The minimum clinically important difference: which direction to take.

Over the past decades in modern medicine, there has been a shift from statistical significance to clinical relevance when it comes to interpreting results from clinical trials. A concept that is increasingly being used as a surrogate for clinical relevance and effect size calculation is the minimum clinically important difference (MCID). In this paper, an overview is presented of the most important aspects of the MCID concept used in research trials and a discussion of what this means for the neurological patient in clinical trials and daily practice is given. Is the MCID the best outcome measure cut-off to be implemented?

Associated conditions in small fiber neuropathy - a large cohort study and review of the literature.

BACKGROUND AND PURPOSE: Small fiber neuropathy (SFN) is a common disorder leading to neuropathic pain and autonomic symptoms. The objective of this study was to investigate associated conditions in a large cohort of SFN patients and compare the prevalence to healthy individuals. METHODS: A total of 921 patients with pure SFN were screened according to a standardized comprehensive diagnostic algorithm and compared with literature findings. RESULTS: No associated condition could be found in 53% of the patients. Autoimmune diseases, sodium channel gene mutations, diabetes mellitus including glucose intolerance, and vitamin B12 deficiencies were more prevalent than reported literature findings, followed by alcohol abuse, chemotherapy, monoclonal gammopathy of undetermined significance, and haemochromatosis. In patients who were already known with a possible underlying condition at screening, additional underlying conditions were still found in another 26.7% of patients. CONCLUSIONS: Based on these results, it is recommended that patients with pure SFN are screened at least for autoimmune diseases, sodium channel gene mutations, diabetes mellitus including glucose intolerance, and vitamin B12 deficiency, even when they already have a potential underlying condition at referral.

Effects of anti-tumour necrosis factor, interleukin-10 and antibiotic therapy in the indometacin-induced bowel inflammation rat model.

BACKGROUND: The administration of indometacin to rats increases intestinal permeability and induces inflammatory pathology of the small bowel. This represents a potential model for Crohn's disease. AIMS: To analyse the pathogenic role of T cells, tumour necrosis factor and bacterial flora in indometacin-induced changes in small bowel permeability and inflammation. METHODS: Rats were given indometacin, 13 mg/kg, on day 1 and day 2. The effects of antibiotic (metronidazole, aztreonam and amoxicillin/clavulanic acid), anti- tumour necrosis factor and interleukin-10 therapy were evaluated. The parameters used were weight change, serum haemoglobin, chromium-51 ethylenediaminetetra-acetate permeability and macro-and microscopic score on day 5. Results in conventionally harboured rats were compared with those in T-cell-free rats. Additional in vitro experiments were carried out to test the effect of metronidazole on tumour necrosis factor production. RESULTS: Indometacin administration resulted in small bowel ulcers and inflammation, independently of T cells. Metronidazole was more potent than amoxicillin/clavulanic acid and anti-tumour necrosis factor in improving the indometacin-induced small bowel inflammation. Only part of the efficacy was through improvement of increased intestinal permeability. Aztreonam and interleukin-10 had no effect. Metronidazole also suppressed in vitro lipopolysaccharide-induced tumour necrosis factor production, suggesting a therapeutic effect of this drug through the inhibition of tumour necrosis factor. CONCLUSIONS: These data implicate anaerobic bacteria and tumour necrosis factor production, but not T cells, as essential elements of the pathogenesis of indometacin-induced small bowel inflammation. Tumour necrosis factor is also involved in the change in intestinal permeability. Metronidazole was the most efficacious drug in this model, probably because it suppressed anaerobic bacteria and directly inhibited tumour necrosis factor production.

RAPD of controlled crosses and clones from the field suggests that hybrids are rare in the Salix alba-Salix fragilis complex.

The polyploid Salix alba-Salix fragilis hybrid complex is rather difficult to study when using only morphological characters. Most of the features have a low diagnostic value for unambiguously identifying the hybrids, introgression patterns and population structures, though morphological traits have proved to be useful in making a hybrid index. Morphology and molecular variation from RAPDs were investigated in several case studies on willows from Belgium. A thorough screening of full-sib progenies of interspecific controlled crosses was made to select homologous amplification products. The selected amplified products proved to be useful in a principal coordinate analysis for the estimation of variability of hybrid progenies. On the basis of genetic similarities and ordination analysis, a method for the identification of clones in the field was established using presumed pure species and presumed introgressants. The chosen reference clones were checked against additional European samples of putative pure species to ensure the reliability of the method beyond a regional scale. The RAPDs suggested that both species have kept their gene pools well separated and that hybridization actually does not seem to be a dominating process. The observation that molecular markers do not always follow the morphological traits or allozyme data is discussed.