Correction: Detection of a Serum Siderophore by LC-MS/ MS as a Potential Biomarker of Invasive Aspergillosis.

[This corrects the article DOI: 10.1371/journal.pone.0151260.].

Detection of a Serum Siderophore by LC-MS/MS as a Potential Biomarker of Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening systemic mycosis caused primarily by Aspergillus fumigatus. Early diagnosis of IA is based, in part, on an immunoassay for circulating fungal cell wall carbohydrate, galactomannan (GM). However, a wide range of sensitivity and specificity rates have been reported for the GM test across various patient populations. To obtain iron in vivo, A. fumigatus secretes the siderophore, N,N',N"-triacetylfusarinine C (TAFC) and we hypothesize that TAFC may represent a possible biomarker for early detection of IA. We developed an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for TAFC analysis from serum, and measured TAFC in serum samples collected from patients at risk for IA. The method showed lower and upper limits of quantitation (LOQ) of 5 ng/ml and 750 ng/ml, respectively, and complete TAFC recovery from spiked serum. As proof of concept, we evaluated 76 serum samples from 58 patients with suspected IA that were investigated for the presence of GM. Fourteen serum samples obtained from 11 patients diagnosed with probable or proven IA were also analyzed for the presence of TAFC. Control sera (n = 16) were analyzed to establish a TAFC cut-off value (≥6 ng/ml). Of the 36 GM-positive samples (≥0.5 GM index) from suspected IA patients, TAFC was considered positive in 25 (69%). TAFC was also found in 28 additional GM-negative samples. TAFC was detected in 4 of the 14 samples (28%) from patients with proven/probable aspergillosis. Log-transformed TAFC and GM values from patients with proven/probable IA, healthy individuals and SLE patients showed a significant correlation with a Pearson r value of 0.77. In summary, we have developed a method for the detection of TAFC in serum that revealed this fungal product in the sera of patients at risk for invasive aspergillosis. A prospective study is warranted to determine whether this method provides improved early detection of IA.

Barriers to collaboration in mental health services for older people: external agency views.

The need for mental health services for older people living in rural areas is increasing in South Australia. Providing such care requires coordination between several types of services across government, hospital and non-government sectors. The purpose of this study was to identify barriers to collaboration from the perspective of external aged care agencies. A total of 42 responses from an online survey were qualitatively analysed. Four categories emerged, within which participants had identified barriers to collaboration: (1) awareness of services and certainty about responsibilities, in particular, a lack of awareness of which services are available; (2) referral criteria and processes, including the specific criteria needed to be eligible for these services; (3) opportunities to collaborate, with a perceived lack of formal opportunities for collaboration between individuals working across agencies; and (4) education of staff, with more joint education between agencies being recognised as having the potential to increase local knowledge and provide an opportunity for networking and relationship building, with greatest barriers experienced between mental health and social care services.

Helping and hindering: perceptions of enablers and barriers to collaboration within a rural South Australian mental health network.

OBJECTIVE: To evaluate clinicians' perceptions of what helps and hinders the delivery of mental health care across a service network in a rural setting. DESIGN: Qualitative, semistructured interviews were conducted with 10 individuals who work in one rural mental health care service network. SETTING: A regional centre in rural South Australia involving representatives of the mental health team, general practice, hospital, community health and nongovernment organisations. RESULTS: Clinicians' perceptions of barriers and enablers to working within their mental health care network were explored. Participants showed a strong shared commitment to effective mental health care delivery and a good understanding of the services that each offers. Interview data suggested that working relationships between local services could be perceived as stronger when a personal or historical element is recognisable. Similarly, the notion of familiarity and community involvement were perceived as facilitators in this network. A perceived barrier for participants was the failure to attract staff with mental health experience, leading to dependence upon the dedication and commitment of existing service providers. CONCLUSIONS: Collaboration is especially necessary in rural areas, where access to health care services is known to be difficult. The informality of relationships between service providers was shown to be the main facilitator in the network. This is both a strength as it promotes the communication between services and service providers that is essential for successful collaboration, yet is also a threat to the sustainability of the network based on the difficulties of staff recruitment and retention to rural settings.

Shared care in mental illness: A rapid review to inform implementation.

BACKGROUND: While integrated primary healthcare for the management of depression has been well researched, appropriate models of primary care for people with severe and persistent psychotic disorders are poorly understood. In 2010 the NSW (Australia) Health Department commissioned a review of the evidence on "shared care" models of ambulatory mental health services. This focussed on critical factors in the implementation of these models in clinical practice, with a view to providing policy direction. The review excluded evidence about dementia, substance use and personality disorders. METHODS: A rapid review involving a search for systematic reviews on The Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects (DARE). This was followed by a search for papers published since these systematic reviews on Medline and supplemented by limited iterative searching from reference lists. RESULTS: Shared care trials report improved mental and physical health outcomes in some clinical settings with improved social function, self management skills, service acceptability and reduced hospitalisation. Other benefits include improved access to specialist care, better engagement with and acceptability of mental health services. Limited economic evaluation shows significant set up costs, reduced patient costs and service savings often realised by other providers. Nevertheless these findings are not evident across all clinical groups. Gains require substantial cross-organisational commitment, carefully designed and consistently delivered interventions, with attention to staff selection, training and supervision. Effective models incorporated linkages across various service levels, clinical monitoring within agreed treatment protocols, improved continuity and comprehensiveness of services. CONCLUSIONS: "Shared Care" models of mental health service delivery require attention to multiple levels (from organisational to individual clinicians), and complex service re-design. Re-evaluation of the roles of specialist mental health staff is a critical requirement. As expected, no one model of "shared" care fits diverse clinical groups. On the basis of the available evidence, we recommended a local trial that examined the process of implementation of core principles of shared care within primary care and specialist mental health clinical services.

Effectiveness of service linkages in primary mental health care: a narrative review part 1.

BACKGROUND: With the move to community care and increased involvement of generalist health care providers in mental health, the need for health service partnerships has been emphasised in mental health policy. Within existing health system structures the active strategies that facilitate effective partnership linkages are not clear. The objective of this study was to examine the evidence from peer reviewed literature regarding the effectiveness of service linkages in primary mental health care. METHODS: A narrative and thematic review of English language papers published between 1998 and 2009. Studies of analytic, descriptive and qualitative designs from Australia, New Zealand, UK, Europe, USA and Canada were included. Data were extracted to examine what service linkages have been used in studies of collaboration in primary mental health care. Findings from the randomised trials were tabulated to show the proportion that demonstrated clinical, service delivery and economic benefits. RESULTS: A review of 119 studies found ten linkage types. Most studies used a combination of linkage types and so the 42 RCTs were grouped into four broad linkage categories for meaningful descriptive analysis of outcomes. Studies that used multiple linkage strategies from the suite of "direct collaborative activities" plus "agreed guidelines" plus "communication systems" showed positive clinical (81%), service (78%) and economic (75%) outcomes. Most evidence of effectiveness came from studies of depression. Long term benefits were attributed to medication concordance and the use of case managers with a professional background who received expert supervision. There were fewer randomised trials related to collaborative care of people with psychosis and there were almost none related to collaboration with the wider human service sectors. Because of the variability of study types we did not exclude on quality or attempt to weight findings according to power or effect size. CONCLUSION: There is strong evidence to support collaborative primary mental health care for people with depression when linkages involve "direct collaborative activity", plus "agreed guidelines" and "communication systems".

Building effective service linkages in primary mental health care: a narrative review part 2.

BACKGROUND: Primary care services have not generally been effective in meeting mental health care needs. There is evidence that collaboration between primary care and specialist mental health services can improve clinical and organisational outcomes. It is not clear however what factors enable or hinder effective collaboration. The objective of this study was to examine the factors that enable effective collaboration between specialist mental health services and primary mental health care. METHODS: A narrative and thematic review of English language papers published between 1998 and 2009. An expert reference group helped formulate strategies for policy makers. Studies of descriptive and qualitative design from Australia, New Zealand, UK, Europe, USA and Canada were included. Data were extracted on factors reported as enablers or barriers to development of service linkages. These were tabulated by theme at clinical and organisational levels and the inter-relationship between themes was explored. RESULTS: A thematic analysis of 30 papers found the most frequently cited group of factors was "partnership formation", specifically role clarity between health care workers. Other factor groups supporting clinical partnership formation were staff support, clinician attributes, clinic physical features and evaluation and feedback. At the organisational level a supportive institutional environment of leadership and change management was important. The expert reference group then proposed strategies for collaboration that would be seen as important, acceptable and feasible. Because of the variability of study types we did not exclude on quality and findings are weighted by the number of studies. Variability in local service contexts limits the generalisation of findings. CONCLUSION: The findings provide a framework for health planners to develop effective service linkages in primary mental health care. Our expert reference group proposed five areas of strategy for policy makers that address organisational level support, joint clinical problem solving, local joint care guidelines, staff training and supervision and feedback.

Secondary prevention of osteoporosis post minimal trauma fracture in an Australian regional and rural population.

OBJECTIVE: Minimal trauma fracture (MTF) is an indication of osteoporosis and risk of future fracture. Our objective was to describe osteoporosis risk identification and secondary prevention in a regional and rural population hospitalised for an MTF. DESIGN: A retrospective inpatient file audit and follow-up telephone interview. SETTING: Patients aged 45 years and over admitted for MTF management to two regional hospitals in northern New South Wales between July 2006 and June 2007. MAIN OUTCOME MEASURES: Proportion of patients who received bone mineral densitometry (BMD) assessment and proportion commenced on osteoporosis medication post fracture. RESULTS: There were 459 patients included in our inpatient file audit. During admission only 16% had osteoporosis risk documented, uptake of vitamin D assay or BMD were minimal and only 22% were discharged on preventive medication. Of 219 patients contacted post discharge, 36% reported discussing osteoporosis risk with their GPs, 22% reported post-discharge BMD and 32% were taking a bisphosphonate. Men were less likely to have commenced preventive medication (OR 0.42, CI, 0.19-0.91) and patients informed of their osteoporosis risk during hospitalisation were more likely to have had BMD (OR 1.93, CI, 1.03-3.61). Neither age nor history of previous MTF was predictive of preventive treatment post discharge. CONCLUSION: Overall, fracture risk identification and initiation of secondary prevention in this regional and rural population was low and this is consistent with findings in recent metropolitan studies. Effective regional and rural strategies are required that ensure identification and effective communication of risk to patients and their GPs.

Service network analysis for agricultural mental health.

BACKGROUND: Farmers represent a subgroup of rural and remote communities at higher risk of suicide attributed to insecure economic futures, self-reliant cultures and poor access to health services. Early intervention models are required that tap into existing farming networks. This study describes service networks in rural shires that relate to the mental health needs of farming families. This serves as a baseline to inform service network improvements. METHODS: A network survey of mental health related links between agricultural support, health and other human services in four drought declared shires in comparable districts in rural New South Wales, Australia. Mental health links covered information exchange, referral recommendations and program development. RESULTS: 87 agencies from 111 (78%) completed a survey. 79% indicated that two thirds of their clients needed assistance for mental health related problems. The highest mean number of interagency links concerned information exchange and the frequency of these links between sectors was monthly to three monthly. The effectiveness of agricultural support and health sector links were rated as less effective by the agricultural support sector than by the health sector (p < .05). The most highly linked across all areas of activity were Rural Financial Counsellors, the Department of Primary Industry Drought Support Workers and Community Health Centres. Hence for a mental health service network targeting farming families these are three key agencies across the spectrum of case work to program development. The study limitations in describing service networks relate to the accuracy of network bounding, self report bias and missing data from non participants. CONCLUSION: Aligning with agricultural agencies is important to build effective mental health service pathways to address the needs of farming populations. Work is required to ensure that these agricultural support agencies have operational and effective links to primary mental health care services. Network analysis provides a baseline to inform this work. With interventions such as local mental health training and joint service planning to promote network development we would expect to see over time an increase in the mean number of links, the frequency in which these links are used and the rated effectiveness of these links.

The two-component system sivS/R regulates virulence in Streptococcus iniae.

Streptococcus iniae causes invasive disease and death in fish, and to a lesser extent, sporadic cases of soft-tissue infections in humans. A two-component system termed sivS/R, which regulates capsule expression, was previously identified and characterized. In this study, it is shown that a sivS/R deletion-insertion mutant, termed 9117Deltasiv, causes transient bacteremia and reduced virulence compared with the parent strain when tested in a murine model of bacteremic infection. Furthermore, real-time PCR studies indicated that SivS/R regulates the expression levels of the streptolysin S structural gene, sagA, as well as the CAMP factor gene, cfi. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of S. iniae spheroplasts revealed downregulation of three surface proteins in the mutant strain compared with the parent strain. These proteins were identified by MS to be a putative lipoprotein, a hyaluronate-associated protein and a pyruvate kinase. This study demonstrates that SivS/R regulates virulence in vivo, and controls the expression of a number of genes in S. iniae.

Narrow-spectrum cephalosporin susceptibility testing of Escherichia coli with the BD Phoenix automated system: questionable utility of cephalothin as a predictor of cephalexin susceptibility.

The resistance of Escherichia coli to cephalothin was found to be overestimated when the Phoenix automated susceptibility system was used to determine resistance compared to reference broth microdilution, a finding that jeopardized the use of cephalexin for first-line treatment of urinary tract infections in children. In addition, using broth microdilution, we studied the accuracy of either cephalothin or cefazolin in predicting cephalexin susceptibility. In contrast to the recommendation of the Clinical Laboratory Standards Institute (CLSI), we found that cephalothin is not a reliable predictor of cephalexin susceptibility. Cefazolin performs no better in this role. We suggest that laboratories should consider testing and reporting cefazolin and cephalexin independently, according to clinical need.

Using problem-based learning in public health service based training.

OBJECTIVES: This study explored the suitability and benefits of problem-based learning (PBL) in competency-based postgraduate public health training. The PBL was delivered within a rural retreat and included site visits. METHODS: Qualitative semistructured interviews with trainee public health officers and key informants. RESULTS: The learning approach (retreat-PBL combination with site visits) was valuable and relevant. Trainees reported a high learning impact with increased knowledge about the problems examined and rural public health practice. They also expressed an openness to work rurally. CONCLUSION: Collaboratively developed and delivered, experiential rural public health PBL provides a positive learning experience for trainees undertaking competency-based training in public health and could play an important workforce role. PBL appears to be suitable in rural and non-rural public health training settings.

Capsule expression regulated by a two-component signal transduction system in Streptococcus iniae.

Streptococcus iniae causes disease in fish and humans and the presence of capsule is associated with virulence. Tn917 transposon mutagenesis was performed to identify capsule-associated genes and a mutant was isolated, with an insertion in a genetic locus encoding a two-component signal transduction system (TCS), which we termed sivS/R. sivS and sivR encode a 506-amino-acid (aa) putative histidine kinase and a 223-aa putative response regulator, respectively. In order to investigate the role of sivS/R, a deletion-insertion mutant was constructed using a PCR ligation technique. Real-time PCR showed that transcription of cpsA, the first gene in the S. iniae capsule operon, was reduced in the mutant, indicating that sivS/R regulates expression of this gene at the transcriptional level. Whole human blood killing assays demonstrated that unlike the parent, the mutant was susceptible to phagocytosis. Transmission electron microscopy showed exopolysaccharide on the surface of the parent strain but not the mutant which showed aberrant asymmetric septae that resulted in clumps of abnormal-shaped cells. Exponential growth rates of the mutant and parent strain were similar, although the mutant exhibited a longer lag phase. We conclude that sivS/R regulates capsule expression, thus affecting the ability to evade phagocytosis.

Cerebral blastomycosis: a case series incorporating voriconazole in the treatment regimen.

Cerebral blastomycosis is a rarely reported disease. We report three cases of cerebral blastomycosis previously treated with standard antifungal therapy, which were subsequently successfully treated with voriconazole. The first is a 29-year-old man who initially presented with concomitant cutaneous and osseous blastomycosis; the second is a 50-year-old man who initially presented with prostatic, pulmonary and cutaneous lesions. The third patient was a 63-year-old man who presented with hemiplegia and multiple intra-cerebral blastomycomas. This report represents the first two documented relapses, in Canada, of CNS blastomycosis following treatment with itraconazole and, to our knowledge, among the first three worldwide human cases of cerebral blastomycosis treated successfully with voriconazole.

Mentoring for population health in general practice divisions.

This paper describes the implementation and evaluation of a three-way model of service development mentoring. This population health mentoring program was funded by the Commonwealth Department of Health and Ageing to enable staff from eight Divisions of General Practice in South Australia to gain a sound understanding of population health concepts relevant to their workplace. The distinguishing features of service development mentoring were that the learning was grounded within an individual's work setting and experience; there was an identified population health problem or issue confronting the Division of General Practice; and there was an expectation of enhanced organisational performance. A formal evaluation found a consensus among all learners that mentoring was a positive and worthwhile experience, where they had achieved what they had set out to do. Mentors found the model of learning agreeable and effective. Division executive officers recognised enhanced skills among their "learner" colleagues, and commented positively on the benefits to their organisations through the development of well researched and relevant projects, with the potential to improve the efficiency of their population health activities.

Sustaining an Aboriginal mental health service partnership.

The Regional Aboriginal Integrated Social and Emotional (RAISE) Wellbeing program commenced in February 2003 as an Aboriginal mental health service partnership between one Aboriginal Health Service and three mainstream services: a community mental health team, a hospital mental health liaison, and an "outback" community counselling service. A case study method was used to describe the drivers (incentives for program development), linkage processes (structures and activities through which the partnership operated), and sustainability of the program. Program drivers were longstanding problems with Aboriginal peoples' access to mental health care, policy direction favouring shared service responsibility, and a relatively small amount of new funding for mental health that allowed the program to commence. Linkage processes were the important personal relationships between key individuals. Developing the program as a part of routine practice within and across the partner organisations is now needed through formal agreements, common care-management tools, and training. The program's sustainability will depend on this development occurring, as well as better collection and use of data to communicate the value of the program and support calls for adequate recurrent funds. The development of care-management tools, training and data systems will require a longer period of start-up funding as well as some external expertise.

A review of Streptococcus pneumoniae infection treatment failures associated with fluoroquinolone resistance.

We reviewed all of the published reports of cases of fluoroquinolone treatment failures for respiratory tract infection due to fluoroquinolone-resistant Streptococcus pneumoniae. There were 20 ciprofloxacin and levofloxacin treatment failures reported. Physicians should be aware, when treating pneumococcal respiratory tract infections in older patients with a fluoroquinolone, that clinical failures might occur, especially for patients with comorbid illnesses and a history of recent fluoroquinolone use.

Identification of a streptolysin S-associated gene cluster and its role in the pathogenesis of Streptococcus iniae disease.

Streptococcus iniae causes meningoencephalitis and death in cultured fish species and soft-tissue infection in humans. We recently reported that S. iniae is responsible for local tissue necrosis and bacteremia in a murine subcutaneous infection model. The ability to cause bacteremia in this model is associated with a genetic profile unique to strains responsible for disease in fish and humans (J. D. Fuller, D. J. Bast, V. Nizet, D. E. Low, and J. C. S. de Azavedo, Infect. Immun. 69:1994-2000, 2001). S. iniae produces a cytolysin that confers a hemolytic phenotype on blood agar media. In this study, we characterized the genomic region responsible for S. iniae cytolysin production and assessed its contribution to virulence. Transposon (Tn917) mutant libraries of commensal and disease-associated S. iniae strains were generated and screened for loss of hemolytic activity. Analysis of two nonhemolytic mutants identified a chromosomal locus comprising 9 genes with 73% homology to the group A streptococcus (GAS) sag operon for streptolysin S (SLS) biosynthesis. Confirmation that the S. iniae cytolysin is a functional homologue of SLS was achieved by PCR ligation mutagenesis, complementation of an SLS-negative GAS mutant, and use of the SLS inhibitor trypan blue. SLS-negative sagB mutants were compared to their wild-type S. iniae parent strains in the murine model and in human whole-blood killing assays. These studies demonstrated that S. iniae SLS expression is required for local tissue necrosis but does not contribute to the establishment of bacteremia or to resistance to phagocytic clearance.