A phase II study of Caelyx, liposomal doxorubicin : lack of activity in patients with advanced gastric cancer

Purpose A phase II study was designed to assess the efficacy and safety of Caelyx (liposomal doxorubicin) in patients with advanced or metastatic gastric cancer. Methods A total of 25 patients with gastric adenocarcinoma were treated with Caelyx 45 mg/m2 every 28 days as first-line therapy for advanced disease. Patients were treated until tumour progression or unacceptable toxicity. Results One patient was withdrawn from the study after experiencing a severe infusion reaction. Of the 24 evaluable patients, 1 had a partial response, 7 had stable disease and the others progressed. Side effects, in particular palmar-plantar erythrodysaesthesia and haematological toxicity, were minor. Conclusions We conclude that while this dose and schedule of Caelyx in this patient group is acceptable, further studies with this regimen cannot be recommended due to the lack of antitumour activity seen.

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma : clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

Background The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. Methods MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Findings Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. Interpretation In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. Funding Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust. © 2011 Elsevier Ltd.

Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients : the European Early Lung Cancer Project

Lung cancer is the most important cause of cancer-related mortality. Resectability and eligibility for treatment with adjuvant chemotherapy is determined by staging according to the TNM classification. Other determinants of tumour behaviour that predict disease outcome, such as molecular markers, may improve decision-making. Activation of the gene encoding human telomerase reverse transcriptase (hTERT) is implicated in the pathogenesis of lung cancer, and consequently detection of hTERT mRNA might have prognostic value for patients with early stage lung cancer. A cohort of patients who underwent a complete resection for early stage lung cancer was recruited as part of the European Early Lung Cancer (EUELC) project. In 166 patients expression of hTERT mRNA was determined in tumour tissue by quantitative real-time RT-PCR and related to that of a house-keeping gene (PBGD). Of a subgroup of 130 patients tumour-distant normal tissue was additionally available for hTERT mRNA analysis. The correlation between hTERT levels of surgical samples and disease-free survival was determined using a Fine and Gray hazard model. Although hTERT mRNA positivity in tumour tissue was significantly associated with clinical stage (Fisher's exact test p=0.016), neither hTERT mRNA detectability nor hTERT mRNA levels in tumour tissue were associated with clinical outcome. Conversely, hTERT positivity in adjacent normal samples was associated with progressive disease, 28% of patients with progressive disease versus 7.5% of disease-free patients had detectable hTERT mRNA in normal tissue [adjusted HR: 3.60 (1.64-7.94), p=0.0015]. hTERT mRNA level in tumour tissue has no prognostic value for patients with early stage lung cancer. However, detection of hTERT mRNA expression in tumour-distant normal lung tissue may indicate an increased risk of progressive disease.

Supporting cooperation and caring through large group experiences

Cooperation and caring are best taught within a group as it promotes connectedness, collaborative effort, and relationship building.

Realigning capital portfolios : international students' educational experiences in higher education

This paper reports on first year experiences of international students who use English as an additional language (EAL) in higher education in Australia. It examines how valued resources can foster a positive educational experience of these students from sociological perspectives. It draws data from an interview study, exploring narrative accounts of 17 EAL international students from nine countries about their educational relations and strategies across their first year of study. Their narratives were analysed through Bourdieu's concepts of field, habitus, capital and legitimation, as well as tools of narrative inquiry. The paper finds that the students took up strategies to realign their capital portfolios with new rules of the game. Their decisions were dependent on their personal trajectories and conditions on offer. This paper suggests that more effort needs to be made to understand international students' differentiated access to valued resources in higher education.

Cross-cultural learning experiences in architectural education

This qualitative study looks at the joint output of 20 architecture students from 2 different countries during their short respective Study Tours to each other’s country to discern the effect of cross-cultural experiences on their learning. This paper uses the students’ joint design efforts and reflective writings to investigate the outcome of this cross-cultural educational exchange. Their joint design efforts resulted in the making of small built structures, drawings and collaborative design proposals for an urban setting. In addition, a short questionnaire and personal interviews were also used as methods to gain insight into their experience and to use as a comparative study. The question is also raised in this paper of whether spontaneous friendship among students is integral to long term learning in a cross-cultural context in comparison to pre-designed learning objectives on the part of the educators. This paper also initiates the dialogue of the extent of cultural influences and universal ideas on collaborative architectural design. With increasing joint design ventures between architectural firms in different countries, there is interest in how collaborative design can be understood in a cross-cultural context. This paper examines short term cross cultural experiences and its contribution to architectural education.

Online belongings : female fan experiences in online soccer forums

Introduction: The Paradox at the Heart of Online Interaction

One night CPAP withdrawal impairs performance at a driving simulator task faster than sleep restriction to 5 hours with treatment in OSA patients

Introduction Sleep restriction and missing 1 night’s continuous positive air pressure (CPAP) treatment are scenarios faced by obstructive sleep apnoea (OSA) patients, who must then assess their own fitness to drive. This study aims to assess the impact of this on driving performance. Method 11 CPAP treated participants (50–75 yrs), drove an interactive car simulator under monotonous motorway conditions for 2 hours on 3 afternoons, following;(i)normal night’s sleep (average 8.2 h) with CPAP (ii) sleep restriction (5 h), with CPAP (iii)normal length of sleep, without CPAP. Driving incidents were noted if the car came out of the designated driving lane. EEG was recorded continually and KSS reported every 200 seconds. Results Driving incidents: Incidents were more prevalent following CPAP withdrawal during hour 1, demonstrating a significant condition time interaction [F(6,60) = 3.40, p = 0.006]. KSS: At the start of driving participants felt sleepiest following CPAP withdrawal, by the end of the task KSS levels were similar following CPAP withdrawal and sleep restriction, demonstrating a significant condition, time interaction [F(3.94,39.41) = 3.39, p = 0.018]. EEG: There was a non significant trend for combined alpha and theta activity to be highest throughout the drive following CPAP withdrawal. Discussion CPAP withdrawal impairs driving simulator performance sooner than restricting sleep to 5 h with CPAP. Participants had insight into this increased sleepiness reflected by the higher KSS reported following CPAP withdrawal. In the practical terms of driving any one incident could be fatal. The earlier impairment reported here demonstrates the potential danger of missing CPAP treatment and highlights the benefit of CPAP treatment even when sleep time is short.

Continuous positive air pressure treatment for obstructive sleep apnoea patients : effects on sleep quality and quantity as measured by actigraphy

Objectives Actigraphy can reliably assess sleep in healthy adults and be used to estimate total sleep time in suspected obstructive sleep apnoea (OSA) patients. We compared sleep quality for Continuous Positive Air Pressure (CPAP) treated OSA patients and controls, evaluating the impact of stopping CPAP for one night. Methods 11 men, aged 51–75 years (m = 65.6 years), compliant CPAP users, treated for 1–19 years (m = 7.8 years) wore Cambridge Neurotechnology Ltd actiwatches for one night while using CPAP and for one night sleeping without CPAP. A control group of 11 healthy men, aged 63–74 years (m = 64.1 years) slept normally whilst wearing an actiwatch. Subsequent daytime sleepiness was recorded using Karolinska sleepiness scores (KSS). Results Actimetry showed no significant differences between actual sleep time, sleep efficiency, sleep disturbance index or number of wake bouts when comparing OSA participants using CPAP, with controls; there was no difference in subsequent daytime sleepiness, control KSS = 4.21, OSA KSS = 4.17. Without CPAP there was no significant difference in sleep length or sleep onset latency compared with using CPAP, but there was a significant impact on sleep quality as shown by: increased sleep disturbance index from 7.9 to 13.8 [t(10) = 3.510, P < 0.05], decreased percent of actual sleep from 92.05% to 86.15% [t(10) = 3.51, P < 0.05], decreased sleep efficiency from 86.6% to 81% [t(10) = 2.204, P < 0.05] and increased number of wake bouts from 29 to 42.5 [t(10) = 3.877, P < 0.05]. Daytime sleepiness became significantly worse increasing from KSS 4.17 to 6.27 [t(10) = )4.96, P < 0.05]. Conclusion There was no disparity in sleep quality or KSS scores between CPAP treated OSA patients and healthy controls of a similar age. Treated OSA patients obtained quality sleep with no elevated day time sleepiness. However, cessation of treatment for one night caused sleep quality to deteriorate despite a comparable sleep time; the deterioration in sleep quality could explain the increase in daytime sleepiness. OSA patients need to know that even short-term noncompliance with CPAP treatment significantly impairs sleep quality, leading to excessive sleepiness during monotonous tasks such as driving. Actigraphy successfully identified nights of non-compliance in treated OSA patients; but did not differentiate between the sleep of CPAP treated OSA patients and healthy controls.

Malnutrition in hospitalised patients and clinical outcomes : a missed opportunity?

This research programme has resulted in 5 published papers in international peer-reviewed journals and contributed to better outcomes for patients. It has provided clear evidence that the adverse outcomes of malnutrition are not just a consequence of the disease process, and lead to substantial increases in length of hospital stay, readmission rate, mortality and hospitalisation cost when compared with well-nourished patients of similar diagnoses and complexities. The research programme led to the development and validation of a new nutrition screening tool called 3-Minute Nutrition Screening (3-MinNS). It has also implemented quality improvement initiatives which proved successful in improving the compliance to 3-MinNS and ensuring referral of malnourished or 'at risk' patients to dietitians. Finally, this research programme has provided an effective method for following up malnourished patients post-discharge, which resulted in improved nutritional status and quality of life.

Recovering from the earthquake : early childhood teachers and children collaboratively telling stories about their experiences

Purpose – Traumatic events can cause post-traumatic stress disorder due to the severity of the often unexpected events. The purpose of this paper is to reveal how conversations around lived experiences of traumatic events, such as the Christchurch earthquake in February 2011, can work as a strategy for people to come to terms with their experiences collaboratively. By encouraging young children to recall and tell of their earthquake stories with their early childhood teachers they can begin to respond, renew, and recover (Brown, 2012), and prevent or minimise more stress being developed. Design/methodology/approach – The study involved collecting data of the participating children taking turns to wear a wireless microphone where their interactions with each other and with teachers were video recorded over one week in November 2011. A total of eight hours and 21 minutes of footage was collected; four minutes and 19 seconds of that footage are presented and analysed in this paper. The footage was watched repeatedly and transcribed using conversation analysis methods (Sacks, 1995). Findings – Through analysing the detailed turn-taking utterances between teachers and children, the orderliness of the co-production of remembering is revealed to demonstrate that each member orients to being in agreement about what actually happened. These episodes of story telling between the teachers and children demonstrate how the teachers encourage the children to tell about their experiences through actively engaging in conversations with them about the earthquake. Originality/value – The conversation analysis approach used in this research was found to be useful in investigating aspects of disasters that the participants themselves remember as important and real. This approach offers a unique insight into understanding how the earthquake event was experienced and reflected on by young children and their teachers, and so can inform future policy and provision in post-disaster situations.

Living in a broken world : how young children's well-being is supported through playing out their earthquake experiences

The therapeutic value of play can be shown in spontaneous play situations following children’s experiences of traumatic events. Following the events of the Christchurch earthquakes in New Zealand in 2010 and 2011, an investigation was conducted of how children used the earthquake event as a catalyst in pretend play with peers and in discussions with teachers. Supporting children’s well-being is a focus area in New Zealand early childhood education as it is a strand of the national curriculum, Te Whāriki (Ministry of Education [MoE], 1996). In this article, children are observed engaging in pretend play episodes and with Learning Story books to explore personal reflections of the earthquake, prompting the children to make reference to things being ‘broken’ and needing 'fixing.' Analysis shows how the content of the pretend play experiences helped the children to come to terms with their experiences. Affording children time and interactional opportunities to play out and discuss traumatic experiences contributes to the psychological well-being of participants following a traumatic event.

Raising awareness of Australian Aboriginal peoples reality : Embedding Aboriginal knowledge in social work education through the use of field experiences

Effective social work practice with Aboriginal peoples and communities requires knowledge of operational communication skills and practice methods. In addition, there is also a need for practitioners to be aware of the history surrounding white engagement with Aboriginal communities and their cultures. Indeed, the Australian Association of Social Workers (AASW) acknowledges the importance of social workers practising cultural safety. Engendering knowledge of cultural safety for social work students is the opportunity to listen and talk with Aboriginal people who have experienced the destructive impacts of colonisation and the subsequent disruption to family and community. This article discusses the use of field experiences within a Masters of Social Work (Qualifying) Program (MSW) as an educational method aimed at increasing student awareness of contemporary Aboriginal issues and how to practice effectively and within a culturally safe manner.

CPD : Using evidence based clinical practice guidelines in the management of anaemia in patients with chronic renal failure

Anaemia is a chronic problem in patients with renal insufficiency, especially chronic renal failure (CRF). In patients with CRF, anaemia is primarily due to a deficiency in erythropoietin (EPO), a glycoprotein growth factor that stimulates RBC production. The long-term effects and burden of anaemia for patients with CRF can be physical, emotional and financial. With efficient, systematic management of anaemia, clinicians have the potential to realise not only better clinical outcomes for CRF patients but also significant cost savings for them and the health system. During the last decade, significant advances have been made in clinicians’ understanding of how best to manage anaemia in this vulnerable population. One of the most important efforts to improve clinical practice has been the development of best practice guidelines.

Neutrophil counts in leptospirosis patients infected with different serovars

In leptospirosis patients, haematological abnormalities have been reported. The aim of this study was to determine if neutrophil counts were different between patients known to be infected with a range of leptospiral serovars. The study retrospectively compared the neutrophil counts from the first blood samples taken from 210 leptospirosis patients at first presentation to a Queensland Health hospital. Significant differences (p <0.001) were observed in neutrophil counts across the 11 different infecting serovars. These findings suggest that neutrophil counts may be useful in the development of an algorithm determining the infecting serovar in suspected leptospirosis patients. Further studies are required to delineate host cytokine responses which may suggest the underlying aetiology of the observed differences in neutrophil counts. Such studies would also provide valuable therapeutic insights into treating the disease.