Long-term ambient air pollution exposure and self-reported morbidity in the Australian Longitudinal Study on Women's Health: A cross-sectional study

- Objective We sought to assess the effect of long-term exposure to ambient air pollution on the prevalence of self-reported health outcomes in Australian women. - Design Cross-sectional study - Setting and participants The geocoded residential addresses of 26 991 women across 3 age cohorts in the Australian Longitudinal Study on Women's Health between 2006 and 2011 were linked to nitrogen dioxide (NO2) exposure estimates from a land-use regression model. Annual average NO2 concentrations and residential proximity to roads were used as proxies of exposure to ambient air pollution. - Outcome measures Self-reported disease presence for diabetes mellitus, heart disease, hypertension, stroke, asthma, chronic obstructive pulmonary disease and self-reported symptoms of allergies, breathing difficulties, chest pain and palpitations. - Methods Disease prevalence was modelled by population-averaged Poisson regression models estimated by generalised estimating equations. Associations between symptoms and ambient air pollution were modelled by multilevel mixed logistic regression. Spatial clustering was accounted for at the postcode level. - Results No associations were observed between any of the outcome and exposure variables considered at the 1% significance level after adjusting for known risk factors and confounders. - Conclusions Long-term exposure to ambient air pollution was not associated with self-reported disease prevalence in Australian women. The observed results may have been due to exposure and outcome misclassification, lack of power to detect weak associations or an actual absence of associations with self-reported outcomes at the relatively low annual average air pollution exposure levels across Australia.

Effect of an interactive therapeutic robotic animal on engagement, mood states, agitation and psychotropic drug use in people with dementia: A cluster-randomised controlled trial protocol

Introduction: Apathy, agitated behaviours, loneliness and depression are common consequences of dementia. This trial aims to evaluate the effect of a robotic animal on behavioural and psychological symptoms of dementia in people with dementia living in long-term aged care. Methods and analysis: A cluster-randomised controlled trial with three treatment groups: PARO (robotic animal), Plush-Toy (non-robotic PARO) or Usual Care (Control). The nursing home sites are Australian Government approved and accredited facilities of 60 or more beds. The sites are located in South-East Queensland, Australia. A sample of 380 adults with a diagnosis of dementia, aged 60 years or older living in one of the participating facilities will be recruited. The intervention consists of three individual 15 min non-facilitated sessions with PARO or Plush- Toy per week, for a period of 10 weeks. The primary outcomes of interest are improvement in agitation, mood states and engagement. Secondary outcomes include sleep duration, step count, change in psychotropic medication use, change in treatment costs, and staff and family perceptions of PARO or Plush-Toy. Video data will be analysed using Noldus XT Pocket Observer; descriptive statistics will be used for participants’ demographics and outcome measures; cluster and individual level analyses to test all hypotheses and Generalised Linear Models for cluster level and Generalised Estimation Equations and/or Multi-level Modeling for individual level data. Ethics and dissemination: The study participants or their proxy will provide written informed consent. The Griffith University Human Research Ethics Committee has approved the study (NRS/03/14/HREC). The results of the study will provide evidence of the efficacy of a robotic animal as a psychosocial treatment for the behavioural and psychological symptoms of dementia. Findings will be presented at local and international conference meetings and published in peer-reviewed journals.

Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in Type 1 diabetes

OBJECTIVE This study determined if deficits in corneal nerve fiber length (CNFL) assessed using corneal confocal microscopy (CCM) can predict future onset of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS CNFL and a range of other baseline measures were compared between 90 nonneuropathic patients with type 1 diabetes who did or did not develop DPN after 4 years. The receiver operator characteristic (ROC) curve was used to determine the capability of single and combined measures of neuropathy to predict DPN. RESULTS DPN developed in 16 participants (18%) after 4 years. Factors predictive of 4-year incident DPN were lower CNFL (P = 0.041); longer duration of diabetes (P = 0.002); higher triglycerides (P = 0.023); retinopathy (higher on the Early Treatment of Diabetic Retinopathy Study scale) (P = 0.008); nephropathy (higher albumin-to-creatinine ratio) (P = 0.001); higher neuropathy disability score (P = 0.037); lower cold sensation (P = 0.001) and cold pain (P = 0.027) thresholds; higher warm sensation (P = 0.008), warm pain (P = 0.024), and vibration (P = 0.003) thresholds; impaired monofilament response (P = 0.003); and slower peroneal (P = 0.013) and sural (P = 0.002) nerve conduction velocity. CCM could predict the 4-year incident DPN with 63% sensitivity and 74% specificity for a CNFL threshold cutoff of 14.1 mm/mm2 (area under ROC curve = 0.66, P = 0.041). Combining neuropathy measures did not improve predictive capability. CONCLUSIONS DPN can be predicted by various demographic, metabolic, and conventional neuropathy measures. The ability of CCM to predict DPN broadens the already impressive diagnostic capabilities of this novel ophthalmic marker.

Destination image: identifying baseline perceptions of Brazil, Argentina and Chile in the nascent Australian long haul travel market

While the popularity of destination image research has increased exponentially in the literature, there has been relatively little published about perceptions held by international consumers of destinations in South America. The purpose of this paper is to report the findings of a research project that aimed to identify the baseline market perceptions of Brazil, Argentina and Chile amongst Australian residents, at the time of the emergence of this long haul market. Of interest was the extent to which Australians differentiate the three distinct countries versus perceiving the continent as a gestalt. These baseline perceptions enable the effectiveness of future marketing communications in Australia by the three national tourism offices to be monitored over time. Importance-Performance Analysis (IPA) is used as a practical analytical tool to guide decision makers. In terms of operationalising destination image, a key research finding was the very high ratio or participants using the ‘Don’t know’ (DK) option for each destination performance scale item. This finding has practical implications for the destination marketers, as well as for researchers engaged in destination image research in long haul and/or emerging markets.

The development of a component to improve the loading safety of bone-anchored prostheses

Use of socket prostheses Currently, for individuals with limb loss, the conventional method of attaching a prosthetic limb relies on a socket that fits over the residual limb. However, there are a number of issues concerning the use of a socket (e.g., blisters, irritation, and discomfort) that result in dissatisfaction with socket prostheses, and these lead ultimately a significant decrease in quality of life. Bone-anchored prosthesis Alternatively, the concept of attaching artificial limbs directly to the skeletal system has been developed (bone anchored prostheses), as it alleviates many of the issues surrounding the conventional socket interface.Bone anchored prostheses rely on two critical components: the implant, and the percutaneous abutment or adapter, which forms the connection for the external prosthetic system (Figure 1). To date, an implant that screws into the long bone of the residual limb has been the most common intervention. However, more recently, press-fit implants have been introduced and their use is increasing. Several other devices are currently at various stages of development, particularly in Europe and the United States. Benefits of bone-anchored prostheses Several key studies have demonstrated that bone-anchored prostheses have major clinical benefits when compared to socket prostheses (e.g., quality of life, prosthetic use, body image, hip range of motion, sitting comfort, ease of donning and doffing, osseoperception (proprioception), walking ability) and acceptable safety, in terms of implant stability and infection. Additionally, this method of attachment allows amputees to participate in a wide range of daily activities for a substantially longer duration. Overall, the system has demonstrated a significant enhancement to quality of life. Challenges of direct skeletal attachment However, due to the direct skeletal attachment, serious injury and damage can occur through excessive loading events such as during a fall (e.g., component damage, peri-prosthetic fracture, hip dislocation, and femoral head fracture). These incidents are costly (e.g., replacement of components) and could require further surgical interventions. Currently, these risks are limiting the acceptance of bone-anchored technology and the substantial improvement to quality of life that this treatment offers. An in-depth investigation into these risks highlighted a clear need to re-design and improve the componentry in the system (Figure 2), to improve the overall safety during excessive loading events. Aim and purposes The ultimate aim of this doctoral research is to improve the loading safety of bone-anchored prostheses, to reduce the incidence of injury and damage through the design of load restricting components, enabling individuals fitted with the system to partake in everyday activities, with increased security and self-assurance. The safety component will be designed to release or ‘fail’ external to the limb, in a way that protects the internal bone-implant interface, thus removing the need for restorative surgery and potential damage to the bone. This requires detailed knowledge of the loads typically experienced by the limb and an understanding of potential overload situations that might occur. Hence, a comprehensive review of the loading literature surrounding bone anchored prostheses will be conducted as part of this project, with the potential for additional experimental studies of the loads during normal activities to fill in gaps in the literature. This information will be pivotal in determining the specifications for the properties of the safety component, and the bone-implant system. The project will follow the Stanford Biodesign process for the development of the safety component.

Direct measurement of inner prosthesis loading during activities of daily living: Proposal for classification of functional outcome

Background The purpose of this presentation is to outline the relevance of the categorization of the load regime data to assess the functional output and usage of the prosthesis of lower limb amputees. The objectives are • To highlight the need for categorisation of activities of daily living • To present a categorization of load regime applied on residuum, • To present some descriptors of the four types of activity that could be detected, • To provide an example the results for a case. Methods The load applied on the osseointegrated fixation of one transfemoral amputee was recorded using a portable kinetic system for 5 hours. The load applied on the residuum was divided in four types of activities corresponding to inactivity, stationary loading, localized locomotion and directional locomotion as detailed in previously publications. Results The periods of directional locomotion, localized locomotion, and stationary loading occurred 44%, 34%, and 22% of recording time and each accounted for 51%, 38%, and 12% of the duration of the periods of activity, respectively. The absolute maximum force during directional locomotion, localized locomotion, and stationary loading was 19%, 15%, and 8% of the body weight on the anteroposterior axis, 20%, 19%, and 12% on the mediolateral axis, and 121%, 106%, and 99% on the long axis. A total of 2,783 gait cycles were recorded. Discussion Approximately 10% more gait cycles and 50% more of the total impulse than conventional analyses were identified. The proposed categorization and apparatus have the potential to complement conventional instruments, particularly for difficult cases.

Solutions for archiving data in long-term studies: A reply to Whitlock et al.

In our recent paper [1], we discussed some potential undesirable consequences of public data archiving (PDA) with specific reference to long-term studies and proposed solutions to manage these issues. We reaffirm our commitment to data sharing and collaboration, both of which have been common and fruitful practices supported for many decades by researchers involved in long-term studies. We acknowledge the potential benefits of PDA (e.g., [2]), but believe that several potential negative consequences for science have been underestimated [1] (see also 3 and 4). The objective of our recent paper [1] was to define practices to simultaneously maximize the benefits and minimize the potential unwanted consequences of PDA.

The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge-ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12-weeks) binge-ethanol intake, compared to short-term (4-weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin- and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency in BLA principal neurons from long-term ethanol consuming mice but not naïve mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long-term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies.

Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: A case study for technology appraisal on the basis of surrogate outcomes evidence

Objectives In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence’s recommendation on the public funding of these first-line treatments for CML. Methods We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR. Results Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21–23 years) following first-line treatment with imatinib, dasatinib, or nilotinib. Conclusions This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).

Hyperferritinemia -cataract syndrome: Long-term ophthalmic observations in an Italian family

Background Hyperferritinemia-cataract syndrome (HCS) is a rare Mendelian condition characterized by bilateral cataract and high levels of serum ferritin in the absence of iron overload. Methods HCS was diagnosed in three adult siblings. In two of them it was possible to assess lens changes initially in 1995 and again in 2013. Serum ferritin, iron, transferrin concentrations and transferrin saturation percentage were also measured, and the Iron Responsive Element (IRE) region of the L-ferritin gene (FTL) was studied. Results Serum ferritin concentrations were considerably elevated while serum iron, transferrin and transferrin saturation levels were within the normal range in each sibling. Cataract changes in our patients were consistent with those previously reported in the literature. Progression of the cataract, an aspect of few studies in this syndrome, appeared to be quite limited in extent. The heterozygous +32G to T (-168G>T) substitution in the IRE of the FTL gene was detected in this family. Conclusions Ophthalmic and biochemical studies together with genetic testing confirmed HCS in three family members. Although the disorder has been extensively described in recent years, little is known regarding cataract evolution over time. In our cases, lens evaluations encompassed many years, identified bilateral cataract of typical morphology and supported the hypothesis that this unique clinical feature of the disease tends to be slowly progressive in nature, at least in adults.

The long-run impact of Information and Communication Technology on economic output: The case of Australia

This paper investigates the cointegration and causal relationships between Information and Communication Technology (ICT) and economic output in Australia using data for about five decades. The framework used in this paper is the single-sector aggregate production function, which is the first comprehensive approach of this kind to include ICT and non-ICT capital and other factors to examine long-run Granger causality. The empirical evidence points to a cointegration relationship between ICT capital and output, and implies that ICT capital Granger causes economic output and multifactor productivity, as does non-ICT capital.

Long-term use of custom-made orthopedic shoes: A 1.5-year follow-up study

This study investigated long-term use of custom-made orthopedic shoes (OS) at 1.5 years follow-up. In addition, the association between short-term outcomes and long-term use was studied. Patients from a previously published study who did use their first-ever pair of OS 3 months after delivery received another questionnaire after 1.5 years. Patients with different pathologies were included in the study (n = 269, response = 86%). Mean age was 63 ± 14 years, and 38% were male. After 1.5 years, 87% of the patients still used their OS (78% frequently [4-7 days/week] and 90% occasionally [1-3 days/week]) and 13% of the patients had ceased using their OS. Patients who were using their OS frequently after 1.5 years had significantly higher scores for 8 of 10 short-term usability outcomes (p-values ranged from <0.001 to 0.046). The largest differences between users and nonusers were found for scores on the short-term outcomes of OS fit and communication with the medical specialist and shoe technician (effect size range = 0.16 to 0.46). We conclude that patients with worse short-term usability outcomes for their OS are more likely to use their OS only occasionally or not at all at long-term follow-up.

Short and long term mortality rates after a lower limb amputation

Objective To determine mortality rates after a first lower limb amputation and explore the rates for different subpopulations. Methods Retrospective cohort study of all people who underwent a first amputation at or proximal to transtibial level, in an area of 1.7 million people. Analysis with Kaplan-Meier curves and Log Rank tests for univariate associations of psycho-social and health variables. Logistic regression for odds of death at 30-days, 1-year and 5-years. Results 299 people were included. Median time to death was 20.3 months (95%CI: 13.1; 27.5). 30-day mortality = 22%; odds of death 2.3 times higher in people with history of cerebrovascular disease (95%CI: 1.2; 4.7, P = 0.016). 1 year mortality = 44%; odds of death 3.5 times higher for people with renal disease (95%CI: 1.8; 7.0, P < 0.001). 5-years mortality = 77%; odds of death 5.4 times higher for people with renal disease (95%CI: 1.8; 16.0,P = 0.003). Variation in mortality rates was most apparent in different age groups; people 75–84 years having better short term outcomes than those younger and older. Conclusions Mortality rates demonstrated the frailty of this population, with almost one quarter of people dying within 30-days, and almost half at 1 year. People with cerebrovascular had higher odds of death at 30 days, and those with renal disease and 1 and 5 years, respectively.

Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children: A systematic review

Background Around the world, guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) vary greatly. To prevent occlusion, most institutions recommend the use of heparin when the CVC is not in use. However, there is debate regarding the need for heparin and evidence to suggest normal saline may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased costs. Objectives To assess the clinical effects (benefits and harms) of heparin versus normal saline to prevent occlusion in long-term central venous catheters in infants, children and adolescents. Design A Cochrane systematic review of randomised controlled trials was undertaken. - Data sources: The Cochrane Vascular Group Specialised Register (including MEDLINE, CINAHL, EMBASE and AMED) and the Cochrane Register of Studies were searched. Hand searching of relevant journals and reference lists of retrieved articles was also undertaken. - Review Methods: Data were extracted and appraisal undertaken. We included studies that compared the efficacy of normal saline with heparin to prevent occlusion. We excluded temporary CVCs and peripherally inserted central catheters. Rate ratios per 1000 catheter days were calculated for two outcomes, occlusion of the CVC, and CVC-associated blood stream infection. Results Three trials with a total of 245 participants were included in this review. The three trials directly compared the use of normal saline and heparin. However, between studies, all used different protocols with various concentrations of heparin and frequency of flushes. The quality of the evidence ranged from low to very low. The estimated rate ratio for CVC occlusion per 1000 catheter days between the normal saline and heparin group was 0.75 (95% CI 0.10 to 5.51, two studies, 229 participants, very low quality evidence). The estimated rate ratio for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37, two studies, 231 participants; low quality evidence). Conclusions It remains unclear whether heparin is necessary for CVC maintenance. More well-designed studies are required to understand this relatively simple, but clinically important question. Ultimately, if this evidence were available, the development of evidenced-based clinical practice guidelines and consistency of practice would be facilitated.

In pursuit of becoming a senior coach: The learning culture for Australian Football League coaches

- Background and Purpose Given the turbulent and highly contested environment in which professional coaches work, a prime concern to coach developers is how coaches learn their craft. Understanding the learning and development of senior coaches (SCs) and assistant coaches (ACs) in the Australian Football League (AFL – the peak organisation for Australian Rules Football) is important to better develop the next generation of performance coaches. Hence the focus of this research was to examine the learning of SC and AC in the AFL. Fundamental to this research was an understanding that the AFL and each club within the league be regarded as learning organisations and workplaces with their own learning cultures where learning takes place. The purpose of this paper was to examine the learning culture for AFL coaches. - Method Five SCs, 6 ACs, and 5 administrators (4 of whom were former coaches) at 11 of the 16 AFL clubs were recruited for the research project. First, demographic data were collected for each participant (e.g. age, playing and coaching experience, development and coach development activities). Second, all participants were involved in one semi-structured interview of between 45 and 90 minutes duration. An interpretative (hierarchical content) analysis of the interview data was conducted to identify key emergent themes. - Results Learning was central to AFL coaches becoming a SC. Nevertheless, coaches reported a sense of isolation and a lack of support in developing their craft within their particular learning culture. These coaches developed a unique dynamic social network (DSN) that involved episodic contact with a number of respected confidantes often from diverse fields (used here in the Bourdieuian sense) in developing their coaching craft. Although there were some opportunities in their workplace, much of their learning was unmediated by others, underscoring the importance of their agentic engagement in limited workplace affordances. - Conclusion The variety of people accessed for the purposes of learning (often beyond the immediate workplace) and the long time taken to establish networks of supporters meant that a new way of describing the social networks of AFL coaches was needed; DSN. However, despite the acknowledged utility of learning from others, all coaches reported some sense of isolation in their learning. The sense of isolation brought about by professional volatility in high-performance Australian Football offers an alternative view on Hodkinson, Biesta and James' attempt in overcoming dualisms in learning.