Do clinical practice guidelines reflect research evidence?

OBJECTIVES: To examine whether existing clinical practice guidelines (CPGs) for cholesterol testing reflect research evidence and hence may control or reduce costs while maintaining or improving the quality of care. METHODS: A systematic search for published and unpublished cholesterol testing CPGs and independent critical appraisal of the CPGs by two researchers using a standard checklist. RESULTS: In four of the five CPGs analysed, the link between the research evidence and the recommendations was not maintained. The appraisal, local experience and the literature all suggest that panel composition is an important explanation, in that the greater the involvement of clinical experts in the development process of the CPGs, the less the recommendations reflected the research evidence. Even though their participation is important for CPG uptake, clinical expert panels appear to have difficulty limiting CPGs to research-based recommendations. CONCLUSIONS: Existing cholesterol testing CPGs are unlikely to improve the quality of care while controlling or reducing costs. The problem lies not with guideline implementation but with the guidelines themselves. It is unclear how best to ensure that recommendations reflect research evidence but this is likely to require significant and progressive changes to the current guideline development process, including a redefinition of the clinical experts' role.     

Physical activity and ethnic differences in hypertension prevalence in the United States

BACKGROUND: In the United States, non-Hispanic blacks have higher rates of hypertension than other ethnic groups. In addition, they have higher rates of physical inactivity, a behavior linked to high blood pressure. We examined associations between ethnicity, leisure-time physical activity (LTPA), and hypertension prevalence in a representative sample of U.S. adults. METHODS: Using data on 16,246 adults in the third National Health and Nutrition Examination Survey, hypertension prevalence was determined for non-Hispanic white, non-Hispanic black, and Mexican Americans at various levels of LTPA (none, 0.1-4.9 bouts/week at any intensity, 5+ bouts/week of moderate-to-vigorous activity). Logistic regression was used to examine relationships between hypertension prevalence, race, LTPA, and other variables. RESULTS: Hypertension prevalence was significantly less in the most active group, compared with their sedentary peers (odds ratio = 0.73, CI 0.59 to 0.90). Blacks had an odds ratio for hypertension of 1.77 (CI 1.49 to 2.10) compared with non-Hispanic whites, after adjusting for gender, age, income, LTPA, smoking, BMI, salt intake, rural/urban dwelling, and alcohol intake. Mexican Americans had an adjusted odds ratio of 0.75 (CI 0.62 to 0.89), relative to non-Hispanic whites. CONCLUSION: Ethnicity and LTPA are both associated with hypertension prevalence after controlling for each other, as well as other confounders. Thus, race and physical activity are important independent contributors to hypertension prevalence.     

Schizophrenia and genetics: new insights

There is consistent evidence that the principal etiology of schizophrenia involves predisposing genetic factors. Recent years have seen several new insights in the genetics of schizophrenia. Several chromosomal regions show significant evidence that they contain schizophrenia susceptibility genes. A clinically relevant genetic subtype of schizophrenia (22q deletion syndrome) has been identified. There is new evidence that spontaneous mutations may play a role. There are new recommendations for genetic counseling. The progress to date suggests that understanding of a neurodevelopmental pathway from genetic susceptibility to schizophrenia will soon be fundamentally altered by molecular genetic advances in this complex disease.     

Limiting factors for maximum oxygen uptake and determinants of endurance performance

In the exercising human, maximal oxygen uptake (VO2max) is limited by the ability of the cardiorespiratory system to deliver oxygen to the exercising muscles. This is shown by three major lines of evidence: 1) when oxygen delivery is altered (by blood doping, hypoxia, or beta-blockade), VO2max changes accordingly; 2) the increase in VO2max with training results primarily from an increase in maximal cardiac output (not an increase in the a-v O2 difference); and 3) when a small muscle mass is overperfused during exercise, it has an extremely high capacity for consuming oxygen. Thus, O2 delivery, not skeletal muscle O2 extraction, is viewed as the primary limiting factor for VO2max in exercising humans. Metabolic adaptations in skeletal muscle are, however, critical for improving submaximal endurance performance. Endurance training causes an increase in mitochondrial enzyme activities, which improves performance by enhancing fat oxidation and decreasing lactic acid accumulation at a given VO2. VO2max is an important variable that sets the upper limit for endurance performance (an athlete cannot operate above 100% VO2max, for extended periods). Running economy and fractional utilization of VO2max also affect endurance performance. The speed at lactate threshold (LT) integrates all three of these variables and is the best physiological predictor of distance running performance.     

Changes in event-related potentials in a three-stimulus auditory oddball task after mild head injury

Previous research has demonstrated changes in event-related potentials in a variety of cognitive tasks after severe closed head injury. We sought to establish if similar changes were present in patients who had sustained only apparently mild head injury (MHI) by recording event-related potentials in a group of 24 mild head injured and 24 control participants during a three-stimulus auditory target detection task. For this ‘oddball’ task participants were required to press a button every time they heard a rare target tone and to ignore rare novel sounds and frequent non-target tones. Neuropsychological test results indicated that the mild head injured group had mild memory and attention impairments. Analysis of behavioural performance on the three-stimulus ‘oddball’ task showed no difference in reaction times or error rates between the two groups. Target condition N2 deflections appeared to be larger in the mild head injured but peak amplitude measures revealed that this effect was not significant. There were no significant differences in the amplitude or latency of the P3b evoked by target stimuli or the P3a evoked by novel stimuli. However, a putative ‘O-wave’ or ‘reorienting negativity’ following the P3a was more negative in the mild head injured group suggesting increased activation of components of the attention network. These findings lend support to the hypothesis that MHI can cause subtle cognitive impairments that are associated with abnormal allocation of attention resources in the context of normal behavioural performance.     

Induction of chromosome-specific aneuploidy and micronuclei in human lymphocytes by metabolites of 1,3-butadiene

1,3-Butadiene is a carcinogen in rodents, but its potential carcinogenicity to humans remains controversial. Numerous studies have shown that butadiene and its metabolites cause sister chromatid exchanges in vitro and in vivo. To test for other types of genotoxicity, the micronucleus assay and fluorescence in situ hybridization (FISH) have been used to detect chromosome damage in human lymphocytes caused by two reactive metabolites of butadiene, diepoxybutane (DEB) and monoepoxybutene (MEB). DEB (0.5-5.0 microM) significantly increased micronucleus formation 4- to 6-fold (P <0.01) and MEB (1-500 microM) by 2- to 4-fold (P <0.01) over control levels. The ability of DEB and MEB to induce aneuploidy of chromosomes 7, 8, 12, and X was examined using dual-color FISH in both interphase and metaphase cells. These chromosomes were chosen because of their involvement in leukemogenesis. Both DEB and MEB caused dose-dependent increases in hyperdiploidy of chromosomes 12 and X, but had no discernible effect on chromosomes 7 and 8. These results suggest that DEB and MEB cause chromosome-specific aneuploidy in human cells. If formed in sufficient amounts, DEB and MEB may produce chromosome damage of the type found in leukemia following exposure to butadiene.