Contaminations occurring in fungal PCR assays.
Successful in vitro amplification of fungal DNA in clinical specimens has been reported recently. In a collaboration among five European centers, the frequency and risk of contamination due to airborne spore inoculation or carryover contamination in fungal PCR were analyzed. The identities of all contaminants were specified by cycle sequencing and GenBank analysis. Twelve of 150 PCR assays that together included over 2,800 samples were found to be contaminated (3.3% of the negative controls were contaminated during the DNA extraction, and 4.7% of the PCR mixtures were contaminated during the amplification process). Contaminants were specified as Aspergillus fumigatus, Saccharomyces cerevisiae, and Acremonium spp. Further analysis showed that commercially available products like zymolyase powder or 10x PCR buffer may contain fungal DNA. In conclusion, the risk of contamination is not higher in fungal PCR assays than in other diagnostic PCR-based assays if general precautions are taken. (+info)
Durability of tobacco control activities in 11 north American communities: life after the Community Intervention Trial for Smoking Cessation (COMMIT).
Durability of tobacco control activities in the 11 intervention sites of the Community Intervention Trial for Heavy Smokers (COMMIT) was examined. Although continuation of COMMIT activities was not a major goal, all communities made plans to continue some tobacco control activity. Information was gathered at focus groups of former COMMIT volunteers and staff who were assembled in each community and asked to describe tobacco control activities in their communities during the past 12-16 months-the period after the termination of COMMIT funding. It was found that a tobacco coalition, board or other structure was still operating in nine of the 11 communities and 10 had some level of paid staff dedicated to smoking control. There was also substantial activity in three of the four channels that COMMIT used as an intervention framework: worksites, public education and cessation resources. Many communities were currently engaged in considerable smoking control activity aimed at youth, an area that was intentionally de-emphasized by COMMIT. Implications for the durability of health promotion programs by communities are discussed. (+info)
Multisite formative assessment for the Pathways study to prevent obesity in American Indian schoolchildren.
We describe the formative assessment process, using an approach based on social learning theory, for the development of a school-based obesity-prevention intervention into which cultural perspectives are integrated. The feasibility phase of the Pathways study was conducted in multiple settings in 6 American Indian nations. The Pathways formative assessment collected both qualitative and quantitative data. The qualitative data identified key social and environmental issues and enabled local people to express their own needs and views. The quantitative, structured data permitted comparison across sites. Both types of data were integrated by using a conceptual and procedural model. The formative assessment results were used to identify and rank the behavioral risk factors that were to become the focus of the Pathways intervention and to provide guidance on developing common intervention strategies that would be culturally appropriate and acceptable to all sites. (+info)
Statistical power of MRI monitored trials in multiple sclerosis: new data and comparison with previous results.
OBJECTIVES: To evaluate the durations of the follow up and the reference population sizes needed to achieve optimal and stable statistical powers for two period cross over and parallel group design clinical trials in multiple sclerosis, when using the numbers of new enhancing lesions and the numbers of active scans as end point variables. METHODS: The statistical power was calculated by means of computer simulations performed using MRI data obtained from 65 untreated relapsing-remitting or secondary progressive patients who were scanned monthly for 9 months. The statistical power was calculated for follow up durations of 2, 3, 6, and 9 months and for sample sizes of 40-100 patients for parallel group and of 20-80 patients for two period cross over design studies. The stability of the estimated powers was evaluated by applying the same procedure on random subsets of the original data. RESULTS: When using the number of new enhancing lesions as the end point, the statistical power increased for all the simulated treatment effects with the duration of the follow up until 3 months for the parallel group design and until 6 months for the two period cross over design. Using the number of active scans as the end point, the statistical power steadily increased until 6 months for the parallel group design and until 9 months for the two period cross over design. The power estimates in the present sample and the comparisons of these results with those obtained by previous studies with smaller patient cohorts suggest that statistical power is significantly overestimated when the size of the reference data set decreases for parallel group design studies or the duration of the follow up decreases for two period cross over studies. CONCLUSIONS: These results should be used to determine the duration of the follow up and the sample size needed when planning MRI monitored clinical trials in multiple sclerosis. (+info)
Plasma lycopene concentrations in humans are determined by lycopene intake, plasma cholesterol concentrations and selected demographic factors.
Higher plasma lycopene concentrations have been associated with a reduced risk of several chronic diseases. Determinants of lycopene concentrations in humans have received limited attention. We had blood lycopene concentrations and lycopene consumption data available from 111 participants in a two-center cancer prevention trial involving beta-carotene and examined determinants of plasma lycopene levels cross-sectionally. The median plasma lycopene level was 0.59 micromol/L (range 0.07-1.79). Low plasma concentrations of lycopene were associated with the following variables in univariate analyses: study site (Florida lower than Connecticut, P = 0.001), being nonmarried (P = 0.02), having lower income (P = 0.003), being nonwhite race/ethnicity (P = 0.03), having lower dietary lycopene intake (r = 0.29, P = 0.002), having lower plasma cholesterol (r = 0. 43, P = 0.0001) and triglyceride levels (r = 0.26, P = 0.005), and consuming less vitamin C (r = 0.20, P = 0.03). Women had slightly higher plasma lycopene levels than men (0.65 vs. 0.58 micromol/L; P = 0.31), despite lower dietary intake of lycopene (1,040 vs. 1,320 microg/d; P = 0.50). Plasma lycopene levels did not differ in smokers and nonsmokers. In stepwise regression analyses, the determinants of plasma lycopene were plasma cholesterol, dietary lycopene, and marital status; these three variables explained 26% of the variance in plasma lycopene. Relatively few lifestyle and demographic factors were important determinants of plasma lycopene levels, with plasma cholesterol, marital status, and lycopene intake being of greatest importance. (+info)
The natural history of multiple sclerosis: a geographically based study. 6. Applications to planning and interpretation of clinical therapeutic trials in primary progressive multiple sclerosis.
The natural history of primary progressive multiple sclerosis (PP-multiple sclerosis) recently has been defined in a geographically based multiple sclerosis population. For a series of prognostically defined hypothetical entry criteria based upon current trends in presentation to the London Multiple Sclerosis Clinic, we determined the number of patients who would have been trial eligible. Using 23 year mean longitudinal natural history data, we identified the observed rate of deterioration for frequently used trial endpoints. Hypothetical entry criteria were based on the practical considerations which would attend the execution of clinical trials in progressive multiple sclerosis. We then developed a series of sample size tables giving the number of patients with PP-multiple sclerosis and the length of observation that would be required to detect a significant result (P = 0.05) for a 25, 50 and 75% decrease in the median time to progression with 80 or 90% power, with treatment efficacy based upon the ability to slow progression on the disability status score. It is expected that the considerations outlined here will prove useful for both trial design and interpretation of trials in PP-multiple sclerosis which will require multi-centre collaborative efforts. (+info)
Management of renovascular disease: a review of renal artery stenting in ten studies.
To evaluate the efficacy and safety of renal artery stents in renovascular disease, we identified 10 descriptive studies containing sufficient information for systematic evaluation. No randomized comparisons of stenting with angioplasty or with surgery were found. Overall, stents were placed in 416 renal arteries in 379 patients, mean age 64 years (range 27-84), 56% male. Of the stenoses, 97% were atheromatous (inter-study range 71-100%), 80% ostial (22-100%) and 31% bilateral (12-87%). The clinical indication for stenting was usually hypertension with or without mild renal impairment. Radiological indications for stenting were: narrowing of > or = 50% (in 9/10 studies) as a result of elastic recoil (58%) or dissection (2%) at the time of angioplasty; restenosis some time after angioplasty (15%); or as a primary procedure (25%). Technical success was reported in 96-100% of procedures. Restenosis (> or = 50% narrowing), evaluated in 312/416 (75%) arteries, generally between 6 and 12 months, was 16% overall. Hypertension was cured by stenting (DBP < or = 90 mmHg on no treatment) in 34/379 (9%) overall and in 34/207 (16%) of those whose renal function was normal initially. Six of 379 (1.6%) patients died within 30 days of stenting, but in only two (0.5%) was death judged to be procedure-related. Complications, other than those which led to dialysis, occurred in 42/379 (13%) patients, one third requiring intervention, ranging from blood transfusion to a surgical bypass procedure. Renal function as judged by serum creatinine concentration (SCC) improved in 26%, stabilized in 48% and deteriorated in 26% of patients whose renal function was impaired initially (SCC > 133 mumol/l). In one study, with average baseline SCC > 200 mumol/l, successful stenting slowed the rate of progression of renal failure when renal function was deteriorating beforehand. Nine of 379 (2.4%) patients, including 7/14 (50%) whose SCC was > or = 400 mumol/l initially, required dialysis after stenting. Stenting should be offered by specialist centres as a secondary procedure for unsuccessful angioplasty, or restenosis following angioplasty, to patients with renovascular disease and uncontrolled hypertension, advancing renal failure or pulmonary oedema. (+info)
The impact of an end-point committee in a large multicentre, randomized, placebo-controlled clinical trial: results with and without the end-point committee's final decision on end-points.
BACKGROUND: A multicentre study permits rapid recruitment of a large number of patients. However, there is a risk of heterogeneities in end-point evaluations, as complex definitions of criteria are interpreted by several local investigators from different hospitals. Reports discussing end-point evaluation are sparse. The TRIM trial was a multicentre trial of a thrombin inhibitor in patients with unstable angina or non-Q myocardial infarction. In this study, an independent end-point committee evaluated all the reported events of death, acute myocardial infarction and refractory angina pectoris in order to obtain uniform judgements of major end-points. STUDY AIMS: To describe the work of the end-point committee, to analyse its possible effect on the final study results and to discuss the impact on the design of future trials. METHOD: The end-point committee consisted of four members, one from each participating country. After the data were processed by the study monitors, completed case record forms and patient files for patients with reported end-points were mailed to the national member of the end-point committee for judgement. The end-point committee met regularly and made final decisions about the end-points. The work of the end-point committee was documented on a separate case record form. RESULTS: The end-point committee assessed 246 events of death, acute myocardial infarction and refractory angina pectoris in 187 of the 1209 patients (15.5%) in the TRIM trial. Misinterpretation of the index event, an inclusion myocardial infarction, as an early cardiac event was found in 12 patients. After end-point committee judgements, the number of patients with acute myocardial infarction or refractory angina pectoris during 30 days of follow-up was reduced from 177 to 153 (13. 6% reduction). The classification of events was changed in 53 of 187 patients (28.3%) with death, acute myocardial infarction or refractory angina pectoris. The data assessed by the safety committee was significantly different from the final database after end-point committee judgements. CONCLUSION: The end-point committee corrected misinterpretations in such a high proportion of cases that the final results differed significantly from the preliminary results delivered to the safety committee. End-point judgements by an end-point committee should be performed in multicentre clinical trials to improve the quality and reliability of study results. (+info)