Does pulmonary rehabilitation work in clinical practice? A review on selection and dropout in randomized controlled trials on pulmonary rehabilitation

Bodil Bjoernshave1, Jens Korsgaard2, Claus Vinther Nielsen31Medical Department, Horsens Regional Hospital, Denmark; 2Aalborg Hospital Science and Innovation Centre, 3Department of Clinical Social Medicine and Rehabilitation, Institute of Public Health, Aarhus University, DenmarkAim: To analyze randomized controlled trials (RCTs) on pulmonary rehabilitation (PR) to determine whether the patients who complete PR form a representative subset of the chronic obstructive pulmonary disease (COPD) target population and to discuss what impact this may have for the generalizability and implementation of PR in practice.Material and methods: A review of 26 RCTs included in a Cochrane Review 2007. We analyzed the selection at three different levels: 1) sampling; 2) inclusion and exclusion; 3) and dropout. Results: Of 26 studies only 3 (12%) described the sampling as the number of patients contacted. In these studies 28% completed PR. In all we found, that 75% of the patients suitable for PR programs were omitted due to sampling exclusion and dropout. Most of the study populations are not representative of the target population.Conclusion: The RCTs selected for the Cochrane review gave sparse information about the sampling procedure. The demand for high internal validity in studies on PR reduced their external validity. The patients completing PR programs in RCTs were not drawn from a representative subset of the target population. The ability to draw conclusions relevant to clinical practice from the results of the RCTs on PR is impaired.Keywords: COPD, rehabilitation, selection, dropout, external validit

Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17β-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17β-Estradiol, 17α-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds—tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p′-DDT, p,p′-DDE, endosulfan, chlomequat chloride, and ethanol—varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods

Comparison of shor-term estrogenicity tests for identification of hormone-disrupting chemicals

The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17β-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17β-Estradiol, 17α-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds—tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p′-DDT, p,p′-DDE, endosulfan, chlomequat chloride, and ethanol—varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.This study was supported by grants from the European Commission (Biomedicine and Health Research and Technological Programme, BMH4-CT96-03 14), the Danish Environmental Research Programme (96.01.015.16), and the Danish Medical Research Council (9401656)