Molecular classification of cutaneous malignant melanoma by gene expression profiling

The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients

Background: High-flow nasal cannulae (HFNC) create positive oropharyngeal airway pressure but it is unclear how their use affects lung volume. Electrical impedance tomography (EIT) allows assessment of changes in lung volume by measuring changes in lung impedance. Primary objectives were to investigate the effects of HFNC on airway pressure (Paw) and end-expiratory lung volume (EELV), and to identify any correlation between the two. Secondary objectives were to investigate the effects of HFNC on respiratory rate (RR), dyspnoea, tidal volume and oxygenation; and the interaction between body mass index (BMI) and EELV. Methods: Twenty patients prescribed HFNC post-cardiac surgery were investigated. Impedance measures, Paw, PaO2/FiO2 ratio, RR and modified Borg scores were recorded first on low flow oxygen (nasal cannula or Hudson face mask) and then on HFNC. Results: A strong and significant correlation existed between Paw and end-expiratory lung impedance (EELI) (r=0.7, p<0.001). Compared with low flow oxygen, HFNC significantly increased EELI by 25.6% (95% CI 24.3, 26.9) and Paw by 3.0 cmH2O (95% CI 2.4, 3.7). RR reduced by 3.4 breaths per minute (95% CI 1.7, 5.2) with HFNC use, tidal impedance variation increased by 10.5% (95% CI 6.1, 18.3) and PaO2/FiO2 ratio improved by 30.6 mmHg (95% CI 17.9, 43.3). HFNC improved subjective dyspnoea scoring (p=0.023). Increases in EELI were significantly influenced by BMI, with larger increases associated with higher BMIs (p<0.001). Conclusions: This study suggests that HFNC improve dyspnoea and oxygenation by increasing both EELV and tidal volume, and are most beneficial in patients with higher BMIs.

The relationship between parents’ self-efficacy beliefs, outcome expectations, child behaviour, and management of atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin condition, characterized by intense pruritis, with a complex aetiology comprising multiple genetic and environmental factors. It is a common chronic health problem among children, and along with other allergic conditions, is increasing in prevalence within Australia and in many countries worldwide. Successful management of childhood AD poses a significant and ongoing challenge to parents of affected children. Episodic and unpredictable, AD can have profound effects on children’s physical and psychosocial wellbeing and quality of life, and that of their caregivers and families. Where concurrent child behavioural problems and parenting difficulties exist, parents may have particular difficulty achieving adequate and consistent performance of the routine management tasks that promote the child’s health and wellbeing. Despite frequent reports of behaviour problems in children with AD, past research has neglected the importance of child behaviour to parenting confidence and competence with treatment. Parents of children with AD are also at risk of experiencing depression, anxiety, parenting stress, and parenting difficulties. Although these factors have been associated with difficulty in managing other childhood chronic health conditions, the nature of these relationships in the context of child AD management has not been reported. This study therefore examined relationships between child, parent, and family variables, and parents’ management of child AD and difficult child behaviour, using social cognitive and self-efficacy theory as a guiding framework. The study was conducted in three phases. It employed a quantitative, cross-sectional study design, accessing a community sample of 120 parents of children with AD, and a sample of 64 child-parent dyads recruited from a metropolitan paediatric tertiary referral centre. In Phase One, instruments designed to measure parents’ self-reported performance of AD management tasks (Parents’ Eczema Management Scale – PEMS) and parents’ outcome expectations of task performance (Parents’ Outcome Expectations of Eczema Management Scale – POEEMS) were adapted from the Parental Self-Efficacy with Eczema Care Index (PASECI). In Phase Two, these instruments were used to examine relationships between child, parent, and family variables, and parents’ self-efficacy, outcome expectations, and self-reported performance of AD management tasks. Relationships between child, parent, and family variables, parents’ self-efficacy for managing problem behaviours, and reported parenting practices, were also examined. This latter focus was explored further in Phase Three, in which relationships between observed child and parent behaviour, and parent-reported self-efficacy for managing both child AD and problem behaviours, were explored. Phase One demonstrated the reliability of both PEMS and POEEMS, and confirmed that PASECI was reliable and valid with modification as detailed. Factor analyses revealed two-factor structures for PEMS and PASECI alike, with both scales containing factors related to performing routine management tasks, and managing the child’s symptoms and behaviour. Factor analysis was also applied to POEEMS resulting in a three-factor structure. Factors relating to independent management of AD by the parent, involving healthcare professionals in management, and involving the child in management of AD were found. Parents’ self-efficacy and outcome expectations had a significant influence on self-reported task performance. In Phase Two, relationships emerged between parents’ self-efficacy and self-reported performance of AD management tasks, and AD severity, child behaviour difficulties, parent depression and stress, conflict over parenting issues, and parents’ relationship satisfaction. Using multiple linear regressions, significant proportions of variation in parents’ self-efficacy and self-reported performance of AD management tasks were explained by child behaviour difficulties and parents’ formal education, and self-efficacy emerged as a likely mediator for the relationships between both child behaviour and parents’ education, and performance of AD management tasks. Relationships were also found between parents’ self-efficacy for managing difficult child behaviour and use of dysfunctional parenting strategies, and child behaviour difficulties, parents’ depression and stress, conflict over parenting issues, and relationship satisfaction. While significant proportions of variation in self-efficacy for managing child behaviour were explained by both child behaviour and family income, family income was the only variable to explain a significant proportion of variation in parent-reported use of dysfunctional parenting strategies. Greater use of dysfunctional parenting strategies (both lax and authoritarian parenting) was associated with more severe AD. Parents reporting lower self-efficacy for managing AD also reported lower self-efficacy for managing difficult child behaviour; likewise, less successful self-reported performance of AD management tasks was associated with greater use of dysfunctional parenting strategies. When child and parent behaviour was directly observed in Phase Three, more aversive child behaviour was associated with lower self-efficacy, less positive outcome expectations, and poorer self-reported performance of AD management tasks by parents. Importantly, there were strong positive relationships between these variables (self-efficacy, outcome expectations, and self-reported task performance) and parents’ observed competence when providing treatment to their child. Less competent performance was also associated with greater parent-reported child behaviour difficulties, parent depression and stress, parenting conflict, and relationship dissatisfaction. Overall, this study revealed the importance of child behaviour to parents’ confidence and practices in the contexts of child AD and child behaviour management. Parents of children with concurrent AD and behavioural problems are at particular risk of having low self-efficacy for managing their child’s AD and difficult behaviour. Children with more severe AD are also at higher risk of behaviour problems, and thus represent a high-risk group of children whose parents may struggle to manage the disease successfully. As one of the first studies to examine the role and correlates of parents’ self-efficacy in child AD management, this study identified a number of potentially modifiable factors that can be targeted to enhance parents’ self-efficacy, and improve parent management of child AD. In particular, interventions should focus on child behaviour and parenting issues to support parents caring for children with AD and improve child health outcomes. In future, findings from this research will assist healthcare teams to identify parents most in need of support and intervention, and inform the development and testing of targeted multidisciplinary strategies to support parents caring for children with AD.

Effects of surgical joint destabilization on load sharing between ligamentous structures in the thoracic spine : a finite element investigation

Background: In vitro investigations have demonstrated the importance of the ribcage in stabilising the thoracic spine. Surgical alterations of the ribcage may change load-sharing patterns in the thoracic spine. Computer models are used in this study to explore the effect of surgical disruption of the rib-vertebrae connections on ligament load-sharing in the thoracic spine. Methods: A finite element model of a T7-8 motion segment, including the T8 rib, was developed using CT-derived spinal anatomy for the Visible Woman. Both the intact motion segment and the motion segment with four successive stages of destabilization (discectomy and removal of right costovertebral joint, right costotransverse joint and left costovertebral joint) were analysed for a 2000Nmm moment in flexion/extension, lateral bending and axial rotation. Joint rotational moments were compared with existing in vitro data and a detailed investigation of the load sharing between the posterior ligaments carried out. Findings: The simulated motion segment demonstrated acceptable agreement with in vitro data at all stages of destabilization. Under lateral bending and axial rotation, the costovertebral joints were of critical importance in resisting applied moments. In comparison to the intact joint, anterior destabilization increases the total moment contributed by the posterior ligaments. Interpretation: Surgical removal of the costovertebral joints may lead to excessive rotational motion in a spinal joint, increasing the risk of overload and damage to the remaining ligaments. The findings of this study are particularly relevant for surgical procedures involving rib head resection, such as some techniques for scoliosis deformity correction.

Associations between young children's emotion attributions and prediction of outcome in differing social situations

Associations between young children's attributions of emotion at different points in a story, and with regard to their own prediction about the story's outcome, were investigated using two hypothetical scenarios of social and emotional challenge (social entry and negative event). First grade children (N = 250) showed an understanding that emotions are tied to situational cues by varying the emotions they attributed both between and within scenarios. Furthermore, emotions attributed to the main protagonist at the beginning of the scenarios were differentially associated with children's prediction of a positive or negative outcome and with the valence of the emotion attributed at the end of the scenario. Gender differences in responses to some items were also found. © 2010 The British Psychological Society.

Reliability of clinical measurement for assessing spinal fusion: An experimental sheep study

Study Design. A sheep study designed to compare the accuracy of static radiographs, dynamic radiographs, and computed tomographic (CT) scans for the assessment of thoracolumbar facet joint fusion as determined by micro-CT scanning. Objective. To determine the accuracy and reliability of conventional imaging techniques in identifying the status of thoracolumbar (T13-L1) facet joint fusion in a sheep model. Summary of Background Data. Plain radiographs are commonly used to determine the integrity of surgical arthrodesis of the thoracolumbar spine. Many previous studies of fusion success have relied solely on postoperative assessment of plain radiographs, a technique lacking sensitivity for pseudarthrosis. CT may be a more reliable technique, but is less well characterized. Methods. Eleven adult sheep were randomized to either attempted arthrodesis using autogenous bone graft and internal fixation (n = 3) or intentional pseudarthrosis (IP) using oxidized cellulose and internal fixation (n = 8). After 6 months, facet joint fusion was assessed by independent observers, using (1) plain static radiography alone, (2) additional dynamic radiographs, and (3) additional reconstructed spiral CT imaging. These assessments were correlated with high-resolution micro-CT imaging to predict the utility of the conventional imaging techniques in the estimation of fusion success. Results. The capacity of plain radiography alone to correctly predict fusion or pseudarthrosis was 43% and was not improved using plain radiography and dynamic radiography with also a 43% accuracy. Adding assessment by reformatted CT imaging to the plain radiography techniques increased the capacity to predict fusion outcome to 86% correctly. The sensitivity, specificity, and accuracy of static radiography were 0.33, 0.55, and 0.43, respectively, those of dynamic radiography were 0.46, 0.40, and 0.43, respectively, and those of radiography plus CT were 0.88, 0.85, and 0.86, respectively. Conclusion. CT-based evaluation correlated most closely with high-resolution micro-CT imaging. Neither plain static nor dynamic radiographs were able to predict fusion outcome accurately. © 2012 Lippincott Williams & Wilkins.

Design and rationale of a Prospective, Observational European Multicenter study on the efficacy of acute surgical decompression after traumatic Spinal Cord Injury: the SCI-POEM study

Objectives:Despite many years of research, there is currently no treatment available that results in major neurological or functional recovery after traumatic spinal cord injury (tSCI). In particular, no conclusive data related to the role of the timing of decompressive surgery, and the impact of injury severity on its benefit, have been published to date. This paper presents a protocol that was designed to examine the hypothesized association between the timing of surgical decompression and the extent of neurological recovery in tSCI patients.Study design: The SCI-POEM study is a Prospective, Observational European Multicenter comparative cohort study. This study compares acute (<12 h) versus non-acute (>12 h, <2 weeks) decompressive surgery in patients with a traumatic spinal column injury and concomitant spinal cord injury. The sample size calculation was based on a representative European patient cohort of 492 tSCI patients. During a 4-year period, 300 patients will need to be enrolled from 10 trauma centers across Europe. The primary endpoint is lower-extremity motor score as assessed according to the 'International standards for neurological classification of SCI' at 12 months after injury. Secondary endpoints include motor, sensory, imaging and functional outcomes at 3, 6 and 12 months after injury.Conclusion:In order to minimize bias and reduce the impact of confounders, special attention is paid to key methodological principles in this study protocol. A significant difference in safety and/or efficacy endpoints will provide meaningful information to clinicians, as this would confirm the hypothesis that rapid referral to and treatment in specialized centers result in important improvements in tSCI patients.Spinal Cord advance online publication, 17 April 2012; doi:10.1038/sc.2012.34.

Outcomes following operative and non-operative management of humeral midshaft fractures: a prospective, observational cohort study of 47 patients

Background Although the non-operative management of closed humeral midshaft fractures has been advocated for years, the increasing popularity of operative intervention has left the optimal treatment choice unclear. Objective To compare the outcomes of operative and non-operative treatment of traumatic closed humeral midshaft fractures in adult patients. Methods A multicentre prospective comparative cohort study across 20 centres was conducted. Patients with AO type 12 A2, A3 and B2 fractures were treated with a functional brace or a retrograde-inserted unreamed humeral nail. Follow-up measurements were taken at 6, 12 and 52 weeks after the injury. The primary outcome was fracture healing after 1 year. Secondary outcomes included sub-items of the Constant score, general patient satisfaction, complications and cost-effectiveness parameters. Functions of the uninjured extremity were used as reference parameters. Intention-to-treat analysis was applied with the use of t-tests, Fisher’s exact tests, Mann–Whitney U-tests and adjusted analysis of variance (ANOVA). Results Forty-seven patients were included. The patient sample consisted of 23 women and 24 men, with a mean age of 52.7 years (range 17–86 years). Of the 47 cases, 14 were treated non-operatively and 33 operatively. The follow-up rate at 1 year was 81%. After 1 year, 11 fractures (100%) healed in the non-operative group and at least 24 fractures (≥89%) healed in the operative group [1 non-union patient (4%) and no data for 2 patients (7%)]. There were no significant differences in pain, range of motion (ROM) of the shoulder and elbow, and return to work after 6 weeks, 12 weeks and 1 year. Although operatively treated patients showed significantly greater shoulder abduction strength (p = 0.036), elbow flexion strength (p = 0.021), functional hand positioning (p = 0.008) and return to recreational activities (p = 0.043) after 6 weeks, no statistically significant differences existed in any outcome measure at the 1-year follow-up. Conclusions Our findings indicate that the non-operative management of humeral midshaft fractures can be expected to have similar functional outcomes and patient satisfaction at 1 year, despite an early benefit to operative treatment. If no radiological evidence of fracture healing exists in non-operatively treated patients during early follow-up, a switch to surgical treatment results in good functional outcomes and patient satisfaction. Keywords: Humeral shaft fracture, Non-operative treatment, Functional brace, Operative treatment, Unreamed humeral nail (UHN), Prospective, Cohort study

Validation of scales measuring self-efficacy and outcome expectancy in evidence-based practice

Background: Evidence-based practice (EBP) is embraced internationally as an ideal approach to improve patient outcomes and provide cost-effective care. However, despite the support for and apparent benefits of evidence-based practice, it has been shown to be complex and difficult to incorporate into the clinical setting. Research exploring implementation of evidence-based practice has highlighted many internal and external barriers including clinicians’ lack of knowledge and confidence to integrate EBP into their day-to-day work. Nurses in particular often feel ill-equipped with little confidence to find, appraise and implement evidence. Aims: The following study aimed to undertake preliminary testing of the psychometric properties of tools that measure nurses’ self-efficacy and outcome expectancy in regard to evidence-based practice. Methods: A survey design was utilised in which nurses who had either completed an EBP unit or were randomly selected from a major tertiary referral hospital in Brisbane, Australia were sent two newly developed tools: 1) Self-efficacy in Evidence-Based Practice (SE-EBP) scale and 2) Outcome Expectancy for Evidence-Based Practice (OE-EBP) scale. Results: Principal Axis Factoring found three factors with eigenvalues above one for the SE-EBP explaining 73% of the variance and one factor for the OE-EBP scale explaining 82% of the variance. Cronbach’s alpha for SE-EBP, three SE-EBP factors and OE-EBP were all >.91 suggesting some item redundancy. The SE-EBP was able to distinguish between those with no prior exposure to EBP and those who completed an introductory EBP unit. Conclusions: While further investigation of the validity of these tools is needed, preliminary testing indicates that the SE-EBP and OE-EBP scales are valid and reliable instruments for measuring health professionals’ confidence in the process and the outcomes of basing their practice on evidence.