Computerized adaptive testing in Dutch mental health care: a new tool to assess depression and anxiety

This thesis aimed to lay the foundation for a new set of Dutch mental health instruments to measure depression and anxiety in an efficient, reliable, valid, and responsive manner. More specifically, the Dutch-Flemish PROMIS adult v1.0 item banks for Depression and Anxiety were psychometrically evaluated for computerized adaptive test (CAT) administration in the Dutch clinical and general population. CAT is a modern methodology that can be used to develop instruments that measure both efficiently and reliably as only the most appropriate questions are administered, and assessment terminates as soon as sufficient reliability is achieved. For the PROMIS CAT instruments, this was demonstrated in the thesis: measuring depression and anxiety in Dutch persons was highly efficient and reliable. Moreover, the CAT instruments were shown to measure depression and anxiety sufficiently responsive and valid as well. This even includes longitudinal validity, which has barely been studied for other Dutch mental health instruments. Overall, it was concluded that the new instruments are an improvement over available instruments. Therefore, using the PROMIS CAT instruments in clinical practice may lead to more efficient and reliable measurement that supports professionals and patients in evaluating patients' treatment.This dissertation was supported by the Foundation for benchmarking mental health care (Stichting Benchmark GGZ; SBG) and the Quality alliance mental health (Alliantie kwaliteit in de geestelijke gezondheidszorg; Akwa GGZ).Stress and Psychopatholog

Support for the higher-order factor structure of the WHODAS 2.0 self-report version in a Dutch outpatient psychiatric setting

Purpose Previous studies of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) interview version suggested a second-order model, with a general disability factor and six factors on a lower level. The goal of this study is to investigate if we can find support for a similar higher-order factor structure of the 36-item self-report version of the WHODAS 2.0 in a Dutch psychiatric outpatient sample. We aim to give special attention to the differences between the non-working group sample and the working group sample. Additionally, we intend to provide preliminary norms for clinical interpretation of the WHODAS 2.0 scores in psychiatric settings. Methods Patients seeking specialized ambulatory treatment, primarily for depressive or anxiety symptoms, completed the WHODAS 2.0 as part of the initial interview. The total sample consisted of 770 patients with a mean age of 37.5 years (SD = 13.3) of whom 280 were males and 490 were females. Several factorial compositions (i.e., one unidimensional model and two second-order models) were modeled using confirmatory factor analysis (CFA). Descriptive statistics, model-fit statistics, reliability of the (sub)scales, and preliminary norms for interpreting test scores are reported. Results For the non-working group, the second-order model with a general disability factor and six factors on a lower level, provided an adequate fit. Whereas, for the working group, the second-order model with a general disability factor and seven factors on a lower level seemed more appropriate. The WHODAS 2.0 36-item self-report form showed adequate levels of reliability. Percentile ranks and normalized T-scores are provided to aid clinical evaluations. Conclusion Our results lend support for a factorial structure of the WHODAS 2.0 36-item self-report version that is comparable to the interview version. While we conjecture that a seven-factor solution might give a better reflection of item content and item variance, further research is needed to assess the clinical relevance of such a model. At this point, we recommend using the second-order structure with six factors that matches past findings of the interview form.Stress-related psychiatric disorders across the life spa

Characterization of a clonal human colon adenocarcinoma line intrinsically resistant to doxorubicin.

Intrinsic low-level resistance to anti-cancer drugs is a major problem in the treatment of gastrointestinal malignancies. To address the problem presented by intrinsically resistant tumours, we have isolated two monoclonal lines from LoVo human colon adenocarcinoma cells: LoVo/C7, which is intrinsically resistant to doxorubicin (DOX); and LoVo/C5, which shows the same resistance index for DOX as the mixed parental cell population. For comparison, we have included in the study a LoVo-resistant line selected by continuous exposure to DOX and expressing a typical multidrug resistant (MDR) phenotype. In these cell lines we have studied the expression and/or activity of a number of proteins, including P-glycoprotein 170 (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathione (GSH)-dependent enzymes and protein kinase C (PKC) isoforms, which have been implicated in anti-cancer drug resistance. Intracellular DOX distribution has been assessed by confocal microscopy. The results of the present study indicate that resistance in LoVo/C7 cells cannot be attributed to alterations in P-gp, LRP or GSH/GSH-dependent enzyme levels. Increased expression of MRP, accompanied by alterations in the subcellular distribution of DOX, has been observed in LoVo/C7 cells; changes in PKC isoform pattern have been detected in both intrinsically and pharmacologically resistant cells

Towards standardization of measuring anxiety and depression: Differential item functioning for language and Dutch reference values of PROMIS item banks.

INTRODUCTION\nMETHODS\nRESULTS\nCONCLUSIONS\nThe outcomes anxiety and depression are measured frequently by healthcare providers to assess the impact of a disease, but with numerous instruments. PROMIS item banks provide an opportunity for standardized measurement. Cross-cultural validity of measures and the availability of reference values are prerequisites for standardized measurement.\nPROMIS Anxiety and Depression item banks were completed by 1002 representative Dutch persons. To evaluate cross-cultural validity, data from US participants in PROMIS wave 1 were used and differential item functioning (DIF) was investigated, using an iterative hybrid of logistic regression and item response theory. McFadden's pseudo R2-change of 2% was the critical threshold. The impact of any DIF on full item banks and short forms was investigated. To obtain Dutch reference values, T-scores for anxiety and depression were calculated for the complete Dutch sample, and age-group and gender subpopulations. Thresholds corresponding to normal limits, mild, moderate and severe symptoms were computed.\nIn both item banks, two items had DIF but with minimal impact on population level T-scores for full item banks and short forms. The Dutch general population had a T-score of 49.9 for anxiety and 49.6 for depression, similar to the T-scores of 50.0 of the US general population. T-scores for age-group and gender subpopulations were also similar to T-scores of the US general population. Thresholds for mild, moderate and severe anxiety and depression were set to 55, 60 and 70, identical to US thresholds.\nThe limited number of items with DIF and its minimal impact, enables the use of standard (US) item parameters and comparisons of scores between Dutch and US populations. The Dutch reference values provide an important tool for healthcare professionals and researchers to evaluate and interpret symptoms of anxiety and depression, stimulating the uptake of PROMIS measures, and contributing to standardized outcome measurement.Stress and Psychopatholog

Altered MRP is associated with multidrug resistance and reduced drug accumulation in human SW-1573 cells.

We have analysed the contribution of several parameters, e.g. drug accumulation, MDR1 P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and topoisomerase (topo) II, to drug resistance in a large set of drug-resistant variants of the human non-small-cell lung cancer cell line SW-1573 derived by selection with low concentrations of doxorubicin or vincristine. Selection with either drug nearly always resulted in MDR clones. The resistance of these clones could be explained by reduced drug accumulation and was associated with a decrease rather than an increase in the low MDR1 mRNA level. To test whether a decrease in MDR1 mRNA indirectly affected resistance in these cells, we introduced a MDR1-specific hammerhead ribozyme into wild-type SW-1573 cells. Although this led to a substantial reduction in MDR1 mRNA, it did not result in resistance. In all resistant clones we found an altered form of the multidrug resistance-associated protein (MRP), migrating slightly slower during SDS-polyacrylamide gel electrophoresis than MRP in parental cells. This altered MRP was also present in non-P-gp MDR somatic cell hybrids of the SW-1573 cells, demonstrating a clear linkage with the MDR phenotype. Treatment of crude cellular membrane fractions with N-glycanase, endoglycosidase H or neuraminidase showed that the altered migration of MRP on SDS-PAGE is due to a post-translational modification. There was no detectable difference in sialic acid content. In most but not all doxorubicin-selected clones, this MDR phenotype was accompanied by a reduction in topo II alpha mRNA level. No reduction was found in the clones selected with vincristine. We conclude from these results that selection of the SW-1573 cell line for low levels of doxorubicin or vincristine resistance, predominantly results in MDR with reduced drug accumulation associated with the presence of an altered MRP protein. This mechanism can be accompanied by other resistance mechanisms, such as reduced topo II alpha mRNA in case of doxorubicin selection