The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma

Objectives: To assess whether cervical mediastinoscopy is necessary before radical resection of malignant pleural mesothelioma (MPM). Methods: Patients who underwent radical excision of MPM in a 48-month period were prospectively followed for evidence of disease recurrence and death. Histological evidence of extra pleural lymph node metastases was correlated with survival. Lymph node size at intraoperative lymphadenectomy was correlated with the presence of metastatic tumour. Results: The 55 patients who underwent radical resection (51 extra pleural pneumonectomies and 4 radical pleurectomies) comprised 50 men and 5 women with a median age of 58 years, range 41-70. Histological examination revealed 50 epithelioid, four biphasic and one sarcomatoid histology. Postoperative IMIG T stage was stage I 4, II 11, III 30 and IV 10. Postoperatively the 17 patients with metastases to the extra pleural lymph nodes had significantly shorter survival (median 4.4 months, 95% CI 3.2-5.4) than those without (median survival 16.3 months, 95% CI 11.6-21.0) P=0.012 Kaplan-Meier analysis. Seventy-seven extra pleural lymph nodes without metastases were measured with a mean long axis diameter of 16.9 mm (range 4-55) ; 22 positive nodes had a mean long axis diameter of 15.2 mm (range 6-30). In 15 of the 17 patients with positive extra pleural nodes, the nodes could have been biopsied at cervical mediastinoscopy. Conclusions: This study confirms that extra pleural nodal metastases are related to poor survival. Pathological nodal involvement cannot be predicted from nodal dimensions. These data suggest that all patients being considered for radical resection of MPM should preferentially undergo preoperative cervical mediastinoscopy irrespective of radiological findings. © 2003 Elsevier B.V. All rights reserved.

Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer

Background: The Lung Cancer Cetuximab Study is an open-label, randomized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone, in patients with advanced EGFR-expressing, non-small-cell lung cancer (NSCLC). End points of the study are activity, safety and pharmacokinetics. Patients and methods: Following randomization, for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m2, day 1) and vinorelbine (25 mg/m2 on days 1 and 8) alone or following cetuximab treatment (initial dose 400 mg/m, followed by 250 mg/m2 weekly thereafter). Results: Eighty-six patients were randomly allocated to the study (43 per arm). Confirmed response rates were 28% in the cisplatin/vinorelbine arm (A) and 35% in the cetuximab plus cisplatin/vinorelbine arm (B). Median progression-free survival (PFS) was 4.6 months in arm A and 5.0 months in arm B, with PFS rates at 12 months of 0% and 15%, respectively. Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0% and 16%, respectively. The cetuximab combination was well tolerated. Conclusion: In the first-line treatment of advanced NSCLC, the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone. © 2007 European Society for Medical Oncology.

Making prevention matter : a survey of child sexual abuse prevention programs in Australia

Throughout Australia, there is considerable concern about the prevalence of child sexual abuse. Sexual abuse is experienced by over 3,500 Australian children each year, causing long-term psychological, health and social problems to children, their families and communities, and significant economic costs to society as a whole. In many countries, the provision of school-based programs has been a core strategy in efforts to prevent child sexual abuse. However, little is known about the range of programs in use in Australia, the numbers of children who have received programs, and the contents and methods used in program delivery. This presentation reports on a detailed National survey of child sexual abuse prevention programs currently used in Australian primary schools. An online survey was conducted over a six-month period from November 2011 to April 2012 yielding detailed data from 38 programs. The presentation will provide an overview of: the scope and reach of programs; program content, teaching strategies and resources; barriers and facilitators to program adoption by schools; and program evaluation strategies.

The effect of extent of local resection on patterns of disease progression in malignant pleural mesothelioma

Background We sought to determine whether or not there are differences in disease progression after radical or nonradical (debulking) surgical procedures for malignant pleural mesothelioma. Methods Over a 49-month period, 132 patients with malignant pleural mesothelioma underwent surgery. Fifty-three underwent extrapleural pneumonectomy and 79 underwent nonradical procedures. Time to evidence of clinical disease progression was recorded, as was the site(s) of that disease. Results One-hundred nineteen patients were evaluable, of which 59% (22 radical; 48 nonradical) had disease progression. Overall 30-day mortality was 8.5% (7.5% radical; 9% nonradical). The median time to overall disease progression was considerably longer after extrapleural pneumonectomy than debulking surgery (319 days vs 197 days, p = 0.019), as was the time to local disease progression (631 days vs 218 days, p = 0.0018). There was no preponderance of earlier stage disease in the radical surgery group. There was a trend toward prolonged survival in those undergoing radical surgery, but no significant difference between the groups (497 days vs 324 days, p = 0.079). In those who had extrapleural pneumonectomy, time-to-disease progression significantly decreased with N2 disease compared with N0/1 involvement (197 days vs 358 days, p = 0.02). Conclusions Extrapleural pneumonectomy may be preferable to debulking surgery in malignant pleural mesothelioma to delay disease progression and give greater control of local disease. Involvement of N2 nodes is associated with accelerated disease progression and is therefore a contraindication to extrapleural pneumonectomy. © 2004 by The Society of Thoracic Surgeons.

Tumour necrosis is an independent prognostic marker in non-small cell lung cancer : correlation with biological variables

Background Tumour necrosis (TN) is recognized to be a consequence of chronic cellular hypoxia. TN and hypoxia correlate with poor prognosis in solid tumours. Methods In a retrospective study the prognostic implications of the extent of TN was evaluated in non-small cell lung cancer (NSCLC) and correlated with clinicopathological variables and expression of epidermal growth factor receptor, Bcl-2, p53 and matrix metalloproteinase-9 (MMP-9). Tissue specimens from 178 surgically resected cases of stage I-IIIA NSCLC with curative intent were studied. The specimens were routinely processed, formalin-fixed and paraffin-embedded. TN was graded as extensive or either limited or absent by two independent observers; disagreements were resolved using a double-headed microscope. The degree of reproducibility was estimated by re-interpreting 40 randomly selected cases after a 4 month interval. Results Reproducibility was attained in 36/40 cases, Kappa score=0.8 P<0.001. TN correlated with T-stage (P=0.001), platelet count (P=0.004) and p53 expression (P=0.031). Near significant associations of TN with N-stage (P=0.063) and MMP-9 expression (P=0.058) were seen. No association was found with angiogenesis (P=0.98). On univariate (P=0.0016) and multivariate analysis (P=0.023) TN was prognostic. Conclusion These results indicate that extensive TN reflects an aggressive tumour phenotype in NSCLC and may improve the predictive power of the TMN staging system. The lack of association between TN and angiogenesis may be important although these variables were not evaluated on serial sections. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Is foot ulcer simulation training (FUST) really effective? Participants’ supervisors speak out

Background Foot ulcers are a common reason for diabetes-related hospitalisation. Foot ulcer simulation training (FUST) programs have increased podiatry participants self-confidence to manage foot ulcers. However, supervisors’ perspectives on their participants attending these simulation programs have not been investigated. This mixed method (quantitative and qualitative) study aimed to investigate home clinical supervisors’ perspectives on any changes to their participants’ competence and practice following FUST. Methods Clinical supervisors of fifteen podiatrists, who participated in a two-day Foot Ulcer Simulation Training (FUST) course, were recruited. Supervisors completed quantitative surveys evaluating their participants’ foot ulcer competence pre-FUST and 6-months post-FUST, via a purposed designed 21-item survey using a five-point Likert scale (1=Very limited, 5=Highly competent). Supervisors also attended a semi-structured qualitative group interview to investigate supervisors’ perspectives on FUST. Results Supervisors surveys returned were pre-FUST (n=10) and post-FUST (n=12). Significant competence improvements were observed at the 6-month survey (mean scores 2.84 cf. 3.72, p < 0.05). Five supervisors attended the group interview. Five sub-themes emerged: i) FUST provided a good foundation for future learning, ii) FUST modelled good clinical behaviour, iii) clinical practice improvement was evident in most participants, iv) clinical improvements were dependent on participant’s willingness to change and existing workplace culture, v) FUST needs to be reinforced back in the home clinic. Conclusion Overall, supervisors of FUST participants indicated that the course improved their participants’ competence and clinical practice. However, the degree of improvement appears dependant on the participants’ home workplace culture and willingness to embrace change.

Foot ulcer simulation training (FUST) : are podiatrists FUST with long-term clinical confidence?

Background Foot ulcers are a leading cause of diabetes-related hospitalisations. Clinical training has been shown to be beneficial in foot ulcer management. Recently, improved self-confidence in podiatrists was reported immediately after foot ulcer simulation training (FUST) pilot programs. This study aimed to investigate the longer-term impacts of the FUST program on podiatrists’ self-confidence over 12 months in a larger sample. Methods Participants were podiatrists attending a two-day FUST course comprising web-based interactive learning, low-fidelity part-tasks and high-fidelity full clinical scenarios. Primary outcome measures included participants’ self-confidence measured pre-, (immediately) post-, 6-month post- and 12-month post-course via a purpose designed 21-item survey using a five-point Likert scale (1=Very limited, 5=Highly confident). Participants’ perceptions of knowledge gained, satisfaction, relevance and fidelity were also investigated. ANOVA and post hoc tests were used to test any differences between groups. Results Thirty-four participants completed FUST. Survey response rates were 100% (pre), 82% (post), 74% (6-month post), and 47% (12-month post). Overall mean scores were 3.13 (pre), 4.49 (post), 4.35 (6-month post) and 4.30 (12-month post) (p < 0.05); post hoc tests indicated no differences between the immediately, 6-month and 12-month post group scores (p > 0.05). Satisfaction, knowledge, relevance and fidelity were all rated highly. Conclusion This study suggests that significant short-term improvements in self-confidence to manage foot ulcers via simulation training are retained over the longer term. It is likely that improved self-confidence leads to improved foot ulcer clinical practice and outcomes; although this requires further research.

Aboriginal dietary intake and a successful nutrition intervention project in a Northern Territory community

This paper summarises the development and testing of the 'store-turnover' method, a non-invasive dietary survey methodology for quantitative measurement of food and nutrient intake in remote, centralised Aboriginal communities. It then describes the use of the method in planning, implementation and evaluation of a community-based nutrition intervention project in a small Aboriginal community in the Northern Territory. During this project marked improvements in both the dietary intake of the community and biological indicators of nutritional health (including vitamin status and the degree and prevalence of several risk factors for non-communicable disease) were measured in the community over a 12-month period following the development of intervention strategies with the community. Although these specific strategies are presented, emphasis is directed towards the process involved, particularly the evaluation procedures used to monitor all stages of the project with the community.

Prevalence of health behaviours in pregnancy at service entry in a Queensland health service district

Objective: Limited prevalence data for unhealthy pregnancy health behaviours make it difficult to prioritise primary prevention efforts for maternal and infant health. This study's objective was to establish the prevalence of cigarette smoking, sufficient fruit and vegetable intake and sufficient physical activity among women accessing antenatal clinics in a Queensland (Australia) health service district. Method: Cross-sectional self-reported smoking status, daily fruit and vegetable intake, weekly physical activity and a range of socio-demographic variables were obtained from women recruited at their initial antenatal clinic visit, over a three-month recruitment phase during 2007. Results: Analyses were based on 262 pregnant women. The study sample was broadly representative of women giving birth in the district and state, with higher representation of women with low levels of education and high income. More than one quarter of women were smoking. Few women met the guidelines for sufficient fruit (9.2%), vegetables (2.7%) or physical activity (32.8%) during pregnancy. Conclusions: There were low levels of adherence to health behaviour recommendations for pregnancy in this sample. Implications: There is a clear need to develop and evaluate effective pregnancy behaviour interventions to improve primary prevention in maternal and infant health. Brief minimal contact interventions that can be delivered through primary care to create a greater primary prevention focus for maternal and infant health would be worth exploring.

A better future for young people leaving care

The Australian National Homelessness Research Agenda funded this study which explored post-care homelessness experiences of young people, asked them what they considered helpful, and identified practice and policy implications. Participants were 48 care leavers aged 19 to 23 years in Queensland and Victoria. Of these 17 young people were interviewed twice over a four month period. In addition focus groups were held with service providers and current postcare service arrangements in the two states mapped. The study found there is a need for policy and practice to more effectively orient towards a holistic and future oriented view of outcomes for young people transitioning from care.

Targeting amino acid transport in metastatic castration-resistant prostate cancer : effects on cell cycle, cell growth, and tumor development

Background L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. Methods We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. Results LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4–7 months of neoadjuvant hormone therapy (4–7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4–mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Conclusion Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

Road safety knowledge exchange and capacity building between China and Australia

Road traffic injuries are one of the major public health burdens worldwide. The United Nations Decade of Action for Road Safety (2011-2020) implores all nations to work to reduce this burden. This decade represents a unique and historic period of time in the field of road safety. Information exchange and co-operation between nations is an important step in achieving the goal. The burden of road crashes, fatalities and injuries is not equally distributed. We know that low and middle-income countries experience the majority of the road trauma burden. Therefore it is imperative that these countries learn from the successes of others that have developed and implemented road safety laws, public education campaigns and countermeasures over many years and have achieved significant road trauma reductions as a result. China is one of the countries experiencing a large road trauma burden. Vulnerable road users such as pedestrians and cyclists make up a large proportion of fatalities and injuries in China. Speeding, impaired/drug driving, distracted driving, vehicle overloading, inadequate road infrastructure, limited use of safety restraints and helmets, and limited road safety training have all been identified as contributing to the problem. Some important steps have been taken to strengthen China’s approach, including increased penalties for drunk driving in May 2011 and increased attention to school bus safety in 2011/12. However, there is still a large amount of work needed to improve the current road safety position in China. This paper provides details of a program to assist with road safety knowledge exchange between China and Australia that was funded by the Australian Government which was undertaken in the latter part of 2012. The four month program provided the opportunity for the first author to work closely with key agencies in Australia that are responsible for policy development and implementation of a broad range of road safety initiatives. In doing so, an in-depth understanding was gained about key road safety strategies in Australia and processes for developing and implementing them. Insights were also gained into the mechanisms used for road safety policy development, implementation and evaluation in several Australian jurisdictions. Road traffic law and enforcement issues were explored with the relevant jurisdictional transport and police agencies to provide a greater understanding of how Chinese laws and practices could be enhanced. Working with agencies responsible for public education and awareness campaigns about road safety in Australia also provided relevant information about how to promote road safety at the broader community level in China. Finally, the program provided opportunities to work closely with several world-renowned Australian research centres and key expert researchers to enhance opportunities for ongoing road safety research in China. The overall program provided the opportunity for the first author to develop knowledge in key areas of road safety strategy development, implementation and management which are directly relevant to the current situation in China. This paper describes some main observations and findings from participation in the program.

Sex-specific compromised bone healing in female rats might be associated with a decrease in mesenchymal stem cell quantity

Introduction The clinically known importance of patient sex as a major risk factor for compromised bone healing is poorly reflected in animal models. Consequently, the underlying cellular mechanisms remain elusive. Because mesenchymal stem cells (MSCs) are postulated to regulate tissue regeneration and give rise to essential differentiated cell types, they may contribute to sex-specific differences in bone healing outcomes. Methods We investigated sex-specific variations in bone healing and associated differences in MSC populations. A 1.5 mm osteotomy gap in the femora of 8 male and 8 female 12-month-old Sprague-Dawley rats was stabilized by an external fixator. Healing was analyzed in terms of biomechanical testing, bridging and callus size over time (radiography at 2, 4, and 6 weeks after surgery), and callus volume and geometry by μCT at final follow-up. MSCs were obtained from bone marrow samples of an age-matched group of 12 animals (6 per gender) and analyzed for numbers of colony-forming units (CFUs) and their capacity to differentiate and proliferate. The proportion of senescent cells was determined by β-galactosidase staining. Results Sex-specific differences were indicated by a compromised mechanical competence of the callus in females compared with males (maximum torque at failure, p = 0.028). Throughout the follow-up, the cross-sectional area of callus relative to bone was reduced in females (p ≤ 0.01), and the bridging of callus was delayed (p 2weeks = 0.041). μCT revealed a reduced callus size (p = 0.003), mineralization (p = 0.003) and polar moment of inertia (p = 0.003) in female animals. The female bone marrow contained significantly fewer MSCs, represented by low CFU numbers in both femora and tibiae (p femur = 0.017, p tibia = 0.010). Functional characteristics of male and female MSCs were similar. Conclusion Biomechanically compromised and radiographically delayed bone formation were distinctive in female rats. These differences were concomitant with a reduced number of MSCs, which may be causative for the suboptimal bone healing.

Differences between first episode schizophrenia and schizoaffective disorder

Background: The diagnostic and clinical overlap between schizophrenia and schizoaffective disorder is an important nosological issue in psychiatry that is yet to be resolved. The aim of this study was to compare the clinical and functional characteristics of an epidemiological treated cohort of first episode patients with an 18-month discharge diagnosis of schizophrenia (FES) or schizoaffective disorder (FESA). Methods: This study was part of the larger First Episode Psychosis Outcome Study (FEPOS) which involved a medical file audit study of all 786 patients treated at the Early Psychosis Prevention and Intervention Centre between 1998 and 2000. Of this cohort, 283 patients had a 18-month discharge diagnosis of FES and 64 had a diagnosis of FESA. DSM-IV diagnoses, clinical and functional ratings were derived and validated by two consultant psychiatrists. Results: Compared to FES patients, those with FESA were significantly more likely to have a later age of onset (p=.004), longer prodrome (p=.020), and a longer duration of untreated psychosis (p<.001). At service entry, FESA patients presented with a higher illness severity (p=.020), largely due to the presence of more severe manic symptoms (p<.001). FESA patients also had a greater number of subsequent inpatient admissions (p=.017), had more severe depressive symptoms (p=.011), and higher levels of functioning at discharge. Discussion: The findings support the notion that these might be considered two discernable disorders; however, further research is required to ascertain the ways and extent to which these disorders are discriminable at presentation and over time.

Imported Dengue cases, weather variation and autochthonous Dengue incidence in Cairns, Australia

BACKGROUND Dengue fever (DF) outbreaks often arise from imported DF cases in Cairns, Australia. Few studies have incorporated imported DF cases in the estimation of the relationship between weather variability and incidence of autochthonous DF. The study aimed to examine the impact of weather variability on autochthonous DF infection after accounting for imported DF cases and then to explore the possibility of developing an empirical forecast system. METHODOLOGY/PRINCIPAL FINDS Data on weather variables, notified DF cases (including those acquired locally and overseas), and population size in Cairns were supplied by the Australian Bureau of Meteorology, Queensland Health, and Australian Bureau of Statistics. A time-series negative-binomial hurdle model was used to assess the effects of imported DF cases and weather variability on autochthonous DF incidence. Our results showed that monthly autochthonous DF incidences were significantly associated with monthly imported DF cases (Relative Risk (RR):1.52; 95% confidence interval (CI): 1.01-2.28), monthly minimum temperature ((o)C) (RR: 2.28; 95% CI: 1.77-2.93), monthly relative humidity (%) (RR: 1.21; 95% CI: 1.06-1.37), monthly rainfall (mm) (RR: 0.50; 95% CI: 0.31-0.81) and monthly standard deviation of daily relative humidity (%) (RR: 1.27; 95% CI: 1.08-1.50). In the zero hurdle component, the occurrence of monthly autochthonous DF cases was significantly associated with monthly minimum temperature (Odds Ratio (OR): 1.64; 95% CI: 1.01-2.67). CONCLUSIONS/SIGNIFICANCE Our research suggested that incidences of monthly autochthonous DF were strongly positively associated with monthly imported DF cases, local minimum temperature and inter-month relative humidity variability in Cairns. Moreover, DF outbreak in Cairns was driven by imported DF cases only under favourable seasons and weather conditions in the study.