Probioticaprofylaxe bij voorspeld ernstige acute pancreatitis : een gerandomiseerde, dubbelblinde, placebogecontroleerde trial

OBJECTIVE: To evaluate whether enteral prophylaxis with probiotics in patients with predicted severe acute pancreatitis prevents infectious complications. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. METHOD: A total of 296 patients with predicted severe acute pancreatitis (APACHE II score > or = 8, Imrie score > or = 3 or C-reactive protein concentration > 150 mg/l) were included and randomised to one of two groups. Within 72 hours after symptom onset, patients received a multispecies preparation of probiotics or placebo given twice daily via a jejunal catheter for 28 days. The primary endpoint was the occurrence of one of the following infections during admission and go-day follow-up: infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis or infected ascites. Secondary endpoints were mortality and adverse reactions. The study registration number is ISRCTN38327949. RESULTS: Treatment groups were similar at baseline with regard to patient characteristics and disease severity. Infections occurred in 30% of patients in the probiotics group (46 of 152 patients) and 28% of those in the placebo group (41 of 144 patients; relative risk (RR): 1.1; 95% CI: 0.8-1.5). The mortality rate was 16% in the probiotics group (24 of 152 patients) and 6% (9 of 144 patients) in the placebo group (RR: 2.5; 95% CI: 1.2-5.3). In the probiotics group, 9 patients developed bowel ischaemia (of whom 8 patients died), compared with none in the placebo group (p = 0.004). CONCLUSION: In patients with predicted severe acute pancreatitis, use of this combination of probiotic strains did not reduce the risk of infections. Probiotic prophylaxis was associated with a more than two-fold increase in mortality and should therefore not be administered in this category of patients.

The cognitive-spiritual dimension - an important addition to the assessment of quality of life: Validation of a questionnaire (SELT-M) in patients with advanced cancer

Questions of meaning and challenge by illness, i.e., the spiritual dimension of quality of life (QL) traditionally played an important role in anthroposophically oriented medicine and have gained importance in palliative medicine and supportive care. In the context of a research project on QL in patients with advanced cancer, we therefore investigated the psychometric properties of a questionnaire covering spiritual QL issues, with the aim of providing a module for the assessment of cognitive-spiritual QL. Patients and methods: We investigated 89 patients with advanced breast and gastro-intestinal cancer. Construct validity of a modified version of the SELT (Skalen zur Erfassung von Lebensqualitat bei Tumorkranken), the SELT-M was tested by multitrait scaling analysis. Discriminant and convergent validity were also tested. The EORTC QLQ-C30 was used as a standard for validation. Results showed the SELT-M as feasible in administration. Four of the five SELT-M subscales were internally consistent (Cronbach's Alpha = ≥0.7). The subscale on spiritual QL showed higher within than outside subscale correlations for six of its eight items. Association of the SELT-M with the EORTC QLQ-C30 was good for the items and subscales covering the same aspects of QL in both questionnaires: emotional (Spearman r = 0.61), physical functioning (r= −0.54) and fatigue (r= −0.75). In accordance with expectations, there was no association between spiritual QL with any EORTC QLQ-C30 subscales. Self-assessed spiritual QL in the SELT-M corresponded well with interviewer assessments (test for trend accross ordered groups, P = 0.0023). Conclusions. Overall there is confirming evidence for the hypothesised structure of the SELT-M, especially for the newly developed module on spiritual QL. This module may be used as a module together with other cancer specific QL questionnaire

Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence

INTRODUCTION: Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association between insulin and insulin analogue treatment and breast cancer development, and plausible mechanisms. METHOD: A systematic literature search was performed on breast cell-line, animal and human studies using the key words 'insulin analogue' and 'breast neoplasia' in MEDLINE at PubMed, EMBASE, and ISI Web of Science databases. A quantitative and qualitative review was performed on the epidemiological data; due to a limited number of reported estimates, a meta-analysis was performed for glargine only. A comprehensive overview was composed for in vitro and animal studies. Protein and gene expression was analysed for the cell lines most frequently used in the included in vitro studies. RESULTS: In total 16 in vitro, 5 animal, 2 in vivo human and 29 epidemiological papers were included. Insulin AspB10 showed mitogenic properties in vitro and in animal studies. Glargine was the only clinically available insulin analogue for which an increased proliferative potential was found in breast cancer cell lines. However, the pooled analysis of 13 epidemiological studies did not show evidence for an association between insulin glargine treatment and an increased breast cancer risk (HR 1.04; 95 % CI 0.91-1.17; p=0.49) versus no glargine in patients with diabetes mellitus. It has to be taken into account that the number of animal studies was limited, and epidemiological studies were underpowered and suffered from methodological limitations. CONCLUSION: There is no compelling evidence that any clinically available insulin analogue (Aspart, Determir, Glargine, Glulisine or Lispro), nor human insulin increases breast cancer risk. Overall, the data suggests that insulin treatment is not involved in breast tumour initiation, but might induce breast tumour progression by up regulating mitogenic signalling pathways

Multiple field inflation

Inflation offers a simple model for very early evolution of our Universe and the origin of primordial perturbations on large scales. Over the last 25 years we have become familiar with the predictions of single-field models, but inflation with more than one light scalar field can alter preconceptions about the inflationary dynamics and our predictions for the primordial perturbations. I will discuss how future observational data could distinguish between inflation driven by one field, or many fields. As an example, I briefly review the curvaton as an alternative to the inflaton scenario for the origin of structure.Comment: 27 pages, no figures. To appear in proceedings of 22nd IAP Colloquium, Inflation +25, Paris, June 200