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BACKGROUND: Successive governments have urged mental health service providers to target their attentions on people with severe and enduring mental illness (SEMI). However, community mental health teams (CMHTs) in general, and community mental health nurses (CMHNs) in particular, have been criticized for failing to meet this requirement. This paper reports selected findings from a wider study that assessed the impact of an initiative designed to facilitate service targeting: the establishment of registers of patients with SEMI in general practices throughout an English health district. The paper describes changes in the nature of community mental health nursing contacts with a sample of patients on these registers. METHODS: Six general practices were randomly selected from the 65 practices in the district and comparisons made between patients on the six mental health registers who either had, or did not have, community mental health nursing contact. These comparisons related to the year before the establishment of the registers, the year during which they were being established and the year following this. RESULTS: A total of 274 patients were included on the sample registers, with practices varying considerably in relation to proportions of mental health registered patients with community mental health nursing contact. Overall, the number of patients in contact with CMHNs was found to have decreased over time, except for those on level 2 of the Care Programme Approach. CONCLUSIONS: No evidence was found to support the hypothesis that the establishment of the registers had improved CMHN targeting of patients with SEMI. However, findings were inconclusive because shortages of CMHNs and the disruption associated with widespread service reorganization meant the registers were never fully implemented in practices during the study period. [ABSTRACT FROM AUTHOR]

Evaluates the introduction of mental health case registers for defining severe or enduring mental illness in Great Britain. Obstacles in identifying high priority group; Guidelines for categorizing people based on prescription; Implications for the development of services for people with severe or enduring mental illness.

The National Institute for Health Research (NIHR) has identified a gap in the number of people it funds who are on a pathway to become future leaders of clinical trials, compared to how much the NIHR invests in clinical trials. In order to support the clinical trials of tomorrow, it is vital that the right people are supported now to lead these trials. To address this issue, NIHR organised a workshop with key stakeholders to understand the barriers to embarking on a clinical trials career and explore initiatives to increase capacity and capability in clinical trials. The output from the workshop was a set of recommendations which NIHR is now considering to shape future support.

Background/objective: Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn's disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed., Methods: British Caucasian subjects with inflammatory bowel disease (n=500) and 877 ethnically matched controls were genotyped for the disease-associated variants in IL23R and ATG16L1. In addition, meta-analyses of 12,991 patients and 14,598 controls, and 11,909 patients and 15,798 controls, were conducted on independently published data for the associations between IL23R and ATG16L1 variants and CD, respectively., Results: In the present cohort, both susceptibility variants showed highly significant associations, including IL23R (rs11209026, P=0.0006; OR 0.37; 95% CI 0.21 to 0.67) and ATG16L1 (rs2241880, P=0.0017; OR 1.36; 95% CI 1.12 to 1.66). The meta-analysis based on the random effects model showed similar combined effects for rs11209026 (n=26, OR 0.41; 95% CI 0.37 to 0.46) and rs2241880 (n=25, OR 1.33; 95% CI 1.28 to 1.39). There was no statistically significant gene-gene interaction between caspase recruitment domain (CARD15) variants and the IL23R or ATG16L1 polymorphisms (P=0.44 and P=0.24, respectively)., Conclusion: The present cohort and meta-analysis provides strong evidence that, in addition to CARD15, polymorphisms in both IL23R and ATG16L1 alter susceptibility to CD and that these effects are consistent across all populations of European ancestry; however, only ATG16L1 is relevant to inflammatory bowel disease in the Asian population.

NK cells acquire the ability to recognize MHC class I molecules during development. Studies with Qa-1(b) tetramers (Qa-1 tetramers) showed that nearly all NK1.1(+) cells from newborn C57BL/6 mice express Qa-1-binding receptors. Cytotoxic activity of these cells is fully inhibited by Qa-1 ligands on target cells. In contrast, neither receptors for H-2K(b) nor H-2D(b) were observed on NK1.1(+) cells from newborn mice. After birth, frequencies of Qa-1 tetramer(+)/ NK1.1(+) cells gradually decrease as the number of Ly49(+) /NK1.1(+) cells increases. Cell transfer studies showed that Qa-1 tetramer(+) cells from newborn mice do not lose expression of Qa-1 receptors, but that they further acquire expression of Ly49 molecules. Acquisition of Qa-1-binding receptors appears largely independent of host MHC class I molecules, as observed in studies using beta2-microglobulin-deficient (beta2m(-/-)) mice as well as K(b)/ D(b-/-) and K(b)/D(b)/beta2m(-/-) mice. The present results suggest that Qa-1-binding receptors play an important role in the specificity of developing NK cells, and suggest that these cells rely mainly on inhibitory receptors specific for non-classical MHC class I molecules to maintain self tolerance during the first weeks of life.

In 1995 the Department of Health issued guidance on continuing health care following the health service commissioner's finding against Leeds Health Authority for failing to provide long-term care. Under this guidance, health authorities were required to agree continuing health care policies and eligibility criteria with fundholders and local authorities. This study sought to investigate the extent to which the drafting of local policies and criteria, within the framework of national guidance, led to consistency between health authorities. A structured content analysis was conducted of all the policies and eligibility criteria in three regions. In particular, it aimed to establish the comprehensiveness of local policies, the nature of local criteria, the consistency of each between authorities and with the guidance, the development of plans for reinvestment and the balance between institutional and domiciliary services. Only a minority of authorities were found to have identified investments in services, notwithstanding the requirement to do so in the guidance. In addition, most documents were not comprehensive in their coverage of client groups, with more information being provided about services for older people and those with mental health problems. Few policies contained action plans to translate general intentions about equity and consistency into practice. Eligibility criteria frequently took the form of descriptions of services and/or were so general that they would be difficult to apply in individual cases. Most documents contained no criteria for community health services. Whilst just over half of them included the aim of moving resources from acute to community sectors, they contained far more detail about institutionally based services and, for a number of reasons, appeared likely to reinforce the imbalance towards the latter. The documents analysed were part of an evolutionary process of understanding the contribution of effective continuing care to managing pressures on acute beds. Their impact on patients and their families must, however, await the findings from subsequent stages of this research.

As the focus of mental health care has shifted from the hospital to the community, so the importance of effectively targeting resources on those with the greatest need has become paramount. One approach to identifying and targeting people deemed to have severe and enduring mental health problems is the establishment of mental health case registers at primary care level. This paper raises a number of conceptual issues associated with these registers and, on the basis of the available literature, offers suggestions to guide those who are contemplating their introduction.

Fetal mouse NK cells are grossly deficient in the expression of Ly49 molecules yet show a limited ability to distinguish between wild-type and MHC class I-deficient target cells. In this paper we report that during their development in vitro from immature thymic progenitors, a proportion of C57BL/6 fetal NK cells acquires receptors for a soluble form of the nonclassical class I molecule Qa1b associated with the Qdm peptide, but not for soluble forms of the classical class I molecules Kb and Db. The acquisition of these Qa1 receptors occurs in a stochastic manner that is strictly controlled by cytokines, and in particular is strongly inhibited by IL-4. All fetal NK clones tested, including those that lack detectable Qa1 receptors, express mRNA for CD94 and for both inhibitory and noninhibitory members of the NKG2 family. Fetal NK cells lacking receptors for Qa1 (and also for classical class I molecules) cannot distinguish between wild-type and class I-deficient blasts but, surprisingly, distinguish efficiently between certain wild-type and class I-deficient tumor cells. A variant line that lacks several members of the NKG2 family kills both types of tumor cell equally well, suggesting the existence of NKG2-containing inhibitory receptors that recognize as yet undefined nonclassical class I molecules of restricted distribution.

The peptide-binding properties of the nonclassical major histocompatibility complex (MHC) class 1b molecule Qa-1 were investigated using a transfected hybrid molecule composed of the alpha 1 and alpha 2 domains of Qa-1b and the alpha 3 domain of H-2Db. This allowed the use of a monoclonal antibody directed against H-2Db whilst retaining the peptide-binding groove of Qa-1b. By comparison with classical MHC class I molecules, intracellular maturation of the chimeric molecule was inefficient with weak intracellular association with beta 2-microglobulin. However, at the cell surface the hybrid molecules were stably associated with beta 2-microglobulin and were recognized by cytotoxic T lymphocyte (CTL) clones specific for the Qa-1b-presented peptide Qdm (AMAPRTLLL). A whole-cell binding assay was used to determine which residues of Qdm were important for binding to Qa-1b and CTL clones served to identify residues important for T cell recognition. Substitutions at position 1 and 5 did not reduce the efficiency of binding and had little effect on CTL recognition. In contrast, substitutions at position 9 resulted in loss of MHC class I binding. Mass spectrometric analysis of peptides eluted from immunopurified Qa-1b/Db molecules indicated that Qdm was the dominant peptide. The closely related peptide, AMVPRTLLL, which is derived from the signal sequence of H-2Dk, was also present, although it was considerably less abundant. The mass profile suggested the presence of additional peptides the majority of which consisted of eight to ten amino acid residues. Finally, the finding that a peptide derived from Klebsiella pneumoniae can bind raises the possibility that this non-classical MHC class I molecule may play a role in the presentation of peptides of microorganisms.

The paper presents an analysis of the psychiatric care histories of people diagnosed with schizophrenia which is set within the policy context of the deinstitutionalisation debate. The durations of successive terms of in-patient and community care were drawn from the records of the Salford Psychiatric Case Register and related to the age, gender and social isolation of each patient. Strong age-sex interactions are revealed by the tendencies for young male patients to exhibit rapid hospital readmission and discharge rates and elderly female patients to experience long terms of in-patient care. The role of social isolation in relation to these care durations turns out to be more restricted.