Recruitment of patients into drug trials is essential in order to evaluate new treatments. Knowing why patients enter drug trials and their fears regarding them can be used in future research to ensure good recruitment and provide a supportive atmosphere for patients. Forty patients with colorectal cancer and 30 patients with colorectal liver metastases were asked to participate in a drug trial involving the oral consumption of a diet-derived agent of unknown therapeutic action. All patients agreeing or refusing to participate were asked to complete a short questionnaire with a series of options detailing the reasons behind their decision. Patients with colorectal hepatic metastases were motivated by altruism in entering the trial (e.g. helping others, helping the investigator) and displayed a realistic expectation that the drug would give little direct benefit to them. Patients with primary colorectal tumours were motivated by more 'selfish' reasons such as helping themselves and displayed an unrealistic expectation concerning any therapeutic benefit from the trial drug. Over 90% of all patients polled stated that their decision was made after reading the patient information leaflet. Patients with different stages of the same disease have very different fears and anticipations of drug trials, which need to be addressed specifically. The importance of the initial contact is demonstrated. Unrealistic expectations regarding the trial drug are common despite clear information to the contrary.
Background Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. Methods In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. Results Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). Conclusions The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.
Cancer chemoprevention involves the chronic administration of a synthetic, natural or biological agent to reduce or delay the occurrence of malignancy. The potential value of this approach has been demonstrated with trials in breast, prostate and colon cancer. The paradigm for developing new chemopreventive agents has changed markedly in the last decade and now involves extensive preclinical mechanistic evaluation of agents before clinical trials are instituted and a focus on defining biomarkers of activity that can be used as early predictors of efficacy. This review will summarise the current status of the field of chemoprevention and highlight potential new developments.
Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin α in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4–6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin α 150 IU kg–1 subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg–1 s.c. three times a week (n = 44). Reductions in epoetin α dosage were made during the study if Hb level increased to >15 g dl–1. The mean weekly dosage was 335 and 612 IU kg–1, respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin α-treated patients experienced anaemia (Hb < 10 g dl–1) during the course of chemotherapy (300 IU kg–1, 39%; 150 IU kg–1, 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg–1, 20% (P < 0.001); 150 IU kg–1, 45% (P < 0.05); untreated, 59%]. Epoetin α was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin α is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC.
A 63-year-old female retired clerical officer was admitted with a 1-week history of profuse diarrhoea. The patient had been diagnosed with non-Hodgkin's lymphoma 4 years previously, and a human immunodeficiency virus (HIV) test at that time was negative. She had received two regimens of chemotherapy, and had been in remission for 3 months with a normal leukocyte count. The diarrhoea was watery with no blood or mucus, and associated with mild nausea and diffuse left-sided abdominal pain relieved by defaecation. The patient had a mild pyrexia and scanty bowel sounds, but the abdomen was not distended. Full blood count and full biochemistry were normal apart from the white cell count (13.8x10 9 /litre — predominantly neutrophils and monocytes). Initial blood cultures and routine viral serology were negative, but the latter was never repeated. Stool samples were negative for bacteria, parasites and toxins.
Abstract Individual differences in diet can play an important role defining a population's ecological niche and its role within food webs and habitats, but individual trophic specialization is rarely considered in a fisheries context. Stocks of European seabass, Dicentrarchus labrax, have declined in recent years, and policy has focused on managing fishing effort. Inshore nursery grounds represent a critical habitat in terms of recruitment to standing stocks, and improved understanding of the ecology of juvenile seabass at the level of the individual may assist the development of management strategies aimed at maximizing their survival and growth. We quantified levels of individual trophic specialization in juvenile seabass using stomach contents and stable isotope analyses at a monthly resolution over an annual cycle. We found significant, seasonally varying levels of individual specialization in stomach contents, with reduced specialization observed in the spring. This was corroborated by stable isotope analyses, where isotopic variance among seabass individuals was significantly higher compared to that in two other concurrently sampled, sympatric bentho-pelagic predators. Our findings suggest that juvenile seabass form trophic-generalist populations composed of specialized individuals. Considering variation in individual behaviours may improve management strategies aimed at protecting the vulnerable life stages of this commercially important species.
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