Biomedical subjects

Louise M Ryan

Publications and source records attributed to Louise M Ryan.

14 recordsLinked to original sources

PubMed2004

Using exposure prediction rules for exposure assessment: an example on whole-body vibration in taxi drivers.

BACKGROUND: It is often difficult and expensive to make direct measurements of an individual's occupational or environmental exposures in large epidemiologic studies. METHODS: In this study, we used information collected in validation studies to develop a prediction rule for assessing exposure in a study with no direct measurement. We established a prediction rule through mixed-effect modeling of direct measurement data and information on observable exposure predictors and their interactions. Specifically, we used 383 measures of whole-body vibration from 247 professional taxi drivers and attempted to quantify vibration exposures for individuals in a large study on low back pain. RESULTS: Using the "jackknife method," we found that our prediction rule had an acceptably low relative prediction error of 11% (95% confidence interval-10-12%). Implementing the prediction rule would result in measurement errors independent of low back pain and of all identified and observable predictors of whole-body vibration. We applied the predicted levels to compute each person's daily exposure, and found a strong association between the predicted daily whole-body vibration exposure and prevalence of low back pain. This supported the construct validity of the exposure prediction rule. CONCLUSIONS: The predictive and construct validity of our prediction rule suggests that this general statistical approach can be useful in other occupational settings to improve the quality of exposure assessment.

Adult↗

PubMed2004

Knee pain and driving duration: a secondary analysis of the Taxi Drivers' Health Study.

OBJECTIVES: We explored a postulated association between daily driving time and knee pain. METHODS: We used data from the Taxi Drivers' Health Study to estimate 1-year prevalence of knee pain as assessed by the Nordic musculoskeletal questionnaire. RESULTS: Among 1242 drivers, the prevalence of knee pain, stratified by duration of daily driving (< or = 6, > 6 through 8, > 8 through 10, and > 10 hours), was 11%, 17%, 19%, and 22%, respectively. Compared with driving 6 or fewer hours per day, the odds ratio of knee pain prevalence for driving more than 6 hours per day was 2.52 (95% confidence interval = 1.36, 4.65) after we adjusted for socioeconomic, work-related, and personal factors in the multiple logistic regression. CONCLUSIONS: The dose-related association between driving duration and knee pain raises concerns about work-related knee joint disorders among professional drivers.

Absenteeism↗

PubMed2004

Depressive symptoms and risk of type 2 diabetes in women.

OBJECTIVE: To explore the relationship between depressive symptoms and incidence of type 2 diabetes in women. RESEARCH DESIGN AND METHODS: We conducted an analysis of 72,178 female nurses aged 45-72 years who did not have diagnosed diabetes and who answered the Medical Outcomes Study 36-Item Short-Form Health Status Survey (SF-36) at baseline in 1992. We calculated relative risks (RR) of type 2 diabetes for women with presence of depressive symptoms (i.e., Five-Item Mental Health Index [MHI-5] score >52). RESULTS: During 4 years of follow-up (282,317 person-years), 973 incident cases of type 2 diabetes were documented. Age-adjusted RR of developing type 2 diabetes for women with presence of depressive symptoms was 1.55 (95% CI 1.27-1.90). Additional adjustment for BMI resulted in a RR of developing type 2 diabetes of 1.36 (1.11-1.67). The multivariate RR of developing type 2 diabetes was 1.22 (1.00-1.50). After excluding women diagnosed with diabetes between 1992 and 1994, 472 incident cases of type 2 diabetes were documented for the follow-up period from 1994 to 1996 (148,889 person-years). The multivariate RR of developing type 2 diabetes for women with depressive symptoms was 1.29 (0.96-1.72). CONCLUSIONS: Our data suggest that depressive symptoms are associated with a modest increase in the risk of type 2 diabetes.

Alcohol Drinking↗

PubMed2003

Fungal levels in the home and lower respiratory tract illnesses in the first year of life.

The association between home dampness and lower respiratory symptoms in children has been well documented. Whether fungal exposures contribute to this association is uncertain. In a prospective birth cohort of 499 children of parents with asthma/allergies, we examined in-home fungal concentrations as predictors of lower respiratory illnesses (LRI) (croup, pneumonia, bronchitis, and bronchiolitis) in the first year. In multivariate analyses, we found a significant increased relative risk (RR) between LRI and high levels (more than the 90th percentile) of airborne Penicillium (RR = 1.73, 95% confidence interval [CI], 1.23, 2.43), dust-borne Cladosporium (RR = 1.52; CI, 1.02, 2.25), Zygomycetes (RR = 1.96; CI, 1.35, 2.83), and Alternaria (RR = 1.51; CI, 1.00, 2.28), after controlling for sex, presence of water damage or visible mold/mildew, born in winter, breastfeeding, and being exposed to other children through siblings. In a multivariate analysis, the RR of LRI was elevated in households with any fungal level at more than the 90th percentile (RR = 1.86; CI, 1.21, 2.88). Exposure to high fungal levels increased the risk of LRI in infancy, even for infants with nonwheezing LRI. Actual mechanisms remain unknown, but fungi and their components (glucans, mycotoxins, and proteins) may increase the risk of LRI by acting as irritants or through increasing susceptibility to infection.

Air Microbiology↗

PubMed2003

Phase II trial of gemcitabine in patients with advanced sarcomas (E1797): a trial of the Eastern Cooperative Oncology Group.

BACKGROUND: The current study was conducted to evaluate the antitumor activity and toxicity of gemcitabine in patients with advanced sarcoma. METHODS: Twenty-five patients with advanced sarcomas, who previously were untreated for metastatic disease, were treated on an Eastern Cooperative Oncology Group Phase II study. Patients ranged in age from 27 to 79 years, with a median age of 59 years. The most common histology was leiomyosarcoma (54%). The grades of the tumors were high in 40%, moderate in 24% and low in 12%. Gemcitabine was given at a dose of 1250 mg/m(2) as a 30-minute infusion weekly for 3 weeks followed by 1 week of rest. RESULTS: One of the 25 patients (4%) (90% confidence interval [90% CI], 0-18%) achieved a partial response lasting 8 months. The estimated overall median survival was 15 months. The 1-year estimated survival rate was 63% (90% CI, 47-84%). The estimated median progression-free survival (PFS) was 13 months with a 1-year PFS rate of 56% (90% CI, 41-76%). Grade 3-4 toxicities (by CTC criteria) were observed in all 25 patients. No lethal toxicity (Grade 5) related to treatment was found. CONCLUSIONS: The results of the current study demonstrated that gemcitabine given at this schedule and dose in this population of patients with advanced sarcoma had limited activity.

Adult↗

PubMed2003

Chorionic villus sampling: a distinctive teratogenic effect on fingers?

BACKGROUND: An increased frequency of major limb malformations, especially terminal transverse limb defects, have been described in several studies of birth defects in children who had been exposed to the prenatal diagnosis procedure known as chorionic villus sampling (CVS). Vascular disruption has been proposed as the mechanism behind the fetal effect. We postulate that this mechanism is more likely to affect one or two middle fingers, rather than all five fingers. A recent report of the frequency of defects in any or all fingers in an unexposed control population enabled us to assess whether CVS is associated with an increased frequency of defects involving one or two fingers, as well as terminal transverse limb defects. METHODS: The frequency of limb-reduction defects affecting one or more fingers or toes, including those with constriction rings and tissue loss, in published studies of 20,236 children who had been exposed to CVS was compared with the frequency in 161,252 newborn infants who had not been exposed to CVS. Children with recognized genetic disorders were excluded. RESULTS: Several aspects of the limb deficiencies were more common in the CVS-exposed infants than in unexposed controls. The former were more likely to have: 1) any type of limb deficiency involving one or more fingers (p < .001); 2) absence/ hypoplasia of two fingers (p < .001); and 3) absence/hypoplasia of all five fingers (p = .015). The absence of the distal portion of the third finger was a distinctive type of limb-reduction defect in CVS-exposed infants. CONCLUSIONS: The occurrence of deficiencies in one or two fingers, including those designated as "amniotic band deformities," are as common as terminal transverse limb defects in CVS-exposed infants, and both are much more common than in unexposed infants. The absence of the distal portion of the third finger, with tapering and stiff joints, appears to be a distinctive effect of exposure to CVS.

Child↗

PubMed2003

Arsenic methylation and bladder cancer risk in Taiwan.

OBJECTIVE: The mechanism of arsenic detoxification in humans remains unclear. Data are especially lacking for low-level arsenic exposure. We hypothesize that arsenic methylation ability, defined as the ratios of monomethylarsonic acid (MMA(V))/inorganic arsenic (primary arsenic methylation index, PMI) and dimethylarsinic acid (DMA(V))/ MMA(V) (secondary arsenic methylation index, SMI), may modify the association between cumulative arsenic exposure (CAE, mg/L-year) and the risk of bladder cancer. In this study we investigated the relationship among arsenic methylation ability, CAE, and the risk of bladder cancer in a hospital-based case-control study in southwestern Taiwan. METHODS: From January 1996 to December 1999 we identified 49 patients with newly diagnosed cases of bladder cancer at the National Cheng-Kung University (NCKU) Medical Center; controls consisted of 224 fracture and cataract patients selected from the same medical center. The levels of four urinary arsenic species: arsenite (As(III)), arsenate (As(V)), MMA(V), and DMA(V)) were determined in all subjects by using the high-performance liquid chromatography hydride-generation atomic absorption spectrometry (HPLC-HGAAS). CAE was estimated by using published data collected in a survey from 1974 to 1976. RESULTS: Compared to a CAE < or = 2 mg/L-year, CAE > 12 mg/L-year was associated with an increased risk of bladder cancer (multivariate odds ratio (OR) 4.23, 95% confidence interval (CI) 1.12-16.01), in the setting of a low SMI (< or = 4.8). Compared to women, smoking men (OR 6.23, 95% CI 1.88-20.62) and non-smoking men (OR 3.25, 95% CI 0.95-11.06) had higher risks of bladder cancer. Given the same level of PMI, smoking men (OR 9.80, 95% CI 2.40-40.10) and non-smoking men (OR 4.45, 95% CI 1.00-19.84) had a higher risk of bladder cancer when compared to women. With the same level of SMI, both smoking men (OR 6.28, 95% CI 1.76-22.39) and non-smoking men (OR 3.31, 95% CI 0.84-12.97) had a higher risk of bladder cancer when compared to women. CONCLUSIONS: Subjects with low SMI have a substantially increased risk of bladder cancer, especially when combined with high CAE levels.

Aged↗

PubMed2003

Genetic polymorphism in p53 codon 72 and skin cancer in southwestern Taiwan.

The Pro/Pro polymorphism of p53 codon 72 has been reported to be related to bladder and lung cancer, but its relationship with skin cancer is unclear. We assessed the hypothesis that there is a relationship between the p53 codon 72, Pro/Pro polymorphism, cumulative arsenic exposure, and the risk of skin cancer in a hospital-based case-control study in southwestern Taiwan. From 1996 to 1999, 93 newly-diagnosed skin cancer patients at the National Cheng-Kung University (NCKU) Hospital and 71 community controls matched on residence were recruited in southwestern Taiwan. The genotype of p53 codon 72 (Arg/Arg, Arg/Pro, or Pro/Pro) was determined for all subjects by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). A questionnaire was administered to each subject for collection of demographic information, personal habits, disease history, diet information, and other relevant questions. The Pro/Pro (homozygous) genotype was more frequent in skin cancer patients (cases, 20%; controls, 12%; P = 0.37). Subjects with the susceptible genotype Pro/Pro and heterozygous (intermediate) genotype Pro/Arg had 2.18 and 0.99 times risk of skin cancer than the wild type Arg/Arg (95% confidence interval, 0.74-4.38; 95% confidence interval, 0.44-2.21), respectively. Compared with subjects with 18.5 < BMI < 23, subjects with BMI > 18.5 had 5.78 times risk of skin cancer (95% confidence interval, 1.06 to 31.36) after adjusting for other risk factors. There was no interaction between BMI and genotype, but the sample size was small. The risk of skin cancer did not significantly vary by tumor cell-type. The risk of skin cancer is increased in individuals with the Pro/Pro genotype. Larger, confirmatory studies are needed to clarify the role of constitutional polymorphisms in p53 and skin cancer risk.

Adult↗

PubMed2003

Scaled marginal models for multiple continuous outcomes.

In studies that involve multivariate outcomes it is often of interest to test for a common exposure effect. For example, our research is motivated by a study of neurocognitive performance in a cohort of HIV-infected women. The goal is to determine whether highly active antiretroviral therapy affects different aspects of neurocognitive functioning to the same degree and if so, to test for the treatment effect using a more powerful one-degree-of-freedom global test. Since multivariate continuous outcomes are likely to be measured on different scales, such a common exposure effect has not been well defined. We propose the use of a scaled marginal model for testing and estimating this global effect when the outcomes are all continuous. A key feature of the model is that the effect of exposure is represented by a common effect size and hence has a well-understood, practical interpretation. Estimating equations are proposed to estimate the regression coefficients and the outcome-specific scale parameters, where the correct specification of the within-subject correlation is not required. These estimating equations can be solved by repeatedly calling standard generalized estimating equations software such as SAS PROC GENMOD. To test whether the assumption of a common exposure effect is reasonable, we propose the use of an estimating-equation-based score-type test. We study the asymptotic efficiency loss of the proposed estimators, and show that they generally have high efficiency compared to the maximum likelihood estimators. The proposed method is applied to the HIV data.

Antiretroviral Therapy, Highly Active↗

PubMed2003

Arsenic methylation and skin cancer risk in southwestern Taiwan.

Arsenic is a known carcinogen, but data are especially lacking on the health effects of low-level exposure, and on the health significance of methylation ability. We conducted a case-control study (76 cases and 224 controls from 1996 to 1999) in southwestern Taiwan to explore the association among primary and secondary arsenic methylation index (PMI and SMI, respectively), cumulative arsenic exposure (CAE), and the risk of skin cancer. As compared with the controls, the skin cancer group reported more sun exposure (P = 0.02) and had a lower BMI (P = 0.03), as well as lower education level (P = 0.01). Skin cancer patients and controls were similar with regard to age, gender, smoking and alcohol consumption. Given a low SMI (< or = 5), CAE > 15 mg/L-year was associated with an increased risk of skin cancer (OR, 7.48; 95% CI, 1.65-33.99) compared to a CAE < or = 2 mg/L-year. Given the same level of PMI, SMI, and CAE, men had a higher risk of skin cancer (OR, 4.04; 95% CI, 1.46-11.22) when compared to women. Subjects with low SMI and high CAE have a substantially increased risk of skin cancer. Males in all strata of arsenic exposure and methylation ability had a higher risk of skin cancer than women.

Adult↗

PubMed2003

Bone resorption is affected by follicular phase length in female rotating shift workers.

Stressors as subtle as night work or shift work can lead to irregular menstrual cycles, and changes in reproductive hormone profiles can adversely affect bone health. This study was conducted to determine if stresses associated with the disruption of regular work schedule can induce alterations in ovarian function which, in turn, are associated with transient bone resorption. Urine samples from 12 rotating shift workers from a textile mill in Anqing, China, were collected in 1996-1998 during pairs of sequential menstrual cycles, of which one was longer than the other (28.4 vs. 37.4 days). Longer cycles were characterized by a prolonged follicular phase. Work schedules during the luteal-follicular phase transition (LFPT) preceding each of the two cycles were evaluated. All but one of the shorter cycles were associated with regular, forward phase work shift progression during the preceding LFPT. In contrast, five longer cycles were preceded by a work shift interrupted either by an irregular shift or a number of "off days." Urinary follicle-stimulating hormone levels were reduced in the LFPT preceding longer cycles compared with those in the LFPT preceding shorter cycles. There was greater bone resorption in the follicular phase of longer cycles than in that of shorter cycles, as measured by urinary deoxypyridinoline. These data confirm reports that changes in work shift can lead to irregularity in menstrual cycle length. In addition, these data indicate that there may be an association between accelerated bone resorption in menstrual cycles and changes of regularity in work schedule during the preceding LFPT.

Adult↗

PubMed2002

A local likelihood proportional hazards model for interval censored data.

We discuss the use of local likelihood methods to fit proportional hazards regression models to right and interval censored data. The assumed model allows for an arbitrary, smoothed baseline hazard on which a vector of covariates operates in a proportional manner, and thus produces an interpretable baseline hazard function along with estimates of global covariate effects. For estimation, we extend the modified EM algorithm suggested by Betensky, Lindsey, Ryan and Wand. We illustrate the method with data on times to deterioration of breast cosmeses and HIV-1 infection rates among haemophiliacs.

Algorithms↗

PubMed2002

Alcohol dehydrogenase 2 genotypes, maternal alcohol use, and infant outcome.

OBJECTIVE: To determine whether different alleles of the ADH2 gene (ADH2-1, ADH2-2 and ADH2-3) with differing levels of enzymatic activity can alter the risk of fetal alcohol effects. STUDY DESIGN: ADH2 genotypes were performed on 404 pregnant high-risk women and 139 infants as part of a larger study of alcohol use in pregnancy. Mothers were interviewed about alcohol use during pregnancy, and their infants were examined for alcohol-related features without knowledge of the exposure status. RESULTS: The ADH2-1/3 genotype was more prevalent among black women (46%) than expected (33%); the rate among white women was low as expected (2%). More black women who reported high alcohol use during the pregnancy had the ADH2-1/3 genotype compared with those who reported no alcohol use (70% vs 44%). Sixty percent of the affected black infants had the ADH2-1/3 genotype compared with 29% of the unaffected infants (P <.045). The maternal genotype correlated with her chance of having an infant with alcohol-related physical features (odds ratio = 2.49). This association remained significant after accounting for confounders, such as smoking and maternal weight gain. Alcohol exposure was not significantly associated with infant outcome in black infants after accounting for genotype, smoking, and maternal weight gain, but this association could only be tested in 10 infants of mothers with high exposure. CONCLUSION: Women with the ADH2-1/3 genotype may be at greater risk for having an affected infant, which may be the result of greater ingestion of alcohol.

Alcohol Dehydrogenase↗

PubMed2002

Concurrent prediction of hospital mortality and length of stay from risk factors on admission.

OBJECTIVE: To develop a method for predicting concurrently both hospital survival and length of stay (LOS) for seriously ill or injured patients, with particular attention to the competing risks of death or discharge alive as determinants of LOS. DATA SOURCES: Previously collected 1995-1996 registry data on 2,646 cases of injured patients from three trauma centers in Maine. STUDY DESIGN: Time intervals were determined for which the rates of discharge or death were relatively constant. Poisson regression was used to develop a model for each type of terminal event, with risk factors on admission contributing proportionately to the subsequent rates for each outcome in each interval. Mean LOS and cumulative survival were calculated from a combination of the resulting piecewise exponential models. PRINCIPAL FINDINGS: Age, Glasgow Coma Scale, Abbreviated Injury Scores, and specific mechanisms of injury were significant predictors of the rates of death and discharge, with effects that were variable in different time intervals. Predicted probability of survival and mean LOS from the model were similar to actual values for categorized patient groups. CONCLUSIONS: Piecewise exponential models may be useful in predicting LOS, especially if determinants of mortality are separated from determinants of discharge alive.

Adult↗