Prevalence of BRCA1 in a hospital-based population of Dutch breast cancer patients

The prevalence of disease-related BRCA1 mutations was investigated in 642 Dutch breast cancer patients not selected for family history or age at diagnosis. They were tested for germline mutations in the BRCA1 gene using an assay which detects small deletions and insertions (DSDI), as well as the two major genomic founder deletions present in the Dutch population. Data on family history and bilateral breast cancer were obtained retrospectively. Ten protein truncating mutations were detected and one in-frame deletion with an unknown relation to disease risk. Four patients carried the Dutch founder deletion of exon 22. Based on these results the estimated prevalence of breast cancer in the general population in the Netherlands attributable to BRCA1 mutations is 2.1%. Under 40 years-of-age and under 50 years-of-age this prevalence is 9.5% and 6.4%, respectively. All mutation carriers were under 50 years-of-age at diagnosis of the first breast cancer, and five did not have any relative with breast cancer. The proportions of bilateral breast cancer in the mutation carriers and non-carriers did not differ from each other. These data indicate that in the general Dutch breast cancer population the great majority of BRCA1 mutations will be found in women diagnosed under 50 years-of-age. © 2000 Cancer Research Campaig

The influence of preoperative determinants on quality of life, functioning and pain after total knee and hip replacement:A pooled analysis of Dutch cohorts

Background: Previous research has identified preoperative determinants that predict health related quality of life (HRQoL), functioning and pain after total knee or hip arthroplasty (TKA/THA), but these differed between studies and had opposite directions. This may be due to lack of power and not adjusting for confounders. The present study aims to identify the preoperative determinants that influence health related quality of life (HRQoL), functioning and pain after total knee or hip arthroplasty (TKA/THA). Methods: We pooled individual patient from 20 cohorts with OA patients data (n = 1783 TKA and n = 2400 THA) in the Netherlands. We examined the influence of age, gender, BMI and preoperative values of HRQoL, functioning and pain on postoperative status and total improvement. Linear mixed models were used to estimate the effect of each preoperative variable on a particular outcome for each cohort separately. These effects were pooled across cohorts using a random effects model. Results: For each increase in preoperative point in HRQoL, the postoperative HRQoL increased by 0.51 points in TKA and 0.37 points in THA (SF-36 scale). Similarly, each point increase in preoperative functioning, resulted in a higher postoperative functioning of 0.31 (TKA) and 0.21 (THA) points (KOOS/HOOS-ADL scale). For pain this was 0.18 (TKA) and 0.15 (THA) points higher (KOOS/HOOS-pain scale) (higher means less pain). Even though patients with better preoperative values achieved better postoperative outcomes, their improvement was smaller. Women and patients with a higher BMI had more pain after a TKA and THA. Higher age and higher BMI was associated with lower postoperative HRQoL and functioning and more pain after a THA.Conclusions: Patients with a better preoperative health status have better outcomes, but less improvement. Even though the independent effects may seem small, combined results of preoperative variables may result in larger effects on postoperative outcomes.</p

Individual quality of life: adaptive conjoint analysis as an alternative for direct weighting?

In the schedule for the evaluation of individual quality of life (SEIQoL) the weights for five individualized quality of life domains have been derived by judgment analysis and direct weighting (DW). We studied the feasibility and validity of adaptive conjoint analysis (ACA) as an alternative method to derive weights in 27 cancer patients and 20 patients with rheumatoid arthritis. Further, we assessed the convergence between direct weights and weights derived by ACA, and their correlation with global quality-of-life scores. All respondents finished the ACA task, but one in five respondents were upset about the ACA task. Further, the task was vulnerable to judgment ‘errors’, such as inconsistent answers. The agreement between the two weights was low. Both weighted index scores were strongly correlated to the unweighted index score. The relationships between the index score and scores on a visual analogue scale for global individual quality of life and global quality of life were similar whether or not the index score was calculated with DW weights, with ACA weights, or without using weights. We conclude that, because weights did not improve the correlation between the index score and global quality of life scores, it seems sufficient to use the unweighted index score as a measure for global individual quality of life

Sick leave and work disability in patients with early arthritis

We studied the occurrence of sick leave and work disability, the presence of workplace adaptations and the usage of professional guidance related to working problems in patients with early arthritis. Inclusion criteria were arthritis symptoms of less than 2 years duration and a paid job at the time of diagnosis. Assessments were done in connection with an early arthritis clinic (EAC) at entry into the cohort and 12 months thereafter by means of a questionnaire comprising questions on sick leave (absenteeism from work reported to the employer), work disability (receiving a full or partial work disability pension), unemployment, work adaptations and professional guidance related to working problems. Fifty-seven of the 69 participants (83%) had an arthritis symptom duration of <6 months. The number of patients with sick leave due to arthritis in the past 12 months decreased from 28 (41%) at study entry to 18 (26%) after 12 months of follow-up. The number of patients receiving a work disability pension increased from 5 (7%) at study entry to 13 (19%) after 12 months of follow-up (10 partial and 3 full). Sick leave in the 12 months before study entry appeared to be the most important predictor of the institution or increase in a work disability pension (odds ratio, 16.1; 95%CI, 1.8–142.8). Between study entry and follow-up, the number of patients with workplace adaptations increased from 20 (29%) to 28 (42%), whereas the number of patients receiving vocational guidance decreased from 48 (70%) to 36 (52%). In patients with early arthritis and a paid job, arthritis-related sick leave was common and occurred in part before patients entered the EAC and a diagnosis was made. About 20% of the patients became permanently work disabled, with partial work disability being more common than full work disability. Considerable proportions of patients received workplace adaptations and professional guidance with working problems

Cross-cultural validation of the Educational Needs Assessment Tool in RA in 7 European countries

<p>Abstract</p> <p>Background</p> <p>The Educational Needs Assessment Tool (the ENAT) is a 39-item patient questionnaire originally developed in the UK to assess educational needs of patients with rheumatoid arthritis (RA). The objective of this study was to assess the cross-cultural validity of the ENAT in 7 European countries.</p> <p>Methods</p> <p>The ENAT was translated into Dutch, Finnish, Norwegian, Portuguese, Spanish and Swedish versions by using Beaton's cross-cultural adaptation process, and was completed by a convenience sample of patients with RA in each country. The generated country-specific data were assessed for construct validity and were then pooled and assessed for cross-cultural invariance using Rasch analysis.</p> <p>Results</p> <p>Individual country-specific analysis showed adequate fit to the Rasch model after adjustment for local dependency within domains. When data from the different countries were pooled, the 39 items deviated significantly from Rasch model's expectations (X²= 977.055, DF = 351, p = 0.000, PSI = 0.976). Again, most items within domains were found to be locally dependent, significantly affecting the fit. Consequently each domain was treated as a unit (i.e. testlet) and the ENAT was re-analysed as a seven-testlet scale resulting into a good fit to the Rasch model (X²= 71.909; DF = 63; p = 0.207, PSI = 0.951). A test of strict unidimensionality confirmed that all domains contributed to measuring a single construct. Cross-cultural non-invariance was discounted by splitting domains for DIF maintaining an excellent fit to the Rasch model. This allowed calibration of the ENAT into an interval scale.</p> <p>Conclusion</p> <p>The ENAT is a simple tool, which is a valid measure of educational needs of people with RA. Adjustment for cross-cultural non-invariance is available if data from the 7 European countries are to be pooled or compared.</p

Looking through the 'window of opportunity': is there a new paradigm of podiatry care on the horizon in early rheumatoid arthritis?

Over the past decade there have been significant advances in the clinical understanding and care of rheumatoid arthritis (RA). Major paradigm changes include earlier disease detection and introduction of therapy, and 'tight control' of follow-up driven by regular measurement of disease activity parameters. The advent of tumour necrosis factor (TNF) inhibitors and other biologic therapies have further revolutionised care. Low disease state and remission with prevention of joint damage and irreversible disability are achievable therapeutic goals. Consequently new opportunities exist for all health professionals to contribute towards these advances. For podiatrists relevant issues range from greater awareness of current concepts including early referral guidelines through to the application of specialist skills to manage localised, residual disease activity and associated functional impairments. Here we describe a new paradigm of podiatry care in early RA. This is driven by current evidence that indicates that even in low disease activity states destruction of foot joints may be progressive and associated with accumulating disability. The paradigm parallels the medical model comprising early detection, targeted therapy, a new concept of tight control of foot arthritis, and disease monitoring