Gaseous air pollution and emergency hospital visits for hypertension in Beijing, China : a time-stratified case-crossover study

Background: A number of epidemiological studies have been conducted to research the adverse effects of air pollution on mortality and morbidity. Hypertension is the most important risk factor for cardiovascular mortality. However, few previous studies have examined the relationship between gaseous air pollution and morbidity for hypertension. ---------- Methods: Daily data on emergency hospital visits (EHVs) for hypertension were collected from the Peking University Third Hospital. Daily data on gaseous air pollutants (sulfur dioxide (SO2) and nitrogen dioxide (NO2)) and particulate matter less than 10 μm in aerodynamic diameter (PM10) were collected from the Beijing Municipal Environmental Monitoring Center. A time-stratified case-crossover design was conducted to evaluate the relationship between urban gaseous air pollution and EHVs for hypertension. Temperature and relative humidity were controlled for. ---------- Results: In the single air pollutant models, a 10 μg/m3 increase in SO2 and NO2 were significantly associated with EHVs for hypertension. The odds ratios (ORs) were 1.037 (95% confidence interval (CI): 1.004-1.071) for SO2 at lag 0 day, and 1.101 (95% CI: 1.038-1.168) for NO2 at lag 3 day. After controlling for PM10, the ORs associated with SO2 and NO2 were 1.025 (95% CI: 0.987-1.065) and 1.114 (95% CI: 1.037-1.195), respectively.---------- Conclusion: Elevated urban gaseous air pollution was associated with increased EHVs for hypertension in Beijing, China.

The effects of muscle fatigue on knee function during landing

The human knee acts as a sophisticated shock absorber during landing movements. The ability of the knee to perform this function in the real world is remarkable given that the context of the landing movement may vary widely between performances. For this reason, humans must be capable of rapidly adjusting the mechanical properties of the knee under impact load in order to satisfy many competing demands. However, the processes involved in regulating these properties in response to changing constraints remain poorly understood. In particular, the effects of muscle fatigue on knee function during step landing are yet to be fully explored. Fatigue of the knee muscles is significant for 2 reasons. First, it is thought to have detrimental effects on the ability of the knee to act as a shock absorber and is considered a risk factor for knee injury. Second, fatigue of knee muscles provides a unique opportunity to examine the mechanisms by which healthy individuals alter knee function. A review of the literature revealed that the effect of fatigue on knee function during landing has been assessed by comparing pre and postfatigue measurements, with fatigue induced by a voluntary exercise protocol. The information is limited by inconsistent results with key measures, such as knee stiffness, showing varying results following fatigue, including increased stiffness, decreased stiffness or failure to detect any change in some experiments. Further consideration of the literature questions the validity of the models used to induce and measure fatigue, as well as the pre-post study design, which may explain the lack of consensus in the results. These limitations cast doubt on the usefulness of the available information and identify a need to investigate alternative approaches. Based on the results of this review, the aims of this thesis were to: • evaluate the methodological procedures used in validation of a fatigue model • investigate the adaptation and regulation of post-impact knee mechanics during repeated step landings • use this new information to test the effects of fatigue on knee function during a step-landing task. To address the aims of the thesis, 3 related experiments were conducted that collected kinetic, kinematic and electromyographic data from 3 separate samples of healthy male participants. The methodologies involved optoelectronic motion capture (VICON), isokinetic dynamometry (System3 Pro, BIODEX) and wireless surface electromyography (Zerowire, Aurion, Italy). Fatigue indicators and knee function measures used in each experiment were derived from the data. Study 1 compared the validity and reliability of repetitive stepping and isokinetic contractions with respect to fatigue of the quadriceps and hamstrings. Fifteen participants performed 50 repetitions of each exercise twice in randomised order, over 4 sessions. Sessions were separated by a minimum of 1 week’s rest, to ensure full recovery. Validity and reliability depended on a complex interaction between the exercise protocol, the fatigue indicator, the individual and the muscle of interest. Nevertheless, differences between exercise protocols indicated that stepping was less effective in eliciting valid and reliable changes in peak power and spectral compression, compared with isokinetic exercise. A key finding was that fatigue progressed in a biphasic pattern during both exercises. The point separating the 2 phases, known as the transition point, demonstrated superior between-test reliability during the isokinetic protocol, compared with stepping. However, a correction factor should be used to accurately apply this technique to the study of fatigue during landing. Study 2 examined alterations in knee function during repeated landings, with a different sample (N =12) performing 60 consecutive step landing trials. Each landing trial was separated by 1-minute rest periods. The results provided new information in relation to the pre-post study design in the context of detecting adjustments in knee function during landing. First, participants significantly increased or decreased pre-impact muscle activity or post-impact mechanics despite environmental and task constraints remaining unchanged. This is the 1st study to demonstrate this effect in healthy individuals without external feedback on performance. Second, single-subject analysis was more effective in detecting alterations in knee function compared to group-level analysis. Finally, repeated landing trials did not reduce inter-trial variability of knee function in some participants, contrary to assumptions underpinning previous studies. The results of studies 1 and 2 were used to modify the design of Study 3 relative to previous research. These alterations included a modified isokinetic fatigue protocol, multiple pre-fatigue measurements and singlesubject analysis to detect fatigue-related changes in knee function. The study design incorporated new analytical approaches to investigate fatiguerelated alterations in knee function during landing. Participants (N = 16) were measured during multiple pre-fatigue baseline trial blocks prior to the fatigue model. A final block of landing trials was recorded once the participant met the operational fatigue definition that was identified in Study 1. The analysis revealed that the effects of fatigue in this context are heavily dependent on the compensatory response of the individual. A continuum of responses was observed within the sample for each knee function measure. Overall, preimpact preparation and post-impact mechanics of the knee were altered with highly individualised patterns. Moreover, participants used a range of active or passive pre-impact strategies to adapt post-impact mechanics in response to quadriceps fatigue. The unique patterns identified in the data represented an optimisation of knee function based on priorities of the individual. The findings of these studies explain the lack of consensus within the literature regarding the effects of fatigue on knee function during landing. First, functional fatigue protocols lack validity in inducing fatigue-related changes in mechanical output and spectral compression of surface electromyography (sEMG) signals, compared with isokinetic exercise. Second, fatigue-related changes in knee function during landing are confounded by inter-individual variation, which limits the sensitivity of group-level analysis. By addressing these limitations, the 3rd study demonstrated the efficacies of new experimental and analytical approaches to observe fatigue-related alterations in knee function during landing. Consequently, this thesis provides new perspectives into the effects of fatigue in knee function during landing. In conclusion: • The effects of fatigue on knee function during landing depend on the response of the individual, with considerable variation present between study participants, despite similar physical characteristics. • In healthy males, adaptation of pre-impact muscle activity and postimpact knee mechanics is unique to the individual and reflects their own optimisation of demands such as energy expenditure, joint stability, sensory information and loading of knee structures. • The results of these studies should guide future exploration of adaptations in knee function to fatigue. However, research in this area should continue with reduced emphasis on the directional response of the population and a greater focus on individual adaptations of knee function.

The application of a profluorescent nitroxide probe to detect reactive oxygen species derived from combustion-generated particulate matter

Particulate pollution has been widely recognised as an important risk factor to human health. In addition to increases in respiratory and cardiovascular morbidity associated with exposure to particulate matter (PM), WHO estimates that urban PM causes 0.8 million premature deaths globally and that 1.5 million people die prematurely from exposure to indoor smoke generated from the combustion of solid fuels. Despite the availability of a huge body of research, the underlying toxicological mechanisms by which particles induce adverse health effects are not yet entirely understood. Oxidative stress caused by generation of free radicals and related reactive oxygen species (ROS) at the sites of deposition has been proposed as a mechanism for many of the adverse health outcomes associated with exposure to PM. In addition to particle-induced generation of ROS in lung tissue cells, several recent studies have shown that particles may also contain ROS. As such, they present a direct cause of oxidative stress and related adverse health effects. Cellular responses to oxidative stress have been widely investigated using various cell exposure assays. However, for a rapid screening of the oxidative potential of PM, less time-consuming and less expensive, cell-free assays are needed. The main aim of this research project was to investigate the application of a novel profluorescent nitroxide probe, synthesised at QUT, as a rapid screening assay in assessing the oxidative potential of PM. Considering that this was the first time that a profluorescent nitroxide probe was applied in investigating the oxidative stress potential of PM, the proof of concept regarding the detection of PM–derived ROS by using such probes needed to be demonstrated and a sampling methodology needed to be developed. Sampling through an impinger containing profluorescent nitroxide solution was chosen as a means of particle collection as it allowed particles to react with the profluorescent nitroxide probe during sampling, avoiding in that way any possible chemical changes resulting from delays between the sampling and the analysis of the PM. Among several profluorescent nitroxide probes available at QUT, bis(phenylethynyl)anthracene-nitroxide (BPEAnit) was found to be the most suitable probe, mainly due to relatively long excitation and emission wavelengths (λex= 430 nm; λem= 485 and 513 nm). These wavelengths are long enough to avoid overlap with the background fluorescence coming from light absorbing compounds which may be present in PM (e.g. polycyclic aromatic hydrocarbons and their derivatives). Given that combustion, in general, is one of the major sources of ambient PM, this project aimed at getting an insight into the oxidative stress potential of combustion-generated PM, namely cigarette smoke, diesel exhaust and wood smoke PM. During the course of this research project, it was demonstrated that the BPEAnit probe based assay is sufficiently sensitive and robust enough to be applied as a rapid screening test for PM-derived ROS detection. Considering that for all three aerosol sources (i.e. cigarette smoke, diesel exhaust and wood smoke) the same assay was applied, the results presented in this thesis allow direct comparison of the oxidative potential measured for all three sources of PM. In summary, it was found that there was a substantial difference between the amounts of ROS per unit of PM mass (ROS concentration) for particles emitted by different combustion sources. For example, particles from cigarette smoke were found to have up to 80 times less ROS per unit of mass than particles produced during logwood combustion. For both diesel and wood combustion it has been demonstrated that the type of fuel significantly affects the oxidative potential of the particles emitted. Similarly, the operating conditions of the combustion source were also found to affect the oxidative potential of particulate emissions. Moreover, this project has demonstrated a strong link between semivolatile (i.e. organic) species and ROS and therefore, clearly highlights the importance of semivolatile species in particle-induced toxicity.

Children with special health care needs : social and learning competence in the early years

The number of children with special health care needs surviving infancy and attending school has been increasing. Due to their health status, these children may be at risk of low social-emotional and learning competencies (e.g., Lightfoot, Mukherjee, & Sloper, 2000; Zehnder, Landolt, Prchal, & Vollrath, 2006). Early social problems have been linked to low levels of academic achievement (Ladd, 2005), inappropriate behaviours at school (Shiu, 2001) and strained teacher-child relationships (Blumberg, Carle, O‘Connor, Moore, & Lippmann, 2008). Early learning difficulties have been associated with mental health problems (Maughan, Rowe, Loeber, & Stouthamer-Loeber, 2003), increased behaviour issues (Arnold, 1997), delinquency (Loeber & Dishion, 1983) and later academic failure (Epstein, 2008). Considering the importance of these areas, the limited research on special health care needs in social-emotional and learning domains is a factor driving this research. The purpose of the current research is to investigate social-emotional and learning competence in the early years for Australian children who have special health care needs. The data which informed this thesis was from Growing up in Australia: The Longitudinal Study of Australian Children. This is a national, longitudinal study being conducted by the Commonwealth Department of Families, Housing, Community Services and Indigenous Affairs. The study has a national representative sample, with data collection occurring biennially, in 2004 (Wave 1), 2006 (Wave 2) and 2008 (Wave 3). Growing up in Australia uses a cross-sequential research design involving two cohorts, an Infant Cohort (0-1 at recruitment) and a Kindergarten Cohort (4-5 at recruitment). This study uses the Kindergarten Cohort, for which there were 4,983 children at recruitment. Three studies were conducted to address the objectives of this thesis. Study 1 used Wave 1 data to identify and describe Australian children with special health care needs. Children who identified as having special health care needs through the special health care needs screener were selected. From this, descriptive analyses were run. The results indicate that boys, children with low birth weight and children from families with low levels of maternal education are likely to be in the population of children with special health care needs. Further, these children are likely to be using prescription medications, have poor general health and are likely to have specific condition diagnoses. Study 2 used Wave 1 data to examine differences between children with special health care needs and their peers in social-emotional competence and learning competence prior to school. Children identified by the special health care needs screener were chosen for the case group (n = 650). A matched case control group of peers (n = 650), matched on sex, cultural and linguistic diversity, family socioeconomic position and age, were the comparison group. Social-emotional competence was measured through Social/Emotional Domain scores taken from the Growing up in Australia Outcome Index, with learning competence measured through Learning Domain scores. Results suggest statistically significant differences in scores between the two groups. Children with special health care needs have lower levels of social-emotional and learning competence prior to school compared to their peers. Study 3 used Wave 1 and Wave 2 data to examine the relationship between special health care needs at Wave 1 and social-emotional competence and learning competence at Wave 2, as children started school. The sample for this study consisted of children in the Kindergarten Cohort who had teacher data at Wave 2. Results from multiple regression models indicate that special health care needs prior to school (Wave 1) significantly predicts social-emotional competence and learning competence in the early years of school (Wave 2). These results indicate that having special health care needs prior to school is a risk factor for the social-emotional and learning domains in the early years of school. The results from these studies give valuable insight into Australian children with special health care needs and their social-emotional and learning competence in the early years. The Australia population of children with special health care needs were primarily male children, from families with low maternal education, were likely to be of poor health and taking prescription medications. It was found that children with special health care needs were likely to have lower social-emotional competence and learning competence prior to school compared to their peers. Results indicate that special health care needs prior to school were predictive of lower social-emotional and learning competencies in the early years of school. More research is required into this unique population and their competencies over time. However, the current research provides valuable insight into an under researched 'at risk' population.

Is adiponectin implicated in venous thromboembolism?

In summary, these results imply that the relationship of adiponectin with lipoproteins is more complex than previously predicted using other methods of lipoprotein fractionation. Higher correlation of adiponectin was shown with large lipoprotein particle size, independent of the apolipoprotein content. Given the small population studied, we could not assess the influence of mild risk factors for venous thrombosis, such as obesity, on the analysis of the results. Thus, we can only state that adiponectin levels appear not to be a strong risk factor for VTE. It is possible that adiponectin deficiency may contribute indirectly to the etiology of VTE by enhancing the inflammatory state. © 2006 International Society on Thrombosis and Haemostasis.

High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men

Background-Although dyslipoproteinemia is associated with arterial atherothrombosis, little is known about plasma lipoproteins in venous thrombosis patients. Methods and Results-We determined plasma lipoprotein subclass concentrations using nuclear magnetic resonance spectroscopy and antigenic levels of apolipoproteins AI and B in blood samples from 49 male venous thrombosis patients and matched controls aged <55 years. Venous thrombosis patients had significantly lower levels of HDL particles, large HDL particles, HDL cholesterol, and apolipoprotein AI and significantly higher levels of LDL particles and small LDL particles. The quartile-based odds ratios for decreased HDL particle and apolipoprotein AI levels in patients compared with controls were 6.5 and 6.0 (95% CI, 2.3 to 19 and 2.1 to 17), respectively. Odds ratios for apolipoprotein B/apolipoprotein AI ratio and LDL cholesterol/HDL cholesterol ratio were 6.3 and 2.7 (95% CI, 1.9 to 21 and 1.1 to 6.5), respectively. When polymorphisms in genes for hepatic lipase, endothelial lipase, and cholesteryl ester transfer protein were analyzed, patients differed significantly from controls in the allelic frequency for the TaqI B1/B2 polymorphism in cholesteryl ester transfer protein, consistent with the observed pattern of lower HDL and higher LDL. Conclusions-Venous thrombosis in men aged <55 years old is associated with dyslipoproteinemia involving lower levels of HDL particles, elevated levels of small LDL particles, and an elevated ratio of apolipoprotein B/apolipoprotein AI. This dyslipoproteinemia seems associated with a related cholesteryl ester transfer protein genotype difference. © 2005 American Heart Association, Inc.

Multiple analysis of three common genetic alterations associated with thrombophilia

We have previously reported the use of a novel mini-sequencing protocol for detection of the factor V Leiden variant, the first nucleotide change (FNC) technology. This technology is based on a single nucleotide extension of a primer, which is hybridized immediately adjacent to the site of mutation. The extended nucleotide that carries a reporter molecule (fluorescein) has the power to discriminate the genotype at the site of mutation. More recently, the prothrombin 20210 and thermolabile methylene tetrahydrofolate reductase (MTHFR) 677 variants have been identified as possible risk factors associated with thrombophilia. This study describes the use of the FNC technology in a combined assay to detect factor V, prothrombin and MTHFR variants in a population of Australian blood donors, and describes the objective numerical methodology used to determine genotype cut-off values for each genetic variation. Using FNC to test 500 normal blood donors, the incidence of Factor V Leiden was 3.6% (all heterozygous), that of prothrombin 20210 was 2.8% (all heterozygous) and that of MTHFR was 10% (homozygous). The combined FNC technology offers a simple, rapid, automatable DNA-based test for the detection of these three important mutations that are associated with familial thrombophilia. (C) 2000 Lippincott Williams and Wilkins.

Helping someone with problem drinking: Mental health first aid guidelines - a Delphi expert consensus study

Background Alcohol is a leading risk factor for avoidable disease burden. Research suggests that a drinker's social network can play an integral role in addressing hazardous (i.e., high-risk) or problem drinking. Often however, social networks do not have adequate mental health literacy (i.e., knowledge about mental health problems, like problem drinking, or how to treat them). This is a concern as the response that a drinker receives from their social network can have a substantial impact on their willingness to seek help. This paper describes the development of mental health first aid guidelines that inform community members on how to help someone who may have, or may be developing, a drinking problem (i.e., alcohol abuse or dependence). Methods A systematic review of the research and lay literature was conducted to develop a 285-item survey containing strategies on how to help someone who may have, or may be developing, a drinking problem. Two panels of experts (consumers/carers and clinicians) individually rated survey items, using a Delphi process. Surveys were completed online or via postal mail. Participants were 99 consumers, carers and clinicians with experience or expertise in problem drinking from Australia, Canada, Ireland, New Zealand, the United Kingdom, and the United States. Items that reached consensus on importance were retained and written into guidelines. Results The overall response rate across all three rounds was 68.7% (67.6% consumers/carers, 69.2% clinicians), with 184 first aid strategies rated as essential or important by ≥80% of panel members. The endorsed guidelines provide guidance on how to: recognize problem drinking; approach someone if there is concern about their drinking; support the person to change their drinking; respond if they are unwilling to change their drinking; facilitate professional help seeking and respond if professional help is refused; and manage an alcohol-related medical emergency. Conclusion The guidelines provide a consensus-based resource for community members seeking to help someone with a drinking problem. Improving community awareness and understanding of how to identify and support someone with a drinking problem may lead to earlier recognition of problem drinking and greater facilitation of professional help seeking.

Quality of life and genetics in men with prostate cancer

As family history has been established as a risk factor for prostate cancer, attempts have been made to isolate predisposing genetic variants that are related to hereditary prostate cancer. With many genetic variants still to be identified and investigated, it is not yet possible to fully understand the impact of genetic variants on prostate cancer development. The high survival rates among men with prostate cancer have meant that other issues, such as quality of life (QoL), have also become important. Through their effect on a person’s health, a range of inherited genetic variants may potentially influence QoL in men with prostate cancer, even prior to treatment. Until now, limited research has been conducted on the relationship between genetics and QoL. Thus, this study contributes to an emerging field by aiming to identify certain genetic variants related to the QoL found in men with prostate cancer. It is hoped that this study may lead to future research that will identify men who have an increased risk of a poor QoL following prostate cancer treatment, which will aid in developing treatments that are individually tailored to support them. Previous studies have established that genetic variants of Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor 1 (IGF-1) may play a role in prostate cancer development. VEGF and IGF-1 have also been reported to be associated with QoL in people with ovarian cancer and colorectal cancer, respectively. This study completed a series of secondary analyses using two major data-sets (from 850 men newly diagnosed with prostate cancer, and approximately 550 men from the general Queensland population), in which genetic variants of VEGF and IGF-1 were investigated for associations with prostate cancer susceptibility and QoL. The first aim of this research was to investigate genetic variants in the VEGF and IGF-I gene for an association with the risk of prostate cancer. It was found that one IGF-1 genetic variant (rs35765) had a statistically significant association with prostate cancer (p = 0.04), and one VEGF genetic variant (rs2146323) had a statistically significant association with advanced prostate cancer (p = 0.02). The estimates suggest that carriers of the CA and AA genotype for rs35765 may have a reduced risk of developing prostate cancer (Odds Ratio (OR) = 0.72, 95% Confidence Interval (CI) = 0.55, 0.95, OR = 0.60, 95% CI = 0.26, 1.39, respectively). Meanwhile, carriers of the CA and AA genotype for rs2146323 may be at increased risk of advanced prostate cancer, which was determined by a Gleason score of above 7 (OR = 1.72, 95% CI = 1.12, 2.63, OR = 1.90, 95% CI = 1.08, 3.34, respectively). Utilising the widely used short-form health survey, the SF-36v2, the second aim of this study was to investigate the relationship between prostate cancer and QoL prior to treatment. Assessing QoL at this time-point was important as little research has been conducted to evaluate if prostate cancer affects QoL regardless of treatment. The analyses found that mean SF-36v2 scale scores related to physical health were higher by at least 0.3 Standard Deviations (SD) among men with prostate cancer than the general population comparison group. This difference was considered clinically significant (defined by group differences in mean SF-36v2 scores by at least 0.3 SD). These differences were also statistically significant (p<0.05). Mean QoL scale scores related to mental health were similar between men with prostate cancer and those from the general population comparison group. The third aim of this study was to investigate genetic variants in the VEGF and IGF-1 gene for an association with QoL in prostate cancer patients prior to their treatment. It was essential to evaluate these relationships prior to treatment, before the involvement of these genes was potentially interrupted by treatment. The analyses found that some genetic variants had a small clinically significant association (0.3 SD) to some QoL domains experienced by these men. However, most relationships were not statistically significant (p>0.05). Most of the associations found identified that a small sub-group of men with prostate cancer (approximately 2%) reported, on average, a slightly better QoL than the majority of the prostate cancer patients. The fourth aim of this research was to investigate whether associations between genetic variants in VEGF and IGF-1 and QoL were specific to men with prostate cancer, or were also applicable to the general male population. It was found that twenty out of one-hundred relationships between the genetic variants of VEGF and IGF-1 and QoL health-measures and scales examined differed between these groups. In the majority of the relationships involving VEGF SNPs that differed, a clinically significant difference (0.3 or more SD) between mean scores among the genotype groups in prostate cancer patients was found, while mean scores among men from the general-population comparison group were similar. For example, prostate cancer participants who carried at least one T allele (CT or TT genotype) for rs3024994 had a clinically significant higher (0.3 SD) mean QoL score in terms of the role-physical scale, than participants who carried the CC genotype. This was not seen among men from the general population sample, as the mean score was similar between genotype groups. The opposite was seen in regards to the IGF-1 SNPs examined. Overall, these relationships were not considered to directly impact on the clinical options for men with prostate cancer. As this study utilised secondary data from two separate studies, there are a number of important limitations that should be acknowledged including issues of multiple comparisons, power, and missing or unavailable data. It is recommended that this study be replicated as a better-designed study that takes greater consideration of the many factors involved in prostate cancer and QoL. Investigation into other genetic variants of VEGF or IGF-1 is also warranted, as is consideration of other genes and their relationship with QoL. Through identifying certain genetic variants that have a modest association to prostate cancer, this project adds to the knowledge surrounding VEGF and IGF-1 and their role in prostate cancer susceptibility. Importantly, this project has also introduced the potential role genetics plays in QoL, through investigating the relationships between genetic variants of VEGF and IGF-1 and QoL.

Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12 566 individuals

The primary genetic risk factor in multiple sclerosis (MS) is the HLA-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has yet to be elucidated. Several lines of evidence support a role for neuroendocrine system involvement in autoimmunity which may, in part, be genetically determined. Here, we comprehensively investigated variation within eight candidate hypothalamic-pituitary-adrenal (HPA) axis genes and susceptibility to MS. A total of 326 SNPs were investigated in a discovery dataset of 1343 MS cases and 1379 healthy controls of European ancestry using a multi-analytical strategy. Random Forests, a supervised machine-learning algorithm, identified eight intronic SNPs within the corticotrophin-releasing hormone receptor 1 or CRHR1 locus on 17q21.31 as important predictors of MS. On the basis of univariate analyses, six CRHR1 variants were associated with decreased risk for disease following a conservative correction for multiple tests. Independent replication was observed for CRHR1 in a large meta-analysis comprising 2624 MS cases and 7220 healthy controls of European ancestry. Results from a combined meta-analysis of all 3967 MS cases and 8599 controls provide strong evidence for the involvement of CRHR1 in MS. The strongest association was observed for rs242936 (OR = 0.82, 95% CI = 0.74-0.90, P = 9.7 × 10-5). Replicated CRHR1 variants appear to exist on a single associated haplotype. Further investigation of mechanisms involved in HPA axis regulation and response to stress in MS pathogenesis is warranted. © The Author 2010. Published by Oxford University Press. All rights reserved.

Attachment Security and Alexithymia in a Heavy Drinking Population

Attachment difficulties have been proposed as a key risk factor for the development of alexithymia, a multifaceted personality trait characterised by difficulties identifying and describing feelings, a lack of imagination and an externally oriented thinking style. The present study investigated the relationship between attachment and alexithymia in an alcohol dependent population. Participants were 210 outpatients in a Cognitive Behavioural Treatment Program assessed on the Toronto Alexithymia Scale (TAS-20) and the Revised Adult Attachment Scale (RAAS). Significant relationships between anxious attachment and alexithymia factors were confirmed. Furthermore, alexithymic alcoholics reported significantly higher levels of anxious attachment and significantly lower levels of closeness (secure attachment) compared to non-alexithymic alcoholics. These findings highlight the importance of assessing and targeting anxious attachment among alexithymic alcoholics in order to improve alcohol treatment outcomes. Keywords: Attachment, alexithymia, alcohol dependence.

Adolescent depression and the family : a paradox

Discusses the role of the family in the development, treatment and prevention of adolescent depression. Studies have demonstrated that between 21–32% of adolescents report mild to severe symptoms of depression. The research points out the need for increased attention to adolescent depression because of its high prevalence, the risk factor for the development of other disorders and suicide, recurrence and tendency to endure into adulthood. Many studies have shown a strong relationship between depressive symptomatology and family factors. Therefore, family interventions should play an important role in the prevention and treatment of adolescent depression. However, there exists a paradox in that the research published to date fails to show that family-intervention programs add to the efficacy of treatments provided to the adolescents. Possible explanations for this paradox are discussed.

P147 Deprivation is associated with increased healthcare utilisation in patients with chronic obstructive pulmonary disease

Deprivation assessed using the index of multiple deprivation (IMD) has been shown to be an independent risk factor for 1-year mortality in outpatients with chronic obstructive pulmonary disease; COPD (Collins et al, 2010). IMD combines a number of economic and social issues (eg, health, education, employment) into one overall deprivation score, the higher the score the higher an individual's deprivation. Whilst malnutrition in COPD has been linked to increased healthcare use it is not clear if deprivation is also independently associated. This study aimed to investigate the influence of deprivation on 1-year healthcare utilisation in outpatients with COPD. IMD was established in 424 outpatients with COPD according to the geographical location for each patient's address (postcode) and related to their healthcare use in the year post-date screened (Nobel et al, 2008). Patients were routinely screened in outpatient clinics for malnutrition using the ‘Malnutrition Universal Screening Tool’, ‘MUST’ (Elia 2003); mean age 73 (SD 9.9) years; body mass index 25.8 (SD 6.3) kg/m2 with healthcare use collected 1 year from screening (Abstract P147 Table 1). Deprivation assessed using IMD (mean 15.9; SD 11.1) was found to be a significant predictor for the frequency and duration of emergency hospital admissions as well as the duration of elective hospital admission. Deprivation was also linked to reduced secondary care outpatient appointment attendance but not an increase in failure to attend and deprivation was not associated with increased disease severity, as classified by the GOLD criteria (p=0.580). COPD outpatients residing in more deprived areas experience increased hospitalisation rates but decreased outpatient appointment attendance. The underlying reason behind this disparity in healthcare use requires further investigation.

Deprivation is an independent predictor of 1-year mortality in outpatients with chronic obstructive pulmonary disease

Deprivation is linked to increased incidence in a number of chronic diseases but its relationship to chronic obstructive pulmonary disease (COPD) is uncertain despite suggestions that the socioeconomic gradient seen in COPD is as great, if not greater, than any other disease (Prescott and Vestbo).1 There is also a need to take into account the confounding effects of malnutrition which have been shown to be independently linked to increased mortality (Collins et al).2 The current study investigated the influence of social deprivation on 1-year survival rates in COPD outpatients, independently of malnutrition. 424 outpatients with COPD were routinely screened for malnutrition risk using the ‘Malnutrition Universal Screening Tool’; ‘MUST’ (Elia),3 between July and May 2009; 222 males and 202 females; mean age 73 (SD 9.9) years; body mass index 25.8 (SD 6.3) kg/m2. Each individual's deprivation was calculated using the index of multiple deprivation (IMD) which was established according to the geographical location of each patient's address (postcode). IMD includes a number of indicators covering economic, housing and social issues (eg, health, education and employment) into a single deprivation score (Nobel et al).4 The lower the IMD score, the lower an individual's deprivation. The IMD was assigned to each outpatient at the time of screening and related to1-year mortality from the date screened. Outpatients who died within 1-year of screening were significantly more likely to reside within a deprived postcode (IMD 19.7±SD 13.1 vs 15.4±SD 10.7; p=0.023, OR 1.03, 95% CI 1.00 to 1.06) than those that did not die. Deprivation remained a significant independent risk factor for 1-year mortality even when adjusted for malnutrition as well as age, gender and disease severity (binary logistic regression; p=0.008, OR 1.04, 95% CI 1.04 to 1.07). Deprivation was not associated with disease-severity (p=0.906) or body mass index, kg/m2 (p=0.921) using ANOVA. This is the first study to show that deprivation, assessed using IMD, is associated with increased 1-year mortality in outpatients with COPD independently of malnutrition, age and disease severity. Deprivation should be considered in the targeted management of these patients.

A randomised, feasibility trial of a tele-health intervention for Acute Coronary Syndrome patients with depression ('MoodCare')

Background Coronary heart disease (CHD) and depression are leading causes of disease burden globally and the two often co-exist. Depression is common after Myocardial Infarction (MI) and it has been estimated that 15-35% of patients experience depressive symptoms. Co-morbid depression can impair health related quality of life (HRQOL), decrease medication adherence and appropriate utilisation of health services, lead to increased morbidity and suicide risk, and is associated with poorer CHD risk factor profiles and reduced survival. We aim to determine the feasibility of conducting a randomised, multi-centre trial designed to compare a tele-health program (MoodCare) for depression and CHD secondary prevention, with Usual Care (UC). Methods Over 1600 patients admitted after index admission for Acute Coronary Syndrome (ACS) are being screened for depression at six metropolitan hospitals in the Australian states of Victoria and Queensland. Consenting participants are then contacted at two weeks post-discharge for baseline assessment. One hundred eligible participants are to be randomised to an intervention or a usual medical care control group (50 per group). The intervention consists of up to 10 × 30-40 minute structured telephone sessions, delivered by registered psychologists, commencing within two weeks of baseline screening. The intervention focuses on depression management, lifestyle factors (physical activity, healthy eating, smoking cessation, alcohol intake), medication adherence and managing co-morbidities. Data collection occurs at baseline (Time 1), 6 months (post-intervention) (Time 2), 12 months (Time 3) and 24 months follow-up for longer term effects (Time 4). We are comparing depression (Cardiac Depression Scale [CDS]) and HRQOL (Short Form-12 [SF-12]) scores between treatment and UC groups, assessing the feasibility of the program through patient acceptability and exploring long term maintenance effects. A cost-effectiveness analysis of the costs and outcomes for patients in the intervention and control groups is being conducted from the perspective of health care costs to the government. Discussion This manuscript presents the protocol for a randomised, multi-centre trial to evaluate the feasibility of a tele-based depression management and CHD secondary prevention program for ACS patients. The results of this trial will provide valuable new information about potential psychological and wellbeing benefits, cost-effectiveness and acceptability of an innovative tele-based depression management and secondary prevention program for CHD patients experiencing depression.