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Papers by Paul Krabbe
After 40 years of deriving metric values for health status or health-related quality of life, the... more After 40 years of deriving metric values for health status or health-related quality of life, the effective quantification of subjective health outcomes is still a challenge. Here, two of the best measurement tools, the discrete choice and the Rasch model, are combined to create a new model for deriving health values. First, existing techniques to value health states are briefly discussed followed by a reflection on the recent revival of interest in patients' experience with regard to their possible role in health measurement. Subsequently, three basic principles for valid health measurement are reviewed, namely unidimensionality, interval level, and invariance. In the main section, the basic operation of measurement is then discussed in the framework of probabilistic discrete choice analysis (random utility model) and the psychometric Rasch model. It is then shown how combining the main features of these two models yields an integrated measurement model, called the multi-attribute preference response (MAPR) model, which is introduced here. This new model transforms subjective individual rank data into a metric scale using responses from patients who have experienced certain health states. Its measurement mechanism largely prevents biases such as adaptation and coping. Several extensions of the MAPR model are presented. The MAPR model can be applied to a wide range of research problems. If extended with the selfselection of relevant health domains for the individual patient, this model will be more valid than existing valuation techniques. Citation: Krabbe PFM (2013) A Generalized Measurement Model to Quantify Health: The Multi-Attribute Preference Response Model. PLoS ONE 8(11): e79494.
Journal of Nuclear Medicine, 2009
In this study, we examined the in vivo relationship between functional tumor vasculature, determi... more In this study, we examined the in vivo relationship between functional tumor vasculature, determined by dynamic contrast-enhanced (DCE-) MRI, and tumor metabolism, determined by dynamic 18 F-FDG PET, during cytotoxic treatment of patients with colorectal liver metastases. Methods: Twenty-three patients underwent DCE-MRI (using gadolinium dimeglumine) and dynamic 18 F-FDG PET at baseline and after 3 treatment cycles, unless treatment was terminated because of toxicity. Parameters for vasculature (rate constant between extravascular extracellular space and blood plasma [k ep ] and volume transfer constant [K trans ]), extracellular space (v e ), tumor size (the maximal axial diameter of each included lesion [MAD]), and metabolism (glucose metabolic rates [MR glc ]) were derived, and changes during treatment were correlated. Overall survival (OS) and progression-free survival (PFS) served as outcome measures for the predictive abilities of pretreatment parameters and of treatment-related parameter changes. Results: Pretreatment MR glc and MAD were individually predictive for OS and PFS. During treatment, K trans increased significantly, but this increase could not be confirmed in a lesion-by-lesion analysis. MR glc decreased significantly (P , 0.001). No correlations were found for changes in DCE-MRI parameters and DMR glc . No relationship was found between changes in DCE-MRI parameters and OS or PFS. DMR glc was able to predict OS (P 5 0.008) after correction for confounders. Conclusion: The efficacy of cytotoxic chemotherapy assessed by reduction in tumor metabolism does not depend on pretreatment properties of the tumor vasculature determined by DCE-MRI. Cytotoxic chemotherapy does not alter DCE-MRI-derived properties of tumor vasculature but decreases glucose consumption of tumor cells.
Value in Health, 2014
Objectives: To describe the research that has been undertaken by the EuroQol Group to improve cur... more Objectives: To describe the research that has been undertaken by the EuroQol Group to improve current methods for health state valuation, to summarize the results of an extensive international pilot program, and to outline the key elements of the five-level EuroQol five-dimensional (EQ-5D-5L) questionnaire valuation protocol, which is the culmination of that work. Methods: To improve on methods of health state valuation for the EQ-5D-5L questionnaire, we investigated the performance of different variants of time tradeoff and discrete choice tasks in a multinational setting. We also investigated the effect of three modes of administration on health state valuation: group interviews, online self-completion, and faceto-face interviews. Results: The research program provided the basis for the EQ-5D-5L questionnaire valuation protocol. Two different types of tasks are included to derive preferences: a newly developed composite time trade-off task and a forced-choice paired comparisons discrete choice task. Furthermore, standardized blocked designs for the selection of the states to be valued by participants were created and implemented together with all other elements of the valuation protocol in a digital aid, the EuroQol Valuation Technology, which was developed in conjunction with the protocol. Conclusions: The EuroQol Group has developed a standard protocol, with accompanying digital aid and interviewer training materials, that can be used to create value sets for the EQ-5D-5L questionnaire. The use of a well-described, consistent protocol across all countries enhances the comparability of value sets between countries, and allows the exploration of the influence of cultural and other factors on health state values.
EQ-5D concepts and methods: A developmental history, 2005
In this discussion paper we bring together a number of considerations which might be relevant to ... more In this discussion paper we bring together a number of considerations which might be relevant to gain insight into the use of negative values for EQ-5D health states. This seems relevant since the introduction of negative values will inevitably lead to a discussion about these values, and the background to these figures has to be explained and documented. In theory and in practice it is possible to avoid the use of negative values even in cases where states are considered to be worse than death (WTD). However if one prefers to avoid explicit negative values for EQ-5D health states, other issues arise and it seems to us to be important to have an understanding of these issues. It is possible to understand the nature of the issues involved because the results and data of the MVH project are available. We consider this project as a milestone in the work on quality of life measurement and wish to make explicit our admiration for this scientific endeavour. It is only because of this project that the EuroQol Group is in a position to discuss tariffs based on a large empirical study in which several measurement methods were applied. Our discussion is thus to be seen as an effort to gain insight into the subtleties of the subject and we hope to contribute to the fruitful and widespread use of the results of the project. The issues raised by the negative values for EQ-5D health states are complex and relevant arguments derive from the fields of psychology, statistics, economics, ethics, and political science. Since it is nearly impossible for somebody who is trained in one of these disciplines to have a clear understanding of all the issues, a discussion at the level of the Group seems to be a fruitful way to obtain a fuller picture. In this paper, the UK Al and A2 tariffs are chosen as a starting point. The results are derived using the Time Trade Off (TTO) method and will be seen by the EuroQol Group and others as nicely fitting into the framework of economic project appraisal. Some elements might also be relevant for VAS tariffs, but for the purposes of this discussion it was decided to concentrate on the Al and A2 tariffs.
The European Journal of Health Economics, 2003
The European Journal of Health Economics, 2003
Annals of Clinical Microbiology and Antimicrobials, 2007
To determine the true incidence of hGISA/GISA and its consequent clinical impact, methods must be... more To determine the true incidence of hGISA/GISA and its consequent clinical impact, methods must be defined that will reliably and reproducibly discriminate these resistant phenotypes from vancomycin susceptible S. aureus (VSSA).
Addiction Biology, 2003
The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification... more The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioiddependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p 5 0.01) and 2 months (RD-GA 93% vs. SMT 33%, p 5 0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p = 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA.
The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification... more The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioiddependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p 5 0.01) and 2 months (RD-GA 93% vs. SMT 33%, p 5 0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p = 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA.
European Journal of Clinical Microbiology & Infectious Diseases, 2007
Complicating infectious foci resulting from haematogenous or local spread of microorganisms are o... more Complicating infectious foci resulting from haematogenous or local spread of microorganisms are observed frequently in patients with Staphylococcus aureus bacteraemia (SAB) or Streptococcus species bacteraemia (SSB). The aim of this study was to compare the epidemiology of complicating infectious foci during SAB and SSB in a university hospital in The Netherlands. The charts of all adult patients diagnosed with SAB or SSB (except for Streptococcus pneumoniae bacteraemia) from July 2002 until December 2004 were reviewed retrospectively. Overall, 180 immunocompetent patients were identified, 127 with SAB and 53 with SSB. The percentage of patients with complicating infectious foci (39% of SAB patients, 25% of SSB patients) did not differ significantly between the groups. Endocarditis and cerebral involvement, however, were significantly more common in the SSB group. Of all complicating infectious foci, 32% lacked guiding signs or symptoms and 10% were detected only at autopsy. Factors associated with the development of complicating infectious foci were a delay in treatment for more than 48 h after the onset of symptoms, community acquisition, persistently positive blood cultures, congenital heart disease, and the presence of foreign bodies or prosthetic valves. Infection-related mortality was 18% in SAB patients and 11% in SSB patients and was significantly higher in patients with complicating infectious foci (29 vs. 9%). In conclusion, complicating infectious foci develop in approximately one-third of all patients with Eur J Clin Microbiol Infect Dis (2007) 26:105-113 SAB and SSB. An active approach that entails searching for the complicating infectious foci is warranted in these patients, because only two-thirds of complicated infectious foci have guiding symptoms or signs, and infection-related mortality is significantly increased in patients with complicating infectious foci compared to patients without these infections.
European Journal of Nuclear Medicine and Molecular Imaging, 2007
Purpose Since 18F-fluorodeoxyglucose (FDG) accumulates in neoplastic cells and in activated infl... more Purpose Since 18F-fluorodeoxyglucose (FDG) accumulates in neoplastic cells and in activated inflammatory cells, positron emission tomography (PET) with FDG could be valuable in diagnosing patients with fever of unknown origin (FUO). The aim of this study was to validate the use of FDG-PET as part of a structured diagnostic protocol in the general patient population with FUO. Methods From December 2003 to
Medicine, 2007
We conducted a prospective study to update our knowledge of fever of unknown origin (FUO) and to ... more We conducted a prospective study to update our knowledge of fever of unknown origin (FUO) and to explore the utility of a structured diagnostic protocol. From December 2003 to July 2005, 73 patients with FUO were recruited from 1 university hospital (n = 40) and 5 community hospitals (n = 33) in the same region in The Netherlands. FUO was
Background: despite firm recommendations to perform echocardiography in high-risk patients with g... more Background: despite firm recommendations to perform echocardiography in high-risk patients with gram-positive bacteraemia, routine echocardiography is not embedded in daily practice in many settings. the aim of this study was to evaluate whether a regime including routine echocardiography results in better outcome. Methods: a total of 115 patients with gram-positive bacteraemia and at least one risk factor for developing metastatic infection were prospectively included. routine echocardiography was advocated and facilitated in these patients. results were compared with a matched historical control group of 230 patients in whom echocardiography was performed at the discretion of the attending physician. endocarditis was diagnosed according to the duke criteria. results: echocardiography was performed more often in the study group (82 vs 27%, p<0.001). endocarditis was diagnosed more often among study patients, 22/115 (19%) vs 17/230 (7%) in the control group (p=0.002). in the study group echocardiography revealed vegetations in 22 of 94 (23%) patients, compared with 17 of 64 (27%) control patients (p=0.7). in the absence of heart murmurs, 70% of patients underwent echocardiography in the study group against 21% in the control group (p<0.001). no differences in adherence to american Heart association guidelines concerning treatment of endocarditis were noticed. in patients with endocarditis, overall mortality was 23% in study patients and 59% in controls (p=0.04). Conclusion: routinely performed echocardiography in patients with gram-positive bacteraemia resulted in diagnosing endocarditis in a larger proportion of o r i g i n a l a r t i C l e patients, which was associated with a significant decrease in mortality rates. in the past, endocarditis was probably detected in a more advanced stage.
Journal of Nuclear Medicine, 2010
The timely detection of metastatic infectious foci in gram-positive bacteremia is crucial, becaus... more The timely detection of metastatic infectious foci in gram-positive bacteremia is crucial, because these foci often require prolonged antibiotic treatment or drainage. The diagnosis of metastatic infectious foci is difficult because localizing symptoms are often absent. We investigated whether 18 F-FDG PET/CT was able to detect such foci and whether detection influenced clinical outcome. Methods: One hundred fifteen nonneutropenic patients with gram-positive bacteremia were prospectively included. Patients with positive blood cultures growing Staphylococcus aureus, Streptococcus species, or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. 18 F-FDG PET/CT was performed within 2 wk after the first positive blood culture. Abnormal 18 F-FDG uptake had to be confirmed by radiologic, microbiologic, or pathologic studies. Results were compared with a matched historical control group of 230 patients in whom no 18 F-FDG PET/CT was performed. Results: Significantly more patients were diagnosed with metastatic foci in the study group (67.8% vs. 35.7%). Of the imaging investigations performed, 18 F-FDG PET/CT was the first to delineate infectious foci in 35 patients (30%). In the remaining 70%, either symptoms on physical examination or other imaging techniques first revealed infectious foci. The sensitivity, specificity, negative predictive value, and positive predictive value of 18 F-FDG PET/CT were 100%, 87%, 100%, and 89%, respectively. Relapse rates decreased from 7.4% to 2.6% among study patients (P 5 0.09) and from 8.9% to 1.4% in patients with S. aureus (P 5 0.04). Overall mortality after 6 mo decreased from 32.2% to 19.1% in the 18 F-FDG PET/CT group (P 5 0.014). Conclusion: In the diagnostic work-up of high-risk patients with gram-positive bacteremia, 18 F-FDG PET/CT is a valuable technique that results in lower mortality rates. In patients with S. aureus bacteremia, relapse rates decreased significantly after the addition of 18 F-FDG PET/CT.
EQ-5D concepts and methods: A developmental history, 2005
In this discussion paper we bring together a number of considerations which might be relevant to ... more In this discussion paper we bring together a number of considerations which might be relevant to gain insight into the use of negative values for EQ-5D health states. This seems relevant since the introduction of negative values will inevitably lead to a discussion about these values, and the background to these figures has to be explained and documented. In theory and in practice it is possible to avoid the use of negative values even in cases where states are considered to be worse than death (WTD). However if one prefers to avoid explicit negative values for EQ-5D health states, other issues arise and it seems to us to be important to have an understanding of these issues. It is possible to understand the nature of the issues involved because the results and data of the MVH project are available. We consider this project as a milestone in the work on quality of life measurement and wish to make explicit our admiration for this scientific endeavour. It is only because of this project that the EuroQol Group is in a position to discuss tariffs based on a large empirical study in which several measurement methods were applied. Our discussion is thus to be seen as an effort to gain insight into the subtleties of the subject and we hope to contribute to the fruitful and widespread use of the results of the project. The issues raised by the negative values for EQ-5D health states are complex and relevant arguments derive from the fields of psychology, statistics, economics, ethics, and political science. Since it is nearly impossible for somebody who is trained in one of these disciplines to have a clear understanding of all the issues, a discussion at the level of the Group seems to be a fruitful way to obtain a fuller picture. In this paper, the UK Al and A2 tariffs are chosen as a starting point. The results are derived using the Time Trade Off (TTO) method and will be seen by the EuroQol Group and others as nicely fitting into the framework of economic project appraisal. Some elements might also be relevant for VAS tariffs, but for the purposes of this discussion it was decided to concentrate on the Al and A2 tariffs.
Social Science & Medicine, 1994
Journal of Nuclear Medicine, 2007
The aim of this prospective study was to evaluate the value of 18 F-FDG PET for the assessment of... more The aim of this prospective study was to evaluate the value of 18 F-FDG PET for the assessment of chemotherapy response in patients with non-small cell lung cancer. Furthermore, part of the objective of this study was to compare 2 methods to quantify changes in glucose metabolism. Methods: In 51 patients, dynamic 18 F-FDG PET was performed before and at 5-8 wk into treatment. Simplified methods to measure glucose metabolism (standardized uptake value [SUV]) and quantitative measures (metabolic rate of glucose [MR Glu ]), derived from Patlak analysis, were evaluated. The overall survival and progression-free survival with respect to MR Glu and SUV were calculated using Kaplan-Meier estimates. Fractional changes in tumor glucose use were stratified by the median value and also the predefined EORTC (European Organization for Research and Treatment of Cancer) metabolic response criteria, and criteria applying cutoff levels similar to those of RECIST (Response Evaluation Criteria in Solid Tumors) were evaluated. Results: When stratifying at the median value of DMR Glu and DSUV, the difference in overall survival (P 5 0.017 for DMR Glu , P 5 0.018 for DSUV) and progressionfree survival (P 5 0.002 for DMR Glu , P 5 0.0009 for DSUV) was highly significant. When applying the predefined criteria for metabolic response, the cutoff levels as also used for size measurement (RECIST) showed significant differences for DSUV between response categories in progression-free survival (P 5 0.0003) as well as overall survival (P 5 0.027). Conclusion: The degree of chemotherapy-induced changes in tumor glucose metabolism as determined by 18 F-FDG PET is highly predictive for patient outcome, stratifying patients into groups with widely differing overall survival and progression-free survival probabilities. The use of 18 F-FDG PET for therapy monitoring seems clinically feasible, because simplified methods to measure tumor glucose use (SUV) are sufficiently reliable and can replace more complex, quantitative measures (MR Glu ) in this patient population.
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of..., Jan 8, 2010
AIM: In therapy response monitoring by [18F]2-fluoro-2-deoxy-D-glucose positron emission tomograp... more AIM: In therapy response monitoring by [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), different tumor delineations are used, resulting in different values for change in glucose metabolic rate (DMRglu). We propose a technique to compare metabolic rates in a region of interest (ROI) based on fixed volumes rather than on fixed thresholds. This method involves change in lesion size. METHODS: In 49 patients with colorectal carcinoma (CRC) and 50 patients with non-small cell lung carcinoma (NSCLC) scheduled for chemotherapy, FDG-PET was performed at baseline and during chemotherapy. A ROIfixed thresholds was determined by using a 50% threshold on both baseline and follow-up FDG-PET. A ROIfixed volumes was determined by using a 50% threshold, determined on the series with the largest tumor volume. This ROIfixed volumes is used on consecutive scans. Predictive effects of both methods were investigated by survival analysis for overall and progression free survival. R...
Headache: The Journal of Head and Face Pain, 1995
Social Science & Medicine, 1997
The objective of the study was to consider five methods for valuing health states with respect to... more The objective of the study was to consider five methods for valuing health states with respect to their comparability (convergent validity, value functions) and reliability. Valuation tasks were performed by 104 student volunteers using five frequently used valuation methods: standard gamble (SG), time trade-off (TTO), rating scale (RS), willinlgness-to-pay (WTP) and the paired comparisons method (PC). Throughout the study, the EuroQol classification system was used to construct 13 health-state descriptions. Validity was investigated using the multitrait-multimethod (MTMM) methodology. The extent to which results of one method could be predicted by another was examined by transformations. Reliability of the methods was studied parametrically with Generalisability Theory (an ANOVA extension), as well as non-parametrically. Mean values for SG were slightly higher than TTO values. The RS could be distinguished from the other methods. After a simple power transformation, the RS values were found to be close to SG and TTO. Mean values of WTP were linearly related to SG and TTO, except at the extremes of the scale. However, the reliability of WTP was low and the number of inconsistencies substantial. Valuations made by the RS proved to be the most reliable. Paired comparisons did not provide stable results. In conclusion, the results of the parametric transformation function between RS and SG/TTO provide evidence to justify the current use of RS (with transformations) not only for reasons of feasibility and reliability but also for reasons of comparability. A definite judgement on PC requires data of a complete design. Due to the specific structure of the correlation matrix which is inherent in valuing health states, we believe that full MTMM is not applicable for the standard analysis of health-state valuations.
After 40 years of deriving metric values for health status or health-related quality of life, the... more After 40 years of deriving metric values for health status or health-related quality of life, the effective quantification of subjective health outcomes is still a challenge. Here, two of the best measurement tools, the discrete choice and the Rasch model, are combined to create a new model for deriving health values. First, existing techniques to value health states are briefly discussed followed by a reflection on the recent revival of interest in patients' experience with regard to their possible role in health measurement. Subsequently, three basic principles for valid health measurement are reviewed, namely unidimensionality, interval level, and invariance. In the main section, the basic operation of measurement is then discussed in the framework of probabilistic discrete choice analysis (random utility model) and the psychometric Rasch model. It is then shown how combining the main features of these two models yields an integrated measurement model, called the multi-attribute preference response (MAPR) model, which is introduced here. This new model transforms subjective individual rank data into a metric scale using responses from patients who have experienced certain health states. Its measurement mechanism largely prevents biases such as adaptation and coping. Several extensions of the MAPR model are presented. The MAPR model can be applied to a wide range of research problems. If extended with the selfselection of relevant health domains for the individual patient, this model will be more valid than existing valuation techniques. Citation: Krabbe PFM (2013) A Generalized Measurement Model to Quantify Health: The Multi-Attribute Preference Response Model. PLoS ONE 8(11): e79494.
Journal of Nuclear Medicine, 2009
In this study, we examined the in vivo relationship between functional tumor vasculature, determi... more In this study, we examined the in vivo relationship between functional tumor vasculature, determined by dynamic contrast-enhanced (DCE-) MRI, and tumor metabolism, determined by dynamic 18 F-FDG PET, during cytotoxic treatment of patients with colorectal liver metastases. Methods: Twenty-three patients underwent DCE-MRI (using gadolinium dimeglumine) and dynamic 18 F-FDG PET at baseline and after 3 treatment cycles, unless treatment was terminated because of toxicity. Parameters for vasculature (rate constant between extravascular extracellular space and blood plasma [k ep ] and volume transfer constant [K trans ]), extracellular space (v e ), tumor size (the maximal axial diameter of each included lesion [MAD]), and metabolism (glucose metabolic rates [MR glc ]) were derived, and changes during treatment were correlated. Overall survival (OS) and progression-free survival (PFS) served as outcome measures for the predictive abilities of pretreatment parameters and of treatment-related parameter changes. Results: Pretreatment MR glc and MAD were individually predictive for OS and PFS. During treatment, K trans increased significantly, but this increase could not be confirmed in a lesion-by-lesion analysis. MR glc decreased significantly (P , 0.001). No correlations were found for changes in DCE-MRI parameters and DMR glc . No relationship was found between changes in DCE-MRI parameters and OS or PFS. DMR glc was able to predict OS (P 5 0.008) after correction for confounders. Conclusion: The efficacy of cytotoxic chemotherapy assessed by reduction in tumor metabolism does not depend on pretreatment properties of the tumor vasculature determined by DCE-MRI. Cytotoxic chemotherapy does not alter DCE-MRI-derived properties of tumor vasculature but decreases glucose consumption of tumor cells.
Value in Health, 2014
Objectives: To describe the research that has been undertaken by the EuroQol Group to improve cur... more Objectives: To describe the research that has been undertaken by the EuroQol Group to improve current methods for health state valuation, to summarize the results of an extensive international pilot program, and to outline the key elements of the five-level EuroQol five-dimensional (EQ-5D-5L) questionnaire valuation protocol, which is the culmination of that work. Methods: To improve on methods of health state valuation for the EQ-5D-5L questionnaire, we investigated the performance of different variants of time tradeoff and discrete choice tasks in a multinational setting. We also investigated the effect of three modes of administration on health state valuation: group interviews, online self-completion, and faceto-face interviews. Results: The research program provided the basis for the EQ-5D-5L questionnaire valuation protocol. Two different types of tasks are included to derive preferences: a newly developed composite time trade-off task and a forced-choice paired comparisons discrete choice task. Furthermore, standardized blocked designs for the selection of the states to be valued by participants were created and implemented together with all other elements of the valuation protocol in a digital aid, the EuroQol Valuation Technology, which was developed in conjunction with the protocol. Conclusions: The EuroQol Group has developed a standard protocol, with accompanying digital aid and interviewer training materials, that can be used to create value sets for the EQ-5D-5L questionnaire. The use of a well-described, consistent protocol across all countries enhances the comparability of value sets between countries, and allows the exploration of the influence of cultural and other factors on health state values.
EQ-5D concepts and methods: A developmental history, 2005
In this discussion paper we bring together a number of considerations which might be relevant to ... more In this discussion paper we bring together a number of considerations which might be relevant to gain insight into the use of negative values for EQ-5D health states. This seems relevant since the introduction of negative values will inevitably lead to a discussion about these values, and the background to these figures has to be explained and documented. In theory and in practice it is possible to avoid the use of negative values even in cases where states are considered to be worse than death (WTD). However if one prefers to avoid explicit negative values for EQ-5D health states, other issues arise and it seems to us to be important to have an understanding of these issues. It is possible to understand the nature of the issues involved because the results and data of the MVH project are available. We consider this project as a milestone in the work on quality of life measurement and wish to make explicit our admiration for this scientific endeavour. It is only because of this project that the EuroQol Group is in a position to discuss tariffs based on a large empirical study in which several measurement methods were applied. Our discussion is thus to be seen as an effort to gain insight into the subtleties of the subject and we hope to contribute to the fruitful and widespread use of the results of the project. The issues raised by the negative values for EQ-5D health states are complex and relevant arguments derive from the fields of psychology, statistics, economics, ethics, and political science. Since it is nearly impossible for somebody who is trained in one of these disciplines to have a clear understanding of all the issues, a discussion at the level of the Group seems to be a fruitful way to obtain a fuller picture. In this paper, the UK Al and A2 tariffs are chosen as a starting point. The results are derived using the Time Trade Off (TTO) method and will be seen by the EuroQol Group and others as nicely fitting into the framework of economic project appraisal. Some elements might also be relevant for VAS tariffs, but for the purposes of this discussion it was decided to concentrate on the Al and A2 tariffs.
The European Journal of Health Economics, 2003
The European Journal of Health Economics, 2003
Annals of Clinical Microbiology and Antimicrobials, 2007
To determine the true incidence of hGISA/GISA and its consequent clinical impact, methods must be... more To determine the true incidence of hGISA/GISA and its consequent clinical impact, methods must be defined that will reliably and reproducibly discriminate these resistant phenotypes from vancomycin susceptible S. aureus (VSSA).
Addiction Biology, 2003
The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification... more The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioiddependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p 5 0.01) and 2 months (RD-GA 93% vs. SMT 33%, p 5 0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p = 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA.
The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification... more The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioiddependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p 5 0.01) and 2 months (RD-GA 93% vs. SMT 33%, p 5 0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p = 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA.
European Journal of Clinical Microbiology & Infectious Diseases, 2007
Complicating infectious foci resulting from haematogenous or local spread of microorganisms are o... more Complicating infectious foci resulting from haematogenous or local spread of microorganisms are observed frequently in patients with Staphylococcus aureus bacteraemia (SAB) or Streptococcus species bacteraemia (SSB). The aim of this study was to compare the epidemiology of complicating infectious foci during SAB and SSB in a university hospital in The Netherlands. The charts of all adult patients diagnosed with SAB or SSB (except for Streptococcus pneumoniae bacteraemia) from July 2002 until December 2004 were reviewed retrospectively. Overall, 180 immunocompetent patients were identified, 127 with SAB and 53 with SSB. The percentage of patients with complicating infectious foci (39% of SAB patients, 25% of SSB patients) did not differ significantly between the groups. Endocarditis and cerebral involvement, however, were significantly more common in the SSB group. Of all complicating infectious foci, 32% lacked guiding signs or symptoms and 10% were detected only at autopsy. Factors associated with the development of complicating infectious foci were a delay in treatment for more than 48 h after the onset of symptoms, community acquisition, persistently positive blood cultures, congenital heart disease, and the presence of foreign bodies or prosthetic valves. Infection-related mortality was 18% in SAB patients and 11% in SSB patients and was significantly higher in patients with complicating infectious foci (29 vs. 9%). In conclusion, complicating infectious foci develop in approximately one-third of all patients with Eur J Clin Microbiol Infect Dis (2007) 26:105-113 SAB and SSB. An active approach that entails searching for the complicating infectious foci is warranted in these patients, because only two-thirds of complicated infectious foci have guiding symptoms or signs, and infection-related mortality is significantly increased in patients with complicating infectious foci compared to patients without these infections.
European Journal of Nuclear Medicine and Molecular Imaging, 2007
Purpose Since 18F-fluorodeoxyglucose (FDG) accumulates in neoplastic cells and in activated infl... more Purpose Since 18F-fluorodeoxyglucose (FDG) accumulates in neoplastic cells and in activated inflammatory cells, positron emission tomography (PET) with FDG could be valuable in diagnosing patients with fever of unknown origin (FUO). The aim of this study was to validate the use of FDG-PET as part of a structured diagnostic protocol in the general patient population with FUO. Methods From December 2003 to
Medicine, 2007
We conducted a prospective study to update our knowledge of fever of unknown origin (FUO) and to ... more We conducted a prospective study to update our knowledge of fever of unknown origin (FUO) and to explore the utility of a structured diagnostic protocol. From December 2003 to July 2005, 73 patients with FUO were recruited from 1 university hospital (n = 40) and 5 community hospitals (n = 33) in the same region in The Netherlands. FUO was
Background: despite firm recommendations to perform echocardiography in high-risk patients with g... more Background: despite firm recommendations to perform echocardiography in high-risk patients with gram-positive bacteraemia, routine echocardiography is not embedded in daily practice in many settings. the aim of this study was to evaluate whether a regime including routine echocardiography results in better outcome. Methods: a total of 115 patients with gram-positive bacteraemia and at least one risk factor for developing metastatic infection were prospectively included. routine echocardiography was advocated and facilitated in these patients. results were compared with a matched historical control group of 230 patients in whom echocardiography was performed at the discretion of the attending physician. endocarditis was diagnosed according to the duke criteria. results: echocardiography was performed more often in the study group (82 vs 27%, p<0.001). endocarditis was diagnosed more often among study patients, 22/115 (19%) vs 17/230 (7%) in the control group (p=0.002). in the study group echocardiography revealed vegetations in 22 of 94 (23%) patients, compared with 17 of 64 (27%) control patients (p=0.7). in the absence of heart murmurs, 70% of patients underwent echocardiography in the study group against 21% in the control group (p<0.001). no differences in adherence to american Heart association guidelines concerning treatment of endocarditis were noticed. in patients with endocarditis, overall mortality was 23% in study patients and 59% in controls (p=0.04). Conclusion: routinely performed echocardiography in patients with gram-positive bacteraemia resulted in diagnosing endocarditis in a larger proportion of o r i g i n a l a r t i C l e patients, which was associated with a significant decrease in mortality rates. in the past, endocarditis was probably detected in a more advanced stage.
Journal of Nuclear Medicine, 2010
The timely detection of metastatic infectious foci in gram-positive bacteremia is crucial, becaus... more The timely detection of metastatic infectious foci in gram-positive bacteremia is crucial, because these foci often require prolonged antibiotic treatment or drainage. The diagnosis of metastatic infectious foci is difficult because localizing symptoms are often absent. We investigated whether 18 F-FDG PET/CT was able to detect such foci and whether detection influenced clinical outcome. Methods: One hundred fifteen nonneutropenic patients with gram-positive bacteremia were prospectively included. Patients with positive blood cultures growing Staphylococcus aureus, Streptococcus species, or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. 18 F-FDG PET/CT was performed within 2 wk after the first positive blood culture. Abnormal 18 F-FDG uptake had to be confirmed by radiologic, microbiologic, or pathologic studies. Results were compared with a matched historical control group of 230 patients in whom no 18 F-FDG PET/CT was performed. Results: Significantly more patients were diagnosed with metastatic foci in the study group (67.8% vs. 35.7%). Of the imaging investigations performed, 18 F-FDG PET/CT was the first to delineate infectious foci in 35 patients (30%). In the remaining 70%, either symptoms on physical examination or other imaging techniques first revealed infectious foci. The sensitivity, specificity, negative predictive value, and positive predictive value of 18 F-FDG PET/CT were 100%, 87%, 100%, and 89%, respectively. Relapse rates decreased from 7.4% to 2.6% among study patients (P 5 0.09) and from 8.9% to 1.4% in patients with S. aureus (P 5 0.04). Overall mortality after 6 mo decreased from 32.2% to 19.1% in the 18 F-FDG PET/CT group (P 5 0.014). Conclusion: In the diagnostic work-up of high-risk patients with gram-positive bacteremia, 18 F-FDG PET/CT is a valuable technique that results in lower mortality rates. In patients with S. aureus bacteremia, relapse rates decreased significantly after the addition of 18 F-FDG PET/CT.
EQ-5D concepts and methods: A developmental history, 2005
In this discussion paper we bring together a number of considerations which might be relevant to ... more In this discussion paper we bring together a number of considerations which might be relevant to gain insight into the use of negative values for EQ-5D health states. This seems relevant since the introduction of negative values will inevitably lead to a discussion about these values, and the background to these figures has to be explained and documented. In theory and in practice it is possible to avoid the use of negative values even in cases where states are considered to be worse than death (WTD). However if one prefers to avoid explicit negative values for EQ-5D health states, other issues arise and it seems to us to be important to have an understanding of these issues. It is possible to understand the nature of the issues involved because the results and data of the MVH project are available. We consider this project as a milestone in the work on quality of life measurement and wish to make explicit our admiration for this scientific endeavour. It is only because of this project that the EuroQol Group is in a position to discuss tariffs based on a large empirical study in which several measurement methods were applied. Our discussion is thus to be seen as an effort to gain insight into the subtleties of the subject and we hope to contribute to the fruitful and widespread use of the results of the project. The issues raised by the negative values for EQ-5D health states are complex and relevant arguments derive from the fields of psychology, statistics, economics, ethics, and political science. Since it is nearly impossible for somebody who is trained in one of these disciplines to have a clear understanding of all the issues, a discussion at the level of the Group seems to be a fruitful way to obtain a fuller picture. In this paper, the UK Al and A2 tariffs are chosen as a starting point. The results are derived using the Time Trade Off (TTO) method and will be seen by the EuroQol Group and others as nicely fitting into the framework of economic project appraisal. Some elements might also be relevant for VAS tariffs, but for the purposes of this discussion it was decided to concentrate on the Al and A2 tariffs.
Social Science & Medicine, 1994
Journal of Nuclear Medicine, 2007
The aim of this prospective study was to evaluate the value of 18 F-FDG PET for the assessment of... more The aim of this prospective study was to evaluate the value of 18 F-FDG PET for the assessment of chemotherapy response in patients with non-small cell lung cancer. Furthermore, part of the objective of this study was to compare 2 methods to quantify changes in glucose metabolism. Methods: In 51 patients, dynamic 18 F-FDG PET was performed before and at 5-8 wk into treatment. Simplified methods to measure glucose metabolism (standardized uptake value [SUV]) and quantitative measures (metabolic rate of glucose [MR Glu ]), derived from Patlak analysis, were evaluated. The overall survival and progression-free survival with respect to MR Glu and SUV were calculated using Kaplan-Meier estimates. Fractional changes in tumor glucose use were stratified by the median value and also the predefined EORTC (European Organization for Research and Treatment of Cancer) metabolic response criteria, and criteria applying cutoff levels similar to those of RECIST (Response Evaluation Criteria in Solid Tumors) were evaluated. Results: When stratifying at the median value of DMR Glu and DSUV, the difference in overall survival (P 5 0.017 for DMR Glu , P 5 0.018 for DSUV) and progressionfree survival (P 5 0.002 for DMR Glu , P 5 0.0009 for DSUV) was highly significant. When applying the predefined criteria for metabolic response, the cutoff levels as also used for size measurement (RECIST) showed significant differences for DSUV between response categories in progression-free survival (P 5 0.0003) as well as overall survival (P 5 0.027). Conclusion: The degree of chemotherapy-induced changes in tumor glucose metabolism as determined by 18 F-FDG PET is highly predictive for patient outcome, stratifying patients into groups with widely differing overall survival and progression-free survival probabilities. The use of 18 F-FDG PET for therapy monitoring seems clinically feasible, because simplified methods to measure tumor glucose use (SUV) are sufficiently reliable and can replace more complex, quantitative measures (MR Glu ) in this patient population.
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of..., Jan 8, 2010
AIM: In therapy response monitoring by [18F]2-fluoro-2-deoxy-D-glucose positron emission tomograp... more AIM: In therapy response monitoring by [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), different tumor delineations are used, resulting in different values for change in glucose metabolic rate (DMRglu). We propose a technique to compare metabolic rates in a region of interest (ROI) based on fixed volumes rather than on fixed thresholds. This method involves change in lesion size. METHODS: In 49 patients with colorectal carcinoma (CRC) and 50 patients with non-small cell lung carcinoma (NSCLC) scheduled for chemotherapy, FDG-PET was performed at baseline and during chemotherapy. A ROIfixed thresholds was determined by using a 50% threshold on both baseline and follow-up FDG-PET. A ROIfixed volumes was determined by using a 50% threshold, determined on the series with the largest tumor volume. This ROIfixed volumes is used on consecutive scans. Predictive effects of both methods were investigated by survival analysis for overall and progression free survival. R...
Headache: The Journal of Head and Face Pain, 1995
Social Science & Medicine, 1997
The objective of the study was to consider five methods for valuing health states with respect to... more The objective of the study was to consider five methods for valuing health states with respect to their comparability (convergent validity, value functions) and reliability. Valuation tasks were performed by 104 student volunteers using five frequently used valuation methods: standard gamble (SG), time trade-off (TTO), rating scale (RS), willinlgness-to-pay (WTP) and the paired comparisons method (PC). Throughout the study, the EuroQol classification system was used to construct 13 health-state descriptions. Validity was investigated using the multitrait-multimethod (MTMM) methodology. The extent to which results of one method could be predicted by another was examined by transformations. Reliability of the methods was studied parametrically with Generalisability Theory (an ANOVA extension), as well as non-parametrically. Mean values for SG were slightly higher than TTO values. The RS could be distinguished from the other methods. After a simple power transformation, the RS values were found to be close to SG and TTO. Mean values of WTP were linearly related to SG and TTO, except at the extremes of the scale. However, the reliability of WTP was low and the number of inconsistencies substantial. Valuations made by the RS proved to be the most reliable. Paired comparisons did not provide stable results. In conclusion, the results of the parametric transformation function between RS and SG/TTO provide evidence to justify the current use of RS (with transformations) not only for reasons of feasibility and reliability but also for reasons of comparability. A definite judgement on PC requires data of a complete design. Due to the specific structure of the correlation matrix which is inherent in valuing health states, we believe that full MTMM is not applicable for the standard analysis of health-state valuations.