Mapping the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory to the Health Utility Index Mark III.

PURPOSE: To map the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) to the Health Utility Index Mark III (HUI3) in people living with dementia (PWD) and to compare the performance of five methods for mapping. METHODS: A cross-sectional study of 346 dyads of community-dwelling PWD and family caregiver was carried out in Singapore. ADCS-ADL and HUI3 were rated by the family caregivers. Disease severity ratings and Mini Mental State Examination (MMSE) results were retrieved from medical records. A recently proposed mapping method called the Mean Rank Method (MRM) was described and applied, and the results were compared with regression-based mapping, including ordinary least squares, censored least absolute deviation (CLAD), Tobit and response mapping. RESULTS: The MRM produced a mapped utility distribution that closely resembled the observed utility distribution. The standard deviations (SDs) of the observed and MRM-mapped utility were both 0.340, whereas the SDs of the other mapped utilities ranged from 0.243 (response mapping) to 0.283 (CLAD). Regressing the MRM- and CLAD-mapped and observed utility values upon disease severity and MMSE gave similar regression lines (each P > 0.05). Regressing the other mapped utility values upon the covariates under- (over-) estimated the utility of good (poor) clinical states. However, regression-based mapping methods gave a better fit at the individual level, as measured by root mean square error, mean absolute error and R2. K fold cross-validation gave similar results. CONCLUSIONS: The MRM is accurate at the group level. The regression-based mapping methods are more accurate for making individual-level prediction. In addition, CLAD also performed reasonably well at the group level.

Validation of the English version of the Kidney Disease Quality of Life questionnaire (KDQOL-36) in haemodialysis patients in Singapore.

BACKGROUND: To validate a widely used health outcomes instrument for patients with chronic kidney disease and on dialysis, the Kidney Disease Quality of Life questionnaire (KDQOL-36), in English-speaking haemodialysis patients in Singapore. METHODS: This study is a secondary data analysis using the KDQOL-SF (version 1.3) data collected from a cross-sectional survey of haemodialysis patients in Singapore. Cronbach's α was used to test internal consistency reliability. Multi-item scales were assessed using item-to-scale correlation and factor analysis. Both confirmatory and exploratory factor analyses were performed separately for generic and disease-targeted scales. Construct validity was assessed by correlation between disease-targeted and generic scales. Criterion validity was assessed by correlation of the physical component summary (PCS-12) and mental component summary (MCS-12) from KDQOL-36 with the corresponding PCS-36 and MCS-36 from the KDQOL-SF. RESULTS: Three hundred ninety-four patients who completed the interviews in English [male 55.8 %, mean age (SD) 52.4 (11.7) years] were involved. Kidney disease scales exhibited desirable internal consistency (Cronbach's α 0.822-0.906) and item-to-scale correlation (range 0.763-0.903), and a three-factor model fit the data well [comparative fit index (CFI) 0.934, root mean square error of approximation (RMSEA) 0.085]. For the generic Short Form 12 Health Survey (SF-12) items, a two-factor model (physical and mental) showed poor overall fit, but a three-factor structure (role, physical and mental functions) achieved good model fit (CFI 0.999, RMSEA 0.027). Correlation between disease-targeted and generic scales was weak to moderate (range 0.286-0.418). Correlation between SF-12 and SF-36 was 0.750 for PCS and 0.797 for MCS. CONCLUSION: The English version of the KDQOL-36 appears to be reliable and valid to measure quality of life for haemodialysis patients in Singapore.

Predictive genetic testing of first degree relatives of mutation carriers is a cost-effective strategy in preventing hereditary non-polyposis colorectal cancer in Singapore.

Colorectal cancer (CRC) is the most common cancer in Singapore. We sought to evaluate the long-term cost-effectiveness of targeted genetic testing and surveillance programs in individuals at high risk of hereditary non-polyposis colorectal cancer (HNPCC), as compared to an unselective clinical surveillance program alone in Singapore. A Markov model analysis from the healthcare service provider's perspective was developed to follow over a lifetime a cohort of cancer-free 21-year-old individuals, who were first-degree relatives of HNPCC patients with a known mutation. Genetic testing strategy provided a lifetime saving of Singapore dollars (SGD) 13,588 per person and gained additional life years of 0.01, as compared to clinical surveillance alone, by sparing non-mutation carriers from unnecessary and invasive intensive clinical surveillance (assuming 100% compliance with recommended surveillance programs in both strategies). Sensitivity analyses showed that as long as the compliance rate in mutation carriers was not lower than that for individuals without genetic testing, pursuing a genetic testing strategy would either be a more favorable option with discounted incremental cost-effectiveness ratios ranging from SGD 6,961 to 17,289 per life year gained or a dominant status achieved (more life year gained and less costly). Genetic testing for individuals at high risk of HNPCC allows targeted clinical surveillance to be directed at mutation carriers, ensuring efficient use of healthcare resources and reduces CRC-related mortality. It can be regarded as a cost-effective strategy in Singapore, if an improved compliance with recommended surveillance protocol is achieved in proven mutation carriers.

The role of microsatellite instability in cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix.

OBJECTIVES: This study was conducted to define the role of microsatellite instability (MSI) in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC) of the cervix. We also tested the validity of using markers recommended for MSI study in colonic carcinoma by the National Cancer Institute (NCI) for cervical neoplasm. METHODS: Twenty normal cervical, 24 low-grade CIN (CIN-L), 59 high-grade CIN (CIN-H), and 93 SCC tissues were examined for MSI after microdissection. A polymerase chain reaction based MSI detection was performed using five markers recommended by the NCI for colonic cancer (panel one) as well as five other markers (panel two) found to be informative in earlier studies. High-frequency MSI (MSI-H) was defined as instability in > or = 2 of 5 loci if one panel was used and > or = 30% of loci when more than five loci were used. Low-frequency MSI (MSI-L) was diagnosed if instability was noted but did not meet the criteria of MSI-H. Findings were correlated with clinicopathologic information. RESULTS: The combined use of panel one and two markers showed no MSI in normal cervical or CIN-L tissue, MSI-L in 1 CIN-H (1.7%), MSI-L in 16 (17.2%), and MSI-H in 11 (11.8%) SCC, respectively. The NCI-recommended panel alone detected 19 of 27 MSI-positive SCC. MSI-positive was not related to patient age, disease stage, and tumor grade. The overall survival of MSI-positive patients was significantly worse than that of microsatellite stable patients (P = 0.02). An increasing trend of MSI-H rate with higher disease stages was noted (P = 0.035) but MSI-H was not associated with poor prognosis. CONCLUSIONS: The NCI recommended panel of markers might not be useful in MSI study for SCC and using more than five markers improves the MSI detection. MSI is rare in cervical dysplasia but is present in a subset of SCC. The association between MSI-positivity and prognosis awaits future confirmation.