Meta-analysis of microarray data identifies GAS6 expression as an independent predictor of poor survival in ovarian cancer

Seeking new biomarkers for epithelial ovarian cancer, the fifth most common cause of death from all cancers in women and the leading cause of death from gynaecological malignancies, we performed a meta-analysis of three independent studies and compared the results in regard to clinicopathological parameters. This analysis revealed that GAS6 was highly expressed in ovarian cancer and therefore was selected as our candidate of choice. GAS6 encodes a secreted protein involved in physiological processes including cell proliferation, chemotaxis, and cell survival. We performed immunohistochemistry on various ovarian cancer tissues and found that GAS6 expression was elevated in tumour tissue samples compared to healthy control samples (P < 0.0001). In addition, GAS6 expression was also higher in tumours from patients with residual disease compared to those without. Our data propose GAS6 as an independent predictor of poor survival, suggesting GAS6, both on the mRNA and on the protein level, as a potential biomarker for ovarian cancer. In clinical practice, the staining of a tumour biopsy for GAS6 may be useful to assess cancer prognosis and/or to monitor disease progression.

Exploring Australian intensive care physicians clinical judgement during donation after cardiac death : an exploratory qualitative study

BACKGROUND: Donation after Cardiac Death (DCD) is one possible solution to the world wide organ shortage. Intensive care physicians are central to DCD becoming successful since they are responsible for making the clinical judgements and decisions associated with DCD. Yet international evidence shows health care professionals have not embraced DCD and are often reluctant to consider it as an option for patients. PURPOSE: To explore intensive care physicians' clinical judgements when selecting a suitable DCD candidate. METHODS: Using interpretative exploratory methods six intensive care physicians were interviewed from three hospital sites in Australia. Following verbatim transcription, data was subjected to thematic analysis. FINDINGS: Three distinct themes emerged. Reducing harm and increasing benefit was a major focus of intensive care physicians during determination of DCD. There was an acceptance of DCD if there was clear evidence that donation was what the patient and family wanted. Characteristics of a defensible decision reflected the characteristics of sequencing, separation and isolation, timing, consensus and collaboration, trust and communication to ensure that judgements were robust and defensible. The final theme revealed the importance of minimising uncertainty and discomfort when predicting length of survival following withdrawal of life-sustaining treatment. CONCLUSION: DCD decisions are made within an environment of uncertainty due to the imprecision associated with predicting time of death. Lack of certainty contributed to the cautious and collaborative strategies used by intensive care physicians when dealing with patients, family members and colleagues around end-of-life decisions, initiation of withdrawal of life-sustaining treatment and the discussion about DCD. This study recommends that nationally consistent policies are urgently needed to increase the degree of certainty for intensive care staff concerning the DCD processes.

A cost-effectiveness analysis of a telephone-linked care intervention for individuals with Type 2 diabetes

AIM: To assess the cost-effectiveness of an automated telephone-linked care intervention, Australian TLC Diabetes, delivered over 6 months to patients with established Type 2 diabetes mellitus and high glycated haemoglobin level, compared to usual care. METHODS: A Markov model was designed to synthesize data from a randomized controlled trial of TLC Diabetes (n=120) and other published evidence. The 5-year model consisted of three health states related to glycaemic control: 'sub-optimal' HbA1c ≥58mmol/mol (7.5%); 'average' ≥48-57mmol/mol (6.5-7.4%) and 'optimal' <48mmol/mol (6.5%) and a fourth state 'all-cause death'. Key outcomes of the model include discounted health system costs and quality-adjusted life years (QALYS) using SF-6D utility weights. Univariate and probabilistic sensitivity analyses were undertaken. RESULTS: Annual medication costs for the intervention group were lower than usual care [Intervention: £1076 (95%CI: £947, £1206) versus usual care £1271 (95%CI: £1115, £1428) p=0.052]. The estimated mean cost for intervention group participants over five years, including the intervention cost, was £17,152 versus £17,835 for the usual care group. The corresponding mean QALYs were 3.381 (SD 0.40) for the intervention group and 3.377 (SD 0.41) for the usual care group. Results were sensitive to the model duration, utility values and medication costs. CONCLUSION: The Australian TLC Diabetes intervention was a low-cost investment for individuals with established diabetes and may result in medication cost-savings to the health system. Although QALYs were similar between groups, other benefits arising from the intervention should also be considered when determining the overall value of this strategy.

NT-ProBNP levels in saliva and its clinical relevance to heart failure

Background: Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and similar to 20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. Methods: Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at -80 degrees C until analysis. A customised homogeneous sandwich AlphaLISA((R)) immunoassay was used to quantify NT-proBNP levels in saliva. Results: Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r(2) = 0.78 (p<0.01, y = 1.705 x +1910.8). The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. Conclusion: We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.

Saliva as an emerging biofluid for clinical diagnosis and applications of MEMS/NEMS in salivary diagnostics

Saliva as a biological fluid is gaining wider acceptance for diagnosing diseases. The growing interest in saliva as a biological fluid is due to its noninvasiveness, ease of use, cost-effectiveness, and multiple sample collection possibilities as well as minimal risk to health care professionals of contracting infectious organisms such as HIV and Hep B. However, the clinical translation of saliva is hampered by our lack of understanding of the biomolecular transportation from blood into saliva, the diurnal variations of biomolecules present in saliva, and relatively low levels of analytes (100th to a 1000th fold less than in blood). We provide information on the current status of salivary research, salivary diagnostics empowered by nanotechnology, and future prospects in this emerging field of saliva diagnostics.

What women want : qualitative analysis of consumer evaluations of maternity care in Queensland, Australia

Background Maternity care reform plans have been proposed at state and national levels in Australia, but the extent to which these respond to maternity care consumers’ expressed needs is unclear. This study examines open-text survey comments to identify women’s unmet needs and priorities for maternity care. It is then considered whether these needs and priorities are addressed in current reform plans. Methods Women who had a live single or multiple birth in Queensland, Australia, in 2010 (n 3,635) were invited to complete a retrospective self-report survey. In addition to questions about clinical and interpersonal maternity care experiences from pregnancy to postpartum, women were asked an open-ended question “Is there anything else you’d like to tell us about having your baby?” This paper describes a detailed thematic analysis of open-ended responses from a random selection of 150 women (10% of 1,510 who responded to the question). Results Four broad themes emerged relevant to improving women’s experiences of maternity care: quality of care (interpersonal and technical); access to choices and involvement in decision-making; unmet information needs; and dissatisfaction with the care environment. Some of these topics are reflected in current reform goals, while others provide evidence of the need for further reforms. Conclusions The findings reinforce the importance of some existing maternity reform objectives, and describe how these might best be met. Findings affirm the importance of information provision to enable informed choices; a goal of Queensland and national reform agendas. Improvement opportunities not currently specified in reform agendas were also identified, including the quality of interpersonal relationships between women and staff, particular unmet information needs (e.g., breastfeeding), and concerns regarding the care environment (e.g., crowding and long waiting times).

Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma : results from the European Thoracic Oncology Platform Lungscape Project

PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.

Clinical perceptions of radiation therapy undergraduate competency standards

Introduction The multifactorial nature of clinical skills development makes assessment of undergraduate radiation therapist competence level by clinical mentors challenging. A recent overhaul of the clinical assessment strategy at Queensland University of Technology has moved away from the high-stakes Observed Structured Clinical Examination (OSCE) to encompass a more continuous measure of competence. This quantitative study aimed to gather stakeholder evidence to inform development of standards by which to measure student competence for a range of levels of progression. Methods A simple anonymous questionnaire was distributed to all Queensland radiation therapists. The tool asked respondents to assign different levels of competency with a range of clinical tasks to different levels of student. All data were anonymous and was combined for analysis using Microsoft Excel. Results Feedback indicated good agreement with tasks that specified amount of direction required and this has been incorporated into the new clinical achievements record that the students need to have signed off. Additional puzzling findings suggested higher expectations with planning tasks than with treatment-based tasks. Conclusion The findings suggest that the amount of direction required by students is a valid indicator of their level and has been adopted into the clinical assessment scheme. Further work will build on this to further define standards of competency for undergraduates.

Cross-sectional analysis of undergraduate nursing students' perceptions of bioscience

Nursing was one of the last health professions to be established in the higher education sector. A lingering challence is the integration of bioscience into nursing curriculum. Research suggests that students perceive bioscience teaching to be difficult thereby contributing to heightened anxiety. It has been proposed that high content volume, lack of secondary school science, and predominance of science lectureres without clinical practice experience, may lead to a bioscience disconnet with curricula. To ascertain the extent of this problem, we undertook a cross-sectional designed study of commencing, second and third year undergraduate nursing students (n=566). They were surveyed about perceptions, knowledge and approaches to bioscience learning. Preliminary analysis revealed similar findings between the three different cohorts. Generally, sudents perceived bioscience subjects to be difficult, more challenging and requiring more study hours than clinical nursing subjects. Interestingly, the perception of difficulty and associated anxieties were found in both commencing and existing students. Moreover, students with secondary school biology combined with another science subject perceived bioscience teaching more favourably compared to those who had studied one secondary school science subject. University coursework needs to embed strategies to minimise anxieties about learning bioscience by using innovative deliveries and scaffolded assessments that target the learner's needs.

Barbara's story : a thematic analysis of a relative's reflection of being in the intensive care unit

Aim The aim of this reflective account is to provide a view of the intensive care unit (ICU) relative’s experiences of supporting and being supported in the ICU. Background Understanding the relatives’ experiences of ICU is important especially because a recent work has identified the potential for this group to develop post-traumatic stress disorder, a condition that is normally equated with the ICU survivor. Design A thematic analysis was used in identifying emerging themes that would be significant in an ICU nursing context. Setting The incident took place in two 8-bedded ICUs (Private and National Health Service) in October. Results Two emergent themes were identified from the reflective story – fear of the technological environment and feeling hopeless and helpless. Conclusion The use of relative stories as an insight into the live experiences of ICU relatives may give a deeper understanding of their life-world. The loneliness, anguish and pain of the ICU relative extends beyond the walls of the ICU, and this is often negated as the focus of the ICU team is the patient. Relevance to clinical practice: Developing strategies to support relatives might include the use of relative diaries used concurrently with patient diaries to support this groups recovery or at the very least a gaining a sense of understanding for their ICU experience. Relative follow-up clinics designed specifically to meet their needs where support and advice can be given by the ICU team, in addition to making timely and appropriate referrals to counselling services and perhaps involving spiritual leaders where appropriate.

A qualitative analysis of how parents assess acute pain in young children

An accurate and comprehensive pain assessment is crucial for adequate pain management in pre- and early verbal children during painful medical procedures. This study used an inductive approach to explore the processes involved in parental pain assessment and to develop a new model of Parental Assessment of Acute Child Pain. Participants were 19 parents of children aged under 3 years who had previously or were potentially about to experience an intravenous cannula or nasogastric tube insertion. Parental affect regulation, while witnessing their child in acute pain/distress, appeared to be critical to the processes involved in assessing their child’s pain.

An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss

Background Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans. Results Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3′ untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass. Conclusions This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.

Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders

Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the 'pure' forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD. © 2013 Springer-Verlag Berlin Heidelberg.

Quantification of functional hand grip using electromyography and inertial sensor-derived accelerations: Clinical implications

Background Assessing hand injury is of great interest given the level of involvement of the hand with the environment. Knowing different assessment systems and their limitations generates new perspectives. The integration of digital systems (accelerometry and electromyography) as a tool to supplement functional assessment allows the clinician to know more about the motor component and its relation to movement. Therefore, the purpose of this study was the kinematic and electromyography analysis during functional hand movements. Method Ten subjects carried out six functional movements (terminal pinch, termino-lateral pinch, tripod pinch, power grip, extension grip and ball grip). Muscle activity (hand and forearm) was measured in real time using electromyograms, acquired with the Mega ME 6000, whilst acceleration was measured using the AcceleGlove. Results Electrical activity and acceleration variables were recorded simultaneously during the carrying out of the functional movements. The acceleration outcome variables were the modular vectors of each finger of the hand and the palm. In the electromyography, the main variables were normalized by the mean and by the maximum muscle activity of the thenar region, hypothenar, first interosseous dorsal, wrist flexors, carpal flexors and wrist extensors. Conclusions Knowing muscle behavior allows the clinician to take a more direct approach in the treatment. Based on the results, the tripod grip shows greater kinetic activity and the middle finger is the most relevant in this regard. Ball grip involves most muscle activity, with the thenar region playing a fundamental role in hand activity. Clinical relevance Relating muscle activation, movements, individual load and displacement offers the possibility to proceed with rehabilitation by individual component.

Medical imaging and Biomechanical analysis of scoliosis progression in the growing adolescent spine

Progression of spinal deformity in children was studied with Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) to identify how gravity affects the deformity and to determine the full three-dimensional character of the deformity. The CT study showed that gravity is significant in deformity progression in some patients which has implications for clinical patient management. The world first MRI study showed that the standard clinical measure used to define the extent of the deformity is inadequate and further use of three-dimensional MRI should be considered by spinal surgeons.