Use of condition-specific patient-reported outcome measures in clinical trials among patients with wrist osteoarthritis : a systematic review

Background. This paper aimed to identify condition-specific patient-reported outcome measures used in clinical trials among people with wrist osteoarthritis and summarise empirical peer-reviewed evidence supporting their reliability, validity, and responsiveness to change. Methods. A systematic review of randomised controlled trials among people with wrist osteoarthritis was undertaken. Studies reporting reliability, validity, or responsiveness were identified using a systematic reverse citation trail audit procedure. Psychometric properties of the instruments were examined against predefined criteria and summarised. Results. Thirteen clinical trials met inclusion criteria. The most common patient-reported outcome was the disabilities of the arm, shoulder, and hand questionnaire (DASH). The DASH, the Michigan Hand Outcomes Questionnaire (MHQ), the Patient Evaluation Measure (PEM), and the Patient-Reported Wrist Evaluation (PRWE) had evidence supporting their reliability, validity, and responsiveness. A post-hoc review of excluded studies revealed the AUSCAN Osteoarthritis Hand Index as another suitable instrument that had favourable reliability, validity, and responsiveness. Conclusions. The DASH, MHQ, and AUSCAN Osteoarthritis Hand Index instruments were supported by the most favourable empirical evidence for validity, reliability, and responsiveness. The PEM and PRWE also had favourable empirical evidence reported for these elements. Further psychometric testing of these instruments among people with wrist osteoarthritis is warranted.

Internet interventions for treatment of alcohol related problems

This is the protocol for a review and there is no abstract. The objectives are as follows: The primary objective of this review will be to assess the effect of internet and mobile phone alcohol-related interventions on reducing participants' alcohol consumption. Secondary objectives will include assessing the impact of the interventions on symptoms of alcohol-related disorders and degree of alcohol dependence, the effects on functioning, and patient acceptability. The review will also assess whether there are different outcomes for different diagnostic groups, and which intervention approaches or components (including therapeutic support) may be contributing to any positive effects.

Lifting the joint venture veil : liability of related entities for misleading conduct of agents engaged by joint venture partners

At common law, a corporation may be liable vicariously for the conduct of its appointed agents, employees or directors. This generally requires the agent or employee to be acting in the course of his or her agency or employment and, in the case of representations, to have actual or implied authority to make the representations. The circumstances in which a corporation may be liable for the conduct of its agents, employees or directors is broadened under the Australian Consumer Law (ACL) to where one of these parties engages in conduct “on behalf of” the corporation. As the decision in Bennett v Elysium Noosa Pty Ltd (in liq) demonstrates, this may extend to liability for the misleading conduct of a salesperson for the joint venture to parties who are not formal members of the joint venture, but where the joint venture activities are within the course of the entity’s “business, affairs or activities”.

A critical evaluation and comparison of two formative measures of system quality using criterion variables

Evaluating the validity of formative variables has presented ongoing challenges for researchers. In this paper we use global criterion measures to compare and critically evaluate two alternative formative measures of System Quality. One model is based on the ISO-9126 software quality standard, and the other is based on a leading information systems research model. We find that despite both models having a strong provenance, many of the items appear to be non-significant in our study. We examine the implications of this by evaluating the quality of the criterion variables we used, and the performance of PLS when evaluating formative models with a large number of items. We find that our respondents had difficulty distinguishing between global criterion variables measuring different aspects of overall System Quality. Also, because formative indicators “compete with one another” in PLS, it may be difficult to develop a set of measures which are all significant for a complex formative construct with a broad scope and a large number of items. Overall, we suggest that there is cautious evidence that both sets of measures are valid and largely equivalent, although questions still remain about the measures, the use of criterion variables, and the use of PLS for this type of model evaluation.

Selective cleavage of human sex hormone-binding globulin by kallikrein-related peptidases and effects on androgen action in LNCaP prostate cancer cells

Stimulation of the androgen receptor via bioavailable androgens, including testosterone and testosterone metabolites, is a key driver of prostate development and the early stages of prostate cancer. Androgens are hydrophobic and as such require carrier proteins, including sex hormone-binding globulin (SHBG), to enable efficient distribution from sites of biosynthesis to target tissues. The similarly hydrophobic corticosteroids also require a carrier protein whose affinity for steroid is modulated by proteolysis. However, proteolytic mechanisms regulating the SHBG/androgen complex have not been reported. Here, we show that the cancer-associated serine proteases, kallikrein-related peptidase (KLK)4 and KLK14, bind strongly to SHBG in glutathione S-transferase interaction analyses. Further, we demonstrate that active KLK4 and KLK14 cleave human SHBG at unique sites and in an androgen-dependent manner. KLK4 separated androgen-free SHBG into its two laminin G-like (LG) domains that were subsequently proteolytically stable even after prolonged digestion, whereas a catalytically equivalent amount of KLK14 reduced SHBG to small peptide fragments over the same period. Conversely, proteolysis of 5α-dihydrotestosterone (DHT)-bound SHBG was similar for both KLKs and left the steroid binding LG4 domain intact. Characterization of this proteolysis fragment by [(3)H]-labeled DHT binding assays revealed that it retained identical affinity for androgen compared with full-length SHBG (dissociation constant = 1.92 nM). Consistent with this, both full-length SHBG and SHBG-LG4 significantly increased DHT-mediated transcriptional activity of the androgen receptor compared with DHT delivered without carrier protein. Collectively, these data provide the first evidence that SHBG is a target for proteolysis and demonstrate that a stable fragment derived from proteolysis of steroid-bound SHBG retains binding function in vitro.

Cellular model systems to study the tumor biological role of kallikrein-related peptidases in ovarian and prostate cancer

Since the identification of the gene family of kallikrein related peptidases (KLKs), their function has been robustly studied at the biochemical level. In vitro biochemical studies have shown that KLK proteases are involved in a number of extracellular processes that initiate intracellular signaling pathways by hydrolysis, as reviewed in Chapters 8, 9, and 15, Volume 1. These events have been associated with more invasive phenotypes of ovarian, prostate, and other cancers. Concomitantly, aberrant expression of KLKs has been associated with poor prognosis of patients with ovarian and prostate cancer (Borgoño and Diamandis, 2004; Clements et al., 2004; Yousef and Diamandis, 2009), with prostate-specific antigen (PSA, KLK3) being a long standing, clinically employed biomarker for prostate cancer (Lilja et al., 2008). Data generated from patient samples in clinical studies, alongwith biochemical activity, suggests that KLKs function in the development and progression of these diseases. To bridge the gap between their function at the molecular level and the clinical need for efficacious treatment and prognostic biomarkers, functional assessment at the in vitro cellular level, using various culture models, is increasing, particularly in a three-dimensional (3D) context (Abbott, 2003; Bissell and Radisky, 2001; Pampaloni et al., 2007; Yamada and Cukierman, 2007).

Systematic variation of the severity of motor vehicle accident-related traumatic brain injury vignettes produces different post-concussion symptom reports

This study investigated the specificity of the post-concussion syndrome (PCS) expectation-as-etiology hypothesis. Undergraduate students (n = 551) were randomly allocated to one of three vignette conditions. Vignettes depicted either a very mild (VMI), mild (MI), or moderate-to-severe (MSI) motor vehicle-related traumatic brain injury (TBI). Participants reported the PCS and PTSD symptoms that they imagined the depicted injury would produce. Secondary outcomes (knowledge of mild TBI, and the perceived undesirability of TBI) were also assessed. After data screening, the distribution of participants by condition was: VMI (n = 100), MI (n = 96), and MSI (n = 71). There was a significant effect of condition on PCS symptomatology, F(2, 264) = 16.55, p < .001. Significantly greater PCS symptomatology was expected in the MSI condition compared to the other conditions (MSI > VMI; medium effect, r = .33; MSI > MI; small-to-medium effect, r = .22). The same pattern of group differences was found for PTSD symptoms, F(2, 264) = 17.12, p < .001. Knowledge of mild TBI was not related to differences in expected PCS symptoms by condition; and the perceived undesirability of TBI was only associated with reported PCS symptomatology in the MSI condition. Systematic variation in the severity of a depicted TBI produces different PCS and PTSD symptom expectations. Even a very mild TBI vignette can elicit expectations of PCS symptoms.

The effect of Tai Chi on health related quality of life in people with elevated blood glucose or diabetes : a randomized controlled trial

Purpose The aim was to assess the effects of a Tai Chi based program on health related quality of life (HR-QOL) in people with elevated blood glucose or diabetes who were not on medication for glucose control. Method 41 participants were randomly allocated to either a Tai Chi intervention group (N = 20) or a usual medical care control group (N = 21). The Tai Chi group involved 3 x 1.5 hour supervised and group-based training sessions per week for 12 weeks. Indicators of HR-QOL were assessed by self-report survey immediately prior to and after the intervention. Results There were significant improvements in favour of the Tai Chi group for the SF36 subscales of physical functioning (mean difference = 5.46, 95% CI = 1.35-9.57, P < 0.05), role physical (mean difference = 18.60, 95% CI = 2.16-35.05, P < 0.05), bodily pain (mean difference = 9.88, 95%CI = 2.06-17.69, P < 0.05) and vitality (mean difference = 9.96, 95% CI = 0.77-19.15, P < 0.05). Conclusions The findings show that this Tai Chi program improved indicators of HR-QOL including physical functioning, role physical, bodily pain and vitality in people with elevated blood glucose or diabetes who were not on diabetes medication.

Organisational culture in airworthiness management programs : developing a measurement model

All civil and private aircraft are required to comply with the airworthiness standards set by their national airworthiness authority and throughout their operational life must be in a condition of safe operation. Aviation accident data shows that over twenty percent of all fatal accidents in aviation are due to airworthiness issues, specifically aircraft mechanical failures. Ultimately it is the responsibility of each registered operator to ensure that their aircraft remain in a condition of safe operation, and this is done through both effective management of airworthiness activities and the effective program governance of safety outcomes. Typically, the projects within these airworthiness management programs are focused on acquiring, modifying and maintaining the aircraft as a capability supporting the business. Program governance provides the structure through which the goals and objectives of airworthiness programs are set along with the means of attaining them. Whilst the principal causes of failures in many programs can be traced to inadequate program governance, many of the failures in large scale projects can have their root causes in the organisational culture and more specifically in the organisational processes related to decision-making. This paper examines the primary theme of project and program based enterprises, and introduces a model for measuring organisational culture in airworthiness management programs using measures drawn from 211 respondents in Australian airline programs. The paper describes the theoretical perspectives applied to modifying an original model to specifically focus it on measuring the organisational culture of programs for managing airworthiness; identifying the most important factors needed to explain the relationship between the measures collected, and providing a description of the nature of these factors. The paper concludes by identifying a model that best describes the organisational culture data collected from seven airworthiness management programs.

Impact of a novel nurse-led prechemotherapy education intervention (ChemoEd) on patient distress, symptom burden, and treatment-related information and support needs : results from a randomised, controlled trial

Background: High levels of distress and need for self-care information by patients commencing chemotherapy suggest that current prechemotherapy education is suboptimal. We conducted a randomised, controlled trial of a prechemotherapy education intervention (ChemoEd) to assess impact on patient distress, treatment-related concerns, and the prevalence and severity of and bother caused by six chemotherapy side-effects. Patients and methods: One hundred and ninety-two breast, gastrointestinal, and haematologic cancer patients were recruited before the trial closing prematurely (original target 352). ChemoEd patients received a DVD, question-prompt list, self-care information, an education consultation ≥24 h before first treatment (intervention 1), telephone follow-up 48 h after first treatment (intervention 2), and a face-to-face review immediately before second treatment (intervention 3). Patient outcomes were measured at baseline (T1: pre-education) and immediately preceding treatment cycles 1 (T2) and 3 (T3). Results: ChemoEd did not significantly reduce patient distress. However, a significant decrease in sensory/psychological (P = 0.027) and procedural (P = 0.03) concerns, as well as prevalence and severity of and bother due to vomiting (all P = 0.001), were observed at T3. In addition, subgroup analysis of patients with elevated distress at T1 indicated a significant decrease (P = 0.035) at T2 but not at T3 (P = 0.055) in ChemoEd patients. Conclusions: ChemoEd holds promise to improve patient treatment-related concerns and some physical/psychological outcomes; however, further research is required on more diverse patient populations to ensure generalisability.

Policy measures for creating an integrated and brand-focused innovation system for film industries in shadow nations : an application to Australia's national film industry

Shadow nations face particular problems in constructing competitive film industries. Shadow nations refer to nations whose relative competitiveness suffers from easy product substitutability by products initiated, produced and distributed by powerful actors, such as media conglomerates located in Hollywood. The dominant literature has so far neglected the developing policy recommendations for dealing explicitly with the challenges of shadow nations. This paper aims to develop and apply a normative model for the development of film industries in shadow nations. The model integrates insights from innovation system studies and place branding. The developed model is applied to the Australian film industry as Australia represents a typical shadow nation within the film industry.

Characterisation of micrinite in the late triassic Callide Coal Measures

Samples from the Callide Coal Measures, Queensland, Australia, containing the minor maceral, micrinite, have been studied using optical and electron-optical techniques to determine the precise compositional and structural nature of micrinite when in association with vitrinite macerals. Emphasis has been placed on direct spatial correlation of optical and electron-optical data due to the fine grain size (<1μm) of micrinite and its relatively low abundance compared with other macerals in the Callide Basin coals. Precise elemental, morphological and structural data, including electron diffraction, provides unambiguous evidence for the presence of kaolinite in the component known as micrinite. Indeed, micrinite consists predominantly of fine-grained kaolinite (>90 per cent of the component) and, as such, should not be considered a maceral.

The human tissue kallikrein and kallikrein-related peptidase family

The human kallikrein-related peptidases are a subgroup of trypsin and chymotrypsin-like serine peptidases that are characterized by their homology to tissue kallikrein or kallikrein 1 (KLK1) encoded by the KLK1 gene (reviewed in[1-4]). The human KLK locus spans an approximately 320 kb region on chromosome 19q13.3-13.4 and contains fifteen genes encoding KLK1 and fourteen other kallikrein-related peptidases, KLK2-KLK15, which have been named contiguously in the locus in the order of their discovery [5-8] (Figure 606.1). It is the largest contiguous cluster of serine protease encoding genes in the human genome which has evolved from gene duplication of KLK1 and then subsequent reduplication of the newly evolved KLK genes [2]. The high conservation noted for KLK1-KLK3 (62-77%) reflects the proposed duplication of the KLK1 gene that produced the KLK2 gene which further generated the KLK3 gene. In contrast, the newer KLK4-KLK15 proteases share much less similarity, from 24-66%, although strong homology between KLK4 and KLK5, KLK9 and KLK11, and KLK10 and KLK12 suggests these genes are duplications of each other [2]...

Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment

High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.

Risk factors for moderate and severe microbial keratitis in daily wear contact lens users

Objective: To establish risk factors for moderate and severe microbial keratitis among daily contact lens (CL) wearers in Australia. Design: A prospective, 12-month, population-based, case-control study. Participants: New cases of moderate and severe microbial keratitis in daily wear CL users presenting in Australia over a 12-month period were identified through surveillance of all ophthalmic practitioners. Case detection was augmented by record audits at major ophthalmic centers. Controls were users of daily wear CLs in the community identified using a national telephone survey. Testing: Cases and controls were interviewed by telephone to determine subject demographics and CL wear history. Multiple binary logistic regression was used to determine independent risk factors and univariate population attributable risk percentage (PAR%) was estimated for each risk factor.; Main Outcome Measures: Independent risk factors, relative risk (with 95% confidence intervals [CIs]), and PAR%. Results: There were 90 eligible moderate and severe cases related to daily wear of CLs reported during the study period. We identified 1090 community controls using daily wear CLs. Independent risk factors for moderate and severe keratitis while adjusting for age, gender, and lens material type included poor storage case hygiene 6.4× (95% CI, 1.9-21.8; PAR, 49%), infrequent storage case replacement 5.4× (95% CI, 1.5-18.9; PAR, 27%), solution type 7.2× (95% CI, 2.3-22.5; PAR, 35%), occasional overnight lens use (<1 night per week) 6.5× (95% CI, 1.3-31.7; PAR, 23%), high socioeconomic status 4.1× (95% CI, 1.2-14.4; PAR, 31%), and smoking 3.7× (95% CI, 1.1-12.8; PAR, 31%). Conclusions: Moderate and severe microbial keratitis associated with daily use of CLs was independently associated with factors likely to cause contamination of CL storage cases (frequency of storage case replacement, hygiene, and solution type). Other factors included occasional overnight use of CLs, smoking, and socioeconomic class. Disease load may be considerably reduced by attention to modifiable risk factors related to CL storage case practice.