A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.     

The use of reflection in a palliative care programme: a quantitative study of the development of reflective skills over an academic year

The use of reflection in a palliative care programme: a quantitative study of the development of reflective skills over an academic year Reflection has gained a reputation for encouraging the integration between theory and practice within professional education. However, this reputation is based on an evidence base that mostly consists of theoretical debate. The aim of this study was to test our experience that the ability to reflect is developmental and that some reflective skills are harder to achieve than others. The research was undertaken by assessing the degree to which registered nurses achieved reflective criteria within assignments submitted for a variety of palliative care undergraduate modules. A total of 160 assignments were analysed using a marking grid constructed from a literature review and the results were compared between students and across academic terms. The results suggest that students are able to describe their practice but find it harder to analyse knowledge, the context of care and to action plan. Nevertheless, reflective abilities developed over time with significant developments made between each term. However, the development of skills indicative of critical reflection was less evident and confined to the ability to raise implications for future learning. The lack of multivariate analysis limits the study. However, the findings build on previous research and prompt questions for future work, particularly with respect to the process of reflection and how this can be supported in order to encourage the development of critical reflective skills.     

Using an antedependence test to analyse post-operative pain measurements

Post-operative pain is frequently measured by a visual analogue scale (VAS). The most common methods for analysing such data are the so-called time-by-time method and repeated measures analysis of variance. In the first, due to correlation between time points, successive tests are not independent and cannot measure the treatment effects over time. In the second, a rather unlikely covariance structure has to be assumed. In a simulation study we have shown that the power of the antedependence test is nearly the same as that of repeated measures of analysis of variance and it does not suffer from some of the latter's shortcomings. We also present an analysis of real data using the antedependence test.     

Feeding during acute diarrhea as a risk factor for persistent diarrhea

Dietary intake during diarrhea in children less than three years of age was estimated from information recorded on illustrated dietary forms used by children's caretakers during the first week of illness in a prospective community-based study of diarrheal diseases in Lima, Peru. The frequency of consumption and the amount consumed of food groups and selected commonly consumed foods were analyzed by the final duration of the diarrheal episode. Cereals were less frequently consumed during the acute phase of diarrheal episodes that ultimately became persistent (>14 days'duration), apparently shortening the duration of the episode by one day (median duration of four days in children not consuming vs three days in children consuming cereals during diarrhea, p <0.02 Kaplan-Meier logrank test). Only roots and tubers (mainly potatoes) were consumed in greater quantity during episodes that became persistent. There was no evidence that consumption of breast milk or non-maternal milk was associated with an alteration in diarrheal duration. This study provides further evidence of the beneficial effects of continuing feeding during diarrhea using foods available at the home level, especially cereals, which are commonly used in the diet of young children.     

The effect of soil type and climate on hookworm (Necator americanus) distribution in KwaZulu-Natal,South Africa

We investigated environmental factors influencing the distribution of hookworm infection in KwaZulu-Natal, South Africa. Prevalence data were sourced from previous studies and additional surveys carried out to supplement the database. When geo-referenced the data revealed that higher prevalences are limited to areas below 150 m above sea level, and low prevalences to areas above this altitude. Using univariate analysis we investigated the differences in environmental factors in the two areas. The relationship between hookworm prevalence, altitude and climate-derived variables was assessed using Pearson correlation coefficient, and that of soil type using the t-test. Multivariate analysis was used to determine environmental factors that combine best to provide favourable conditions for hookworm distribution. The results revealed that areas 150 m above sea level, i.e. inland, supported low mean hookworm prevalences (x = 6, n = 21), and were characterized by soils with a clay content of more than 45%, variable temperatures and moderate rainfall. Hookworm prevalence also decreased southwards as temperatures became slightly cooler, rainfall remained more-or-less constant and the coastal plain narrowed. In the multivariate model prevalence was most significantly correlated with the mean daily minimum temperature for January followed by the mean number of rainy days for January. This indicates the importance of summer conditions in the transmission of hookworm infection in KwaZulu-Natal and suggests that transmission may be seasonal.     

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

Background  

There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study.