Search PubMed⌕ Search

Biomedical subjects

Stephen R Cole

Publications and source records attributed to Stephen R Cole.

At least 19 recordsLinked to original sources
PubMed2007

Relation of stavudine discontinuation to anthropometric changes among HIV-infected women.

OBJECTIVE: To characterize changes in regional anthropometry associated with stavudine exposure and discontinuation. DESIGN: Seven hundred thirty-four HIV-infected participants who reported using stavudine (574 of whom later discontinued stavudine) and 698 HIV-uninfected participants from the Women's Interagency HIV Study provided anthropometrics at 8706 semiannual visits between July 1999 and March 2005. METHODS: Changes in weight, waist, chest, upper arm, hip, and midthigh circumferences were evaluated using linear regression with generalized estimating equations. RESULTS: HIV-uninfected women demonstrated increases in regional anthropometry at every body site, whereas HIV-infected women demonstrated decreases in weight and circumferences of the waist, chest, hip, and thigh. A smaller annual decrease in hip circumference was seen after discontinuing stavudine for >2.25 years compared with the decrease observed while on stavudine (P = 0.01). Discontinuing stavudine for >2.25 years was associated with smaller (P < 0.05) decreases in hip (-0.06 cm/y) and thigh (-0.005 cm/y) circumference compared with the decreases observed between 1 and 2.25 years (hip: -0.46 cm/y, thigh: -0.24 cm/y) or < or =1 year (hip: -0.64 cm/y, thigh: -0.27 cm/y) after stavudine discontinuation. CONCLUSIONS: Regardless of continuing or discontinuing stavudine, HIV-infected women demonstrate decreases in weight and body circumference measurements over time. The lower limb seems to be most affected by stavudine exposure, with stabilization observed more than 2 years after discontinuation.

Adult↗
PubMed2006

The association of anemia and hypoalbuminemia with accelerated decline in GFR among adolescents with chronic kidney disease.

We sought to describe rates of kidney function decline and to identify modifiable risk factors for CKD progression in a multicenter prospective cohort study of adolescents with CKD aged 11 to 18 years seen semiannually for up to three years. Of the 23 subjects meeting inclusion criteria, the average estimated GFR was 51 +/- 27 ml/min/1.73 m(2) (0.85 +/- 0.45 ml/s/1.73 m(2)) at entry. The overall annualized decline in GFR was 5.6 ml/min/1.73 m(2) (0.093 ml/s/1.73 m(2)) per year (95% confidence interval [95% CI]: 1.9 to 9.3 [0.032 to 0.16]). The adjusted annualized decline in GFR was found to be accelerated in males, as well as among those over 15 years of age. The adjusted annualized decline in GFR was greater among those with either anemia (hematocrit below 36%), or hypoalbuminemia (albumin below 4 g/dl [40 g/L]). After adjustment, anemia was associated with an accelerated decline of 7.8 ml/min/1.73 m(2) (0.13 ml/s/1.73 m(2)) (95% CI: 3.3 to 12 [0.055 to 0.20]) and hypoalbuminemia was associated with an accelerated decline of 17 ml/min/1.73 m(2) (0.28 ml/s/1.73 m(2)) (95% CI: 11 to 22 [0.18 to 0.37]). Further study is needed to evaluate whether treatment of anemia or hypoalbuminemia, as outlined in current clinical care guidelines for CKD, may slow the progression of CKD in adolescents.

Adolescent↗
PubMed2006

Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a sensitive guaiac-based fecal occult blood test in detection of colorectal neoplasia.

BACKGROUND: Fecal immunochemical tests (FIT) are an advanced fecal occult blood test (FOBT) technology that reduces barriers to population screening by simplifying the logistics of stool-sampling. The current study was conducted to undertake a paired comparison of a sensitive guaiac FOBT (GFOBT; Hemoccult II Sensa, Beckman Coulter, Fullerton, CA) with a brush-sampling FIT (InSure; Enterix, North Ryde, NSW, Australia), to determine whether this FIT improves detection of significant neoplasia. METHODS: Individuals sampled consecutive stools, at home, with both FIT and GFOBT sampling devices while following dietary restrictions appropriate for GFOBT. Study populations included a screening cohort (n = 2351) and a symptomatic diagnostic group (n = 161). Paired comparison of positivity rates was undertaken in those found to have cancer and/or significant adenoma (high-grade dysplasia, villous change, > or =10 mm, serrated histology or > or =3 polyps), benign pathology, or no pathology. RESULTS: Combined results for both cohorts showed that the FIT returned a true-positive result significantly more often in cancer (n = 24; 87.5% vs. 54.2%) and in significant adenomas (n = 61; 42.6% vs. 23.0%). Of all UICC Stage I cancers, the FIT was positive in 12 of 13 compared with 4 of 13 with the GFOBT (P = .002). In analyses of just the screening cohort, the FIT remained significantly better at detecting cancers and significant adenomas; the false-positive rate for any neoplasia was marginally higher with the FIT than the GFOBT (3.4% vs. 2.5%; 95% CI of difference, 0-1.8%), whereas positive predictive values were 41.9% and 40.4%, respectively. CONCLUSIONS: This brush-sampling FIT is more sensitive for cancers and significant adenomas than a sensitive GFOBT. As such, it should deliver greater reductions in colorectal cancer mortality and incidence than the GFOBT.

Adenoma↗
PubMed2006

Confidence intervals for biomarker-based human immunodeficiency virus incidence estimates and differences using prevalent data.

Prevalent biologic specimens can be used to estimate human immunodeficiency virus (HIV) incidence using a two-stage immunologic testing algorithm that hinges on the average time, T, between testing HIV-positive on highly sensitive enzyme immunoassays and testing HIV-positive on less sensitive enzyme immunoassays. Common approaches to confidence interval (CI) estimation for this incidence measure have included 1) ignoring the random error in T or 2) employing a Bonferroni adjustment of the box method. The authors present alternative Monte Carlo-based CIs for this incidence measure, as well as CIs for the biomarker-based incidence difference; standard approaches to CIs are typically appropriate for the incidence ratio. Using American Red Cross blood donor data as an example, the authors found that ignoring the random error in T provides a 95% CI for incidence as much as 0.26 times the width of the Monte Carlo CI, while the Bonferroni-box method provides a 95% CI as much as 1.57 times the width of the Monte Carlo CI. Further research is needed to understand under what circumstances the proposed Monte Carlo methods fail to provide valid CIs. The Monte Carlo-based CI may be preferable to competing methods because of the ease of extension to the incidence difference or to exploration of departures from assumptions.

Algorithms↗
PubMed2006

Combined analysis of retrospective and prospective occurrences in cohort studies: HIV-1 serostatus and incident pneumonia.

BACKGROUND: The authors show how information collected on retrospective occurrence times may be combined with prospective occurrence times in the analysis of recurrent events from cohort studies. METHODS: We demonstrate how the observed data can be expanded from one to two records per participant and account for the within-individual dependence when estimating variances. We illustrate our methods using data from the Women's Interagency HIV Study, which recorded 384 retrospective and 352 prospective occurrences of pneumonia in 9478 retrospective and 7857 prospective person-years among 2610 adult women. RESULTS: The hazard of non-Pneumocystis carinii pneumonia among the 2056 HIV-1 infected women was 2.24 times (95% confidence limits: 1.74, 2.89) that of the 554 uninfected women, independent of age. This hazard ratio was homogeneous across retrospective and prospective occurrences (P for interaction = 0.96) and combining occurrence types increased the precision by reducing the standard error by about a fourth. CONCLUSIONS: As expected, HIV-1 infection increases the hazard of pneumonia, with more precise inference obtained by combining information available on bidirectional occurrences. The proposed method for the analysis of bidirectional occurrence times will improve precision when the estimated associations are homogeneous across occurrence types, or may provide added insight into either the data collection or disease process when the estimated associations are heterogeneous.

AIDS-Related Opportunistic Infections↗
PubMed2006

Sample size and statistical power assessing the effect of interventions in the context of mixture distributions with detection limits.

Often in randomized clinical trials and observational cohort studies, a non-negative continuously distributed response variable is measured in treatment and control groups. In the presence of true zeros for the response variable, a two-part zero-inflated log-normal model (which assumes that the data has a probability mass at zero and a continuous response for values greater than zero) is usually recommended. However, in some environmental health and human immunodeficiency virus (HIV) studies, quantitative assays for metabolites of toxicants, or quantitative HIV RNA measurements are subject to left-censoring due to values falling below the limit of detection (LD). Here, a zero-inflated log-normal mixture model is often suggested since true zeros are indistinguishable from left-censored values due to the LD. When the probabilities of true zeros in the two groups are not restricted to be equal, the information contributed by values falling below LD is used only to estimate the probability of true zeros in the context of mixture distributions. We derived the required sample size to assess the effect of a treatment in the context of mixture models with equal and unequal variances based on the left-truncated log-normal distribution. Methods for calculation of statistical power are also presented. We calculate the required sample size and power for a recent study estimating the effect of oltipraz on reducing urinary levels of the hydroxylated metabolite aflatoxin M(1) (AFM(1)) in a randomized, placebo-controlled, double-blind phase IIa chemoprevention trial in Qidong, China. A Monte Carlo simulation study is conducted to investigate the performance of the proposed methods.

Aflatoxin M1↗
PubMed2006

Sensitivity analysis of misclassification: a graphical and a Bayesian approach.

PURPOSE: Misclassification can produce bias in measures of association. Sensitivity analyses have been suggested to explore the impact of such bias, but do not supply formally justified interval estimates. METHODS: To account for exposure misclassification, recently developed Bayesian approaches were extended to incorporate prior uncertainty and correlation of sensitivity and specificity. Under nondifferential misclassification, a contour plot is used to depict relations among the corrected odds ratio, sensitivity, and specificity. RESULTS: Methods are illustrated by application to a case-control study of cigarette smoking and invasive pneumococcal disease while varying the distributional assumptions about sensitivity and specificity. Results are compared with those of conventional methods, which do not account for misclassification, and a sensitivity analysis, which assumes fixed sensitivity and specificity. CONCLUSION: By using Bayesian methods, investigators can incorporate uncertainty about misclassification into probabilistic inferences.

Bayes Theorem↗
PubMed2006

A symptom survey and quality of life questionnaire for nasolacrimal duct obstruction in children.

PURPOSE: To develop and validate a new parental questionnaire addressing symptoms and health-related quality of life (HRQL) in childhood nasolacrimal duct obstruction (NLDO). DESIGN: Cross-sectional study. PARTICIPANTS: Children ages 6 to younger than 48 months with and without clinical signs of NLDO. METHODS: A new questionnaire was developed using semistructured interviews with parents of children with NLDO and through discussions with expert clinicians. Questionnaires were completed by parents of children with and without NLDO. Cronbach's alpha was calculated as a measure of internal-consistency reliability. Factor analysis was used to evaluate a priori subscales: symptoms and HRQL. Discriminant construct validity was assessed by comparing questionnaire scores between children with and without NLDO and between affected and unaffected eyes of children with unilateral NLDO. Instrument responsiveness was determined by comparing presurgical and postsurgical intervention scores in a subset of NLDO patients who underwent surgical treatment. MAIN OUTCOME MEASURE: The NLDO questionnaire score. RESULTS: Eighty-seven children were enrolled, 56 with and 31 without NLDO. All but 2 questions on the questionnaire showed a good distribution of responses, a high correlation with the rest of the questionnaire, and excellent discrimination between patients with and without NLDO. Cronbach's alpha values were good for the overall questionnaire (0.95), and for 2 predetermined subscales: symptoms (0.95) and HRQL (0.85). On a 0 to 4 scale, NLDO patients had worse scores compared with non-NLDO patients for both symptoms (mean difference, 2.1; 95% confidence interval [CI], 1.9-2.3) and HRQL (mean difference, 1.2; 95% CI, 0.9-1.5) subscales. The NLDO patients had worse scores before intervention compared with after intervention for both the symptoms (mean difference, 2.2; 95% CI, 1.6-2.9) and HRQL (mean difference, 1.4; 95% CI, 0.8-2.1) subscales. Finally, NLDO patients had worse symptom scores for affected eyes compared with unaffected eyes (mean difference, 2.3; 95% CI, 1.9-2.6). CONCLUSIONS: This novel NLDO questionnaire is useful in quantifying parental perception of symptoms and HRQL in childhood NLDO. The questionnaire may have a role in future clinical studies of NLDO.

Child, Preschool↗
PubMed2006

Multiple-imputation for measurement-error correction.

BACKGROUND: There are many methods for measurement-error correction. These methods remain rarely used despite the ubiquity of measurement error. METHODS: Treating measurement error as a missing-data problem, the authors show how multiple-imputation for measurement-error (MIME) correction can be done using SAS software and evaluate the approach with a simulation experiment. RESULTS: Based on hypothetical data from a planned cohort study of 600 children with chronic kidney disease, the estimated hazard ratio for end-stage renal disease from the complete data was 2.0 [95% confidence limits (95% CL) 1.4, 2.8] and was reduced to 1.5 (95% CL 1.1, 2.1) using a misclassified exposure of low glomerular filtration rate at study entry (sensitivity of 0.9 and specificity of 0.7). The MIME correction hazard ratio was 2.0 (95% CL 1.2, 3.3), the regression calibration (RC) hazard ratio was 2.0 (95% CL 1.1, 3.7), and restriction to a 25% validation substudy yielded a hazard ratio of 2.0 (95% CL 1.0, 3.7). Based on Monte Carlo simulations across eight scenarios, MIME was approximately unbiased, had approximately correct coverage, and was sometimes more powerful than misclassified or RC analyses. Using root mean squared error as a criterion, the MIME bias correction is sometimes outweighed by added imprecision. CONCLUSION: The choice between MIME and RC depends on performance, ease, and objectives. The usefulness of MIME correction in specific applications will depend upon the sample size or the proportion validated. MIME correction may be valuable in interpreting imperfectly measured epidemiological data.

Bias↗
PubMed2006

Estimating biomarker-based HIV incidence using prevalence data in high risk groups with missing outcomes.

The novel two-step serologic sensitive/less sensitive testing algorithm for detecting recent HIV seroconversion (STARHS) provides a simple and practical method to estimate HIV-1 incidence using cross-sectional HIV seroprevalence data. STARHS has been used increasingly in epidemiologic studies. However, the uncertainty of incidence estimates using this algorithm has not been well described, especially for high risk groups or when missing data is present because a fraction of sensitive enzyme immunoassay (EIA) positive specimens are not tested by the less sensitive EIA. Ad hoc methods used in practice provide incorrect confidence limits and thus may jeopardize statistical inference. In this report, we propose maximum likelihood and Bayesian methods for correctly estimating the uncertainty in incidence estimates obtained using prevalence data with a fraction missing, and extend the methods to regression settings. Using a study of injection drug users participating in a drug detoxification program in New York city as an example, we demonstrated the impact of underestimating the uncertainty in incidence estimates using ad hoc methods. Our methods can be applied to estimate the incidence of other diseases from prevalence data using similar testing algorithms when missing data is present.

Bayes Theorem↗
PubMed2006

A general approach for sample size and statistical power calculations assessing of interventions using a mixture model in the presence of detection limits.

A zero-inflated log-normal mixture model (which assumes that the data has a probability mass at zero and a continuous response for values greater than zero) with left censoring due to assay measurements falling below detection limits has been applied to compare treatment groups in randomized clinical trials and observational cohort studies. The sample size calculation (for a given type I error rate and a desired statistical power) has not been studied for this type of data under the assumption of equal proportions of true zeros in the treatment and control groups. In this article, we derive the sample sizes based on the expected differences between the non-zero values of individuals in treatment and control groups. Methods for calculation of statistical power are also presented. When computing the sample sizes, caution is needed as some irregularities occur, namely that the location parameter is sometimes underestimated due to the mixture distribution and left censoring. In such cases, the aforementioned methods fail. We calculated the required sample size for a recent randomized chemoprevention trial estimating the effect of oltipraz on reducing aflatoxin. A Monte Carlo simulation study was also conducted to investigate the performance of the proposed methods. The simulation results illustrate that the proposed methods provide adequate sample size estimates. However, when the aforementioned irregularity occurs, our methods are restricted and further research is needed.

Anticarcinogenic Agents↗
PubMed2006

Sexually transmitted infections and prostatic inflammation/cell damage as measured by serum prostate specific antigen concentration.

PURPOSE: Although inflammation and cell damage due to STIs are hypothesized to contribute to the later development of prostate disease, few clinical studies have been done to investigate the extent to which sexually transmitted agents infect and induce an inflammatory immune response in the prostate. We indirectly investigated this question by measuring serum PSA, a possible marker of prostatic inflammation and cell damage, in men with documented STIs. MATERIALS AND METHODS: Archived serum specimens from young men with laboratory confirmed exudative STIs, including gonorrhea, chlamydia and trichomonosis, and young men with no STI diagnoses were identified in 2 prospective studies of patients at Baltimore City STI clinics, that is 84 in the STI Transmission and Acquisition Study, and 61 in the Mucosal Immunity Study. Serum specimens from visits before, during and after STI diagnoses in men with at least 1 exudative STI diagnosis and from all visits in men with no STI diagnoses were tested for total PSA concentration. RESULTS: After combining the studies patients with STIs were more likely to have a 40% or greater increase in PSA than patients with no STI diagnoses (32% vs 2%, p <0.01). CONCLUSIONS: These findings suggest that STIs may contribute to prostatic inflammation and cell damage in a subset of infected men. Further studies are warranted to replicate study findings and determine host and infection characteristics associated with large PSA increases.

Adolescent↗
PubMed2006

Many participants in fecal occult blood test population screening have a higher-than-average risk for colorectal cancer.

OBJECTIVES: Population-based colorectal cancer screening by fecal occult blood testing reduces cancer-specific mortality. Current guidelines recommend this strategy for average risk individuals. This study investigated the prevalence of higher-than-average risk characteristics, and rate of prior colonoscopy, in participants in fecal occult blood test screening programs. METHODS: Randomly selected individuals aged 50-74 years in urban Adelaide were offered free fecal occult blood test screening by mail, without prior knowledge of their medical status. Each invitation included a questionnaire to record the prevalence of higher-than-average risk characteristics related to symptoms, family history or comorbidity, as well as prior colonoscopy. The definition of average risk was taken from updated guidelines published by the US Multisociety Task Force on Colorectal Cancer. RESULTS: Of 2538 responses analyzed, 425 individuals had had a colonoscopy within the last 5 years, 106 fulfilled family history criteria for an initial screening colonoscopy, 209 had past polyps and 26 had had colorectal cancer. Eighty-three reported recent rectal bleeding. By current guidelines, 23% of the screened population did not warrant fecal occult blood test, because either prior colonoscopy rendered it unnecessary or particular patient characteristics made colonoscopy a more appropriate initial investigation. CONCLUSIONS: Fecal occult blood test screening programs capture a sizeable number of higher-than-average risk individuals that may warrant colonoscopic rather than fecal occult blood test screening. Other participants have had a recent colonoscopy and probably warrant a delay in screening. Mass population fecal occult blood test-based screening programs need to more effectively target those at average risk and should divert those of higher or lower risk to more individualized assessment.

Aged↗
PubMed2006

Shared and unique contributions of anger, anxiety, and depression to coronary heart disease: a prospective study in the normative aging study.

BACKGROUND: Anger, anxiety, and depression have each been identified as risk factors for coronary heart disease (CHD). Whether the apparent risk is a function of unique aspects of each emotion or due to a shared underlying dimension of negative affectivity is unclear. PURPOSE: The goal of this study was to assess shared and unique contributions of anger, anxiety, and depression to incident CHD. METHODS: Data are from the Veterans Administration Normative Aging Study, an ongoing cohort of older men. Measures of anger, anxiety, and depression were obtained from 1,306 men completing the revised Minnesota Multiphasic Personality Inventory in 1986. From these measures we derived three near-orthogonal scales termed iso(lated)-anger, iso-anxiety, and iso-depression and a fourth scale measuring general distress. RESULTS: During an average of 10.9 years of follow-up, 161 cases of incident CHD occurred. When considered individually, iso-anxiety, iso-anger, and shared general distress were each associated with CHD risk. When all emotions were considered simultaneously, only iso-anxiety and shared general distress were associated with incident CHD. CONCLUSIONS: Considering shared versus unique aspects of negative emotions may clarify the nature of their apparent toxicity in relation to CHD risk. General distress shared across negative emotions is an important component in the emotion-CHD relation. Aspects of anxiety may also independently increase CHD risk.

Adult↗
PubMed2005

Changes in physical and psychosocial functioning among adolescents with chronic kidney disease.

Little research has been published assessing changes in the functional health status of children and adolescents with chronic kidney disease (CKD). We know little about which clinical parameters influence functional status or health-related quality of life in these young people. In a prospective study using data from semi-annual visits over a 4-year period from 78 adolescents with CKD aged 11 years to 18 years, we detail the impact of several clinical measures (i.e., kidney function, albumin, hematocrit, height) on short-term changes in health-related quality of life. The 50-item Child Health Questionnaire Parent Form, a validated health-related quality of life measure in children, was used to obtain physical and psychosocial functioning summary scores at each visit. After adjustment for the variables mentioned above, the physical summary score on the Child Health Questionnaire (CHQ) declined as glomerular filtration rate declined. Increasing height was associated with a positive change in physical and psychosocial summary scores. We conclude that decline in kidney function is associated with a subsequent decline in health-related quality of life, particularly in terms of physical activity.

Activities of Daily Living↗