Development of a core descriptor set for Crohn's anal fistula

AIM: Crohn's anal fistula (CAF) is a complex condition, with no agreement on which patient characteristics should be routinely reported in studies. The aim of this study was to develop a core descriptor set of key patient characteristics for reporting in all CAF research. METHOD: Candidate descriptors were generated from published literature and stakeholder suggestions. Colorectal surgeons, gastroenterologists and specialist nurses in inflammatory bowel disease took part in three rounds of an international modified Delphi process using nine-point Likert scales to rank the importance of descriptors. Feedback was provided between rounds to allow refinement of the next ratings. Patterns in descriptor voting were assessed using principal component analysis (PCA). Resulting PCA groups were used to organize items in rounds two and three. Consensus descriptors were submitted to a patient panel for feedback. Items meeting predetermined thresholds were included in the final set and ratified at the consensus meeting. RESULTS: One hundred and thirty three respondents from 22 countries completed round one, of whom 67.0% completed round three. Ninety seven descriptors were rated across three rounds in 11 PCA-based groups. Forty descriptors were shortlisted. The consensus meeting ratified a core descriptor set of 37 descriptors within six domains: fistula anatomy, current disease activity and phenotype, risk factors, medical interventions for CAF, surgical interventions for CAF, and patient symptoms and impact on quality of life. CONCLUSION: The core descriptor set proposed for all future CAF research reflects characteristics important to gastroenterologists and surgeons. This might aid transparent reporting in future studies

Application of a Poisson distribution quality control measure to the analysis of two human hookworm drug treatment studies in Ghana

We examined faecal egg count reduction tests (FECRTs) conducted with hookworm-infected humans in Ghana in 2007 (study 1) and 2010 (study 2) in order to explore aspects of the test analysis. Some subjects showed increased FEC following drug treatment. This occurred mostly in <150. epg pre-treatment FEC subjects. We sought a means to remove 'erroneous' negative drug efficacy cases from the FECRT analysis. Pre- and post-treatment FECs from negative drug efficacy cases were examined to determine whether they represented replicates from a single randomly distributed sample, that is, if they were consistent with a Poisson distribution. Cases where the post-treatment FEC was greater than that expected if it and the pre-treatment sample had been taken from a single random distribution of eggs were excluded from the FECRT. We suggest that these cases most likely represent non-random distribution of eggs in stools, day-to-day variations in egg excretion, or worm patency onset after drug treatment, and hence are not accurate measurements of drug efficacy. This led to exclusion of the most extreme negative drug efficacy cases, with significant increases in overall drug efficacy for study 1 (81.6% vs 89.2%) and study 2 (86.7% vs 89.4%). Excluding FEC <150 individuals from the analysis also increased the study 1 efficacy (81.6% vs 88.9%), however, this resulted in the exclusion of 45% of the study subjects, compared to the exclusion of just 5% using the Poisson distribution method. While low FEC subjects are excluded from livestock FECRTs, the significant prevalence of such subjects in human FECRTs suggests that their exclusion may not be practical. Hence, we suggest that the influence of low FECs can be minimised by excluding 'erroneous' negative efficacy cases using a simple Poisson distribution analysis

Investigation of intestinal nematode responses to naphthalophos and pyrantel using a larval development assay

Responses of several nematode species to naphthalophos and pyrantel/levamisole were examined using a larval development assay in order to determine the potential of this assay for detection of resistance. Haemonchus contortus and Ostertagia circumcincta showed concentration-dependent responses to naphthalophos, however, the assay was unsuitable for Trichostrongylus colubriformis due to the low toxicity of the drug to the larval stages of this nematode. Measurement of concentration-dependent response to pyrantel in susceptible T. colubriformis was limited by a reduced toxicity against larvae at high drug concentrations, resulting in a parabolic response with a development-inhibition maxima of less than 100%. This limits the usefulness of the assay to detect pyrantel resistance in this species as the presence of a small resistant fraction in a field isolate may be indistinguishable from the parabolic susceptible response. On the other hand, responses of susceptible T. colubriformis to levamisole, and susceptible H. contortus to pyrantel and levamisole showed 100% development-inhibition over a range of drug concentrations, indicating that the appearance of a resistant fraction in a field population would be readily discernible from the susceptible response, allowing resistance detection for these drug/parasite combinations. This study has highlighted the varied suitability of the larval development assay technique for resistance detection with different combinations of drugs and parasite species

Synergism of rotenone by piperonyl butoxide in Haemonchus contortus and Trichostrongylus colubriformis in vitro: Potential for drug-synergism through inhibition of nematode oxidative detoxification pathways

The anthelmintic properties of rotenone and its activity in combination with the cytochrome P450 inhibitor piperonyl butoxide, were examined in in vitro assays with adults and larvae of Haemonchus contortus and larvae of Trichostrongylus colubriformis. Rotenone was toxic to larvae of both species, with LC50 values in larval development assays of 0.54 and 0.64 μg/ml for H. contortus and T. colubriformis, respectively. The compound also caused complete cessation of movement in adult H. contortus after 72 h at a concentration of 20 μg/ml. Toxicity of rotenone towards the larvae of both species was increased in the presence of piperonyl butoxide (synergism ratios of 3-4-fold at the LC50) and the activity against adult H. contortus was also significantly enhanced following pre-treatment with piperonyl butoxide. This significant synergism suggests that these nematode species are able to utilize a cytochrome P450 enzyme system to detoxify rotenone and indicates that a role may exist for cytochrome P450 inhibitors to act as synergists for other anthelmintics which are susceptible to oxidative metabolism within the nematode

Low cost high benefit improvements to Ben Schoeman freeway

Paper presented at the South African Transport Conference 17 - 20 July 2000 "Action in transport for the new millennium", CSIR International Convention Centre, Pretoria, South Africa.This paper was transferred from the original CD ROM created for this conference. The material on the CD ROM was published using Adobe Acrobat technology. The original CD ROM was produced by Document Transformation Technologies Postal Address: PO Box 560 Irene 0062 South Africa. Tel.: +27 12 667 2074 Fax: +27 12 667 2766 E-mail: [email protected] URL: http://www.doctech.co.z