Investigation of the 1758G>C and 2880A>G variants within the NCOA3 gene in a breast cancer affected Australian population

NCOA3 is a known low to moderate-risk breast cancer susceptibility gene, amplified in 5–10% and over expressed in about 60% of breast tumours. Additionally, this over expression is associated with Tamoxifen resistance and poor prognosis. Previously, two variants of NCOA3, 1758G > C and 2880A > G have been associated with breast cancer in two independent populations. Here we assessed the influence of the two NCOA3 variants on breast cancer risk by genotyping an Australian case–control study population. 172 cases and 178 controls were successfully genotyped for the 1758G > C variant and 186 cases and 182 controls were successfully genotyped for the 2880A > G variant using high-resolution melt analysis (HRM). The genotypes of the 1758G > C variant were validated by sequencing. χ2 tests were performed to determine if significant differences exist in the genotype and allele frequencies between the cases and controls. χ2 analysis returned no statistically significant difference (p > 0.05) for genotype frequencies between cases and controls for 1758G > C (χ2 = 0.97, p = 0.6158) or 2880A > G (χ2 = 2.09, p = 0.3516). Similarly, no statistical difference was observed for allele frequencies for 1758G > C (χ2 = 0.07, p = 0.7867) or 2880A > G (χ2 = 0.04, p = 0.8365). Haplotype analysis of the two SNPs also showed no difference between the cases and the controls (p = 0.9585). Our findings in an Australian Caucasian population composed of breast cancer sufferers and an age matched control population did not support the findings of previous studies demonstrating that these markers play a significant role in breast cancer susceptibility. Here, no significant difference was detected between breast cancer patients and healthy matched controls by either the genotype or allele frequencies for the investigated variants (all p ≥ 0.05). While an association of the two variants and breast cancer was not detected in our case–control study population, exploring these variants in a larger population of the same kind may obtain results in concordance with previous studies. Given the importance of NCOA3 and its involvement in biological processes involved in breast cancer and the possible implications variants of the gene could have on the response to Tamoxifen therapy, NCOA3 remains a candidate for further investigations.

The concept of congruent patient-centred care for hepatitis C management

Patient-centred care has been touted as the cornerstone of an effective and efficient primary health care system. However, primary care by its nature is a fragmented system. The system co-evolves in response to needs rather than being planned. In recent years, Medicare Locals were formed in Australia with the intention to tap into this pragmatic nature of primary care and foster health services delivery which is responsive to community and individual patient needs i.e. ‘patient-centred care’. However, it remains to be seen what and how theoretical framework/s can inform this work. For this presentation we aim to illustrate with a case study how hepatitis C is currently managed in primary care and hypothesise what a congruent model of patient-centred care for hepatitis C management could look like.

Interferon-free therapy for hepatitis C, how prepared is Australia for biosimilars?

The Hepatitis C virus (HCV) affects some 150 million people worldwide. However, unlike hepatitis A and B there is no vaccination for HCV and approximately 75% of people exposed to HCV develop chronic hepatitis. In Australia, around 226,700 people live with chronic HCV infection costing the government approximately $252 million per year. Historically, the standard approved/licenced treatment for HCV is pegylated interferon with ribavirin. There are major drawbacks with interferon-based therapy including side effects, long duration of therapy, limited access and affordability. Our previous survey of an at-risk population reported HCV treatment coverage of only 5%. Since April 2013, a new class of interferon-free treatments for chronic HCV is subsidised under the Pharmaceutical Benefits Scheme: boceprevir and telaprevir - estimated to cost the Australian Government in excess of $220 million over five years. Other biologic interferon-free therapeutic agents are scheduled to enter the Australian market. Use of small molecule generic pharmaceuticals has been advocated as a means of public cost savings. However, with the new biologic agents, generics (biosimilars) may not be feasible or straightforward, due to long patent life; marketing exclusivity; and regulatory complexity for these newer products.

An investigation of the C77G and C772T variations within the human protein tyrosine phosphatase receptor type C gene for association with multiple sclerosis in an Australian population

Multiple sclerosis (MS) is a common cause of neurological disability in young adults. The disease generally manifests in early to middle adulthood and causes various neurological deficits. Autoreactive T lymphocytes and their associated antigens have long been presumed important features of MS pathogenesis. The Protein tyrosine phosphatase receptor type C gene (PTPRC) encodes the T-cell receptor CD45. Variations within PTPRC have been previously associated with diseases of autoimmune origin such as type 1 diabetes mellitus and Graves' disease. We set out to investigate two variants within the PTPRC gene, C77G and C772T in subjects with MS and matched healthy controls to determine whether significant differences exist in these markers in an Australian population. We employed high resolution melt analysis (HRM) and restriction length polymorphism (RFLP) techniques to determine genotypic and allelic frequencies. Our study found no significant difference between frequencies for PTPRC C77G by either genotype (Χ2 = 0.65, P = 0.72) or allele (Χ2 = 0.48, P = 0.49). Similarly, we did not find evidence to suggest an association between PTPRC C772T by genotype (Χ2 = 1.06, P = 0.59) or allele (Χ2 = 0.20, P = 0.66). Linkage disequilibrium (LD) analysis showed strong linkage disequilibrium between the two tested markers (D' = 0.9970, SD = 0.0385). This study reveals no evidence to suggest that these markers are associated with MS in the tested Australian Caucasian population. Although the PTPRC gene has a significant role in regulating CD4+ and CD8+ autoreactive T-cells, interferon-beta responsiveness, and potentially other important processes, our study does not support a role for the two tested variants of this gene in MS susceptibility in the Australian population.

Industrial land price and its impact on urban growth : a Chinese case study

China is experiencing rapid progress in industrialization, with its own rationale toward industrial land development based on a deliberate change from an extensive to intensive form of urban land use. One result has been concerted attempts by local government to attract foreign investment by a low industrial land price strategy, which has resulted in a disproportionally large amount of industrial land within the total urban land use structure at the expense of the urban sprawl of many cities. This paper first examines “Comparable Benchmark Price as Residential land use” (CBPR) as the theoretical basis of the low industrial land price phenomenon. Empirical findings are presented from a case study based on data from Jinyun County, China. These data are analyzed to reveal the rationale of industrial land price from 2000 to 2010 concerning the CBPR model. We then explore the causes of low industrial land prices in the form of a “Centipede Game Model”, involving two neighborhood regions as “major players” to make a set of moves (or strategies). When one of the players unilaterally reduces the land price to attract investment with the aim to maximize profits arising from the revenues generated from foreign investment and land premiums, a two-player price war begins in the form of a dynamic game, the effect of which is to produce a downward spiral of prices. In this context, the paradox of maximizing profits for each of the two players are not accomplished due to the inter-regional competition of attracted investment leading to a lose-lose situation for both sides’ in competing for land premium revenues. A short-term solution to the problem is offered involving the establishment of inter-regional cooperative partnerships. For the longer term, however, a comprehensive reform of the local financial system, more adroit regional planning and an improved means of evaluating government performance is needed to ensure the government's role in securing pubic goods is not abandoned in favor of one solely concerned with revenue generation.

Development and evaluation of a program to improve clinician and patient communication during a telehealth consultation : C.R.I.S.P. Telehealth

Introduction: The delivery of health care in the 21st century will look like no other in the past. The fast paced technological advances that are being made will need to transition from the information age into clinical practice. The phenomenon of e-Health is the over-arching form of information technology and telehealth is one arm of that phenomenon. The uptake of telehealth both in Australia and overseas, has changed the face of health service delivery to many rural and remote communities for the better, removing what is known as the tyranny of distance. Many studies have evaluated the satisfaction and cost-benefit analysis of telehealth across the organisational aspects as well as the various adaptations of clinical pathways and this is the predominant focus of most studies published to date. However, whilst comments have been made by many researchers about the need to improve and attend to the communication and relationship building aspects of telehealth no studies have examined this further. The aim of this study was to identify the patient and clinician experiences, concerns, behaviours and perceptions of the telehealth interaction and develop a training tool to assist these clinicians to improve their interaction skills. Methods: A mixed methods design combining quantitative (survey analysis and data coding) and qualitative (interview analysis) approaches was adopted. This study utilised four phases to firstly qualitatively explore the needs of clients (patients) and clinicians within a telehealth consultation then designed, developed, piloted and quantitatively and qualitatively evaluated the telehealth communication training program. Qualitative data was collected and analysed during Phase 1 of this study to describe and define the missing 'communication and rapport building' aspects within telehealth. This data was then utilised to develop a self-paced communication training program that enhanced clinicians existing skills, which comprised of Phase 2 of this study to develop the interactive program. Phase 3 included evaluating the training program with 26 clinicians and results were recorded pre and post training, whilst phase 4 was the pilot for future recommendations of this training program using a patient group within a Queensland Health setting at two rural hospitals. Results: Comparisons of pre and post training data on 1) Effective communication styles, 2) Involvement in communication training package, 3) satisfaction pre and post training, and 4) health outcomes pre and post training indicated that there were differences between pre and post training in relation to effective communication style, increased satisfaction and no difference in health outcomes between pre and post training for this patient group. The post training results revealed over half of the participants (N= 17, 65%) were more responsive to non-verbal cues and were better able to reflect and respond to looks of anxiousness and confusion from a 'patient' within a telehealth consultation. It was also found that during post training evaluations, clinicians had enhanced their therapeutic communication with greater detail to their own body postures, eye contact and presentation. There was greater time spent looking at the 'patient' with an increase of 35 second intervals of direct eye contact and less time spent looking down at paperwork which decreased by 20 seconds. Overall 73% of the clinicians were satisfied with the training program and 61% strongly agreed that they recognised areas of their communication that needed improving during a telehealth consultation. For the patient group there was significant difference post training in rapport with a mean score from 42 (SD = 28, n = 27) to 48 (SD = 5.9, n = 24). For communication comfort of the patient group there was a significant difference between the pre and post training scores t(10) = 27.9, p = .002, which meant that overall the patients felt less inhibited whilst talking to the clinicians and more understood. Conclusion: The aim of this study was to explore the characteristics of good patient-clinician communication and unmet training needs for telehealth consultations. The study developed a training program that was specific for telehealth consultations and not dependent on a 'trainer' to deliver the content. In light of the existing literature this is a first of its kind and a valuable contribution to the research on this topic. It was found that the training program was effective in improving the clinician's communication style and increased the satisfaction of patient's within an e-health environment. This study has identified some historical myths that telehealth cannot be part of empathic patient centred care due to its technology tag.

Electrochemical detection of dopamine and cytochrome c at a nanostructured gold electrode

A nanostructured gold surface consisting of closely packed outwardly growing spikes is investigated for the electrochemical detection of dopamine and cytochrome c. A significant electrocatalytic effect for the electrooxidation of both dopamine and ascorbic acid at the nanostructured electrode was found due to the presence of surface active sites which allowed the detection of dopamine in the presence of excess ascorbic acid to be achieved by differential pulse voltammetry. By simple modification with a layer of Nafion, the enhanced electrocatalytic properties of the nanostructured surface was maintained while increasing the selectivity of dopamine detection in the presence of interfering species such as excess ascorbic and uric acids. Also, upon modification of the nanostructured surface with a monolayer of cysteine, the electrochemical response of immobilised cytochrome c in two distinct conformations was observed. This opens up the possibility of using such a nanostructured surface for the characterisation of other biomolecules and in bio-electroanalytical applications.

Risk factors for ocular surface squamous neoplasia recurrence after treatment with topical mitomycin C and interferon alpha-2b

Purpose To determine the rate of recurrence and associated risk factors following the use of mitomycin C (MMC) and/or interferon alpha-2b (IFN) for management of non-invasive ocular surface squamous neoplasia (OSSN). Design Retrospective non-comparative interventional case series. Methods Clinical practice setting of 135 patients treated consecutively with topical MMC (0.4 mg/mL) and/or IFN (1 million units/mL) for OSSN observed for clinical recurrence. Results Clinical recurrences were diagnosed in 19 of 135 (14.1%) eyes following topical treatment. The mean time to recurrence was 17.2 months (range 4 - 61) with 14 (73.7%) recurring within a two year period. There was no greater risk of recurrence identified for variables including lesion size, lesion location, gender, age, treatment type or duration. Post-hoc log-Rank pairwise comparisons revealed that lesions initially treated using surgery alone had significantly reduced time to recurrence (21.1 ± 5.6 months) compared to previous topical treatment with MMC (with or without surgery) (29.6 ± 4.7 months) (p = 0.04) and primary OSSN (23.2 ± 1.8 months) (p = 0.09). Conclusions Topical MMC and IFN are an effective treatment modality for a wide range of non-invasive OSSN. Topical therapy avoids the morbidity of excisional surgery with equivalent or reduced recurrence rates and should be considered as primary therapy.

Hepatitis C, mental health and equity of access to antiviral therapy : a systematic narrative review

Introduction Access to hepatitis C (hereafter HCV) antiviral therapy has commonly excluded populations with mental health and substance use disorders because they were considered as having contraindications to treatment, particularly due to the neuropsychiatric effects of interferon that can occur in some patients. In this review we examined access to HCV interferon antiviral therapy by populations with mental health and substance use problems to identify the evidence and reasons for exclusion. Methods We searched the following major electronic databases for relevant articles: PsycINFO, Medline, CINAHL, Scopus, Google Scholar. The inclusion criteria comprised studies of adults aged 18 years and older, peer-reviewed articles, date range of (2002--2012) to include articles since the introduction of pegylated interferon with ribarvirin, and English language. The exclusion criteria included articles about HCV populations with medical co-morbidities, such as hepatitis B (hereafter HBV) and human immunodeficiency virus (hereafter HIV), because the clinical treatment, pathways and psychosocial morbidity differ from populations with only HCV. We identified 182 articles, and of these 13 met the eligibility criteria. Using an approach of systematic narrative review we identified major themes in the literature. Results Three main themes were identified including: (1) pre-treatment and preparation for antiviral therapy, (2) adherence and treatment completion, and (3) clinical outcomes. Each of these themes was critically discussed in terms of access by patients with mental health and substance use co-morbidities demonstrating that current research evidence clearly demonstrates that people with HCV, mental health and substance use co-morbidities have similar clinical outcomes to those without these co-morbidities. Conclusions While research evidence is largely supportive of increased access to interferon by people with HCV, mental health and substance use co-morbidities, there is substantial further work required to translate evidence into clinical practice. Further to this, we conclude that a reconsideration of the appropriateness of the tertiary health service model of care for interferon management is required and exploration of the potential for increased HCV care in primary health care settings.

An Analysis of Cancer Patients' Survival and Influent Factors from 1993 to 1999 in Linqu County, Shandong Province [山东省临朐县1993~1999年恶性肿瘤患者的生存率及其影响因素分析]

To understand the survival status of cancer patients and influencing factors, an analysis was undertaken using data of 6450 cancer patients living in Linqu County, Shandong, diagnosed between 1993 and 1999. Survival rates were calculated using life table method with SAS 9.0 software. Overall 1-5 year survival rates for all patients were 53.16%, 28.65%, 21.57%, 18.36% and 17.87%, respectively. Cancers with a 5-year survival rate over 25% included ovarium, breast, uterus, stomach and colorectal cancers. Cancers with a 5-year survival lower than 10% were cancers on liver, cervical, lung and bones.Survival rates differed significantly across gender, age of onset, economic status, year of diagnosis and evidence of diagnosis. Patients' economic status, age of diagnosis and year of diagnosis seem to have strong effects on survival. [目的] 了解临朐县恶性肿瘤患者生存现状,探讨影响生存率的因素. [方法] 对临朐县1993～1999年发病的6450例肿瘤患者的生存资料进行分析,利用SAS9.0软件寿命表法计算生存率. [结果] 临朐县1993～1999年的恶性肿瘤患者1～5年生存率分别为53.16%、28.65%、21.57%、18.36%和17.87%,5年生存率超过25%的恶性肿瘤有卵巢癌、乳腺癌、宫体癌、胃癌、结直肠癌,5年生存率低于10%的有肝癌、宫颈癌、肺癌、骨恶性肿瘤.不同性别、发病年龄、经济状况、诊断时间和诊断依据的恶性肿瘤生存率有显著性差异. [结论] 患者经济条件、诊断年龄和诊断时间影响恶性肿瘤生存率.

An analysis on trend of malignancies incidence and mortality in Linqu County, Shandong Province [山东省临朐县恶性肿瘤发病与 死亡趋势分析]

Purpose To investigate the trend of malignancies incidence and mortality in Linqu county, and to provide scientific evidence for the government to design and adjust polices on cancer prevention and control. [Methods] The cancer registration data of new cases from 1995 to 2004 and death cases from 1998 to 2004 were used to analyse the incidence and mortality and the trend in Linqu county. Results Cancer general incidence significantly increased from 1995 to 2004 (P<0.05). The increasing speed incidence in male was faster than that in female. The incidence of lung cancer, colon/rectum cancer and pancreas cancer increased significantly (P<0.05), especially of lung cancer with an acceleration incidence rate of 2.12/100,000 peryear in average. The general mortality increased gradually from 1998 to 2004 with no significance (P>0.05). Both incidence and mortality in population aged 80 or over increased significantly (P<0.05). Conclusion The cancer incidence is rising during recent 10 years , and the prevention and control for lung cancer are getting increasingly important. [目的] 了解临朐县恶性肿瘤发病与死亡趋势,为政府制订和调整防治对策提供科学依据. [方法] 利用临朐县1995～2004年恶性肿瘤发病登记资料和1998～2004年的死亡登记资料,计算各种癌症发病率和死亡率,并做趋势分析. [结果] 1995～2004年临朐县恶性肿瘤总发病率呈明显上升趋势(P＜0.05),男性发病率上升速度高于女性.肺癌、肠癌、胰腺癌发病率上升显著(P＜0.05),以肺癌最为迅速(年均升高2.12/10万).1998～2004年恶性肿瘤总死亡率略有上升,但无显著性(P＞0.05);80岁及以上人群恶性肿瘤发病率与死亡率均呈上升趋势. [结论] 临朐县恶性肿瘤发病率近10年来呈现上升趋势,肺癌防治地位日益突出.

A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/ cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer : a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1)

Background: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. Patients and methods: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m 2, carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m 2, ifosfamide 3 g/m 2 and cisplatin 50 mg/m 2 or mitomycin 6 mg/ m 2, vinblastine 6 mg/m 2 and cisplatin 50 mg/m 2, respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. Results: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. Conclusions: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained. © 2006 European Society for Medical Oncology.

A phase II study of mitomycin C and oral etoposide for advanced adenocarcinoma of the upper gastrointestinal tract

Background: Mitomycin C and etoposide have both demonstrated activity against gastric carcinoma. Etoposide is a topoisomerase II inhibitor with evidence for phase-specific and schedule-dependent activity. Patients and method. Twenty-eight consecutive patients with advanced upper gastrointestinal adenocarcinoma were treated with intravenous (i.v.) bolus mitomycin C 6 mg/m2 on day 1 every 21 days to a maximum of four courses. Oral etoposide capsules 50 mg b.i.d. (or 35 mg b.i.d. liquid) were administered days 1 to 10 extending to 14 days in subsequent courses if absolute neutrophil count >1.5 x 109/l on day 14 of first course, for up to six courses. Results: Twenty-six patients were assessed for response of whom 12 had measurable disease and 14 evaluable disease. Four patients had a documented response (one complete remission, three partial remissions) with an objective response rate of 15% (95% confidence interval (95% CI) 4%-35%). Eight patients had stable disease and 14 progressive disease. The median survival was six months. The schedule was well tolerated with no treatment-related deaths. Nine patients experienced leucopenia (seven grade II and two grade III). Nausea and vomiting (eight grade II, one grade III), fatigue (eight grade II, two grade III) and anaemia (seven grade II, two grade III) were the predominant toxicities. Conclusion: This out-patient schedule is well tolerated and shows modest activity in the treatment of advanced upper gastrointestinal adenocarcinoma. Further studies using protracted schedules of etoposide both orally and as infusional treatment should be developed.

bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer

Tumour angiogenesis has been recently recognised as one of the most important prognostic factors in lung cancer. Although a variety of angiogenic factors have been identified, the angiogenesis process remains poorly understood. Bcl-2, c-erbB-2 and p53 are well-known oncogenes involved in non- small-cell lung cancer pathogenesis. A direct correlation of thymidine phosphorylase (TP) and of vascular endothelial growth factor (VEGF) with intratumoural angiogenesis has been reported. In the present study we investigated the possible regulatory role if bcl-2, c-erB-2 proteins in angiogenesis and in VEGF and TP expression in non-small-cell lung cancer. Two hundred sixteen specimens from T1,2-NO, 1 staged patients treated with surgery alone were immunohistochemically examined. Bcl-2 and c-erbB-2 were significantly inversely related to each other (P = 0.04) and both were inversely associated with microvessel density (P < 0.02). High TP and VEGF reactivity was statistically related to loss of bcl-2 expression (P < 0.01). A significant co-expression of c-erbB-2 with TP was noted (P = 0.01). However, TP expression was related to high angiogenesis only in cases with absence of c-erB-2 expression (P < 0.0001). c-erbB-2 expression in poorly vascularised tumours was linked with poor outcome (P = 0.03). The present study provides strong evidence that the bcl-2 gene has a suppressive function over genes involved in both angiogenesis (VEGF and TP) and cell migration (c- erbB-2) in NSCLC. TP and c-erbB-2 proteins are significantly, and often simultaneously, expressed in bcl-2 negative cases. However, expression of the c-erbB-2 abolishes the TP-related angiogenic activity. Whether this is a result of a direct activity of the c-erbB-2 protein or a consequence of a c- erbB-2-related immune response remains to be further investigated.