Development and implementation of the Australian universities radiation therapy student clinical assessment form

Purpose: Prior to 2009, one of the problems faced by radiation therapists who supervised and assessed students on placement in Australian clinical centres, was that each of the six Australian universities where Radiation Therapy (RT) programmes were conducted used different clinical assessment and reporting criteria. This paper describes the development of a unified national clinical assessment and reporting form that was implemented nationally by all six universities in 2009. Methods: A four phase methodology was used to develop the new assessment form and user guide. Phase 1 included university consensus around domains of student practice and assessment, and alignment with national competency standards; Phase 2 was a national consensus workshop attended by radiation therapists involved in student supervision and assessment; Phase 3 was an action research re-iterative Delphi technique involving two rounds of a mail-out to gain further expert consensus; and stage 4 was national piloting of the developed assessment form. Results: The new assessment form includes five main domains of practice and 19 sub-domain criteria which students are assessed against during placement. Feedback from the pilot centre participants was positive, with the new form being assessed to be comprehensive and complemented by the accompanying user guide. Conclusion: The new assessment form has improved both the formative and summative assessment of students on placement, as well as enhancing the quality of feedback to students and the universities. The new national form has high acceptance from the Australian universities and has been subject to wide review by the profession.

Clinical outcomes of vitamin D deficiency and supplementation in cancer patients

Results of recent studies suggest that circulating levels of vitamin D may play an important role in cancer-specific outcomes. The present systematic review was undertaken to determine the prevalence of vitamin D deficiency (<25 nmol/L) and insufficiency (25-50 nmol/L) in cancer patients and to evaluate the association between circulating calcidiol (the indicator of vitamin D status) and clinical outcomes. A systematic search of original, peer-reviewed studies on calcidiol at cancer diagnosis, and throughout treatment and survival, was conducted yielding 4,706 studies. A total of 37 studies met the inclusion criteria for this review. Reported mean blood calcidiol levels ranged from 24.7 to 87.4 nmol/L, with up to 31% of patients identified as deficient and 67% as insufficient. The efficacy of cholecalciferol supplementation for raising the concentration of circulating calcidiol is unclear; standard supplement regimens of <1,000 IU D3 /day may not be sufficient to maintain adequate concentrations or prevent decreasing calcidiol. Dose-response studies linking vitamin D status to musculoskeletal and survival outcomes in cancer patients are lacking.

Effect of vitamin D supplementation on antibiotic use : a randomized controlled trial

BACKGROUND: Observational data suggested that supplementation with vitamin D could reduce risk of infection, but trial data are inconsistent. OBJECTIVE: We aimed to examine the effect of oral vitamin D supplementation on antibiotic use. DESIGN: We conducted a post hoc analysis of data from pilot D-Health, which is a randomized trial carried out in a general community setting between October 2010 and February 2012. A total of 644 Australian residents aged 60-84 y were randomly assigned to receive monthly doses of a placebo (n = 214) or 30,000 (n = 215) or 60,000 (n = 215) IU oral cholecalciferol for ≤12 mo. Antibiotics prescribed during the intervention period were ascertained by linkage with pharmacy records through the national health insurance scheme (Medicare Australia). RESULTS: People who were randomly assigned 60,000 IU cholecalciferol had nonsignificant 28% lower risk of having antibiotics prescribed at least once than did people in the placebo group (RR: 0.72; 95% CI: 0.48, 1.07). In analyses stratified by age, in subjects aged ≥70 y, there was a significant reduction in antibiotic use in the high-dose vitamin D compared with placebo groups (RR: 0.53; 95% CI: 0.32, 0.90), whereas there was no effect in participants <70 y old (RR: 1.07; 95% CI: 0.58, 1.97) (P-interaction = 0.1). CONCLUSION: Although this study was a post hoc analysis and statistically nonsignificant, this trial lends some support to the hypothesis that supplementation with 60,000 IU vitamin D/mo is associated with lower risk of infection, particularly in older adults. The trial was registered at the Australian New Zealand Clinical Trials Registry (anzctr.org.au) as ACTRN12609001063202.

Vitamin D related behaviours among pregnant women in Australia

Vitamin D deficiency is common in pregnancy, and it has numerous health implications in both the mother and the baby. Vitamin D is made by skin from sun exposure or ingested from the diet. As there is a high prevalence of vitamin D deficiency in pregnant women, it is important to understand how pregnant women behave in relation to sun exposure and for vitamin D intake. This thesis aimed to answer this question. Through this study, public health and other intervention strategies to facilitate appropriate sun exposure and vitamin D intake will be developed.

An exploratory study to evaluate whether medical nutrition therapy can improve dietary intake in hospital patients who eat poorly

Background and aims The Australasian Nutrition Care Day Survey (ANCDS) reported two-in-five patients consume ≤50% of the offered food in Australian and New Zealand hospitals. After controlling for confounders (nutritional status, age, disease type and severity), the ANCDS also established an independent association between poor food intake and increased in-hospital mortality. This study aimed to evaluate if medical nutrition therapy (MNT) could improve dietary intake in hospital patients eating poorly. Methods An exploratory pilot study was conducted in the respiratory, neurology and orthopaedic wards of an Australian hospital. At baseline, percentage food intake (0%, 25%, 50%, 75%, and 100%) was evaluated for each main meal and snack for a 24-hour period in patients hospitalised for ≥2 days and not under dietetic review. Patients consuming ≤50% of offered meals due to nutrition-impact symptoms were referred to ward dietitians for MNT. Food intake was re-evaluated on the seventh day following recruitment (post-MNT). Results 184 patients were observed over four weeks; 32 patients were referred for MNT. Although baseline and post-MNT data for 20 participants (68±17years, 65% females) indicated a significant increase in median energy and protein intake post-MNT (3600kJ/day, 40g/day) versus baseline (2250kJ/day, 25g/day) (p<0.05), the increased intake met only 50% of dietary requirements. Persistent nutrition impact symptoms affected intake. Conclusion In this pilot study whilst dietary intake improved, it remained inadequate to meet participants’ estimated requirements due to ongoing nutrition-impact symptoms. Appropriate medical management and early enteral feeding could be a possible solution for such patients.

Complications of perioperative warfarin therapy in total knee arthroplasty

Patients presenting for knee replacement on warfarin for medical reasons often require higher levels of anticoagulation peri-operatively than primary thromboprophylaxis and may require bridging therapy with heparin. We performed a retrospective case control study on 149 consecutive primary knee arthroplasty patients to investigate whether anti-coagulation affected short-term outcomes. Specific outcome measures indicated significant increases in prolonged wound drainage (26.8% of cases vs 7.3% of controls, p<0.001); superficial infection (16.8% vs 3.3%, p<0.001); deep infection (6.0% vs 0%, p<0.001); return-to-theatre for washout (4.7% vs 0.7%, p=0.004); and revision (4.7% vs 0.3%, p=0.001). Management of patients on long-term warfarin therapy following TKR is particularly challenging, as the surgeon must balance risk of thromboembolism against post-operative complications on an individual patient basis in order to optimise outcomes.

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 evaluation of dog-assisted therapy for residents of aged care facilities with dementia.

Although some research suggests that dog-assisted therapy may be beneficial for people with dementia living in residential aged care facilities, the intervention has not been adequately investigated. To address this shortcoming, we conducted a randomized controlled trial of dog-assisted therapy versus a human-therapist-only intervention for this population. Fifty-five residents with mild to moderate dementia living in three Australian residential aged care facilities completed an 11-week trial of the interventions. Allocation to the intervention was random and participants completed validated measures of mood, psychosocial functioning, and quality of life (QOL), both prior to and following the intervention. No adverse events were associated with the dog-assisted intervention, and following it participants who had worse baseline depression scores demonstrated significantly improved depression scores relative to participants in the human-therapist-only intervention. Participants in the dogassisted intervention also showed significant improvements on a measure of QOL in one facility compared with those in the human-therapist-only group (although worse in another facility that had been affected by an outbreak of gastroenteritis). This study provides some evidence that dog-assisted therapy may be beneficial for some residents of aged care facilities with dementia.

Advances in the systemic therapy of malignant pleural mesothelioma

Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.

Implementing cognitive remediation therapy : lessons from two public mental health services

Objective: Neurocognitive deficits are a core symptom domain of schizophrenia, occurring in 75 -90 % of people with this diagnosis and influencing long term functional outcomes. This article aims to describe the pilot implementation of cognitive remediation therapy (CRT) in two large public mental health services and detail changes made to the delivery of this therapy after this trial. Conclusions: CRT provides an evidence based approach to targeting cognitive deficits but the translation of this therapy from a research setting to clinical practice has not been well evaluated.

Oxidative stress induced lung cancer and COPD : opportunities for epigenetic therapy

Reactive oxygen species (ROS) form as a natural by-product of the normal metabolism of oxygen and play important roles within the cell. Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants. If however, this balance is disturbed a situation called oxidative stress occurs. Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer. Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease. Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression. In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non-small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial

INTRODUCTION In retrospective analyses of patients with nonsquamous non-small-cell lung cancer treated with pemetrexed, low thymidylate synthase (TS) expression is associated with better clinical outcomes. This phase II study explored this association prospectively at the protein and mRNA-expression level. METHODS Treatment-naive patients with nonsquamous non-small-cell lung cancer (stage IIIB/IV) had four cycles of first-line chemotherapy with pemetrexed/cisplatin. Nonprogressing patients continued on pemetrexed maintenance until progression or maximum tolerability. TS expression (nucleus/cytoplasm/total) was assessed in diagnostic tissue samples by immunohistochemistry (IHC; H-scores), and quantitative reverse-transcriptase polymerase chain reaction. Cox regression was used to assess the association between H-scores and progression-free/overall survival (PFS/OS) distribution estimated by the Kaplan-Meier method. Maximal χ analysis identified optimal cutpoints between low TS- and high TS-expression groups, yielding maximal associations with PFS/OS. RESULTS The study enrolled 70 patients; of these 43 (61.4%) started maintenance treatment. In 60 patients with valid H-scores, median (m) PFS was 5.5 (95% confidence interval [CI], 3.9-6.9) months, mOS was 9.6 (95% CI, 7.3-15.7) months. Higher nuclear TS expression was significantly associated with shorter PFS and OS (primary analysis IHC, PFS: p < 0.0001; hazard ratio per 1-unit increase: 1.015; 95%CI, 1.008-1.021). At the optimal cutpoint of nuclear H-score (70), mPFS in the low TS- versus high TS-expression groups was 7.1 (5.7-8.3) versus 2.6 (1.3-4.1) months (p = 0.0015; hazard ratio = 0.28; 95%CI, 0.16-0.52; n = 40/20). Trends were similar for cytoplasm H-scores, quantitative reverse-transcriptase polymerase chain reaction and other clinical endpoints (OS, response, and disease control). CONCLUSIONS The primary endpoint was met; low TS expression was associated with longer PFS. Further randomized studies are needed to explore nuclear TS IHC expression as a potential biomarker of clinical outcomes for pemetrexed treatment in larger patient cohorts. © 2013 by the International Association for the Study of Lung Cancer.

Combination therapy with gefitinib and rofecoxib in patients with platinum-pretreated relapsed non-small-cell lung cancer

Purpose: In non-small-cell lung cancer (NSCLC), the epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) play major roles in tumorigenesis. This phase I/II study evaluated combined therapy with the EGFR tyrosine kinase inhibitor (TKI) gefitinib and the COX-2 inhibitor rofecoxib in platinum-pretreated, relapsed, metastatic NSCLC (n = 45). Patients and Methods: Gefitinib 250 mg/d was combined with rofecoxib (dose escalated from 12.5 to 25 to 50 mg/d through three cohorts, each n = 6). Because the rofecoxib maximum-tolerated dose was not reached, the 50 mg/d cohort was expanded for efficacy evaluation (n = 33). Results: Among the 42 assessable patients, there was one complete response (CR) and two partial responses (PRs) and 12 patients with stable disease (SD); disease control rate was 35.7% (95% CI, 21.6% to 52.0%). Median time to tumor progression was 55 days (95% CI, 47 to 70 days), and median survival was 144 days (95% CI, 103 to 190 days). In a pilot study, matrix-assisted laser desorption/ionization (MALDI) proteomics analysis of baseline serum samples could distinguish patients with an objective response from those with SD or progressive disease (PD), and those with disease control (CR, PR, and SD) from those with PD. The regimen was generally well tolerated, with predictable toxicities including skin rash and diarrhea. Conclusion: Gefitinib combined with rofecoxib provided disease control equivalent to that expected with single-agent gefitinib and was generally well tolerated. Baseline serum proteomics may help identify those patients most likely to benefit from EGFR TKIs. © 2007 by American Society of Clinical Oncology.

Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer : potential targets for chemoprevention and systemic therapy

The epidermal growth factor receptor (EGFR) is part of a family of plasma membrane receptor tyrosine kinases that control many important cellular functions, from growth and proliferation to cell death. Cyclooxygenase (COX)-2 is an enzyme which catalyses the conversion of arachidonic acid to prostagladins and thromboxane. It is induced by various inflammatory stimuli, including the pro-inflammatory cytokines, Interleukin (IL)-1β, Tumour Necrosis Factor (TNF)-α and IL-2. Both EGFR and COX-2 are over-expressed in non-small cell lung cancer (NSCLC) and have been implicated in the early stages of tumourigenesis. This paper considers their roles in the development and progression of lung cancer, their potential interactions, and reviews the recent progress in cancer therapies that are directed toward these targets. An increasing body of evidence suggests that selective inhibitors of both EGFR and COX-2 are potential therapeutic agents for the treatment of NSCLC, in the adjuvant, metastatic and chemopreventative settings. © 2002 Elsevier Science Ireland Ltd. All rights reserved.