Sequence analysis reveals extensive polymorphism and evidence of deletions within the E2 glycoprotein gene of several strains of murine hepatitis virus.

Direct RNA sequence analysis of the E2 gene of wild-type MHV-4 and of neutralization resistant, neuroattenuated variants has identified a polymorphic region with respect to deletions. These variants had large deletions of 142 to 159 amino acids mapping to a localized region in the amino-terminal domain of the peplomer glycoprotein. The nucleotide sequence of the E2 gene for wild-type strain MHV-4 was found to be very similar to that of MHV-JHM but had an insertion of 423 nucleotides resulting in the addition of a stretch of 141 unique amino acids in the amino-terminal domain of E2. We propose that deletions reflect a major source of heterogeneity in the E2 protein of MHV

The V5A13.1 envelope glycoprotein deletion mutant of mouse hepatitis virus type-4 is neuroattenuated by its reduced rate of spread in the central nervous system.

Following intracerebral inoculation of adult Balb/c Byj mice, the MHV-4 strain of mouse hepatitis virus (MHV) had an LD50 of less than 0.1 PFU, whereas its monoclonal antibody resistant variant V5A13.1 had an LD50 of 10(4.2) PFU. To determine the basis for this difference in neurovirulence we have studied the acute central nervous system (CNS) infection of these two viruses by in situ hybridization. Both viruses infected the same, specific neuroanatomical areas, predominantly neurons, and spread via the cerebrospinal fluid, along neuronal pathways and between adjacent cells. The neuronal nuclei infected and the spread of virus within the brain are described. The main difference between the parental and variant viruses was the rate at which the infection spread. MHV-4 spread rapidly, destroying large numbers of neurons and the animals died within 4 days of infection. The variant virus spread to the same areas of the brain but at a slower rate. This difference in the rate of virus spread was also apparent from the brain virus titers. The slower rate of spread of the variant virus appears to allow intervention by the immune response. Consistent with this, the variant virus spread slowly in athymic nu/nu mice, but in the absence of an intact immune response, infection and destruction of neurons eventually reached the same extent as that of the parental virus and the mice died within 6 days of infection. We conclude that the V5A13.1 variant of MHV-4 is neuroattenuated by its slower rate of spread in the CNS

Consultation liaison in primary care for people with mental disorders

BACKGROUND: Approximately 25% of people will be affected by a mental disorder at some stage in their life. Despite the prevalence and negative impacts of mental disorders, many people are not diagnosed or do not receive adequate treatment. Therefore primary health care has been identified as essential to improving the delivery of mental health care. Consultation liaison is a model of mental health care where the primary care provider maintains the central role in the delivery of mental health care with a mental health specialist providing consultative support. Consultation liaison has the potential to enhance the delivery of mental health care in the primary care setting and in turn improve outcomes for people with a mental disorder. OBJECTIVES: To identify whether consultation liaison can have beneficial effects for people with a mental disorder by improving the ability of primary care providers to provide mental health care. SEARCH METHODS: We searched the EPOC Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), and bibliographic databases: MEDLINE, EMBASE, CINAHL and PsycINFO, in March 2014. We also searched reference lists of relevant studies and reviews to identify any potentially relevant studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) which compared consultation liaison to standard care or other service models of mental health care in the primary setting. Included participants were people attending primary care practices who required mental health care or had a mental disorder, and primary care providers who had direct contact with people in need of mental health care. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of identified studies against the inclusion criteria and extracted details including the study design, participants and setting, intervention, outcomes and any risk of bias. We resolved any disagreements by discussion or referral to a third author. We contacted trial authors to obtain any missing information.We collected and analysed data for all follow-up periods: up to and including three months following the start of treatment; between three and 12 months; and more than 12 months following the start of therapy.We used a random-effects model to calculate the risk difference (RD) for binary data and number needed to treat for an additional beneficial outcome (NNTB), if differences between groups were significant. The mean difference (MD) or standardised mean difference (SMD) was calculated for continuous data. MAIN RESULTS: There were 8203 citations identified from database searches and reference lists. We included 12 trials with 2605 consumer participants and more than 905 primary care practitioner participants. Eleven trials compared consultation liaison to standard care and one compared consultation liaison to collaborative care, with a case manager co-ordinating mental health care. People with depression were included in eight trials; and one trial each included people with a variety of disorders: depression, anxiety and somatoform disorders; medically unexplained symptoms; and drinking problems. None of the included trials reported separate data for children or older people.There was some evidence that consultation liaison improved mental health up to three months following the start of treatment (two trials, n = 445, NNTB 8, 95% CI 5 to 25) but there was no evidence of its effectiveness between three and 12 months. Consultation liaison also appeared to improve consumer satisfaction (up to three months: one trial, n = 228, NNTB 3, 95% CI 3 to 5; 3 to 12 months: two trials, n = 445, NNTB 8, 95% CI 5 to 17) and adherence (3 to 12 months: seven trials, n = 1251, NNTB 6, 95% CI 4 to 13) up to 12 months. There was also an improvement in the primary care provider outcomes of providing adequate treatment between three to 12 months (three trials, n = 797, NNTB 7, 95% CI 4 to 17) and prescribing pharmacological treatment up to 12 months (four trials, n = 796, NNTB 13, 95% CI 7 to 50). There was also some evidence that consultation liaison may not be as effective as collaborative care in regards to symptoms of mental disorder, disability, general health status, and provision of treatment.The quality of these findings were low for all outcomes however, apart from consumer adherence from three to 12 months, which was of moderate quality. Eight trials were rated a high risk of performance bias because consumer participants were likely to have known whether or not they were allocated to the intervention group and most outcomes were self reported. Bias due to attrition was rated high in eight trials and reporting bias was rated high in six. AUTHORS' CONCLUSIONS: There is evidence that consultation liaison improves mental health for up to three months; and satisfaction and adherence for up to 12 months in people with mental disorders, particularly those who are depressed. Primary care providers were also more likely to provide adequate treatment and prescribe pharmacological therapy for up to 12 months. There was also some evidence that consultation liaison may not be as effective as collaborative care in terms of mental disorder symptoms, disability, general health status, and provision of treatment. However, the overall quality of trials was low particularly in regards to performance and attrition bias and may have resulted in an overestimation of effectiveness. More evidence is needed to determine the effectiveness of consultation liaison for people with mental disorders particularly for those with mental disorders other than depression

Is there a gap between recommended and ‘real world’ practice in the management of depression in young people? A medical file audit of practice

BACKGROUND: Literature has shown that dissemination of guidelines alone is insufficient to ensure that guideline recommendations are incorporated into every day clinical practice. METHODS: We aimed to investigate the gaps between guideline recommendations and clinical practice in the management of young people with depression by undertaking an audit of medical files in a catchment area public mental health service for 15 to 25 year olds in Melbourne, Australia. RESULTS: The results showed that the assessment and recording of depression severity to ensure appropriate treatment planning was not systematic nor consistent; that the majority of young people (74.5%) were prescribed an antidepressant before an adequate trial of psychotherapy was undertaken and that less than 50% were monitored for depression symptom improvement and antidepressant treatment emergent suicide related behaviours (35% and 30% respectively). Encouragingly 92% of first line prescriptions for those aged 18 years or under who were previously antidepressant-naïve was for fluoxetine as recommended. CONCLUSIONS: This research has highlighted the need for targeted strategies to ensure effective implementation. These strategies might include practice system tools that allow for systematic monitoring of depression symptoms and adverse side effects, particularly suicide related behaviours. Additionally, youth specific psychotherapy that incorporates the most effective components for this age group, delivered in a youth friendly way would likely aid effective implementation of guideline recommendations for engagement in an adequate trial of psychotherapy before medication is initiated

Evidence translation in a youth mental health service: clinician perspectives

An evidence–practice gap is well established in the mental health field, and knowledge translation is identified as a key strategy to bridge the gap. This study outlines a knowledge translation strategy, which aims to support clinicians in using evidence in their practice within a youth mental health service ( headspace). We aim to evaluate the strategy by exploring clinicians’ experiences and preferences. The translation strategy includes the creation and dissemination of evidence translation resources that summarize the best available evidence and practice guidelines relating to the management of young people with mental disorders. Semi-structured interviews were conducted with 14 youth mental health clinicians covering three topics: experiences with evidence translation resources, preferences for evidence presentation, and suggestions regarding future translation efforts. Interviews were recorded, transcribed verbatim, coded, and analyzed using thematic analysis. Themes were both predetermined by interview topic and identified freely from the data. Clinicians described their experiences with the evidence translation resources as informing decision making, providing a knowledge base, and instilling clinical confidence. Clinicians expressed a preference for brief, plain language summaries and for involvement and consultation during the creation and dissemination of resources. Suggestions to improve the dissemination strategy and the development of new areas for evidence resources were identified. The knowledge translation efforts described support clinicians in the provision of mental health services for young people. The preferences and experiences described have valuable implications for services implementing knowledge translation strategies

Development of practice principles for the management of ongoing suicidal ideation in young people diagnosed with major depressive disorder

Objectives: There is a lack of clear guidance regarding the management of ongoing suicidality in young people experiencing major depressive disorder. This study utilised an expert consensus approach in identifying practice principles to complement relevant clinical guidelines for the treatment of major depressive disorder in young people. The study also sought to outline a broad treatment framework for clinical intervention with young people experiencing ongoing suicidal ideation. Methods: In-depth focus groups were undertaken with a specialist multidisciplinary clinical team (the Youth Mood Clinic at Orygen Youth Health Clinical Program, Melbourne) working with young people aged 15–25 years experiencing ongoing suicidal ideation. Each focus group was audio recorded and transcribed verbatim using orthographic conventions. Principles of grounded theory and thematic analysis were used to analyse and code the resultant data. Results: The identified codes were subsequently synthesised into eight practice principles reflecting engagement and consistency of care, ongoing risk assessment and documentation, individualised crisis planning, engaging systems of support, engendering hopefulness, development of adaptive coping, management of acute risk, and consultation and supervision. Conclusions: The identified practice principles provide a broad management framework, and may assist to improve treatment consistency and clinical management of young people experiencing ongoing suicidal ideation. The practice principles may be of use to health professionals working within a team-based setting involved in the provision of care, even if peripherally, to young people with ongoing suicidal ideation. Findings address the lack of treatment consistency and shared terminology and may provide containment and guidance to multidisciplinary clinicians working with this at-risk group

H α fluxes and extinction distances for planetary nebulae in the IPHAS survey of the northern galactic plane

We report H α filter photometry for 197 Northern hemisphere planetary nebulae (PNe) obtained using imaging data from the IPHAS survey. H α+[N II] fluxes were measured for 46 confirmed or possible PNe discovered by the IPHAS survey and for 151 previously catalogued PNe that fell within the area of the northern Galactic Plane surveyed by IPHAS. After correcting for [N II] emission admitted by the IPHAS H α filter, the resulting H α fluxes were combined with published radio free–free fluxes and H β fluxes, in order to estimate mean optical extinctions to 143 PNe using ratios involving their integrated Balmer line fluxes and their extinction-free radio fluxes. Distances to the PNe were then estimated using three different 3D interstellar dust extinction mapping methods, including the IPHAS-based H-MEAD algorithm of Sale (2014). These methods were used to plot dust extinction versus distance relationships for the lines of sight to the PNe; the intercepts with the derived dust optical extinctions allowed distances to the PNe to be inferred. For 17 of the PNe in our sample reliable GaiaDR2 distances were available and these have been compared with the distances derived using three different extinction mapping algorithms as well as with distances from the nebular radius versus H α surface brightness relation of Frew et al. (2016). That relation and the H-MEAD extinction mapping algorithm yielded the closest agreement with the Gaia DR2 distances