The POWER-tool: Recommendations for involving patient representatives in choosing relevant outcome measures during rare disease clinical trial design.

In clinical trials, it is relevant to ask patients and/or their caregivers which aspects concerning their disease they consider important to measure when a new intervention is being investigated. Those aspects, useful as outcome measures in a trial, are of pivotal importance for the result of the trial and the subsequent decision-making. In rare diseases the choice of outcome measures may be even more important, due to the small numbers and heterogeneity of the patients that are included. We have developed a tool to involve patients in the determination of outcome measures and the choice of measurement instruments. This tool was developed together with a patient think tank, consisting of a group of rare disease patient representatives, and by interviewing end users. We have road-tested our tool in an ongoing trial, and evaluated it during a focus group meeting. The tool consists of three steps: 1) Preparation, 2) Consultation of patients, 3) Follow-up during which the consultation results are implemented in the trial design. The tool provides guidelines for researchers to include the patient's opinion in the choice of outcome measures in the trial design stage. We describe the development of the POWER-tool (Patient participation in Outcome measure WEighing for Rare diseases), and first experiences of the tool in an ongoing trial.

Semi-automatic measurement of left ventricular function on dual source computed tomography using five different software tools in comparison with magnetic resonance imaging.

PURPOSE: To compare left ventricular (LV) function assessment using five different software tools on the same dual source computed tomography (DSCT) datasets with the results of MRI. MATERIALS AND METHODS: Twenty-six patients, undergoing cardiac contrast-enhanced DSCT were included (20 men, mean age 59±12 years). Reconstructions were made at every 10% of the RR-interval. Function analysis was performed with five different, commercially available workstations. In all software tools, semi-automatic LV function measurements were performed, with manual corrections if necessary. Within 0-22 days, all 26 patients were scanned on a 1.5 T MRI-system. Bland-Altman analysis was performed to calculate limits of agreement between DSCT and MRI. Pearson's correlation coefficient was calculated to assess the correlation between the different DSCT software tools and MRI. Repeated measurements were performed to determine intraobserver and interobserver variability. RESULTS: For all five DSCT workstations, mean LV functional parameters correlated well with measurements on MRI. Bland-Altman analysis of the comparison of DSCT and MRI showed acceptable limits of agreement. Best correlation and limits of agreement were obtained by DSCT software tools with software algorithms comparable to MRI software. CONCLUSION: The five different DSCT software tools we examined have interchangeable results of LV functional parameters compared to regularly analysed results by MRI. The best correlation and the narrowest limits of agreement were found when the same software algorithm was used for both DSCT and MRI examinations, therefore our advice for clinical practice is to always evaluate images with the same type of post-processing tools in follow-up.

Breast magnetic resonance imaging as a problem-solving modality in mammographic BI-RADS 3 lesions.

The probability of a mammographic Breast Imaging Reporting and Data System (BI-RADS) 3 lesion being cancer is considered to be less than 2%. Therefore, the work-up of a mammographic BI-RADS 3 lesion should be biopsy or follow-up mammography after 6 months. However, most patients referred for biopsy have benign disease. Although the negative predictive value (NPV) of magnetic resonance imaging (MRI) is highest of all imaging techniques, it is not yet common practice to use breast MRI as a problem-solving modality to exclude patients for further diagnostic work-up. Therefore, in this meta-analysis the usefulness of breast MRI as a problem-solving modality in mammographic BI-RADS 3 lesions is investigated. After a systematic search only 5 out of 61 studies met the inclusion criteria. The NPV in 2 of those studies was reported to be 100%. It was concluded that MRI can be used as an adjunctive tool to mammographic BI-RADS 3 findings to exclude patients for further diagnostic work-up. The other 3 studies assessed the accuracy of MRI in mammographic BI-RADS 3 microcalcifications. These studies reported an NPV of MRI between 76% and 97%. Therefore, MRI cannot be implemented as a diagnostic tool to evaluate mammographic microcalcifications at this time. The first solid data indicate that breast MRI might be useful as a problem-solving modality to exclude patients with non-calcified mammographic BI-RADS 3 lesions for further diagnostic work-up. However, further research is needed to verify these results.

[Granted, undecided, withdrawn and refused requests for euthanasia and physician-assisted suicide in the Netherlands; 2000-2002]. / Ingewilligde, onbesliste, ingetrokken en geweigerde verzoeken om euthanasie en hulp bij zelfdoding in Nederland; 2000-2002.

OBJECTIVE: To determine the characteristics of patients who request euthanasia or physician-assisted suicide and whether these characteristics differ among those whose request is granted, those who die before the procedure, those who die before completion of the approval process, those who withdraw their request, and lastly, those whose request is refused by the physician. DESIGN: Questionnaire study. METHOD: All general practitioners in 18 of the 23 Dutch general practitioner districts received a written questionnaire in which they were asked to describe the most recent request for euthanasia or physician-assisted suicide that they had received (response 60%, n=3614). RESULTS: Of all explicit requests, 44% resulted in euthanasia or physician-assisted suicide. Thirteen percent of patients died before the procedure, 13% died before completion of the approval process, 13% withdrew their request and 12% were refused by the physician. The most prominent symptoms were 'feeling bad', 'tiredness', and 'lack of appetite'. The most frequently mentioned reasons for requesting euthanasia or physician-assisted suicide were 'pointless suffering', 'loss of dignity', and 'general weakness'. The patients' situation met the official requirements for accepted practice best in the group of requests that resulted in euthanasia or physician-assisted suicide and least in the group of refused requests. A lesser degree of competence and less unbearable and hopeless suffering had the strongest associations with the refusal of a request. CONCLUSION: The complexity of euthanasia or physician-assisted suicide decision-making is reflected in the fact that, besides granting and refusing a request, 3 other situations could be distinguished. The decisions physicians made, the reasons for their decisions and the way they arrived at their decisions appeared to be based on patient evaluations and on the official requirements for accepted practice.