Biomedical subjects

Louise M Ryan

Publications and source records attributed to Louise M Ryan.

At least 19 recordsLinked to original sources

PubMed2006

Maternal social and pyschological conditions and physical growth in low-income children in Piauí, Northeast Brazil.

Prevalence of child undernutrition remains high in many developing countries. In settings with scarce resources, modifiable maternal social conditions may influence feeding and parenting practices, in turn affecting child growth. This study aims to quantify the association between maternal social support and depression to children's physical growth outcomes in Teresina, Piauí, northeast Brazil. Interviews were conducted with a random sample of 595 mothers of children 6-24 months old in four low-income sections of Teresina, Piauí. We collected data on sociodemographic factors, mothers' social support, mothers' depressive symptomatology, and child's weight and recumbent length. Weight-for-height z-scores (WHZ), height-for-age z-scores (HAZ) and weight-for-age z-scores (WAZ) were calculated using the National Center for Chronic Disease Prevention and Health Promotion Center SAS program based on the 2000 Centers for Disease Control reference growth curves. Multivariable linear regression was used to model the association between maternal social support and depression to child growth, adjusting for biological and socio-demographic variables. Interviewer and neighborhood variation was accounted for through the inclusion of random effects. In adjusted models, material support, measured by number of friends or family members available to mothers when needing food or milk, was related to 0.3 higher average WHZ and 0.2 higher average WAZ in their children. Maternal positive social interaction, which reflects engagement in leisure-time activities with others, was associated with 0.3 higher average WHZ. Mothers' affectionate support was related to 0.2 higher average children's WHZ and WAZ, whereas social support for resolving a conflict was associated with 0.2 lower average HAZ. Maternal depression was not associated with child growth. It is concluded that inadequate growth in children may be sensitive to maternal social support.

Brazil↗

PubMed2006

Mode of delivery and cord blood cytokines: a birth cohort study.

BACKGROUND: The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown. OBJECTIVE: To examine whether cesarean section results in neonatal secretion of cytokines that are associated with increased risk of atopy and/or asthma in childhood. To examine whether the association between mode of delivery and neonatal immune responses is explained by exposure to the maternal gut flora (a marker of the vaginal flora). METHODS: CBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN-gamma, and IL-10 (at baseline and after stimulation with antigens [dust mite and cat dander allergens, phytohemagglutinin, and lipopolysaccharide]) was quantified by ELISA. Total and specific microbes were quantified in maternal stool. The relation between mode of delivery and cord blood cytokines was examined by linear regression. The relation between maternal stool microbes and cord blood cytokines was examined by Spearman's correlation coefficients. RESULTS: Cesarean section was associated with increased levels of IL-13 and IFN-gamma. In multivariate analyses, cesarean section was associated with an increment of 79.4 pg/ml in secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P < 0.001). Among children born by vaginal delivery, gram-positive anaerobes and total anaerobes in maternal stool were positively correlated with levels of IL-10, and gram-negative aerobic bacteria in maternal stool were negatively correlated with levels of IL-13 and IFN-gamma. CONCLUSION: Cesarean section is associated with increased levels of IL-13 and IFN-gamma, perhaps because of lack of labor and/or reduced exposure to specific microbes (e.g., gram-positive anaerobes) at birth.

Journal Article↗

PubMed2006

Associations of cord blood fatty acids with lymphocyte proliferation, IL-13, and IFN-gamma.

BACKGROUND: N-3 and n-6 polyunsaturated fatty acids (PUFAs) have been hypothesized to have opposing influences on neonatal immune responses that might influence the risk of allergy or asthma. However, both n-3 eicosapentaenoic acid (EPA) and n-6 arachidonic acid (AA) are required for normal fetal development. OBJECTIVE: We evaluated whether cord blood fatty acid levels were related to neonatal immune responses and whether n-3 and n-6 PUFA responses differed. METHODS: We examined the relation of cord blood plasma n-3 and n-6 PUFAs (n = 192) to antigen- and mitogen-stimulated cord blood lymphocyte proliferation (n = 191) and cytokine (IL-13 and IFN-gamma; n = 167) secretion in a US birth cohort. RESULTS: Higher levels of n-6 linoleic acid were correlated with higher IL-13 levels in response to Bla g 2 (cockroach, P = .009) and Der f 1 (dust mite, P = .02). Higher n-3 EPA and n-6 AA levels were each correlated with reduced lymphocyte proliferation and IFN-gamma levels in response to Bla g 2 and Der f 1 stimulation. Controlling for potential confounders, EPA and AA had similar independent effects on reduced allergen-stimulated IFN-gamma levels. If neonates had either EPA or AA levels in the highest quartile, their Der f 1 IFN-gamma levels were 90% lower (P = .0001) than those with both EPA and AA levels in the lowest 3 quartiles. Reduced AA/EPA ratio was associated with reduced allergen-stimulated IFN-gamma level. CONCLUSION: Increased levels of fetal n-3 EPA and n-6 AA might have similar effects on attenuation of cord blood lymphocyte proliferation and IFN-gamma secretion. CLINICAL IMPLICATIONS: The implications of these findings for allergy or asthma development are not yet known.

Allergens↗

PubMed2006

Analysis of repeated pregnancy outcomes.

Women tend to repeat reproductive outcomes, with past history of an adverse outcome being associated with an approximate two-fold increase in subsequent risk. These observations support the need for statistical designs and analyses that address this clustering. Failure to do so may mask effects, result in inaccurate variance estimators, produce biased or inefficient estimates of exposure effects. We review and evaluate basic analytic approaches for analysing reproductive outcomes, including ignoring reproductive history, treating it as a covariate or avoiding the clustering problem by analysing only one pregnancy per woman, and contrast these to more modern approaches such as generalized estimating equations with robust standard errors and mixed models with various correlation structures. We illustrate the issues by analysing a sample from the Collaborative Perinatal Project dataset, demonstrating how the statistical model impacts summary statistics and inferences when assessing etiologic determinants of birth weight.

Adolescent↗

PubMed2006

Does living near a Superfund site contribute to higher polychlorinated biphenyl (PCB) exposure?

We assessed determinants of cord serum polychlorinated biphenyl (PCB) levels among 720 infants born between 1993 and 1998 to mothers living near a PCB-contaminated Superfund site in Massachusetts, measuring the sum of 51 PCB congeners (capital sigmaPCB) and ascertaining maternal address, diet, sociodemographics, and exposure risk factors. Addresses were geocoded to obtain distance to the Superfund site and neighborhood characteristics. We modeled log10(capital sigmaPCB) as a function of potential individual and neighborhood risk factors, mapping model residuals to assess spatial correlates of PCB exposure. Similar analyses were performed for light (mono-tetra) and heavy (penta-deca) PCBs to assess potential differences in exposure pathways as a function of relative volatility. PCB-118 (relatively prevalent in site sediments and cord serum) was assessed separately. The geometric mean of capital sigmaPCB levels was 0.40 (range, 0.068-18.14) ng/g serum. Maternal age and birthplace were the strongest predictors of capital sigmaPCB levels. Maternal consumption of organ meat and local dairy products was associated with higher and smoking and previous lactation with lower capital sigmaPCB levels. Infants born later in the study had lower capital sigmaPCB levels, likely due to temporal declines in exposure and site remediation in 1994-1995. No association was found between capital sigmaPCB levels and residential distance from the Superfund site. Similar results were found with light and heavy PCBs and PCB-118. Previously reported demographic (age) and other (lactation, smoking, diet) correlates of PCB exposure, as well as local factors (consumption of local dairy products and Superfund site dredging) but not residential proximity to the site, were important determinants of cord serum PCB levels in the study community.

Adult↗

PubMed2005

Infant home endotoxin is associated with reduced allergen-stimulated lymphocyte proliferation and IL-13 production in childhood.

BACKGROUND: Infant endotoxin exposure has been proposed as a factor that might protect against allergy and the early childhood immune responses that increase the risk of IgE production to allergens. OBJECTIVE: Using a prospective study design, we tested the hypothesis that early-life endotoxin exposure is associated with allergen- and mitogen-induced cytokine production and proliferative responses of PBMCs isolated from infants with a parental history of physician-diagnosed asthma or allergy. METHODS: We assessed household dust endotoxin at age 2 to 3 months and PBMC proliferative and cytokine responses to cockroach allergen (Bla g 2), dust mite allergen (Der f 1), cat allergen (Fel d 1), and the nonspecific mitogen PHA at age 2 to 3 years. RESULTS: We found that increased endotoxin levels were associated with decreased IL-13 levels in response to cockroach, dust mite, and cat allergens, but not mitogen stimulation. Endotoxin levels were not correlated with allergen- or mitogen-induced IFN-gamma, TNF-alpha, or IL-10. Increased endotoxin levels were associated with decreased lymphocyte proliferation after cockroach allergen stimulation. An inverse, although nonsignificant, association was also found between endotoxin and proliferation to the other tested stimuli. CONCLUSION: Increased early-life exposure to household endotoxin was associated with reduced allergen-induced production of the TH2 cytokine IL-13 and reduced lymphoproliferative responses at age 2 to 3 years in children at risk for allergy and asthma. Early-life endotoxin-related reduction of IL-13 production might represent one pathway through which increased endotoxin decreases the risk of allergic disease and allergy in later childhood.

Allergens↗

PubMed2005

Individual and population penalized regression splines for accelerated longitudinal designs.

In an accelerated longitudinal design (ALD), individuals enter the study at different points of their growth trajectory and are observed over a short time span relative to the entire time span of interest. ALD data are combined across independent units to provide an estimate of an overall population curve and predictions of individual patterns of change. As a modest extension of the work of Ruppert et al. (2003, Semiparametric Regression, Cambridge University Press), we develop a computationally efficient procedure for the application of longitudinal semiparametric methods under ALD sampling schemes. We compare balanced and complete longitudinal designs to ALDs using the Berkeley Growth Study data and apply our method to longitudinal magnetic resonance imaging (MRI) brain structure size (volume) measurements from an ongoing developmental study. Potential applications extend beyond growth studies to many other fields in which cost and feasibility constraints impose restrictions on sample size and on the numbers and timings of repeated measurements across subjects.

Adolescent↗

PubMed2005

Fungal levels in the home and allergic rhinitis by 5 years of age.

Studies have repeatedly demonstrated that sensitization to fungi, such as Alternaria, is strongly associated with allergic rhinitis and asthma in children. However, the role of exposure to fungi in the development of childhood allergic rhinitis is poorly understood. In a prospective birth cohort of 405 children of asthmatic/allergic parents from metropolitan Boston, Massachusetts, we examined in-home high fungal concentrations (> 90th percentile) measured once within the first 3 months of life as predictors of doctor-diagnosed allergic rhinitis in the first 5 years of life. In multivariate Cox regression analyses, predictors of allergic rhinitis included high levels of dust-borne Aspergillus [hazard ratio (HR) = 3.27; 95% confidence interval (CI), 1.50-7.14], Aureobasidium (HR = 3.04; 95% CI, 1.33-6.93), and yeasts (HR = 2.67; 95% CI, 1.26-5.66). The factors controlled for in these analyses included water damage or mild or mildew in the building during the first year of the child's life, any lower respiratory tract infection in the first year, male sex, African-American race, fall date of birth, and maternal IgE to Alternaria > 0.35 U/mL. Dust-borne Alternaria and nonsporulating and total fungi were also predictors of allergic rhinitis in models excluding other fungi but adjusting for all of the potential confounders listed above. High measured fungal concentrations and reports of water damage, mold, or mildew in homes may predispose children with a family history of asthma or allergy to the development of allergic rhinitis.

Boston↗

PubMed2004

Analysis of clustered and interval censored data from a community-based study in asthma.

Many authors in recent years have proposed extensions of familiar survival analysis methodologies to apply in dependent data settings, for example, when data are clustered or subject to repeated measures. However, these extensions have been considered largely in the context of right censored data. In this paper, we discuss a parametric frailty model for the analysis of clustered and interval censored failure time data. Details are presented for the specific case where the underlying time to event data follow a Weibull distribution. Maximum likelihood estimates will be obtained using commercially available software and the empirical efficiency of these estimators will be explored via a simulation study. We also discuss a score test to make inferences about the magnitude and significance of over-dispersion in clustered data settings. These methods will be illustrated using data from the East Boston Asthma Study.

Asthma↗

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↗