Dehydroepiandrosterone for systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory, multisystem autoimmune condition. Dehydroepiandrosterone (DHEA) is a naturally occurring inactive steroid which may possess disease activity modifying properties as well as the ability to reduce flares and steroid requirements. OBJECTIVES: To assess the effectiveness and safety of dehydroepiandrosterone compared to placebo in the treatment of people with systemic lupus erythematosus. SEARCH STRATEGY: We searched The Cochrane Library (Issue 2, 2006), MEDLINE, Pub Med, EMBASE, Science Citation Index and ISI Proceedings as well as searching web sites of Genelabs, FDA and EMEA. (Searches undertaken in June 2006 unless otherwise specified). SELECTION CRITERIA: We included randomised controlled trials of at least three months duration comparing DHEA to a placebo in people with SLE. DATA COLLECTION AND ANALYSIS: Two review authors assessed quality and extracted data. MAIN RESULTS: From the seven RCTs identified (842 participants) to date there is 'gold' ranking evidence (www.cochranemsk.org) that DHEA: had little clinical effect on disease activity in those with mild/moderate disease (measured by SLEDAI or SLAM) but one study demonstrated evidence of stabilisation or improvement in 8.3% more patients than those treated with placebo; had a modest but clinically significant improvement in health related quality of life measured by Patient Global Assessment, estimated as 11.5% (11.5 mm on a 100 mm scale) by meta-analysis; resulted in a greater number of patients experiencing adverse events, particularly androgenic effects such as acne where patients risk was doubled when compared to placebo (RR 2.2; 95% CI 1.65 to 2.83) AUTHORS' CONCLUSIONS: Studying effectiveness of DHEA for SLE is difficult, reflecting the problems of studying any treatment for a disease as complex as SLE. From the seven RCTs to date, there was evidence that DHEA had a modest but clinically significant impact on health related quality of life in the short term. Impact on disease activity was inconsistent, with DHEA showing no benefit over placebo in terms of change in SLEDAI in all but one of the 6 studies reporting this outcome. Long term outcomes and safety remain unstudied.

Meglitinide analogues for type 2 diabetes mellitus.

BACKGROUND: In type 2 diabetes mellitus, impairment of insulin secretion is an important component of the disease. Meglitinide analogues are a class of oral hypoglycaemic agents that increase insulin secretion, in particular, during the early phase of insulin release. OBJECTIVES: The aim of this review was to assess the effects of meglitinide analogues in patients with type 2 diabetes mellitus. SEARCH STRATEGY: We searched several databases including The Cochrane Library, MEDLINE and EMBASE. We also contacted manufacturers and searched ongoing trials databases, and the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) websites. SELECTION CRITERIA: We included randomised controlled, parallel or cross-over trials comparing at least 10 weeks of treatment with meglitinide analogues to placebo, head-to-head, metformin or in combination with insulin. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. MAIN RESULTS: Fifteen trials involving 3781 participants were included. No studies reported the effect of meglitinides on mortality or morbidity. In the eleven studies comparing meglitinides to placebo, both repaglinide and nateglinide resulted in a reductions in glycosylated haemoglobin (0.1% to 2.1% reduction in HbA1c for repaglinide; 0.2% to 0.6% for nateglinide). Only two trials compared repaglinide to nateglinide (342 participants), with greater reduction in glycosylated haemoglobin in those receiving repaglinide. Repaglinide (248 participants in three trials) had a similar degree of effect in reducing glycosylated haemoglobin as metformin. Nateglinide had a similar or slightly less marked effect on glycosylated haemoglobin than metformin (one study, 355 participants). Weight gain was generally greater in those treated with meglitinides compared with metformin (up to three kg in three months). Diarrhoea occurred less frequently and hypoglycaemia occurred more frequently but rarely severely enough as to require assistance. AUTHORS' CONCLUSIONS: Meglitinides may offer an alternative oral hypoglycaemic agent of similar potency to metformin, and may be indicated where side effects of metformin are intolerable or where metformin is contraindicated. However, there is no evidence available to indicate what effect meglitinides will have on important long-term outcomes, particularly mortality.

Making literature searches easier: a rapid and sensitive search filter for retrieving randomized controlled trials from PubMed.

AIMS: To develop and test the sensitivity and precision of a rapid and simple search filter (RSSF), suitable for busy clinicians wanting to find randomised controlled trials (RCTs) in PubMed. Ideally it should retrieve all the RCTs, but as few irrelevant studies as possible, and be easy to use. METHODS: The RSSF consisted of the search term 'Randomized Controlled Trial' limited to the Publication Type field. Journals that published the highest numbers of diabetes RCTs between 2000 and 2005 were identified, and then handsearched in order define a set of known RCTs. The sensitivity of the RSSF was tested by measuring the proportion of the known RCTs retrieved, and the precision by checking the proportion of the retrieved studies which were RCTs. The RSSF was compared to a highly sensitive search strategy (HSSS) developed for PubMed. Embase was checked for trials not in PubMed. RESULTS: Sixteen journals were found to contain half of all published RCTs in diabetes. 820 diabetes RCTs were identified by handsearching. Measured against these, the RSSF gave a sensitivity of 96.0% (95% CI, 94.8% to 97.1%), and a precision of 93.6% (95% CI 91.7% to 95.0%). Compared to the HSSS, the RSSF reduced the filtering required by 87%. An Embase search for diabetes RCTs found 36 (2.1%) not in PubMed. CONCLUSIONS: A rapid simple search filter for PubMed can find almost all diabetes RCTs, while excluding most studies not required, thereby greatly reducing the time cost of searching and filtering results, and of searching other databases.

Sources of evidence for systematic reviews of interventions in diabetes.

AIMS: To analyse the effect on systematic reviews in diabetes interventions of including only trials that are indexed in medline, and to assess the impact of adding trials from other databases and the grey literature. METHODS: All systematic reviews of diabetes interventions which included a meta-analysis of randomized controlled trials, and were published since 1996, were selected. The impact on the meta-analysis of including only those trials indexed in medline, and the effect of then adding trials from other sources, was assessed. Where possible this was measured quantitatively, by redoing the meta-analysis, otherwise a qualitative estimate was made. RESULTS: Forty-four systematic reviews met our inclusion criteria. There were 120 articles reporting trial data which were not indexed in medline. These came from 52% of the reviews. In 34% of the reviews, basing a meta-analysis on a search of only medline would miss trials that could affect the result. Sources of non-medline data which had the biggest effect on the meta-analyses were journal articles from central and embase (mainly in Diabetes, Nutrition and Metabolism) and unpublished data (mainly from industry). The exceptions were journal articles on herbal medicine, mostly indexed in Chinese language databases. CONCLUSIONS: A search of only the medline database is insufficient for systematic reviews of diabetes, because in about 34% of reviews the missed trials could affect the results of the meta-analysis. It is recommended that central (on the Cochrane Library) also be searched. Scanning meeting abstracts, and seeking unpublished data are also recommended if the intervention has only recently been introduced.

Genetic circularity of the Pseudomonas aeruginosa PAO chromosome.

Genetic circularity of the Pseudomonas aeruginosa PAO chromosome was demonstrated by a series of two- and three-factor crosses and double-selection experiments with Cma plasmids FP2, FP5, FP110, and R68.45. A range of additional markers, including catabolic markers, were located on the chromosome map. Plasmid FP2, known to have a major origin of chromosome transfer (0 min) was shown to have at least one other minor origin from which it can transfer the chromosome in the direction opposite to that found for the major origin.

Relationship between R and FP plasmids in Pseudomonas aeruginosa.

The plasmid FP110 possessing chromosome mobilizing ability for Pseudomonas aeruginosa but carrying no determinants for antibiotic resistance, is found to be related by incompatibility, entry exclusion, and other criteria to the independently isolated R plasmids R18-1 and R56Be which carry resistance determinants for carbenicillin. The frequency of FP plasmid appearance in clinical isolates of P. aeruginosa suggests the possibility that they may be a source of R plasmids in this bacterium.