Biomedical subjects

S L Hui

Publications and source records attributed to S L Hui.

At least 37 records · Page 2Linked to original sources

PubMed1999

Sibling pair linkage and association studies between bone mineral density and the insulin-like growth factor I gene locus.

A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Insulin-like growth factor I (IGF-I) is an attractive candidate gene for osteoporosis susceptibility, because IGF-I has marked effects on bone cells and has been implicated in the pathogenesis of osteoporosis. The IGF-I gene contains a microsatellite repeat polymorphism approximately 1 kb upstream from the IGF-I gene transcription start site, and previous investigators have found a higher prevalence of the 192/192 genotype of this polymorphism among men with idiopathic osteoporosis compared to controls. In this study we used this IGF-I polymorphism to test for an association between this polymorphism and BMD in our large population of premenopausal women (1 sister randomly chosen from 292 Caucasian and 71 African-American families). We also used this polymorphism to detect linkage to BMD elsewhere in the IGF-I gene or in a nearby gene using sibling pair linkage analysis in healthy premenopausal sister pairs (542 sibling pairs: 418 Caucasian and 124 African-American). Neither test provided any evidence of linkage or association between the IGF-I gene locus and spine or femoral neck BMD in Caucasians or African-Americans.

Adult↗

PubMed1998

Mortality, symptoms, and functional impairment in late-life depression.

OBJECTIVE: To determine whether depressive symptoms measured at baseline are associated with mortality and to describe the course of depressive symptoms and their relation to physical decline in patients over a 6-year period. DESIGN: Prospective cohort study conducted from 1990 through 1996. SETTING: Urban academic primary care group practice. PATIENTS: A cohort of 3,767 patients aged 60 years and older screened for depressive symptoms during routine office visits using the Centers for Epidemiologic Studies Depression Scale (CES-D) participated in the mortality study. A subsample of 300 patients with CES-D scores 16 or above and a subsample of 100 patients with CES-D scores less than 16 participated in the study of the course of depressive symptoms and physical decline. MEASUREMENTS AND MAIN RESULTS: Mortality by December 1995 was measured for all screened patients; reinterviewed patients completed the CES-D and the Sickness Impact Profile (SIP). The mean follow-up period was 45 months (+/- SD 12.2 months); 561 (14.9%) of the patients died by December 1995. In proportional hazards models, age, gender, race, history of smoking, serum albumin value, and an ideal body weight in the lowest 10% were significant correlates of time to death, but the baseline CES-D was not. Patients with depressive symptoms had significantly worse physical and psychosocial functioning scores on the SIP than did patients without depressive symptoms. Using the generalized estimating equation method, the strongest predictor of the current CES-D score was the patient's prior CES-D score. However, worsening physical functioning score on the SIP was also independently correlated with worse CES-D scores p < or = .001). CONCLUSIONS: Symptoms of depression were not associated with mortality in this cohort of older adults. However, patients with depressive symptoms reported greater functional impairment than did those without depressive symptoms. Moreover, decline in physical functioning was independently correlated with a concurrent increase in depressive symptoms.

Activities of Daily Living↗

PubMed1998

Predictors of mobility and basic ADL difficulty among adults aged 70 years and older.

We use data from the 1993-1995 Assets and Health Dynamics of the Oldest-Old survey to estimate predictors of onset of mobility difficulty, onset of basic activity of daily living (ADL) difficulty, and improvement to no mobility difficulty. Onset of mobility difficulty occurred among 20% of those with no difficulty at baseline (n = 2,857) and was most likely among those 85 years of age or over, women, those with a body-mass index of 30 or over, and those who reported lung disease, arthritis, frequent pain, and poor memory. For those with mobility difficulty at baseline (n = 1,871), improvement occurred among 24% and onset of basic ADL difficulty occurred among 25%. Improvement was more likely among those with difficulty in just one mobility item at baseline, and onset of ADL difficulty was most common among those with difficulty in three or more mobility items at baseline.

Activities of Daily Living↗

PubMed1998

Evaluation of diagnostic tests without gold standards.

This paper reviews statistical methods developed to estimate the sensitivity and specificity of screening or diagnostic tests when the fallible tests are not evaluated against a gold standard. It gives a brief summary of the earlier historical developments and focuses on the more recent methods. It covers Bayesian approaches and longitudinal studies with repeated testing. In particular, it reviews the procedures that do not require the assumption of independence between tests conditional on the true disease status.

Bayes Theorem↗

PubMed1998

Cognitive decline and education in mild dementia.

Recent studies suggested that education may modify the clinical expression of dementia and Alzheimer's disease through its association with a brain reserve capacity. We studied whether education would be related to degree of cognitive decline in mild dementia. Equations to estimate premorbid cognitive ability were derived from a representative normative sample of 83 community-dwelling African Americans using age, education, and gender as independent variables and Word List Learning (WLL) and Animal Fluency (AF) scores from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery as dependent variables. These equations were applied to a second sample of 131 African Americans (22 with dementia, 109 healthy) who completed CERAD test batteries as part of an epidemiologic study of dementia in the community. Differences between obtained and estimated premorbid WLL and AF test scores were calculated and then analyzed in a 2 (Education) x 2 (Diagnosis) ANOVA. A significant interaction association between Education and Diagnosis on WLL scores and a borderline significant interaction on AF scores showed that the high-education demented group had a greater cognitive decline from estimated premorbid levels than the low-education demented group. Thus, at comparable levels of clinical dementia severity, greater cognitive decline occurred in highly educated patients than in low-educated patients.

Aged↗

PubMed1998

Treatment outcome of tacrine therapy depends on apolipoprotein genotype and gender of the subjects with Alzheimer's disease.

We studied the effects of apolipoprotein E (APOE) genotype and gender on clinical response to tacrine in patients with mild to moderate Alzheimer's disease (AD). We analyzed data from a previously reported 30-week, double-blind, placebo-controlled trial of tacrine, in which APOE genotypes were determined from previously collected plasma samples. Patients were assigned to placebo or tacrine with daily dosages of 80, 120, or 160 mg/day. The outcome measures were Alzheimer's Disease Assessment Scale-Cognitive Component, Clinician Interview Based Impression, Mini-Mental State Examination, and the Caregiver-rated Clinical Global Impression of Change. An intent-to-treat (ITT) analysis of patients with available genotypes (n = 528) did not reveal response differences by genotype, although the effect size was twice as large in the epsilon2-3 as the epsilon4 group (-2.62 versus -1.25). The association of treatment effect with APOE genotype varied significantly according to gender (p < 0.002 for ITT; p < 0.05 for evaluables). The treatment effect was larger in the epsilon2-3 compared with epsilon4 women (ITT, 4.24 points, p = 0.03; evaluable, 7.20 points, p = 0.01). In contrast, treatment effect size was not different between epsilon2-3 and epsilon4 of men with AD. APOE genotype and gender may predict response to tacrine in patients with AD.

Aged↗

PubMed1998

Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12-13.

Osteoporosis is a leading public health problem that is responsible for substantial morbidity and mortality. A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Recent linkage of three Mendelian BMD-related phenotypes, autosomal dominant high bone mass, autosomal recessive osteoporosis-pseudoglioma, and autosomal recessive osteopetrosis to chromosome 11q12-13 led us to evaluate this region to determine if the underlying gene(s) could also contribute to variation in BMD in the normal population. We performed a linkage study in a sample of 835 premenopausal Caucasian and African-American sisters to identify genes underlying BMD variation. A maximum multipoint LOD score of 3.50 with femoral neck BMD was obtained near the marker D11S987, in the same chromosomal region as the three Mendelian traits mentioned above. Our results suggest that the gene(s) underlying these Mendelian phenotypes also play a role in determining peak BMD in the normal population and are the first using linkage methods to establish a chromosomal location for a gene important in determining peak BMD. These findings support the hypothesis that a gene responsible for one or more of the rare Mendelian BMD traits linked to chromosome 11q12-13 has an important role in osteoporosis in the general population.

Adult↗

PubMed1998

Risk factors and Alzheimer's disease: a comparative study of two communities.

OBJECTIVE: To determine the association between demographic, lifestyle and medical history factors to Alzheimer's disease (AD), we studied samples of two community dwelling populations with significantly different prevalence rates of AD in Indianapolis, USA (6.24%) and Ibadan, Nigeria (1.4%). METHODS: The samples were drawn from African-American community dwelling residents 65 years of age and over in Indianapolis, and Yoruba community-dwelling residents 65 years of age and over in Ibadan. A two-stage epidemiological design was used in which diagnosis of AD was by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria. RESULTS: In Indianapolis, age (odds ratio [OR] = 1.16; 95% confidence interval [CI] = 1.11-1.21), family history of dementia (OR = 5.40; 95% CI = 1.99-14.62), low education (0-6 years, OR = 3.49; 95% CI = 1.06-11.48) and rural residence (OR = 2.49; 95% CI = 1.05-5.88) were associated with a higher risk of AD. In Ibadan, age (OR = 1.15; 95% CI = 1.12-1.18) and female gender (OR = 13.9; 95% CI = 3.85-50.28) were associated with a higher risk of AD. CONCLUSIONS: The remarkably similar odds ratios between age and AD between sites suggest that biological processes associated with ageing are essential elements in the development of AD but that genetic and environmental risk factors may alter age-specific rates. In our longitudinal study, we intend to investigate in more depth the interaction between these ageing, genetic and environmental factors.

Aged↗

PubMed1997

Logistic regression models with missing covariate values for complex survey data.

Maximum likelihood methods are used to incorporate partially observed covariate values in fitting logistic regression models. We extend these methods to data collected through complex surveys using the pseudo-likelihood approach. One can obtain parameter estimates of the logistic regression model using standard statistical software and their standard errors by Taylor series expansion or the jackknife method. We apply the approach to data from a two-phase survey screening for dementia in a community sample of African Americans age 65 and older living in Indianapolis. The binary response variable is dementia and the covariate with missing values is a daily functioning score collected from interviews with a relative of the study subject.

Black or African American↗

PubMed1997

Methods for comparison of cost data.

BACKGROUND: Researchers are increasingly interested in examining costs of care, and large administrative and clinical databases have made relevant data readily available. Because a few patients incur high costs relative to most patients, the distribution of cost data is often skewed. How robust are the usual methods of cost analysis against the skewed distribution of cost data? OBJECTIVE: To determine the methods commonly used for comparing cost data, describe their limitations, and provide an alternate method of analysis. DESIGN: Review of statistical methods used in studies of medical costs published in medical journals between January 1991 and January 1996. Description of a Z-score method appropriate for testing the equality of mean costs between two log-normal samples; and reanalysis of published two-sample comparison results done by using the Z-score method. RESULTS: For two-sample comparisons, three methods were commonly used: the Student t-test on untransformed costs, the Wilcoxon test on untransformed costs, and the Student t-test on log-transformed costs. The t-test on untransformed costs ignores the skewness in cost data, the Wilcoxon test ignores unequal variances, and the t-test on log-transformed costs tests the wrong null hypothesis unless variances in the log-scale are equal. Eleven articles included two-sample tests and had enough information to allow reanalysis of the data using the Z-score method. These articles described a total of 23 Wilcoxon tests and 24 t-tests on untransformed costs. Most results did not change on reanalysis, but six results changed enough to alter conclusions. Specifically, reanalysis of data for which one Wilcoxon test had shown statistically significant results showed nonsignificant results; reanalysis of data for which two Wilcoxon tests had shown nonsignificant results showed statistically significant results. In articles that used t-tests on untransformed costs, two statistically significant results became nonsignificant on reanalysis and one nonsignificant result became statistically significant on reanalysis. CONCLUSIONS: The methods commonly used to compare costs of two groups have limitations. Some limitations may change some conclusions, and the direction of the change cannot be predicted. The Z-score method is designed to adjust for skewness in cost data and is appropriate for comparing means of log-normally distributed cost data.

Costs and Cost Analysis↗

PubMed1997

Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens.

The purpose of this study was to determine whether bone density in older men was associated with serum sex steroids or sex hormone binding globulin (SHBG). Bone density and sex steroids were measured in men over age 65 at 6-mo intervals for an average of 2.1 yr. Bone density was significantly positively associated with greater serum E2 concentrations (+0.21 < r < +0.35; 0.01 < P < 0.05) at all skeletal sites. There were weak negative correlations between serum testosterone and bone density (-0.20 < r < -0.28; 0.03 < P < 0.10) at the spine and hip. SHBG was negatively associated only with bone density in the greater trochanter (r = -0.26, P < 0.05). Greater body weight was associated with lower serum testosterone and SHBG, and greater E2. Because of these associations, regression models which adjusted for age, body weight, and serum sex steroids were constructed; these accounted for 10-30% of the variability in bone density, and showed consistent, significant positive associations between bone density and serum E2 concentrations in men, even after adjustments for weight and SHBG. These data suggest that estrogens may play an important role in the development or maintenance of the male skeleton, much as is the case for the female skeleton. These data also indicate that, within the normal range, lower serum testosterone concentrations are not associated with low bone density in men.

Aged↗

PubMed1997

Apolipoprotein E-associated risk for Alzheimer's disease in the African-American population is genotype dependent.

As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE epsilon4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in epsilon4 homozygotes was 4.83 (95% confidence interval [CI], 1.71-13.64) compared with the epsilon3/epsilon3 genotype, but the OR for AD with the epsilon3/epsilon4 genotype did not reach significance (1.20; 95% CI, 0.58-2.45). These findings suggest that the association between ApoE epsilon4 and AD is weaker in African Americans than in whites.

Aged↗

PubMed1997

Universal standardization of bone density measurements: a method with optimal properties for calibration among several instruments.

The International Dual-Photon X-Ray Absorptiometry (DXA) Standardization Committee (IDSC) conducted a cross-calibration study among three models of DXA machines from three different manufacturers. In that study, 100 subjects were scanned on all three machines. A set of equations were derived to convert bone mineral density (BMD) on each machine to a "standardized BMD" (sBMD) such that sBMD from the same subject derived from different machines would be approximately the same. In a reanalysis of the cross-calibration data, we showed that the conversion method used in the IDSC study did not achieve several optimal properties desirable in such conversions. We derived new conversion equations to sBMD based on minimizing differences among sBMD from the three machines. More important is that the new conversions have no residual bias that was present in the IDSC conversions. The performance of the methods were compared on the cross-calibration data as well as an external data set. We conclude that the IDSC conversions are adequate for clinical use on other machines worldwide, but that researchers should standardize their own machines in a laboratory using the new method.

Absorptiometry, Photon↗

PubMed1997

Methods for comparing the means of two independent log-normal samples.

Standard methods of using the t-test and the Wilcoxon test have deficiencies for comparing the means of two skewed log-normal samples. In this paper, we propose two new methods to overcome these deficiencies: (1) a likelihood-based approach and (2) a bootstrap-based approach. Our simulation study shows that the likelihood-based approach is the best in terms of the type I error rate and power when data follow a log-normal distribution.

Biometry↗

PubMed1996

Relationship of age, education, and occupation with dementia among a community-based sample of African Americans.

OBJECTIVE: To explore the relationship between age, education, and occupation with dementia among African Americans. DESIGN: Community-based survey to identify subjects with and without evidence of cognitive impairment and subsequent diagnostic evaluation of a stratified sample of these subjects using formal diagnostic criteria for dementia. SETTING: Urban neighborhoods in Indianapolis, Ind. SUBJECTS: A random sample of 2212 African Americans aged 65 years and older residing in 29 contiguous census tracts. MEASUREMENTS: Subjects's scores on the Community Screening Instrument for Dementia (CSI-D), formal diagnostic clinical assessments for dementia, years of education, rural residence, primary occupation, self-reported disease, and alcohol and smoking history. Caseness was defined by four separate criteria: (1) cognitive impairment as defined by the subject's performance on the CSI-D cognitive scale; (2) cognitive impairment as defined by the total CSI-D score that included a relative's assessment of the subject's functional abilities; (3) dementia as defined by explicit diagnostic criteria; and (4) possible or probable Alzheimer's disease as defined by explicit diagnostic criteria. RESULTS: The mean age was 74 years (age range, 65 to 100 years), 65% of subjects were women, the mean education was 9.6 years (age range, 0 to 16 years), 98% of the subjects were literate, and 32% reported living in a rural area until age 19 years. Service, domestic, and production occupations accounted for 55.2% of the subjects' primary occupations with a mean of 25.8 years (range, 1 to 75 years) in the primary occupation. Years of education, rural residence to age 60 years, and primary occupation were highly correlated. Caseness defined by any of the four criteria was associated with functional impairment, but the frequency of impairment increased with increasing diagnostic specificity. Age, education, and rural residence to age 60 years were significantly independently associated with caseness for cognitive impairment, dementia, and Alzheimer's type dementia. White-collar occupation was independently associated only with caseness for cognitive impairment. History of stroke was associated with caseness for cognitive impairment and dementia but not Alzheimer's disease, while history of smoking was negatively correlated with Alzheimer's disease. CONCLUSIONS: Education was independently associated with cognitive impairment and dementia among a representative community-based sample of African Americans and the association remains significant across a variety of sensitivity analyses designed to control for measurement and confounding biases. The potential protective role of education against the development of dementia among African Americans deserves further evaluation.

Black or African American↗

PubMed1996

The genetics of proximal femur geometry, distribution of bone mass and bone mineral density.

To estimate genetic effects on femoral neck geometry and the distribution of bone mineral within the proximal femur a cross-sectional twin analysis was carried out at a university hospital that compared correlations in these traits in pairs of mono- and dizygotic female twins. Monozygotic (MZ, n = 51 pairs, age 49.1 +/- 9.3 years) and dizygotic (DZ, n = 26 pairs, age 45.7 +/- 11.3 years) twins were randomly selected from a larger sample of twins previously studied. Measurements of bone mineral density (BMD), femoral neck angles and length, cross-sectional area and moment of interia, the center of mass of the narrowest cross-section of the femoral neck, and BMDs of regions within the femoral neck were made. A summary index of the resistance of the femoral neck to forces experienced in a fall with impact on the greater trochanter (Fall Index, FI) was calculated. MZ pair intraclass correlations (rMZ) were significantly (p < 0.05) different from zero for all bone mass and femoral geometry variables (0.35 < rMZ < 0.82). DZ pair correlations (rDZ) were lower than rMZ for all variables (0.04 < rDZ < 0.52) except femoral neck length (rDZ = 0.38, rMZ = 0.36). After adjustment for BMD of the femoral neck, rMZ was significantly greater than rDZ, yielding high heritability estimates for regional BMDs (0.72 < H2 < 0.78), the center of mass of the femoral neck (H2 = 0.70, -0.04 to 1.43 95% CI) and the resistance of the femoral neck to forces experienced in a fall (FI, H2 = 0.94, 0.06 to 1.85 95% CI), but not for femoral neck length. Adjustments for age did not alter these findings. It is concluded that there are significant familial influences on the distribution of femoral bone mass and on the calculated structural strength of the proximal femur, but not on femoral neck length. If the assumptions of the twin model are correct, this is evidence for genetic factors influencing these traits.

Absorptiometry, Photon↗

PubMed1996

The relationship between alcohol consumption, cognitive performance, and daily functioning in an urban sample of older black Americans.

OBJECTIVE: To report on moderate alcohol consumption and measurements of cognitive function and activities of daily living in an older, urban, community-dwelling sample of black Americans. DESIGN: As part of a community prevalence study of dementia, information on alcohol consumption and cognitive performance was collected on 2040 randomly selected black subjects living in Indianapolis. MEASUREMENTS: From questions in the screening interview, alcohol consumption was grouped into four categories: lifetime abstainers, regular drinkers less than 4 drinks per week, 4 to 10 drinks per week, and more than 10 drinks per week. Current and past drinkers were analyzed separately. Three measurements were used: (1) a total cognitive score; (2) the delayed recall score from the East Boston Memory Test; (3) a score for daily functioning based upon information from the informant. Multiple regression models were fitted with drinking variables as the major predictor, including covariates of age, gender, education, history of stroke, hypertension, being treated for depression, and a family history of dementia. MAIN RESULTS: In all analyses, there was a very consistent pattern for both current and past drinkers. There was a small but significant dose effect of drinking for the drinkers, with subjects in the heaviest drinking category scoring poorest, i.e., lowest scores in cognitive tests and highest scores in scales of daily functioning indicating more impairment. The scores of abstainers were worse than those of subjects in the lightest drinking category. The pattern of scores for cognitive performance and daily functioning was similar between current and past drinkers. These patterns remained the same even after potential confounders were included. CONCLUSIONS: Previous research on effects of alcohol on health indices have suggested a J-shaped relationship between amounts of alcohol consumption and measurements of heart disease, stroke, and mortality rates. Our study provides some support for the concept of a similar J-shaped relationship between cognitive performance and alcohol consumption, but the differences between drinking categories were modest and the clinical significance of these findings uncertain.

Activities of Daily Living↗

PubMed1996

An intervention on discharge polypharmacy.

OBJECTIVE: To determine if providing a way to cancel pre-admission prescriptions would reduce the number of active drug prescriptions (RXs) at discharge. DESIGN: A randomized non-blinded clinical trial. SETTING: Inpatient acute medical service of a university affiliated Veterans Administration medical center. PARTICIPANTS: Twelve medicine ward teams were randomized to control and intervention groups. Patients controlled had been discharged from these teams during 12 weeks and were receiving outpatient medications from this facility at hospital admission; control = 180, intervention = 168. INTERVENTION: At discharge, intervention teams used a computer-generated drug list to cancel or renew previous outpatient RXs or to prescribe new medications. Control teams could not cancel outpatient drugs and wrote all medications on individual prescriptions. MEASUREMENTS: The difference between admission and discharge RXs. RESULTS: There were no significant differences in patients' age, sex, race, Charlson Index (CI), or LOS between patient groups at discharge. The intervention group had fewer RXs on admission (5.4 vs 6.2, P < .05) and at discharge was not significantly different (2.9 vs 2.9, P = .87) from the control group. CONCLUSIONS: Providing a method for canceling pre-admission medications did not reduce the number of RXs at discharge. Further research is needed to evaluate the appropriateness of the large increase in RXs from admission to discharge for patients in acute hospital settings.

Analysis of Variance↗