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.

Phase II trial of Oxaliplatin and 5-Fluorouracil/Leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy

Objective To evaluate the efficacy and toxicity of Oxaliplatin and 5-Fluorouracil (5-FU)/Leucovorin (LV) combination in ovarian cancer relapsing within 2 years of prior platinum-based chemotherapy in a phase II trial. Methods Eligible patients had at least one prior platinum-based chemotherapy regimen, elevated CA-125 ≥ 60 IU/l, radiological evidence of disease progression and adequate hepatic, renal and bone marrow function. Patients with raised CA-125 levels alone as marker of disease relapse were not eligible. Oxaliplatin (85 mg/m 2) was given on day 1, and 5-Fluorouracil (370 mg/m 2) and Leucovorin (30 mg) was given on days 1 and 8 of a 14-day cycle. Results Twenty-seven patients were enrolled. The median age was 57 years (range 42-74 years). The median platinum-free interval (PFI) was 5 months (range 0-17 months) with only 30% of patients being platinum sensitive (PFI > 6 months). Six patients (22%) had two prior regimens of chemotherapy. A total of 191 cycles were administered (median 7; range 2-12). All patients were evaluable for toxicity. The following grade 3/4 toxicities were noted: anemia 4%; neutropenia 15%; thrombocytopenia 11%; neurotoxicity 8%; lethargy 4%; diarrhea 4%; hypokalemia 11%; hypomagnesemia 11%. Among 27 enrolled patients, 20 patients were evaluable for response by WHO criteria and 25 patients were evaluable by Rustin's CA-125 criteria. The overall response rate (RR) by WHO criteria was 30% (95% CI: 15- 52) [three complete responses (CRs) and three partial responses (PRs)]. The CA-125 response rate was 56% (95% CI: 37-73). Significantly, a 25% (95% CI: 9-53) radiological and a 50% (95% CI: 28-72) CA-125 response rate were noted in platinum resistant patients (PFI < 6 months). The median response duration was 4 months (range 3-12) and the median overall survival was 10 months. Conclusion Oxaliplatin and 5-Fluorouracil/ Leucovorin combination has a good safety profile and is active in platinum-pretreated advanced epithelial ovarian cancer. © 2004 Elsevier Inc. All rights reserved.

The potential role of lycopene for the prevention and therapy of prostate cancer : from molecular mechanisms to clinical evidence

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Denial predicts outcome in anxiety following group cognitive behavioral therapy

This study aimed to explore whether participants' pretherapy coping strategies predicted the outcome of group cognitive behavioral therapy (CBT) for anxiety and depression. It was hypothesized that adaptive coping strategies such as the use of active planning and acceptance would be associated with higher reductions, whereas maladaptive coping strategies such as denial and disengagement would be associated with lower reductions in anxious and depressed symptoms following psychotherapy. There were 144 participants who completed group CBT for anxiety and depression. Measures of coping strategies were administered prior to therapy, whereas measures of depression and anxiety were completed both prior to and following therapy. The results showed that higher levels of denial were associated with a poorer outcome, in terms of change in anxiety but not depression, following therapy. These findings suggest the usefulness of using the Denial subscale from the revised Coping Orientation to Problems Experienced (COPE) as a predictor of outcome in group CBT for anxiety.

Impact of cognitive behaviour therapy via mail for cessation of benzodiazepine use : a series of case reports

Benzodiazepines are widely prescribed to manage sleep disorders, anxiety and muscular tension. While providing short-term relief, continued use induces tolerance and withdrawal, and in older users, increases the risk of falls. However, long-term prescription remains common, and effective interventions are not widely available. This study developed a self-managed cognitive behaviour therapy package for cessation of benzodiazepine use delivered to participants via mail (M-CBT) and trialled its effectiveness as an adjunct to a general practitioner (GP)-managed dose reduction schedule. In the pilot trial, participants were randomly assigned to GP management with immediate or delayed M-CBT. Significant recruitment and engagement problems were experienced, and only three participants were allocated to each condition. After immediate M-CBT, two participants ceased use, while none receiving delayed treatment reduced daily intake by more than 50%. Across the sample, doses at 12 months remained significantly lower than baseline, and qualitative feedback from participants was positive. While M-CBT may have promise, improved engagement of GPs and participants is needed for this approach to substantially impact on community-wide benzodiazepine use.

The radiation therapy patient as a student assessor

Background Radiation Therapy students at Queensland University of Technology undertake clinical placement across a wide range of sites Interpersonal skills with clinical staff and patients are an essential component: – Lectures – Role playing – Expert patient input

Oxygen; my view

Oxygen has been the “holy grail” of contact lens wear for over 100 years, but it is just one piece of a complex jigsaw puzzle. Clearly, high oxygen transmissibility (Dk/t) silicone hydrogel lenses meet the oxygen needs of the cornea. The Dk/t of these lenses is over 75 Dk units, which is far above that of the “best” hydrogel lenses (30 Dk units). Clinical trials have failed to reveal any hypoxic problemswith silicone hydrogel lenses. Thus, conditions such as epithelial microcysts, limbal redness, hypoxic staining, stromal neovascularisation, oedema and endothelial polymegethism do not occur with these lenses. My view is that – looking at the “big picture” – we are far better off now that we have silicone hydrogel lenses.

Autism : an introduction to behavioural therapy models used for autism and nursing the person with autism in the primary care setting

Childhood autism falls under the guise of autism spectrum disorders and is generally found in children over two years of age. There are of course variations in severity and clinical manifestations, however the most common features being disinterest in social interaction and engagement in ritualistic and repetitive behaviours. In Singapore the incidence of autism is on the rise as parents are becoming more aware of the early signs of autism and seek healthcare programmes to ensure the quality of life for their child is optimised. Two such programmes, Applied Behaiour Analysis and Floortime approach have proven successful in alleviating some of the behavioural and social skills problems associated with autism. Using positive behaviour reinforcement both Applied Behaviour Analysis and Floortime approach reward behaviour associated with positive social responses.

Mixed venous oxygen saturation monitoring revisited : thoughts for critical care nursing practice

Background Less invasive methods of determining cardiac output are now readily available. Using indicator dilution technique, for example has made it easier to continuously measure cardiac output because it uses the existing intra-arterial line. Therefore gone is the need for a pulmonary artery floatation catheter and with it the ability to measure left atrial and left ventricular work indices as well the ability to monitor and measure a mixed venous saturation (SvO2). Purpose The aim of this paper is to put forward the notion that SvO2 provides valuable information about oxygen consumption and venous reserve; important measures in the critically ill to ensure oxygen supply meets cellular demand. In an attempt to portray this, a simplified example of the septic patient is offered to highlight the changing pathophysiological sequelae of the inflammatory process and its importance for monitoring SvO2. Relevance to clinical practice SvO2 monitoring, it could be argued, provides the gold standard for assessing arterial and venous oxygen indices in the critically ill. For the bedside ICU nurse the plethora of information inherent in SvO2 monitoring could provide them with important data that will assist in averting potential problems with oxygen delivery and consumption. However, it has been suggested that central venous saturation (ScvO2) might be an attractive alternative to SvO2 because of its less invasiveness and ease of obtaining a sample for analysis. There are problems with this approach and these are to do with where the catheter tip is sited and the nature of the venous admixture at this site. Studies have shown that ScvO2 is less accurate than SvO2 and should not be used as a sole guiding variable for decision-making. These studies have demonstrated that there is an unacceptably wide range in variance between ScvO2 and SvO2 and this is dependent on the presenting disease, in some cases SvO2 will be significantly lower than ScvO2. Conclusion Whilst newer technologies have been developed to continuously measure cardiac output, SvO2 monitoring is still an important adjunct to clinical decision-making in the ICU. Given the information that it provides, seeking alternatives such as ScvO2 or blood samples obtained from femorally placed central venous lines, can unnecessarily lead to inappropriate treatment being given or withheld. Instead when using ScvO2, trending of this variable should provide clinical determinates that are useable for the bedside ICU nurse, remembering that in most conditions SvO2 will be approximately 16% lower.

Effects of dissolved oxygen availability and culture biomass at induction upon the intracellular expression of monoamine oxidase by recombinant E. coli in fed batch bioprocesses

The effects of oxygen availability and induction culture biomass upon production of an industrially important monoamine oxidase (MAO) were investigated in fed-batch cultures of a recombinant E. coli. For each induction cell biomass 2 different oxygenation methods were used, aeration and oxygen enriched air. Induction at higher biomass levels increased the culture demand for oxygen, leading to fermentative metabolism and accumulation of high levels of acetate in the aerated cultures. Paradoxically, despite an almost eight fold increase in acetate accumulation to levels widely reported to be highly detrimental to protein production, when induction wet cell weight (WCW) rose from 100% to 137.5%, MAO specific activity in these aerated processes showed a 3 fold increase. By contrast, for oxygenated cultures induced at WCW's 100% and 137.5% specific activity levels were broadly similar, but fell rapidly after the maxima were reached. Induction at high biomass levels (WCW 175%) led to very low levels of specific MAO activity relative to induction at lower WCW's in both aerated and oxygenated cultures. Oxygen enrichment of these cultures was a useful strategy for boosting specific growth rates, but did not have positive effects upon specific enzyme activity. Based upon our findings, consideration of the amino acid composition of MAO and previous studies on related enzymes, we propose that this effect is due to oxidative damage to the MAO enzyme itself during these highly aerobic processes. Thus, the optimal process for MAO production is aerated, not oxygenated, and induced at moderate cell density, and clearly represents a compromise between oxygen supply effects on specific growth rate/induction cell density, acetate accumulation, and high specific MAO activity. This work shows that the negative effects of oxygen previously reported in free enzyme preparations, are not limited to these acellular environments but are also discernible in the sheltered environment of the cytosol of E. coli cells.

Contemporary cultures of service delivery to families : implications for music therapy

Family-centred and early intervention and prevention programs are a strong focus of current policy objectives within Australia, and a significant area of practice within the music therapy community. Recent shifts in the culture of policy and practice increasingly reflect ecological understandings by focussing on integrated and place-based approaches to service delivery. Further, current funding opportunities are strongly concerned with the extent to which interventions are able to reach out to highly vulnerable families that typically do not engage with services easily. Music therapy holds unique promise within these cultural shifts and thus advocates must develop a solid understanding of the concepts and related language in order to confidently engage with both funding and service systems. This paper uses an integrative review to first define and summarise current knowledge in three key areas relevant to contemporary Australian policy and practice: hard-to-reach families, home visiting as assertive outreach, and integrated or place-based service delivery. Evidence for the effectiveness of music therapy in relation to these key themes is then presented. Finally, the paper discusses the implications for the future of music therapy within the current Australian early intervention and prevention policy context and makes recommendations for moving forward on both practice and research fronts. While there is growing evidence and theory to suggest that music therapy may be uniquely efficacious in this area, greater Australian Journal of Music Therapy Vol 25, 2014 149 advocacy, documentation, research and adjustment of practices and language will further cement the position of the industry.