Biomedical subjects

Jianwen Cai

Publications and source records attributed to Jianwen Cai.

At least 19 recordsLinked to original sources

PubMed2024

Genetics of Latin American Diversity Project: Insights into population genetics and association studies in admixed groups in the Americas.

Latin Americans are underrepresented in genetic studies, increasing disparities in personalized genomic medicine. Despite available genetic data from thousands of Latin Americans, accessing and navigating the bureaucratic hurdles for consent or access remains challenging. To address this, we introduce the Genetics of Latin American Diversity (GLAD) Project, compiling genome-wide information from 53,738 Latin Americans across 39 studies representing 46 geographical regions. Through GLAD, we identified heterogeneous ancestry composition and recent gene flow across the Americas. Additionally, we developed GLAD-match, a simulated annealing-based algorithm, to match the genetic background of external samples to our database, sharing summary statistics (i.e., allele and haplotype frequencies) without transferring individual-level genotypes. Finally, we demonstrate the potential of GLAD as a critical resource for evaluating statistical genetic software in the presence of admixture. By providing this resource, we promote genomic research in Latin Americans and contribute to the promises of personalized medicine to more people.

Humans↗

PubMed2006

Association between reproductive factors and breast cancer survival in younger women.

This analysis investigated whether reproductive factors such as age at menarche, parity, and timing and outcomes of pregnancies were associated with survival among women with breast cancer younger than 55 years. Female residents of Atlanta, Georgia, and central New Jersey who were diagnosed with a primary, incident invasive breast cancer between 1990 and 1992 and enrolled in a population-based study (n = 1,264) were followed for 8-10 years. Detailed exposure and covariate information was collected via in-person interviews administered shortly after diagnosis. Vital status as of January 1, 2000 was ascertained through the National Death Index via the state cancer registries (n = 292 deaths). Cox regression methods were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for confounders. Parity of 4 or more births, as compared with nulliparity, was positively associated with all-cause mortality, [HR (95% CI) = 1.71 (1.09-2.67)]. Increased mortality was associated with having given birth within 5 years prior to diagnosis ( 5 years) [1.78 (1.28-2.47)], and was more pronounced among women with a pre-diagnostic body mass index of <25 kg/m2 [2.54 (1.61-4.00)]. Early age at menarche and early age at first birth also modestly increased mortality; history of miscarriage, induced abortion, and ever breastfeeding were not related to survival. These results may help elucidate breast cancer progression mechanisms and enable a better understanding of how reproductive characteristics influence breast cancer survival.

Adult↗

PubMed2006

Pesticide exposure and timing of menopause: the Agricultural Health Study.

Age at menopause has implications for fertility and risk of hormonally related chronic diseases. Some pesticides disrupt reproductive hormones or are toxic to the ovary, but little is known about the association between pesticide exposure and timing of menopause. Cox proportional hazards modeling was used to examine the association between use of pesticides and age at menopause among 8,038 women living and working on farms in Iowa and North Carolina. Premenopausal women aged 35-55 years were followed from enrollment (1993-1997) to the date of their last menstrual period, or their follow-up interview (1999-2003) if still premenopausal. Women who experienced surgical menopause were censored at the date of surgery. Approximately 62% of the women reported ever mixing or applying pesticides; women who had never used pesticides were the comparison group for all analyses. After control for age, smoking status, and past use of oral contraceptives, the median time to menopause increased by approximately 3 months for women who used pesticides (hazard ratio = 0.87, 95% confidence interval: 0.78, 0.97) and by approximately 5 months for women who used hormonally active pesticides (hazard ratio = 0.77, 95% confidence interval: 0.65, 0.92). Pesticide use may be associated with a later age at menopause.

Adult↗

PubMed2005

Bootstrap analysis of multivariate failure time data.

Multivariate failure time data often arise in research. Cox proportional hazards modelling is a widely used method of analysing failure time data for independent observations. However, when failure times are correlated the Cox proportional hazards model does not yield valid estimates of standard errors or significance tests. Many methods for the analysis of multivariate failure time data have been proposed. These methods commonly test hypotheses about the regression parameters, a practice which averages the treatment effect across time. The purpose of this paper is to examine the bootstrap method for obtaining standard errors in the multivariate failure time case, particularly when the focus is the survival probability or the treatment effect at a single time point such as in a surgical trial. Our motivating example comes from the Asymptomatic Carotid and Atherosclerosis Study (ACAS) in which the outcome of stroke or perioperative complications could be observed for either or both carotid arteries within each patient. Extensive simulation studies were conducted to examine the bootstrap procedure for analysing correlated failure time data under a variety of conditions including a range of treatment effects, cluster sizes, intercluster correlation values and for both proportional and non-proportional data. We found that the bootstrap method was able to estimate the standard error adequately for survival probabilities at a specific time and the standard error for the survival difference and the relative risk at a specific time. We illustrated the bootstrap method for calculating the standard error for the survival probability and statistical testing at a specific time value by analysing the two arteries per patient from the ACAS study.

Biometry↗

PubMed2005

Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis.

BACKGROUND: Predictors of treatment resistance and relapse have not been well described in antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis. OBJECTIVE: To identify clinical, pathologic, and serologic predictors of treatment resistance and relapse in a community-based cohort of patients with ANCA-associated vasculitis. DESIGN: Cohort of patients identified at or near the time of biopsy diagnosis and followed as clinically indicated. SETTING: The Glomerular Disease Collaborative Network. PATIENTS: 350 patients who received a new diagnosis of ANCA-associated vasculitis between 1985 and 2003 and were followed for a median of 49 months. MEASUREMENTS: Patients were categorized according to whether they had antiproteinase-3 (anti-PR3) antibodies or antimyeloperoxidase (anti-MPO) antibodies. Organ involvement was determined by biopsy or by well-defined clinical criteria. Treatment resistance was defined as progressive decline in kidney function with active urine sediment or the persistence or appearance of extrarenal manifestations. Relapse was defined as the time to the resurgence of vasculitic symptoms. RESULTS: Treatment resistance affected 23% of 334 treated patients and was associated with female sex, black ethnicity, and presentation with severe kidney disease (odds ratio per serum creatinine elevation of 100 micromol/L [1.13 mg/dL], 1.28 [95% CI, 1.16 to 1.39]). The following factors were associated with relapse in 258 (77%) patients who attained remission: seropositivity for anti-PR3 antibodies (hazard ratio, 1.87 [CI, 1.11 to 3.14]) and disease of the lung (hazard ratio, 1.71 [CI, 1.04 to 2.81]) or upper respiratory tract (hazard ratio, 1.73 [CI, 1.04 to 2.88]). Relapses occurred in 26% of patients with no risk factors versus 73% of patients with all 3 risk factors (hazard ratio, 3.7 [CI, 1.4 to 9.7]). Among 143 patients attaining remission who subsequently stopped all immunosuppressant therapy, relapse rates were similar for those who had received cyclophosphamide therapy for 6 months or less (34%) compared with those treated for a longer duration (35%), even after adjusting for risk factors for relapse (hazard ratio, 1.41 [CI, 0.80 to 2.50]). LIMITATIONS: The cohort mostly included patients with biopsy-proven kidney disease. Patients were not followed with uniform treatment protocols, and only limited information about their clinical course before diagnosis was available. CONCLUSIONS: Female or black patients, or those with severe kidney disease, may be resistant to initial treatment more often than other patients with ANCA-associated small-vessel vasculitis. Increased risk for relapse appears to be related to the presence of lung or upper airway disease and anti-PR3 antibody seropositivity.

Adrenal Cortex Hormones↗

PubMed2005

The effect of weight history on glucose and lipids: the Atherosclerosis Risk in Communities Study.

Few studies have examined the impact of weight history. Extant data from the Atherosclerosis Risk in Communities Study were used to compare risk factors for normal-weight (body mass index: 18.5-24.9 kg/m(2)) adults with a history of weight loss (n = 775) with those for persons with a history of weight maintenance (n = 5,164). In this 1987-1998 US study, the authors also compared risk factors for pre-obese (body mass index: 25.0-29.9 kg/m(2)) adults with a history of weight gain (n = 1,296) versus weight maintenance (n = 6,721). They used mixed-models regression to adjust for ethnicity, gender, age, education, field center, smoking, alcohol consumption, follow-up time, and follow-up body mass index. Compared with adults with a history of weight maintenance, adults with a 3-year history of weight loss had more favorable total and low density lipoprotein cholesterol levels and similar glucose, high density lipoprotein cholesterol, and triglyceride levels. In contrast, pre-obese adults with a 3-year history of weight gain had equivalent glucose and lipid levels at follow-up compared with adults with a history of weight maintenance. These findings suggest that, in addition to current weight, weight history may impact glucose and lipid levels.

Alcohol Drinking↗

PubMed2005

Analysis of clustered recurrent event data with application to hospitalization rates among renal failure patients.

End-stage renal disease (commonly referred to as renal failure) is of increasing concern in the United States and many countries worldwide. Incidence rates have increased, while the supply of donor organs has not kept pace with the demand. Although renal transplantation has generally been shown to be superior to dialysis with respect to mortality, very little research has been directed towards comparing transplant and wait-list patients with respect to morbidity. Using national data from the Scientific Registry of Transplant Recipients, we compare transplant and wait-list hospitalization rates. Hospitalizations are subject to two levels of dependence. In addition to the dependence among within-patient events, patients are also clustered by listing center. We propose two marginal methods to analyze such clustered recurrent event data; the first model postulates a common baseline event rate, while the second features cluster-specific baseline rates. Our results indicate that kidney transplantation offers a significant decrease in hospitalization, but that the effect is negated by a waiting time (until transplant) of more than 2 years. Moreover, graft failure (GF) results in a significant increase in the hospitalization rate which is greatest in the first month post-GF, but remains significantly elevated up to 4 years later. We also compare results from the proposed models to those based on a frailty model, with the various methods compared and contrasted.

Biometry↗

PubMed2005

Glutathione S-transferase polymorphisms and survival from head and neck cancer.

BACKGROUND: The purpose of this study was to evaluate the prognostic ability of polymorphisms of three genes involved in the metabolism of tobacco carcinogens (GSTT1, GSTM1, GSTP1) and one polymorphism of a DNA repair gene (XRCC1) for patients diagnosed with squamous cell carcinoma (SCC). METHODS: Cox proportional hazard models were used to estimate risk of death for a prospective cohort of 190 patients. RESULTS: Individuals with the GSTT1 functional genotype were twice as likely to die from any cause (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.13-4.97) and were three times as likely to die from SCC (HR, 3.4; 95% CI, 1.33-8.41) after adjustment for age, primary therapy, and stage of disease. The XRCC1 399 Gln genotype was predictive of disease recurrence. CONCLUSIONS: Our findings, from one of the first studies to examine this research question, suggest that genomic markers of carcinogen metabolism and DNA repair capability may serve as prognostic indicators of disease recurrence and death.

Carcinoma, Squamous Cell↗

PubMed2005

Simultaneous modelling of survival and longitudinal data with an application to repeated quality of life measures.

In biomedical studies, interest often focuses on the relationship between patient's characteristics or some risk factors and both quality of life and survival time of subjects under study. In this paper, we propose a simultaneous modelling of both quality of life and survival time using the observed covariates. Moreover, random effects are introduced into the simultaneous models to account for dependence between quality of life and survival time due to unobserved factors. EM algorithms are used to derive the point estimates for the parameters in the proposed model and profile likelihood function is used to estimate their variances. The asymptotic properties are established for our proposed estimators. Finally, simulation studies are conducted to examine the finite-sample properties of the proposed estimators and a liver transplantation data set is analyzed to illustrate our approaches.

Algorithms↗

PubMed2005

Semiparametric methods for clustered recurrent event data.

In biomedical studies, the event of interest is often recurrent and within-subject events cannot usually be assumed independent. In addition, individuals within a cluster might not be independent; for example, in multi-center or familial studies, subjects from the same center or family might be correlated. We propose methods of estimating parameters in two semi-parametric proportional rates/means models for clustered recurrent event data. The first model contains a baseline rate function which is common across clusters, while the second model features cluster-specific baseline rates. Dependence structures for patients-within-cluster and events-within-patient are both unspecified. Estimating equations are derived for the regression parameters. For the common baseline model, an estimator of the baseline mean function is proposed. The asymptotic distributions of the model parameters are derived, while finite-sample properties are assessed through a simulation study. Using data from a national organ failure registry, the proposed methods are applied to the analysis of technique failures among Canadian dialysis patients.

Analysis of Variance↗

PubMed2005

Role of weight history on functional limitations and disability in late adulthood: the ARIC study.

OBJECTIVE: To examine associations of weight history with functional limitations and disability in white and African-American men and women. RESEARCH METHODS AND PROCEDURES: Data were from the Atherosclerosis Risk in Communities study (n = 11,177). Associations of recalled weight status at age 25 and weight change from age 25 to ages 45 to 64 with functional limitations, activities of daily living (ADLs), and instrumental activities of daily living (IADLs) at follow-up (ages 52 to 75) were examined using logistic regression. RESULTS: Obesity (BMI > or = 30 kg/m2) at age 25 was associated with functional limitations and ADL and IADL impairment at follow-up in white and African-American men and women. For example, obese compared with normal weight (BMI, 18.5 to 24.9 kg/m(2)) white women had higher odds of mild [odds ratio (95% confidence interval), 1.97 (1.18 to 3.29)] and severe [9.81 (5.92 to 16.27)] functional limitations and ADL [3.48 (2.36 to 5.13)] and IADL [2.95 (2.00 to 4.33)] impairment. In African-American women, obesity was associated with higher odds of mild [2.71 (1.14 to 6.41)] and severe [6.01 (2.53 to 14.26)] functional limitations and ADL [1.82 (1.10 to 3.00)] and IADL [2.39 (1.47 to 3.90)] impairment. Similar associations were found in men. Compared with weight maintenance (+/-10 lbs), large weight gain (>30 lbs) from age 25 to ages 45 to 64 was also associated with functional limitations and ADL and IADL impairment in white and African-American men and women. DISCUSSION: Maintenance of a healthy body weight throughout adulthood may play a role in preventing or delaying the onset of functional limitations and disability, resulting in increased quality of life and decreased health care costs.

Activities of Daily Living↗

PubMed2005

Dairy, fruit, and vegetable intakes and functional limitations and disability in a biracial cohort: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Dairy, fruit, and vegetable intakes may be associated with functional limitations and disability through their role in muscle function, osteoporosis, and prevention of the oxidative damage associated with aging and chronic disease. OBJECTIVE: The associations between dairy, fruit, and vegetable intakes and functional limitations and disability were examined in African Americans and whites (baseline age: 45-64 y; n=9404) in the Atherosclerosis Risk in Communities (ARIC) Study. DESIGN: Logistic regression analyses were used to ascertain the associations between usual dairy, fruit, and vegetable intakes obtained at baseline by using a food-frequency questionnaire and lower-extremity function, activities of daily living (ADLs), and instrumental ADLs (IADLs) self-reported approximately 9 y later in models stratified by race and sex. RESULTS: Baseline dairy, fruit, and vegetable intakes tended to be inversely associated with impaired lower-extremity function, ADLs, and IADLs approximately 9 y later, particularly in African American women. For example, in African American women, baseline dairy intakes were inversely associated with impaired ADLs and IADLs [odds ratio (95% CI): 0.60 (0.40, 0.90) and 0.69 (0.48, 0.98), respectively [corrected] in the 3rd versus the [corrected] 1st tertile of intake (P [corrected] for trend<0.05]. Combined baseline intakes of fruit and vegetables were also inversely associated with impaired lower-extremity function, ADLs, and IADLs [odds ratio (95% CI): 0.67 (0.47, 0.95), 0.52 (0.36, 0.76), and 0.64 (0.45, 0.90), respectively; P for trend<0.05]. CONCLUSIONS: Dairy, fruit, and vegetable intakes may be inversely associated with functional limitations and disability. Further research is needed to ascertain the effect of diet on subsequent functional limitations and disability.

Activities of Daily Living↗

PubMed2005

Quantile regression models with multivariate failure time data.

As an alternative to the mean regression model, the quantile regression model has been studied extensively with independent failure time data. However, due to natural or artificial clustering, it is common to encounter multivariate failure time data in biomedical research where the intracluster correlation needs to be accounted for appropriately. For right-censored correlated survival data, we investigate the quantile regression model and adapt an estimating equation approach for parameter estimation under the working independence assumption, as well as a weighted version for enhancing the efficiency. We show that the parameter estimates are consistent and asymptotically follow normal distributions. The variance estimation using asymptotic approximation involves nonparametric functional density estimation. We employ the bootstrap and perturbation resampling methods for the estimation of the variance-covariance matrix. We examine the proposed method for finite sample sizes through simulation studies, and illustrate it with data from a clinical trial on otitis media.

Biometry↗

PubMed2005

Root canal filled versus non-root canal filled teeth: a retrospective comparison of survival times.

OBJECTIVE: This matched cohort study used data from a large dental HMO in the Pacific Northwest to evaluate the degree to which pulpal involvement and subsequent endodontic therapy affects tooth survival. Root canal filled (RCF) teeth were used as an indicator of pulpal involvement. Our hypothesis was that RCF teeth would be extracted sooner than non-RCF teeth matched within subjects, controlling for tooth-level variables of interest. METHODS: The HMO's treatment databases and a subsequent chart audit were used to identify 202 eligible subjects, each of whom had one tooth endodontically treated in 1987-88 and a similar contralateral tooth that was non-RCF at that time. Both teeth were followed from the endodontic access date through the extraction date, the endodontic access date (for initially non-RCF teeth), or 12/31/94, whichever was earliest. Time-to-event analyses were carried out, with Kaplan-Meier curves generated and multivariable marginal proportional hazards regression models fitted to describe the effect of RCF status on tooth survival. All statistical analyses accounted for the complex sampling strategy used in generating the dataset. RESULTS: Teeth were followed for up to eight (median = 6.7) years. RCF teeth had substantially worse survival than their non-RCF counterparts (p < 0.001), with a greater effect of RCF status evident among molars than non-molars. Adjusted hazard ratios (95% confidence intervals) for loss of RCF versus non-RCF molars and non-molars were 7.4 (3.2-15.1) and 1.8 (0.7-4.6), respectively. CONCLUSION: Though endodontic therapy can prolong tooth survival, pulpal involvement still may hasten tooth loss, underscoring the importance of caries prevention and prompt restorative care.

Adult↗

PubMed2004

Non-parametric estimation of gap time survival functions for ordered multivariate failure time data.

Times between sequentially ordered events (gap times) are often of interest in biomedical studies. For example, in a cancer study, the gap times from incidence-to-remission and remission-to-recurrence may be examined. Such data are usually subject to right censoring, and within-subject failure times are generally not independent. Statistical challenges in the analysis of the second and subsequent gap times include induced dependent censoring and non-identifiability of the marginal distributions. We propose a non-parametric method for constructing one-sample estimators of conditional gap-time specific survival functions. The estimators are uniformly consistent and, upon standardization, converge weakly to a zero-mean Gaussian process, with a covariance function which can be consistently estimated. Simulation studies reveal that the asymptotic approximations are appropriate for finite samples. Methods for confidence bands are provided. The proposed methods are illustrated on a renal failure data set, where the probabilities of transplant wait-listing and kidney transplantation are of interest.

Acute Kidney Injury↗

PubMed2004

Total cholesterol and mortality in China, Poland, Russia, and the US.

PURPOSE: To examine the relationships of total and cause-specific mortality to serum cholesterol in four diverse populations. METHODS: Chinese, Polish, Russian, and US population-based samples were studied. The relationship between cholesterol levels and mortality was assessed by Cox proportional hazard regression with restricted piecewise cubic splines. RESULTS: The cholesterol and total mortality relationship was statistically significantly J-shaped for all men combined. In country-specific relationships, cholesterol was significantly, linearly, and positively related to total mortality in Russian and US men. For women, the relationship was non-linear, but not statistically significant, and became statistically significant upon adjustment for other risk factors. For Polish women, a statistically significant inverse relationship existed. CHD mortality and cardiovascular disease (CVD) mortality increased linearly with cholesterol in Polish, Russian, and US men and the aggregate of men, but there was no relationship for women. Cancer mortality was not related to cholesterol except for the Polish cohort and Russian women, where there was an inverse relationship. CONCLUSIONS: Serum cholesterol was a strong, consistent predictor of CHD and CVD mortality in Polish, Russian, and US men despite their social diversity. In contrast to CHD mortality, the relation of cholesterol to total mortality and non-CVD mortality varied by country and gender.

Adult↗

PubMed2004

Marginal means/rates models for multiple type recurrent event data.

Recurrent events are frequently observed in biomedical studies, and often more than one type of event is of interest. Follow-up time may be censored due to loss to follow-up or administrative censoring. We propose a class of semi-parametric marginal means/rates models, with a general relative risk form, for assessing the effect of covariates on the censored event processes of interest. We formulate estimating equations for the model parameters, and examine asymptotic properties of the parameter estimators. Finite sample properties of the regression coefficients are examined through simulations. The proposed methods are applied to a retrospective cohort study of risk factors for preschool asthma.

Asthma↗

PubMed2004

Effect of cardiorespiratory fitness on mortality among hypertensive and normotensive women and men.

BACKGROUND: The effects of fitness on mortality either from cardiovascular disease (CVD) or from all causes, among hypertensive adults, are not fully understood, especially among women. The objective of this study was to examine the effect of fitness on all-cause and CVD mortality among hypertensive and normotensive women and men. METHODS: Using the Lipids Research Clinics Prevalence Study, we examined the relationship of fitness with mortality among 2712 women and 3000 men followed from 1972-1976 to 1998. Cardiorespiratory fitness was measured using a treadmill test. Sex-specific hazard ratios (HRs) were calculated from proportional hazard models of fitness predicting all-cause or CVD mortality, adjusted for age, education, race, smoking, alcohol, body mass index, and hyperlipidemic sampling strata. RESULTS: Comparing the lowest with the highest quintile of fitness, the adjusted all-cause mortality among hypertensive women was 1.7 (95% confidence interval = 0.9-3.2) and among normotensive women was 2.3 (1.5-3.7). Comparing the same quintiles of fitness, the adjusted all-cause mortality among hypertensive men was 2.0 (1.2-3.4), and among normotensive men it was 1.9 (1.3-2.7). Elevated risks were also observed for CVD mortality. CONCLUSION: Higher levels of fitness were associated with a lower risk of all-cause and CVD mortality among both hypertensive and normotensive women and men.

Adult↗