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The randomized multicentre trial of continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in patients with advanced head and neck cancer showed no good evidence of a difference in any of the major clinical outcomes of survival, freedom from metastases, loco-regional control and disease-free survival. Therefore an assessment of the effect of treatment on physical and psychological symptoms is vital to balance the costs and benefits of the two treatments. A total of 615 patients were asked to complete a Rotterdam Symptom Checklist and the Hospital Anxiety and Depression Scale, which cover a variety of physical and psychological symptoms, at a total of ten time points. The data consisted of short-term data (the initial 3 months) and long-term data (1 and 2 years). The short-term data was split into an exploratory data set and a confirmatory data set, and analysed using subject-specific and group-based methods. Differences were only claimed if hypotheses generated in the exploratory data set were confirmed in the confirmatory data set. The long-term data was not split into two data sets and was analysed using a group-based approach. There was evidence of significantly worse symptoms of pain at day 21 in those treated with CHART and significantly worse symptoms of cough and hoarseness at 6 weeks in those treated conventionally. There was also evidence to suggest a higher degree of decreased sexual interest at 1 year and sore muscles at 2 years in those treated with conventional radiotherapy. There is no clear indication that one regimen is superior to the other in terms of 'quality of life', generally the initially more severe reaction in the CHART group being offset by the longer duration of symptoms in the conventionally treated group. [ABSTRACT FROM AUTHOR]

Studies of the association between the presence of osteoarthritis (OA) and the risk of osteoporotic fractures have produced conflicting results. To address this question further, we have examined the association between self-reported, validated fractures and radiological OA at multiple sites in a large population of normal Caucasian women aged 45–65 yr. Despite having increased bone mineral density (BMD) of 5.3%, subjects with hip OA had a significantly increased risk of fracture [odds ratio (OR) 2.38, 95% CI 1.06–5.35] compared to controls. Subjects with lumbar spine OA, however, had a significantly reduced risk of fracture (OR 0.45, 95% CI 0.23–0.80) compared to controls. This association was not explained by differences in BMD, weight, sex hormones or physical activity. No clear association was seen with fracture for hand or knee OA. These data suggest that the increased risk of fracture in subjects with OA of the hip is most likely to be due to mechanical and locomotor factors, such as the risk of falling [ABSTRACT FROM PUBLISHER]

Aims: To assess the activity of a continuous infusion of 5-fluorouracil in patients with recurrent locally advanced or metastatic transitional cell carcinoma of the urinary tract., Materials and Methods: Eight centres within the UK entered 50 patients into the study. Twenty-four weeks of continuously infused 5-fluorouracil, 300mg/m(2)/day through a mini-pump, were planned. The primary outcome was tumour response at 8 weeks after the start of treatment., Results: The median age of the patients was 68 years and 37 (80.4%) had a World Health Organization performance status of 0 or 1. The overall response rate at 8 weeks, according to the response evaluation criteria in solid tumors (RECIST) criteria in 46 evaluable patients, was 15% (95% confidence interval 5-26%) and 20% (95% confidence interval 8-31%) when assessments at all time points were included. The median progression-free survival was 1.9 months (95% confidence interval 1.8-2.7 months) and the median overall survival was 6.5 months (95% confidence interval 4.1-8.5 months). The most frequent grade 3/4 toxicities were mucositis and diarrhoea (each in 6.5% of patients) and nausea/vomiting and hand-foot syndrome (each in 4.3% of patients)., Conclusions: Continuous infusional 5-fluorouracil has activity in transitional cell carcinoma of the urinary tract. Prolonged fluoropyrimidine administration may be a useful component of future combination regimens for this disease, particularly in patients with poor renal function.

Background: In judging whether or not to continue enrolling patients into a randomised clinical trial, most data-monitoring and ethics committees (DMECs) rely on the p value for the difference in effect between the study groups. In the 1990s, two randomised controlled trials-one in patients with lung cancer and one in those with head and neck cancer-were instead monitored by Bayesian methods. We assessed the value of this approach in the monitoring of these clinical trials., Methods: Before the trials opened, participating clinicians were asked their opinions on the expected difference between the study treatment (continuous hyperfractionated accelerated radiotherapy [CHART]) and conventional radiotherapy. These opinions were used to form an "enthusiastic" and a "sceptical" prior distribution. These prior distributions were combined with the trial data at each of the annual DMEC meetings. If, during monitoring, a result in favour of CHART was seen, the DMEC was to decide whether the results were sufficiently convincing to persuade a sceptic that CHART was worthwhile. Conversely, if there was apparently no or little difference, the DMEC was asked whether they thought the results sufficiently convincing to persuade an enthusiast that CHART was not worthwhile., Findings: At each of the annual meetings, the DMEC concluded that there was insufficient evidence to convert either sceptics or enthusiasts, and that the trials should therefore remain open to recruitment. Neither trial was closed to recruitment earlier than planned. However if a conventional (p-value-based) stopping rule had been used, the lung-cancer trial would probably have been stopped., Interpretation: This Bayesian approach to monitoring is simple to implement and straightforward for members of the DMEC to understand. In our opinion, it is more intuitively appealing than conventional approaches.