorer engagement but not by increased use of crisis and home treatment services. CONCLUSIONS: Enhancing multi-disciplinary CMHTs with FACT provides a clinically effective alternative to AO teams. FACT offers a cost-effective model compared to AO.

NKT cell responses to glycolipid activation.

NKT cells are a distinct lineage of T lymphocytes that are usually identified by the co-expression of the semi-invariant CD1d-restricted alphabeta TCR and the NK1.1 allelic marker of NK lineage receptors in the C57BL/6 mice and related strains. NKT cells can be subdivided based on CD4/CD8 expression and on tissue of origin. NKT cells express significantly the TCR gene products Valpha24 JalphaQ in humans, the homolog of mouse Valpha14 Jalpha18, paired with Vbeta11, the homolog of mouse Vbeta8.2. NKT cells are most frequent in liver (up to 30% of T cells in mice and approximately 4% of hepatic T cells in human), bone marrow, and thymus and represent a smaller proportion of T cells in other tissues including spleen, lymph nodes, blood, and lung. NKT cells recognize a broad array of glycolipids in the context of CD1d presentation, and many studies have characterized a cascade of functions following in vitro and in vivo stimulation by alpha-GalCer, including production of high levels of immune-regulatory cytokines and bystander activation of several cell types including NK, B, T, and dendritic cells. Both in vitro and in vivo methods have been developed for the study of NKT responses to glycolipid presentation by CD1d. In practice, CD1d-glycolipid-loaded tetramers would most reliably identify these cells. In vitro, splenocytes can be used to monitor cytokine release as this population contains all the cells necessary for sequestering, loading onto CD1d molecules, and presentation of glycolipids to NKT cells. Another system involves the use of NKT cell hybridoma and CD1d coated onto plastic plates to measure responses limited to NKT cells more precisely. In vivo, responses are typically measured by injecting the glycolipid into mice and monitoring plasma cytokine levels or DC maturation in the spleen. This chapter describes methods that can be used to identify NKT cells and to asses in vitro and in vivo their activation and expansion.

Vaccine adjuvants: scientific challenges and strategic initiatives.

The majority of vaccine antigens currently under investigation represent recombinant molecules or subunits of pathogens with little or no inherent immunostimulatory property. The development of safe and potent immunologic adjuvants that can increase and direct vaccine-specific immunity is, therefore, required urgently. At the same time, the discovery of Toll-like receptors and other innate immune receptors with the ability to bridge innate immune responses and adaptive immunity is offering unprecedented opportunities for the development of novel adjuvants. However, research on vaccine adjuvants has so far received little attention as an independent scientific priority from most of the main research-funding agencies and policy makers. Further, adjuvant research and development is currently spread over a wide number of highly diverse organizations, including large commercial companies, small biotech enterprises as well as publicly funded research organizations and academia. More efforts are, therefore, needed to highlight the importance of vaccine adjuvants on the global research agenda and to encourage collaboration and flow of information between different stakeholders. This article attempts to underline scientific challenges and strategic priorities in the development of vaccine adjuvants for human use.

Vaccine adjuvant formulation: a relatively neglected field that is crucial to vaccine success.

This 3-day conference, with a focus on formulation, is part of a series of conferences organized by Meetings Management on different aspects of vaccine adjuvants. The previous Modern Vaccine/Adjuvants Formulation took place in Prague in 2004 and it was interesting to observe what has changed and what since then remains the same.

ECG score predicts those with the greatest percentage of perfusion defects due to acute pulmonary thromboembolic disease.

BACKGROUND: More aggressive management may be warranted for patients with acute pulmonary embolism (PE) and the greatest pulmonary vascular obstruction. We hypothesized that a scoring system based on the ECG might identify such patients. METHODS: Consecutive patients investigated for PE at Christchurch Hospital between 1997 and 2002 with high-probability ventilation/perfusion (V/Q) scan findings were studied. The ECG obtained closest to and within 48 h of the scan was scored by two independent observers, and the mean ECG score was calculated. V/Q scan findings were categorized into those with < 30%, 30 to 50%, and > 50% perfusion defect by two independent observers experienced in V/Q interpretation. A consensus score was taken when disagreement occurred. RESULTS: Two hundred twenty-nine patients were included in the study. The interobserver agreement for ECG score was 0.96 (Cronbach alpha) and V/Q score was 0.55 (kappa). The ECG predicted those with the greatest amount of perfusion defects. Mean ECG score was 2.6 (SD 2.8) in patients with < 30% perfusion defect, 3.2 (SD 2.9) in patients with 30 to 50% perfusion defect, and 5.3 (SD 3.7) in patients with > 50% perfusion defect. The area under the receiver operating characteristic curve for ECG score and those with > 50% perfusion defect was 0.71 (SE 0.04). An ECG score of > or = 3 predicted those with > 50% perfusion defect with a sensitivity of 70% (95% confidence interval [CI], 59 to 81%), and a specificity of 59% (95% CI, 51 to 67%). CONCLUSION: An ECG score, simple to derive, predicts those with the greatest percentage of perfusion defect. Using the ECG for management warrants prospective evaluation.

The adjuvant OM-174 induces both the migration and maturation of murine dendritic cells in vivo.

The aim of this study was to test the capacity of the novel adjuvant OM-174, a lipid A analog, to induce the migration and the maturation of murine dendritic cells (DC) in vivo, a step which is considered as the initiation of the adaptive immune response. BALB/c mice were injected intravenously or subcutaneously with OM-174. The spleen and popliteal lymph nodes were harvested, and analyzed for DC localization and phenotype. The data presented here clearly show that, OM-174 induces the migration of DC from the periphery to the T cell areas of lymphoid organs, and their maturation into cells expressing high levels of MHC class II and co-stimulatory molecules, with a potency close to that of Escherichia coli lipopolysaccharide (LPS).