Controlled clinical trials in cystic fibrosis--are we doing better?

We have previously reported the time trends, design and interventions in randomised controlled trials (RCTs) in cystic fibrosis (CF) from 1961 through 1997 [Cheng K, Smyth RL, Motley J, O'Hea U, Ashby D, Randomised controlled trials in cystic fibrosis (1966-1997) categorized by time, design, and intervention. Pediatr Pulmonol 2000, 29:1-7.]. We maintain an ongoing register of all RCTs and controlled clinical trials (CCTs) in CF and have noted that in the five years since 1997 there has been a 48% increase in published trials. We aimed to assess whether this increase has been associated with an improvement in design quality. All RCTs and CCTs from 1961-2002 were assessed. Two epochs were then compared, 1961-1997 and 1998-2002. For each trial we recorded the design, participant numbers and the intervention studied. 261 trials in 1998-2002 were compared with 544 trials in 1961-1997. Comparing the two epochs a similar proportion of trials were parallel, double-blind and placebo controlled; also the median number of participants was similar. In the later epoch 25% of trials were multicentre, compared with 11% previously. Whilst this recent increase in clinical trials in CF is welcome, this has not been associated with improvements in quality. The trend for an increasing proportion of trials to be multicentre is encouraging. There are however, still deficiencies in the design of clinical trials in CF.     

The complex enterprise of modelling prenatal exposure to cigarettes: what is ‘enough’?

While there is a burgeoning body of research linking smoking during pregnancy to problem behaviour in offspring, a major criticism of this work has been the crude measurement of exposure in these studies (e.g. retrospective, self-reported only) that could lead to biased estimates. To address this issue, we used a pregnancy cohort with repeated prospective measures of exposure as well as biological assays to generate estimates of exposure patterns using a range of modelling techniques. In this paper we report on the analytical approaches we have developed, including patterns of exposure over time and best-estimate approaches that combine self-report and cotinine measures, and compare their predictive value in relation to different dimensions of fetal growth as a first step towards examining the utility of greater precision of exposure measurement.
Surprisingly, in this sample the more complex assessments of exposure, including biological measures, generally did not perform better than simple indicators of exposure based on repeated self-report measures, with one exception: a combined self-report cotinine 'best estimate' of third trimester exposure was uniquely associated with lower brain : body ratio. Further study is needed using more sophisticated cotinine assays and testing prediction of a range of outcomes to ascertain whether these findings represent true differences or are specific to the sample, methods and outcomes used. Such research will inform the development of guidelines for adequate exposure characterisation in developmental studies.     

Immunopotentiation of bovine herpes virus subunit vaccination by interleukin-2.

Cattle were immunized with glycoprotein IV (gIV) from bovine herpes virus-1 (BHV-1). Groups of five animals were then given either 2, 3, 4, or 5 doses of interleukin-2 (IL-2) (0.5 microgram/kg) at 12-hr intervals. Animals that received no IL-2 exhibited specific immune responses that are typical for BHV-1 infection, i.e. enhanced specific cytotoxicity, lymphocyte proliferative responses to gIV, and increased gIV-specific (ELISA) and virus-neutralizing antibodies. Treatment of animals with five doses of IL-2 significantly augmented all of these responses except serum neutralization (P less than 0.05). Furthermore, the dose of IL-2 that was selected did not induce any non-specific responses, i.e. hypergamma-globulinaemia, changes in blood chemistry, increased lymphokine-activated killer (LAK) cell activity, changes in mitogen responsiveness or alterations in the phenotypic profile of circulating lymphocytes. Nor were there any clinical changes associated with IL-2 therapy (e.g. depression, pyrexia, diarrhea). Animals that were treated with less than five doses of IL-2 also exhibited elevated immune responses, but they were not significantly different from untreated immunized controls. Interestingly, animals given five doses of IL-2 responded to minor contaminants present in the gIV preparation. This allows speculation that this dose regimen of IL-2 is not only a potent adjuvant for conventional vaccine immunizing doses, but will also allow the use of minute quantities of antigen for immunization.     

The Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) evaluated in insulin glargine trials shows greater responsiveness to improvements than the original DTSQ

Background  

The results of using status measures to identify any changes in treatment satisfaction strongly suggest a need for specific change instruments designed to overcome the ceiling effects frequently observed at baseline. Status measures may leave little room to show improvement in situations where baseline ceiling effects are observed. A change version of the DTSQ (DTSQc) is compared here with the original status (now called DTSQs) version to test the instruments' comparative ability to demonstrate change.