Predictors of quality of life, functional status, depression and fatigue in early arthritis: comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these "at-risk" stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA. METHODS: Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables. RESULTS: Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, "mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations." In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs. CONCLUSIONS: Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.

Achieving COVID-19 vaccination equity in South Eastern Metropolitan Victoria, Australia: a population-based study.

Background: We describe COVID-19 first and second vaccine uptake across Local Government Areas (LGAs) in Victoria using southeast metropolitan Melbourne catchment as a case study. We explore key policy and implementation strategies that contributed to equitable uptake. Methods: Population level data within the South East Public Health Unit (SEPHU) was used to compare trends in COVID-19 vaccination first and second dose uptake for each of the 11 LGAs in year 2021. Changes in vaccination uptake over the year were reviewed against social and public health measures used during the COVID-19 pandemic in Victoria and strategies in the SEPHU vaccination program. Findings: By September 2021, 57% of the eligible population in the least disadvantaged LGA, Bayside, had received their second dose vaccination compared to 32% in the most disadvantaged LGA, Greater Dandenong. By end of 2021, the gap had narrowed with 95% in Bayside and 92% in Greater Dandenong having received their second dose. The increase in vaccination uptake for both LGAs was bimodal. Government policies on vaccine eligibility and the opening of mass vaccination sites preceded the first peak in vaccination uptake. Strong community engagement, addressing misinformation, providing culturally appropriate vaccination services and mass outbreaks preceded the second peak in vaccination uptake. Interpretation: Vaccine equity across culturally and economically diverse populations can be achieved through a combination of robust, targeted community engagement, mass deployment of appropriate workforce, vaccination services tailored to cultural needs and sensitivities and accessibility to mass vaccination sites on a backdrop of state-wide policies that incentivise vaccination. Funding: None.

The value of ultrasound-defined tenosynovitis and synovitis in the prediction of persistent arthritis.

OBJECTIVES: The value of US-defined tenosynovitis in predicting the persistence of inflammatory arthritis is not well described. In particular, the predictive utility of US-defined tenosynovitis of larger tendons is yet to be reported. We assessed the value of US-defined tenosynovitis alongside US-defined synovitis and clinical and serological variables in predicting persistent arthritis in an inception cohort of DMARD-naïve patients with early arthritis. METHODS: One hundred and fifty DMARD-naïve patients with clinically apparent synovitis of one or more joints and a symptom duration of ≤3 months underwent baseline clinical, laboratory and US (of 19 bilateral joints and 16 bilateral tendon compartments) assessments. Outcomes were classified as persistent or resolving arthritis after 18 months' follow-up. The predictive value of US-defined tenosynovitis for persistent arthritis was compared with those of US-defined synovitis, and clinical and serological variables. RESULTS: At 18 months, 99 patients (66%) had developed persistent arthritis and 51 patients (34%) had resolving disease. Multivariate logistic regression analysis showed that US-detected digit flexor tenosynovitis [odds ratio (OR): 6.6, 95% CI: 2.0 , 22.1, P = 0.002] provided independent predictive data for persistence over and above the presence of US-detected joint synovitis and RF antibodies. In the RF/ACPA-negative subcohort, US-defined digit flexor tenosynovitis remained a significant predictive variable (OR: 4.7, 95% CI: 1.4, 15.8, P = 0.012), even after adjusting for US-defined joint synovitis. CONCLUSION: US-defined tenosynovitis provided independent predictive data for the development of persistent arthritis. The predictive role of US-defined digit flexor tenosynovitis should be further assessed; investigators should consider including this tendon site as a candidate variable when designing imaging-based predictive algorithms for persistent inflammatory arthritis development.

Pragmatic pluralism: Mutual tolerance of contested understandings between orthodox and alternative practitioners in autologous stem cell transplantation.

High-dose chemotherapy and autologous stem cell transplantation (ASCT) is used to treat some advanced malignancies. It is a traumatic procedure, with a high complication rate and significant mortality. ASCT patients and their carers draw on many sources of information as they seek to understand the procedure and its consequences. Some seek information from beyond orthodox medicine. Alternative beliefs and practices may conflict with conventional understanding of the theory and practice of ASCT, and 'contested understandings' might interfere with patient adherence to the strict and demanding protocols required for successful ASCT.The present study, conducted in Sydney, Australia, examines narrative-style interviews with 10 sequentially recruited ASCT patients and nine of their carers conducted at the time of transplant and three months later. Transcripts were read for instances of mention of alternative advice, and for instances of contested understanding of information relevant to the transplant.Patients and carer pairs expressed closely concordant views about alternative advice. Five pairs were consulting alternative practitioners. Contested understanding was expressed in four domains-understandings of the transplant itself and its underlying theory, of the relationship between the components of the 'transplant', of the nature and role of stem cells, and of beliefs about bodily function and life-style. Contested understandings of the transplant treatment were expressed as predominantly personal interpretations of orthodox informationPatients and carers seemed to recognise that alternative and conventional systems were discordant, yet they were able to separate the two, and adhere to each practice without prejudicing their medical treatment. A single case of late, post-transplant repudiation of Western medicine is discussed to emphasise some of the possible determinants of dissonance when it does occur.

A narrative-informed evaluation of tree of life for parents of children with physical health conditions.

BACKGROUND: Parents of children with chronic health conditions can face many challenges. The Tree of Life narrative therapy group intervention aims to connect parents with their skills and resources before collectively exploring the 'storms' (challenges) they face. A narrative-informed evaluation aimed to story the parents' experiences of attending the group. METHODS: Seven parents attended a Tree of Life group intervention and then participated in a narrative-informed group interview to generate stories regarding their experience of the group. The interview was recorded with consent and later transcribed. RESULTS: A thematic analysis was undertaken and highlighted that the group offered parents a 'safe place to stand' to talk about difficulties; a different perspective on their situation; connection with the skills of other parents; new ideas to introduce more independence to their child; and togetherness within the 'storms' (challenges). CONCLUSIONS: The narrative-informed evaluation offered opportunities to further thicken parents' preferred identity stories whilst also contributing to the evidence base of narrative-informed group interventions for parents.

Development and formative evaluation of patient research partner involvement in a multi-disciplinary European translational research project.

PLAIN ENGLISH SUMMARY: Patient and public involvement (PPI) improves the quality of health research and ensures that research is relevant to patients' needs. Though PPI is increasingly evident in clinical and health services research, there are few examples in the research literature of effective PPI in translational and laboratory-based research. In this paper, we describe the development and evaluation of PPI in a multi-centre European project (EuroTEAM - Towards Early biomarkers in Arthritis Management) that included both translational and laboratory-based and psychosocial research. We found that although most PPI in EuroTEAM was centred around the psychosocial research, there were examples of PPI in the laboratory studies. As the project evolved, researchers became better at accommodating PPI and identifying PPI opportunities. It was generally agreed that PPI had a positive impact on the project overall, particularly on public engagement with the research. We concluded that the inclusion of both psychosocial and laboratory-based research in the same project facilitated PPI across all aspects of the research. In future projects, we would try to specify individual PPI activities in more detail at the project-planning stage, and better accommodate patient partners who are not native speakers of English. ABSTRACT: Background Patient and public involvement (PPI) enhances research quality and relevance and is central to contemporary health policy. The value of PPI has been recognised in rheumatology research, though there are limited examples of PPI in basic and translational science. The EU FP7 funded 'EuroTEAM' (Towards Early biomarkers in Arthritis Management) project was established to develop biomarker-based approaches to predict the future development of rheumatoid arthritis and incorporated psychosocial research to investigate the perceptions of 'at risk' individuals about predictive testing, and to develop informational resources about rheumatoid arthritis (RA) risk. Patient involvement was central to EuroTEAM from the inception of the project. The objective of this paper is to describe the development of PPI in EuroTEAM, formatively assess the impact of PPI from the perspectives of researchers and patient research partners (PRPs), reflect on successes and lessons learned, and formulate recommendations to guide future projects.Methods Two mixed-methods surveys (for PRPs and researchers) and a teleconference were undertaken to assess the impact of PPI on individual work packages and on EuroTEAM overall.Results There was consensus about the positive impact of PPI on the research and on the experiences of those involved. In particular, the positive impact of PPI on the personal development of researchers, and on effective public engagement with EuroTEAM research were highlighted. Researchers described adapting their practice in future projects to facilitate PPI. Spin-off projects and ongoing collaborations between PRPs and researchers reflected the value of PPI to participants. PPI was more frequently integrated in psychosocial research, though examples of PPI in laboratory/translational science were also described. PRPs asked for more opportunities to contribute meaningfully to basic scientific research and for more extensive feedback on their contributions.Conclusions The findings were used to formulate recommendations to guide effective involvement of patients in future similar projects, including identifying specific training requirements for PRPs and researchers, the identification of PRP focused tasks/deliverables at the project planning stage, and supporting access to involvement for all PRPs. Importantly, the distinctive multidisciplinary approach of EuroTEAM, incorporating both basic science and psychosocial research, facilitated patient involvement in the project overall.

Outcomes and compliance with standards of care in anti-neutrophil cytoplasmic antibody-associated vasculitis-insights from a large multiregion audit.

OBJECTIVES: We aimed to conduct a large audit of routine care for patients with ANCA-associated vasculitis. METHODS: We invited all 34 hospitals within one health region in England to undertake a retrospective case note audit of all patients newly diagnosed or treated with CYC or rituximab (RTX) for ANCA-associated vasculitis from April 2013 to December 2014. We compared clinical practice to the British Society for Rheumatology guidelines for the management of adults with ANCA-associated vasculitis and the use of RTX with the National Health Service (NHS) England commissioning policy and National Institute for Health and Care Excellence (NICE) technology appraisal. RESULTS: We received data from 213 patients. Among 130 newly diagnosed patients, delay from admission to diagnosis ranged from 0 to 53 days (median 6, interquartile range 3-10.5) for those diagnosed as inpatients. BVAS was recorded in 8% of patients at diagnosis. Remission at 6 months was achieved in 83% of patients. The 1-year survival was 91.5%. A total of 130 patients received CYC for new diagnosis or relapse. The correct dose of i.v. CYC (within 100 mg of the target dose calculated for age, weight and creatinine) was administered in 58% of patients. A total of 25% of patients had an infection requiring hospital admission during or within 6 months of completing their CYC therapy. Seventy-six patients received RTX for new diagnosis or relapse. A total of 97% of patients met the NHS England or NICE eligibility criteria. Pneumocystis jiroveci pneumonia prophylaxis (recommended in the summary of product characteristics) was given in only 65% of patients. CONCLUSION: We identified opportunities to improve care, including compliance with safety standards for delivery of CYC. Development of a national treatment protocol/checklist to reduce this heterogeneity in care should be considered as a priority.

"Cancer Put My Life on Hold": Work-Related Challenges Among Middle-aged Adults 12 Months After a Diagnosis of Colorectal Cancer.

BACKGROUND: Colorectal cancer affects a wide range of working-age people. Little is known about the consequent work limitations. OBJECTIVE: The aim of this study was to understand the extent and changing nature of work-related limitations of middle-aged (45-64 years) people over the first 12 months of colorectal cancer. METHODS: Surveys were administered to participants recruited via the Queensland Cancer Registry, at 6 and 12 months after diagnosis. Among those who returned to work, the Work Limitations Questionnaire measured 4 job performance domains (time management, physical, mental-interpersonal, and output demands) and an overall productivity score. Open-ended questions supplemented the Work Limitations Questionnaire, and responses were thematically analyzed. RESULTS: Of 239 participants, 8% did not continue in the study, and 20% left employment by 12 months, leaving 171 participants eligible for this analysis. Open-ended responses for why participants stopped work included bowel problems and stoma, loss of strength, and medication adverse effects. At 12 months, 22% to 39% of participants reported work limitations, but there was no overall significant change in work limitations between 6 and 12 months. Qualitative data highlighted the key work-related issues were changes in work functioning, attitudes of employers and colleagues, financial pressures, and emotional responses. CONCLUSIONS: While a significant proportion left work because of treatment-related problems, and the majority of participants did not experience workplace limitations, some reported considerable work-related challenges. IMPLICATIONS FOR PRACTICE: Discussions with health professionals about the possible impact of treatment adverse effects on employment, good communication with employers, and workplace flexibility may facilitate return to work for this population.

Lipid and Metabolic Changes in Rheumatoid Arthritis.

While the most obvious manifestations of rheumatoid arthritis (RA) involve inflammation and damage in the synovial joints, the systemic effects of the condition are widespread and life-threatening. Of particular interest is the 'lipid paradox' of RA, where patients with a numerically equivocal starting lipid profile have a significantly raised risk of cardiovascular (CV) events and response to therapy results in a 'normalization' of lipid levels and reduction in events. Changes in lipids can be seen before overt disease manifestations which suggest that they are closely linked to the more widespread inflammation-driven metabolic changes associated with tumour necrosis factor (TNF). Cachexia involves a shift in body mass from muscle to fat, which may or may not directly increase the cardiovascular risk. However, since TNF inhibition is associated with reduction in cardiovascular events, it does suggest that these widespread metabolic changes involving lipids are of importance. Analysis of single lipids or metabolites have been used to identify some of the key changes, but more recently, metabolomic and lipidomic approaches have been applied to identify a broad spectrum of small molecule changes and identify potentially altered metabolic pathways. Further work is needed to understand fully the metabolic changes in lipid profiles and identify novel ways of targeting desired profile changes, but work so far does suggest that a better understanding may allow management of patients to downregulate the systemic effects of their disease that puts them at risk of cardiovascular complications.

How Can the Use of Evidence in Mental Health Policy Be Increased? A Systematic Review.

OBJECTIVE: The aim of this review was to explore what is known about the effectiveness of strategies to increase the use of research in mental health policies. METHODS: PsycINFO, MEDLINE, PubMed and EMBASE were searched for peer-reviewed journal articles by using the terms information dissemination OR knowledge OR diffusion of innovation OR knowledge transfer OR knowledge exchange OR evidence based OR evidence informed AND mental health policy OR decision makers. Searches were limited to articles pertaining to humans, written in English, and published from 1995 to 2013. Studies were excluded if they did not include a component related either to mental health policy or to mental health policy and decision makers or did not describe the development, implementation, or evaluation of an intervention that included a component aimed at increasing use of evidence. Reference lists were scanned to identify additional papers. RESULTS: The search returned 2,677 citations. Fifty additional papers were identified via reference lists of relevant articles. Nine separate intervention studies were identified that included a component aimed at increasing use of evidence in mental health policy. All employed at least three strategies to increase evidence use, mostly in regard to implementation of a particular evidence-based policy. Methodologies of the identified studies did not enable estimation of the effectiveness of individual strategies to increase evidence use. CONCLUSIONS: Little research has examined how to increase the use of evidence in mental health policy. Available research suggests a number of potentially effective strategies for increasing the use of evidence that warrant further examination.

Pathomx: an interactive workflow-based tool for the analysis of metabolomic data.

BACKGROUND: Metabolomics is a systems approach to the analysis of cellular processes through small-molecule metabolite profiling. Standardisation of sample handling and acquisition approaches has contributed to reproducibility. However, the development of robust methods for the analysis of metabolomic data is a work-in-progress. The tools that do exist are often not well integrated, requiring manual data handling and custom scripting on a case-by-case basis. Furthermore, existing tools often require experience with programming environments such as MATLAB® or R to use, limiting accessibility. Here we present Pathomx, a workflow-based tool for the processing, analysis and visualisation of metabolomic and associated data in an intuitive and extensible environment. RESULTS: The core application provides a workflow editor, IPython kernel and a HumanCyc™-derived database of metabolites, proteins and genes. Toolkits provide reusable tools that may be linked together to create complex workflows. Pathomx is released with a base set of plugins for the import, processing and visualisation of data. The IPython backend provides integration with existing platforms including MATLAB® and R, allowing data to be seamlessly transferred. Pathomx is supplied with a series of demonstration workflows and datasets. To demonstrate the use of the software we here present an analysis of 1D and 2D (1)H NMR metabolomic data from a model system of mammalian cell growth under hypoxic conditions. CONCLUSIONS: Pathomx is a useful addition to the analysis toolbox. The intuitive interface lowers the barrier to entry for non-experts, while scriptable tools and integration with existing tools supports complex analysis. We welcome contributions from the community.

The return to work experiences of middle-aged Australian workers diagnosed with colorectal cancer: a matched cohort study.

BACKGROUND: Few studies have been undertaken to understand the employment impact in patients with colorectal cancer and none in middle-aged individuals with cancer. This study described transitions in, and key factors influencing, work participation during the 12 months following a diagnosis of colorectal cancer. METHODS: We enrolled 239 adults during 2010 and 2011 who were employed at the time of their colorectal cancer diagnosis and were prospectively followed over 12 months. They were compared to an age- and gender-matched general population group of 717 adults from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Data were collected using telephone and postal surveys. Primary outcomes included work participation at 12 months, changes in hours worked and time to work re-entry. Multivariable logistic and Cox proportional hazards models were undertaken. RESULTS: A significantly higher proportion of participants with colorectal cancer (27%) had stopped working at 12 months than participants from the comparison group (8%) (p < 0.001). Participants with cancer who returned to work took a median of 91 days off work (25-75 percentiles: 14-183 days). For participants with cancer, predictors of not working at 12 months included: being older, lower BMI and lower physical well-being. Factors related to delayed work re-entry included not being university-educated, working for an employer with more than 20 employees in a non-professional or managerial role, longer hospital stay, poorer perceived financial status and having or had chemotherapy. CONCLUSIONS: In middle-adulthood, those working and diagnosed with colorectal cancer can expect to take around three months off work. Individuals treated with chemotherapy, without a university degree and from large employers could be targeted for specific assistance for a more timely work entry. TRIAL REGISTRATION: ACTRN12611000530921.

Effect of prone versus supine positioning on left ventricular ejection fraction (LVEF) and heart rate using ECG gated Tl-201 myocardial perfusion scans and gated cardiac blood pool scans.

INTRODUCTION: There is limited data on the effect of posture on LVEF. The study aim was to determine any difference in LVEF using gated cardiac blood pool scanning (GCBPS) and Tl-201 gated myocardial perfusion scanning (MPS) in prone or supine positions. METHOD: In 50 patients undergoing evaluation for varying heart conditions, automated LVEF, end diastolic volume (EDV), end systolic volume (ESV) measurements were obtained at rest during gated MPS on Discovery NM 530c (GE Healthcare). In another 50 patients, semi-automated LVEF measurements were obtained using GCBPS on dual-headed gamma cameras. Average heart rate (HR) was recorded. Differences between prone and supine LVEF, HR, EDV and ESV were compared using paired two-tailed t-tests (P < 0.05 considered significant). Pearson's correlation, difference plots, mean, standard deviation and 95% confidence interval of the differences were also derived to analyse LVEF results. RESULTS: Using GCPBS or MPS, no significant difference in LVEF or LV volumes (from gated MPS) was demonstrated between postures. Increased HR was noted in prone positioning. CONCLUSION: Posture did not affect measured LVEF or LV volumes. However HR was higher on prone imaging.

Optimal reproducibility of gated sestamibi and thallium myocardial perfusion study left ventricular ejection fractions obtained on a solid-state CZT cardiac camera requires operator input.

AIM: To evaluate the reproducibility of serial re-acquisitions of gated Tl-201 and Tc-99m sestamibi left ventricular ejection fraction (LVEF) measurements obtained on a new generation solid-state cardiac camera system during myocardial perfusion imaging and the importance of manual operator optimization of left ventricular wall tracking. METHODS: Resting blinded automated (auto) and manual operator optimized (opt) LVEF measurements were measured using ECT toolbox (ECT) and Cedars-Sinai QGS software in two separate cohorts of 55 Tc-99m sestamibi (MIBI) and 50 thallium (Tl-201) myocardial perfusion studies (MPS) acquired in both supine and prone positions on a cadmium zinc telluride (CZT) solid-state camera system. Resting supine and prone automated LVEF measurements were similarly obtained in a further separate cohort of 52 gated cardiac blood pool scans (GCBPS) for validation of methodology and comparison. Appropriate use of Bland-Altman, chi-squared and Levene's equality of variance tests was used to analyse the resultant data comparisons. RESULTS: For all radiotracer and software combinations, manual checking and optimization of valve planes (+/- centre radius with ECT software) resulted in significant improvement in MPS LVEF reproducibility that approached that of planar GCBPS. No difference was demonstrated between optimized MIBI/Tl-201 QGS and planar GCBPS LVEF reproducibility (P = .17 and P = .48, respectively). ECT required significantly more manual optimization compared to QGS software in both supine and prone positions independent of radiotracer used (P < .02). CONCLUSIONS: Reproducibility of gated sestamibi and Tl-201 LVEF measurements obtained during myocardial perfusion imaging with ECT toolbox or QGS software packages using a new generation solid-state cardiac camera with improved image quality approaches that of planar GCBPS however requires visual quality control and operator optimization of left ventricular wall tracking for best results. Using this superior cardiac technology, Tl-201 reproducibility also appears at least equivalent to sestamibi for measuring LVEF.

The Working After Cancer Study (WACS): a population-based study of middle-aged workers diagnosed with colorectal cancer and their return to work experiences.

BACKGROUND: The number of middle-aged working individuals being diagnosed with cancer is increasing and so too will disruptions to their employment. The aim of the Working After Cancer Study is to examine the changes to work participation in the 12 months following a diagnosis of primary colorectal cancer. The study will identify barriers to work resumption, describe limitations on workforce participation, and evaluate the influence of these factors on health-related quality of life. METHODS/DESIGN: An observational population-based study has been designed involving 260 adults newly-diagnosed with colorectal cancer between January 2010 and September 2011 and who were in paid employment at the time they were diagnosed. These cancer cases will be compared to a nationally representative comparison group of 520 adults with no history of cancer from the general population. Eligible cases will have a histologically confirmed diagnosis of colorectal cancer and will be identified through the Queensland Cancer Registry. Data on the comparison group will be drawn from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Data collection for the cancer group will occur at 6 and 12 months after diagnosis, with work questions also asked about the time of diagnosis, while retrospective data on the comparison group will be come from HILDA Waves 2009 and 2010. Using validated instruments administered via telephone and postal surveys, data will be collected on socio-demographic factors, work status and circumstances, and health-related quality of life (HRQoL) for both groups while the cases will have additional data collected on cancer treatment and symptoms, work productivity and cancer-related HRQoL. Primary outcomes include change in work participation at 12 months, time to work re-entry, work limitations and change in HRQoL status. DISCUSSION: This study will address the reasons for work cessation after cancer, the mechanisms people use to remain working and existing workplace support structures and the implications for individuals, families and workplaces. It may also provide key information for governments on productivity losses. STUDY REGISTRATION: Australian and New Zealand Clinical Trial Registry No. ACTRN12611000530921.

You have to make something of all that rubbish, do you? An empirical investigation of the social process of qualitative research.

In this article, we examine participants' talk about qualitative research. We provide empirical support for post-structural theorizations of the interview and propose three distinct but related dimensions of qualitative research: emotional, purposive/relational, and epistemic/ontological. In this study, participants often became upset but constructed participation as enjoyable and cathartic. The purpose of participation was to assist the communities to which one belonged. Participation was an active, reflexive practice that reconstructed the self and changed knowledge about one's self. This latter epistemic/ontological dimension of participation appeared to be the most compelling for participants, but it is also the hardest to observe, with implications for how we consider the costs and benefits of participation. We suggest two practical measures for researchers and institutional review boards to consider in light of our findings: routinely asking questions about the research experience in qualitative studies and reformulating patient information statements to particularize them to qualitative research.

Pragmatic pluralism: mutual tolerance of contested understandings between orthodox and alternative practitioners in autologous stem cell transplantation.

High-dose chemotherapy and autologous stem cell transplantation (ASCT) is used to treat some advanced malignancies. It is a traumatic procedure, with a high complication rate and significant mortality. ASCT patients and their carers draw on many sources of information as they seek to understand the procedure and its consequences. Some seek information from beyond orthodox medicine. Alternative beliefs and practices may conflict with conventional understanding of the theory and practice of ASCT, and 'contested understandings' might interfere with patient adherence to the strict and demanding protocols required for successful ASCT. The present study, conducted in Sydney, Australia, examines narrative-style interviews with 10 sequentially recruited ASCT patients and nine of their carers conducted at the time of transplant and three months later. Transcripts were read for instances of mention of alternative advice, and for instances of contested understanding of information relevant to the transplant. Patients and carer pairs expressed closely concordant views about alternative advice. Five pairs were consulting alternative practitioners. Contested understanding was expressed in four domains--understandings of the transplant itself and its underlying theory, of the relationship between the components of the 'transplant', of the nature and role of stem cells, and of beliefs about bodily function and life-style. Contested understandings of the transplant treatment were expressed as predominantly personal interpretations of orthodox information. Patients and carers seemed to recognise that alternative and conventional systems were discordant, yet they were able to separate the two, and adhere to each practice without prejudicing their medical treatment. A single case of late, post-transplant repudiation of Western medicine is discussed to emphasise some of the possible determinants of dissonance when it does occur.

Current perspectives on NMDA-type glutamate signalling in bone.

Bone is a complex, evolving tissue, architecturally defined by the activities of osteoclasts and osteoblasts that continually resorb and replace the mineralised matrix. Numerous regulatory mechanisms exist to control bone remodelling and the maintenance of bone mass. The consequences of inappropriate or uncoupled bone resorption and formation are significant and invariably lead to different disease states, the most prevalent being osteoporosis. In recent years, much attention has focused on unravelling the systemic and local signalling interactions that influence the differentiation and function of bone cells with a view to developing our understanding of bone biology and identifying potential new targets for therapeutic intervention. Several lines of evidence indicate that neurotransmitters and neuromodulators have influential roles to play in the regulation of bone remodelling and much of this research has involved analysis of the excitatory amino acid glutamate. This review will summarise current understanding of glutamate signalling in bone cells, addressing specifically the function of N-methyl-D-aspartate (NMDA)-type glutamate receptor signalling mechanisms, and will address the functional significance and future prospects for this area of research.