The EORTC QLQ-CR29 quality of life questionnaire for colorectal cancer: validation of the Dutch version.

PURPOSE: To validate the Dutch version of the EORTC QLQ-CR29 quality of life questionnaire for colorectal cancer. METHODS: We translated and pilot-tested the original questionnaire in the Netherlands, following EORTC guidelines. We assessed factor structure, reliability and construct validity in different samples of patients from four hospitals. RESULTS: Of 296 patients, 236 (80 %) returned the questionnaire, and 27 out of 48 patients returned the retest questionnaire. In addition to the original three scales, we found a reliable bowel functioning scale (α = 0.80), reducing the number of individual items by five. Two of the other scales had sufficient to good reliability (urinary frequency, α = 0.71, original α = 0.75, body image α = 0.80, original α = 0.84), the third, blood and mucus in stool, only moderate (α = 0.56, original α = 0.69). Item functioning was sufficient to excellent for all but two items (urinary incontinence and dysuria). Construct validity was similar to that in earlier studies. CONCLUSION: We found a very satisfactory scale for bowel problems, in patients both with and without stoma. The body image and urinary incontinence scales were reliable, and construct validity was sufficient. We suggest the questionnaire to be adapted to decrease the number of individual items, improve the scales, and therefore increase reliability of the entire questionnaire.

CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects.

Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. From a prospective study population of early breast cancer patients using tamoxifen (CYPTAM: NTR1509), 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months. The escalated dose was calculated by multiplying the individual's endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg (120 mg maximum). Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. In intermediate metabolizers, dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers. In poor metabolizers, the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers. In all patients, the endoxifen threshold of 5.97 ng/ml (=16.0 nM) reported by Madlensky et al. was reached following dose escalation. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored.

Trade-off preferences regarding adjuvant endocrine therapy among women with estrogen receptor-positive breast cancer.

BACKGROUND: There is substantial nonadherence to effective adjuvant endocrine therapy for breast cancer prevention. We therefore examined patients' trade-offs between the efficacy, side-effects, and regimen duration, and whether trade-offs predicted nonadherence. PATIENTS AND METHODS: Trade-offs from 241 women were assessed with an Adaptive Conjoint Analysis (ACA) choice task that was customized to each individual patient. From the estimated ACA utilities, the relative importance of each treatment property was calculated and a benefit/drawback ratio between the importance of the efficacy versus that of the side-effects and other treatment properties. Nonadherence was assessed through composites of validated self-report measures. RESULTS: Efficacy was most important. The side-effects joint and muscle pain and risk of endometrial cancer were almost as important. The benefit/drawback ratio showed 16% of the women to value the efficacy less than the side-effects and other treatment properties. A higher benefit/drawback ratio was associated with decreased nonadherence [adjusted odds ratio (OR) 0.1, 95% confidence interval 0.03-0.3]. CONCLUSIONS: One in six women do not consider the efficacy of endocrine therapy to outweigh its drawbacks. Knowing women's trade-offs is likely to identify women at risk for nonadherence and to help clinicians in tailoring their communication and care to different needs of individual women.

The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels.

PURPOSE: Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the (13)C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. METHODS: In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. RESULTS: CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5% (R(2) = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90%, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min (DOB(50)) values of 0.7-0.9) and genotype (CYP2D6 gene activity score of 1.0). CONCLUSION: DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype.

The relative importance of quality of care information when choosing a hospital for surgical treatment: a hospital choice experiment.

OBJECTIVE: To assess the impact of quality of care and other hospital information on patients' choices between hospitals. METHODS: 665 former surgical patients were invited to respond to an Internet-based questionnaire including a choice-based conjoint analysis. Each patient was presented with 12 different comparisons of 2 hospitals, with each hospital characterized by 6 attributes containing 2 levels. Hospital attributes were included if frequently reported by patients as most important for future hospital choices. These included both general hospital information (e.g., atmosphere), information on quality of care (e.g., percentage of patients with "textbook outcome"), and surgery-specific information (e.g., possibility for minimally invasive procedure). Hierarchial Bayes estimation was used to estimate the utilities for each attribute level for each patient. Based on the ranges of these utilities, the relative importance of each hospital attribute was determined for each participant as a measure of the impact on patients' choices. RESULTS: 308 (46.3%) questionnaires were available for analysis. Of the hospital attributes that patients considered, surgery-specific information on average had the highest relative importance (25.7 [23.9-27.5]), regardless of gender, age, and education. Waiting time and hospital atmosphere were considered least important. The attribute concerning the percentage of patients with "textbook outcomes" had the second greatest impact (18.3 [16.9-19.6]), which was similar for patients with different adverse outcome experience. CONCLUSIONS: Surgery-specific and quality of care information are more important than general information when patients choose between hospitals.

The importance of experienced adverse outcomes on patients' future choice of a hospital for surgery.

OBJECTIVE: To assess whether patients who experience adverse outcomes during hospitalisation or after discharge differ in the information they would use for future choices of a hospital for surgery compared with patients without any adverse outcomes. DESIGN: Cross-sectional questionnaire study, including questions on (1) adverse outcome occurrence during hospitalisation and after discharge, (2) information patients would use for future hospital choice and (3) priority of information. SETTING: Three hospitals in the western part of The Netherlands. STUDY SAMPLE: All 2122 patients who underwent elective aorta reconstruction (for treatment of aneurysm), cholecystectomy, colon resection, inguinal hernia repair, oesophageal resection or thyroid surgery in the period 2005-2006, of whom 1329 (62.6%) responded. RESULTS: Patients who experienced postdischarge adverse outcomes intend to use more information items to choose a future hospital (on average 1.6 items more). They more often would use the item on information provision during hospitalisation (OR 2.35 (1.37 to 4.03)) and information on various quality-of-care measures, compared with patients without adverse outcomes. Patients who experienced in-hospital adverse outcomes would not use more information items but more often would use the item on mortality after surgery (OR 1.93 (1.27 to 2.94)) and extended hospital stay (OR 1.61 (1.10 to 2.36)). However, when asked for priority of information, previous treatment in that hospital is mentioned as the most important item by most patients (32%), regardless of adverse outcome occurrence, followed by hospital reputation and waiting time. CONCLUSIONS: Adverse outcome experience may change the information patients use (on quality of care) to choose a future hospital.

Improved diagnosis and treatment of soft tissue sarcoma patients after implementation of national guidelines: a population-based study.

AIM: The majority of clinicians, radiologists and pathologists have limited experience with soft tissue sarcomas. In 2004, national guidelines were established in The Netherlands to improve the quality of diagnosis and treatment of these rare tumours. This study evaluates the compliance with the guidelines over time. PATIENTS: Population-based series of 119 operated patients with a soft tissue sarcoma (STS) diagnosed in 1998-1999 (79 before implementation of new guidelines) and in 2006 (40 after implementation). METHODS: Coded information regarding patient and tumour characteristics as well as (the results of) pathology review was collected from the medical patient file by two experienced data-managers. RESULTS: Diagnostic imaging of the tumour was performed according to the guidelines in 75-100% depending on the site of the tumour (abdominal versus non-abdominal) as well as the time of diagnosis. Adherence to the guidelines with respect to invasive diagnostic procedures in patients with non-abdominal STS improved over time. A pre-operative histological diagnosis was obtained in 42% of the patients in 1998-1999 and in 72% of the patients in 2006 (p<0.001). The guidelines for reporting on pathology were increasingly adhered to. In 2006, (nearly) all pathology reports mentioned tumour size, morphology, tumour grade, resection margins and radicality. This represents a major improvement compared to the pathology reports in 1998-1999, where these aspects were not mentioned in 14-40% of the cases. The proportion of prospective pathology reviews by (a member of) the expert panel increased from 60% in 1998-1999 to 90% in 2006 (p=0.001). DISCUSSION: The compliance with the guidelines has been optimised by the increased attention to this group of patients. Most important factors have been the reporting of the results of the first evaluation and (discussions about) the centralisation of treatment. Further improvements could be reached by the prospective web based registry monitoring logistic aspects as well as parameters useful for the evaluation of the quality of care.

Follow-up of colorectal cancer patients: quality of life and attitudes towards follow-up.

The aims of our study were to assess the effect of follow-up on the quality of life of colorectal cancer patients and to assess the attitudes of patients towards follow-up as a function of patient characteristics. Patients who had been treated with curative intent were selected from four types of hospitals. Eighty-two patients were interviewed using a structured questionnaire, whereas 130 patients received the questionnaire by mail. To assess the effect of follow-up on the quality of life, the interviewed patients were randomly allocated to three groups and interviewed at different times in relation to the follow-up visit. Analysis did not show an effect of the follow-up visit on quality of life. Patients reported a positive attitude towards follow-up: it reassured them, they judged the communication with the physician to be positive, and they experienced only slight nervous anticipation and few other disadvantages. Patients reported a strong preference for follow-up, and a large majority would prefer follow-up even if it would not lead to earlier detection of a recurrence. Apart from living situation, no patient characteristics were clearly associated with the attitude towards follow-up. Implications for clinical practice are discussed.

Job satisfaction among stayers and leavers of dental group practices in The Netherlands.

Working in group dental practices has increased during the last few decades. In the present study all the dentists (n = 82) who had participated in group practices in the Netherlands for at least 10 years were interviewed and questioned about the nature of their practices, their working conditions and their 'job satisfaction'. Most of them (78 per cent) had a second appointment, besides that in the group practice. During the past 10 years 32 per cent of the dentists had left the group practice because of personal conflicts, the wish to change to solo practice or a different appointment, organisational problems, or dissatisfaction with practice space. Eighty-two per cent of them declared that they were, in general, (very) satisfied with their work; these included 94 per cent of the 'stayers' and 63 per cent of the 'leavers'. The main motives for joining a group practice rather than working in a solo practice were: being less isolated, having the possibility of mutual consultation, the stimulation of working with colleagues, and the more efficient use of staff and equipment. These motives were satisfactorily realised, according to the 'stayers'; and 'leavers' scored less favourably, but still at a high level. The same picture was also seen in the other features studied; the 'stayers' were very satisfied with their working conditions and the future possibilities of the group practice, while the 'leavers' reacted less positively, but, on average, not negatively.

Internal biliary drainage, parenteral nutrition, and variation in the total parenteral nutrition feeding solutions: influence on the healing of colon anastomosis in jaundiced rats.

The influence of preoperative internal biliary drainage and various types of total parenteral nutrition (TPN) on the healing of a colon anastomosis in 50 jaundiced rats was investigated. Jaundice was induced by division and ligation of the common bile duct. After 5 days a colon anastomosis was made. Ten days thereafter the bursting pressure of the anastomosis was measured as an assessment of wound healing. Bursting pressures were significantly lower in jaundiced rats compared with a sham-operated nonjaundiced group. Preoperative internal biliary drainage significantly improved bursting pressure (p less than 0.001) as did preoperative TPN (p less than 0.001). In the second part of the study the influence of four different feeding solutions on the healing of a colon anastomosis was tested. Solutions with and without 20% fat emulsion and a solution with branched-chain amino acids were tested as well as glucose only. No significant differences were observed among these four groups on the parameters tested.