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Thomas Lumley

Publications and source records attributed to Thomas Lumley.

At least 19 recordsLinked to original sources
PubMed2006

Effects of subchronic and chronic exposure to ambient air pollutants on infant bronchiolitis.

Ambient air pollutant exposure has been linked to childhood respiratory disease, but infants have received little study. The authors tested the hypotheses that subchronic and chronic exposure to fine particulate matter (particulate matter < or = 2.5 microm in aerodynamic diameter (PM2.5)), nitrogen dioxide, carbon monoxide, and ozone increases risk of severe infant bronchiolitis requiring hospitalization. Study subjects were derived from linked birth-hospital-discharge records of infants born in 1995-2000 in the South Coast Air Basin of California. Cases with a hospital discharge for bronchiolitis in infancy were matched to 10 age- and gestational-age-matched controls. Exposures in the month prior to hospitalization (subchronic) and mean lifetime exposure (chronic) referenced to the case diagnosis date were assessed on the basis of data derived from the California Air Resources Board. In conditional logistic regression, only subchronic and chronic PM2.5 exposures were associated with increased risk of bronchiolitis hospitalization after adjustment for confounders (per 10-microg/m3 increase, adjusted odds ratio = 1.09 (95% confidence interval: 1.04, 1.14) for both). Ozone was associated with reduced risk in the single-pollutant model, but this relation did not persist in multipollutant models including PM2.5. These unique US data suggest that infant bronchiolitis may be added to the list of adverse effects of PM2.5 exposure.

Air Pollutants↗
PubMed2006

Risk of new-onset atrial fibrillation in relation to body mass index.

BACKGROUND: Obesity is associated with increased risk of atrial fibrillation (AF), but it is unknown whether the association differs by duration or persistence of AF. It is also unknown to what extent cardiovascular risk factors may mediate this association. METHODS: This population-based case-control study included 425 subjects with new-onset AF and 707 controls. The AF cases were identified through International Classification of Diseases, Ninth Revision codes for inpatient and outpatient visits and verified by medical record review. Medical records provided data on height, weight, and cardiovascular risk factors. RESULTS: On average, AF risk was 3% higher (95% confidence interval [CI], 1%-5%) per unit increment in body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared). For sustained AF (duration > or =6 months), risk was higher by 7% (95% CI, 3%-11%) per unit BMI increment; for intermittent AF (duration > or =8 days or recurrent), 4% (95% CI, 1%-6%); and for transitory AF (duration <8 days), 1% (95% CI, -1% to +4%). Compared with those with normal BMI, the odds ratios for overweight and obese subjects were as follows: overweight, 0.97 (95% CI, 0.68-1.38); obese class 1, 1.18 (95% CI, 0.80-1.73); obese class 2, 1.34 (95% CI, 0.82-2.18); and obese class 3, 2.31 (95% CI, 1.36-3.91) (P = .002 for trend). When diabetes mellitus, a possible mediator, was added to the model, the odds ratio per unit increment of BMI decreased from 1.034 to 1.028. Adjustment for other cardiovascular risk factors including hyperlipidemia and blood pressure did not attenuate the BMI-AF association. CONCLUSIONS: The association with BMI was stronger for sustained AF than for transitory or intermittent AF. The obesity-AF association appears to be partially mediated by diabetes mellitus but minimally through other cardiovascular risk factors.

Adult↗
PubMed2006

Logic regression for analysis of the association between genetic variation in the renin-angiotensin system and myocardial infarction or stroke.

Recent developments in genetic sequencing technology now make it possible to genotype large numbers of single nucleotide polymorphisms (SNPs) in large samples. Many association studies using SNP data are now being carried out. Typically, these observational studies establish whether certain haplotypes or individual SNPs are associated with a health outcome. Few methods exist for finding interaction effects among multiple SNPs or between SNPs and environmental factors. In this paper, the authors describe logic regression, an exploratory method with which to identify interactions for further research. They illustrate this method using data from a US case-control study of myocardial infarction and stroke (1995-1999) carried out among 1,614 persons in Washington State who were genotyped for 32 SNPs on five genes in the renin-angiotensin system.

Angiotensins↗
PubMed2006

Conjugated equine estrogen, esterified estrogen, prothrombotic variants, and the risk of venous thrombosis in postmenopausal women.

BACKGROUND: Joint exposure to oral conjugated equine estrogen (CEE) and prothrombotic genetic variants factor II G20210A or factor V G1601A (Leiden) increase venous thrombotic risk 6- to 16-fold in postmenopausal women. Esterified estrogen (EE), an alternative estrogenic compound, appears not to be associated with increased risk and nothing is known about the joint risk with prothrombotic genetic variants. METHODS AND RESULTS: We conducted a population-based, case-control study among postmenopausal women within a health maintenance organization. Subjects included 328 cases who sustained a first venous thrombosis and 1591 controls. Current hormone use was defined using electronic pharmacy records and variants FII G20210A and FV Leiden were genotyped using blood samples. FII and FV Leiden variants were associated with 2.1-fold and 3.7-fold increases in venous thrombotic risk, respectively. Overall, CEE use was associated with a 2.5-fold increase in risk compared with no hormone use, whereas EE use was not associated with a statistically increased risk. Compared with no hormone use and no variant, joint exposure to CEE and either prothrombotic variant was associated with an odds ratio (OR) of 9.1 (95% CI: 4.5 to 18.2), whereas joint exposure to EE and either variant was associated with an OR of 2.1 (0.6 to 6.8). When analyses were restricted to hormone users with either variant, CEE use was associated with an OR of 5.3 (1.3 to 21.7) compared with EE use. CONCLUSIONS: These findings need replication and suggest EE use is associated with less risk than CEE use especially among 5% to 10% of women who are carriers of a prothrombotic variant.

Administration, Cutaneous↗
PubMed2006

Ambient air pollution and asthma exacerbations in children: an eight-city analysis.

The authors investigated the relation between ambient concentrations of five of the Environmental Protection Agency's criteria pollutants and asthma exacerbations (daily symptoms and use of rescue inhalers) among 990 children in eight North American cities during the 22-month prerandomization phase (November 1993-September 1995) of the Childhood Asthma Management Program. Short-term effects of carbon monoxide, nitrogen dioxide, particulate matter less than 10 mum in aerodynamic diameter (PM10), sulfur dioxide, and warm-season ozone were examined in both one-pollutant and two-pollutant models, using lags of up to 2 days. Lags in carbon monoxide and nitrogen dioxide were positively associated with both measures of asthma exacerbation, and the 3-day moving sum of sulfur dioxide levels was marginally related to asthma symptoms. PM10 and ozone were unrelated to exacerbations. The strongest effects tended to be seen with 2-day lags, where a 1-parts-per-million change in carbon monoxide and a 20-parts-per-billion change in nitrogen dioxide were associated with symptom odds ratios of 1.08 (95% confidence interval (CI): 1.02, 1.15) and 1.09 (95% CI: 1.03, 1.15), respectively, and with rate ratios for rescue inhaler use of 1.06 (95% CI: 1.01, 1.10) and 1.05 (95% CI: 1.01, 1.09), respectively. The authors believe that the observed carbon monoxide and nitrogen dioxide associations can probably be attributed to mobile-source emissions, though more research is required.

Air Pollutants↗
PubMed2006

Esterified estrogen and conjugated equine estrogen and the risk of incident myocardial infarction and stroke.

BACKGROUND: Clinical trials of conjugated equine estrogen (CEE) or estradiol vs placebo in postmenopausal women have found no effect or an elevated risk of myocardial infarction (MI) and stroke. The association of these end points with the use of esterified estrogen (EE) is unknown. METHODS: We examined the risk of MI and stroke associated with current use of CEE, use of EE, or nonuse of hormones in a population-based case-control study in a health maintenance organization. Cases were all postmenopausal women with an incident MI (n = 1644) or stroke (n = 1080). Controls (n = 4205) consisted of a random sample of postmenopausal women without MI or stroke. Current use of postmenopausal hormones was assessed using a computerized pharmacy database. RESULTS: There was no difference in risk of MI or stroke associated with current use of CEE or EE compared with nonuse or for current use of CEE compared with EE. In analyses restricted to hormone users, there was a suggestion of higher ischemic stroke risk associated with CEE alone (without progestin) compared with EE alone (odds ratio, 1.57; 95% confidence interval, 0.98-2.53). There was also a suggestion that when initiated in the previous 6 months, CEE was associated with a higher risk of MI than EE (odds ratio, 2.33; 95% confidence interval, 0.93-5.82). CONCLUSION: Further study may be warranted of the effects of EE on the risk of cardiovascular end points.

Adult↗
PubMed2006

Common genetic variation in the prothrombin gene, hormone therapy, and incident nonfatal myocardial infarction in postmenopausal women.

Genetic variants in coagulation factors are associated with myocardial infarction and may modify the association between hormone therapy and cardiovascular disease risk. This study assessed whether common variation in the prothrombin gene was associated with incident nonfatal myocardial infarction in postmenopausal women and whether this association differed according to current estrogen use. Eight variants representing 98% of common prothrombin variants were selected using publicly available genomic variation data. These variants and the functional G20210A variant were genotyped and used to infer haplotypes in a population-based Washington State case-control study of postmenopausal Caucasian women (1995-1999; 273 cases and 788 controls). Women carrying a nonsynonymous polymorphism in exon 6 (C5467T) had an increased risk of myocardial infarction (for each additional copy, relative to women with one fewer copy, odds ratio = 1.4, 95% confidence interval: 1.0, 1.8). Prothrombin haplotypes were also associated with myocardial infarction (with minimal adjustment, global p = 0.056; with full adjustment, p = 0.034). Associations between haplotypes and myocardial infarction were similar among users of hormone therapy and nonusers (global p = 0.61), though statistical power was limited. These preliminary results suggest that common genetic variants in the prothrombin gene or other variants in linkage disequilibrium are associated with myocardial infarction in postmenopausal women.

Aged↗
PubMed2006

Simple estimates of haplotype relative risks in case-control data.

Methods of varying complexity have been proposed to efficiently estimate haplotype relative risks in case-control data. Our goal was to compare methods that estimate associations between disease conditions and common haplotypes in large case-control studies such that haplotype imputation is done once as a simple data-processing step. We performed a simulation study based on haplotype frequencies for two renin-angiotensin system genes. The iterative and noniterative methods we compared involved fitting a weighted logistic regression, but differed in how the probability weights were specified. We also quantified the amount of ambiguity in the simulated genes. For one gene, there was essentially no uncertainty in the imputed diplotypes and every method performed well. For the other, approximately 60% of individuals had an unambiguous diplotype, and approximately 90% had a highest posterior probability greater than 0.75. For this gene, all methods performed well under no genetic effects, moderate effects, and strong effects tagged by a single nucleotide polymorphism (SNP). Noniterative methods produced biased estimates under strong effects not tagged by an SNP. For the most likely diplotype, median bias of the log-relative risks ranged between -0.49 and 0.22 over all haplotypes. For all possible diplotypes, median bias ranged between -0.73 and 0.08. Results were similar under interaction with a binary covariate. Noniterative weighted logistic regression provides valid tests for genetic associations and reliable estimates of modest effects of common haplotypes, and can be implemented in standard software. The potential for phase ambiguity does not necessarily imply uncertainty in imputed diplotypes, especially in large studies of common haplotypes.

Algorithms↗
PubMed2006

A case-crossover study of wintertime ambient air pollution and infant bronchiolitis.

UNLABELLED: We examined the association of infant bronchiolitis with acute exposure to ambient air pollutants. DESIGN: We employed a time-stratified case-crossover method and based the exposure windows on a priori, biologically based hypotheses. PARTICIPANTS: We evaluated effects in 19,901 infants in the South Coast Air Basin of California in 1995-2000 with a hospital discharge record for bronchiolitis in the first year of life (International Classification of Diseases, 9th Revision, CM466.1). EVALUATIONS/MEASUREMENTS: Study subjects' ZIP code was linked to ambient air pollution monitors to derive exposures. We estimated the risk of bronchiolitis hospitalization associated with increases in wintertime ambient air pollutants using conditional logistic regression. RESULTS: We observed no increased risk after acute exposure to particulate matter < or = 2.5 microm in aerodynamic diameter (PM2.5), carbon monoxide, or nitrogen dioxide. PM2.5 exposure models suggested a 26-41% increased risk in the most premature infants born at gestational ages between 25 and 29 weeks; however, these findings were based on very small numbers. CONCLUSIONS: We found little support for a link between acute increases in ambient air pollution and infant bronchiolitis except modestly increased risk for PM2.5 exposure among infants born very prematurely. In these infants, the periods of viral acquisition and incubation concurred with the time of increased risk. RELEVANCE TO PROFESSIONAL PRACTICE: We present novel data for the infant period and the key respiratory disease of infancy, bronchiolitis. Incompletely explained trends in rising bronchiolitis hospitalization rates and increasing number of infants born prematurely underscore the importance of evaluating the impact of ambient air pollution in this age group in other populations and studies.

Air Pollutants↗
PubMed2006

New-onset diabetes and risk of all-cause and cardiovascular mortality: the Cardiovascular Health Study.

OBJECTIVE: Cardiovascular risk associated with new-onset diabetes is not well characterized. We hypothesized that risk of all-cause and cardiovascular mortality would be similar among participants with and without new-onset diabetes in the first years of follow-up and rise over time for new-onset diabetes. RESEARCH DESIGN AND METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of cardiovascular risk factors in adults aged > or =65 years. We used CHS participants to define a cohort (n = 282) with new-onset diabetes during 11 years of follow-up. New-onset diabetes was defined by initiation of antidiabetes medication or by fasting plasma glucose >125 mg/dl among CHS participants without diabetes at study entry. Three CHS participants without diabetes were matched for age, sex, and race to each participant with new-onset diabetes at the time of diabetes identification (n = 837). Survival analysis provided adjusted hazard ratios (HRs) for all-cause and cardiovascular mortality. RESULTS: During a median of 5.9 years of follow-up, there were 352 deaths, of which 41% were cardiovascular. In adjusted analyses, new-onset diabetes was associated with an HR of 1.9 (95% CI 1.4-2.5) for all-cause and 2.2 (1.4-3.4) for cardiovascular mortality compared with no diabetes. Mortality risks were elevated within 2 years of onset, especially cardiovascular risk (4.3 [95% CI 1.7-10.8]), and did not increase over time. CONCLUSIONS: Our findings indicate that there may be a mortality differential soon after diabetes onset in older adults and suggest that long-term macrovascular damage from atherosclerosis may not be primarily responsible for increased risk.

Aged↗
PubMed2005

The sensitivity and specificity of markers for event times.

The statistical literature on assessing the accuracy of risk factors or disease markers as diagnostic tests deals almost exclusively with settings where the test, Y, is measured concurrently with disease status D. In practice, however, disease status may vary over time and there is often a time lag between when the marker is measured and the occurrence of disease. One example concerns the Framingham risk score (FR-score) as a marker for the future risk of cardiovascular events, events that occur after the score is ascertained. To evaluate such a marker, one needs to take the time lag into account since the predictive accuracy may be higher when the marker is measured closer to the time of disease occurrence. We therefore consider inference for sensitivity and specificity functions that are defined as functions of time. Semiparametric regression models are proposed. Data from a cohort study are used to estimate model parameters. One issue that arises in practice is that event times may be censored. In this research, we extend in several respects the work by Leisenring et al. (1997) that dealt only with parametric models for binary tests and uncensored data. We propose semiparametric models that accommodate continuous tests and censoring. Asymptotic distribution theory for parameter estimates is developed and procedures for making statistical inference are evaluated with simulation studies. We illustrate our methods with data from the Cardiovascular Health Study, relating the FR-score measured at enrollment to subsequent risk of cardiovascular events.

Aged↗
PubMed2005

Congestive heart failure incidence and prognosis: case identification using central adjudication versus hospital discharge diagnoses.

PURPOSE: We compared hospitalized congestive heart failure (CHF) incidence and prognosis estimates using hospital discharge diagnoses or central adjudication. METHODS: We used the Cardiovascular Health Study (CHS), a population-based cohort study of 5888 elderly adults. A physician committee adjudicated potential CHF events, confirmed by signs, symptoms, clinical tests, and/or medical therapy. A CHF discharge diagnosis included any of these ICD-9 codes in any position: 428, 425, 398.91, 402.01, 402.11, 402.91, and 997.1. We constructed an inception cohort of 1209 hospitalized, nonfatal, incident CHF cases, identified by discharge diagnosis, adjudication, or both. RESULTS: Incidence rates for hospitalized CHF were 24.6 per 1000 person-years using discharge diagnoses and 17.1 per 1000 person-years using central adjudication. Compared to the group identified as having CHF by both methods, the group with only a discharge diagnosis (hazard ratio=0.77, 95% confidence interval=0.65-0.91) and the group with central adjudication only (hazard ratio=0.72, 95% confidence interval=0.55-0.94) had lower mortality rates. CONCLUSIONS: In the elderly, studies using only discharge diagnoses, as compared to central adjudication, may estimate higher rates of incident hospitalized CHF. Mortality following CHF onset may be similar for these methods and higher if both methods are used together.

Aged↗
PubMed2005

Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study.

Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, beta-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women > or = 65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.

Aged↗
PubMed2005

Overlap bias in the case-crossover design, with application to air pollution exposures.

The case-crossover design uses cases only, and compares exposures just prior to the event times to exposures at comparable control, or 'referent' times, in order to assess the effect of short-term exposure on the risk of a rare event. It has commonly been used to study the effect of air pollution on the risk of various adverse health events. Proper selection of referents is crucial, especially with air pollution exposures, which are shared, highly seasonal, and often have a long-term time trend. Hence, careful referent selection is important to control for time-varying confounders, and in order to ensure that the distribution of exposure is constant across referent times, a key assumption of this method. Yet the referent strategy is important for a more basic reason: the conditional logistic regression estimating equations commonly used are biased when referents are not chosen a priori and are functions of the observed event times. We call this bias in the estimating equations overlap bias. In this paper, we propose a new taxonomy of referent selection strategies in order to emphasize their statistical properties. We give a derivation of overlap bias, explore its magnitude, and consider how the bias depends on properties of the exposure series. We conclude that the bias is usually small, though highly unpredictable, and easily avoided.

Air Pollution↗
PubMed2005

Association of beta-blocker use with mortality among patients with congestive heart failure in the Cardiovascular Health Study (CHS).

BACKGROUND: In clinical trials, beta-blocker therapy reduces all-cause mortality among people with congestive heart failure (CHF) characterized by depressed systolic function, but few trials included large numbers of elderly participants. This study assessed the association between beta-blocker therapy and mortality among community-dwelling older adults with CHF. METHODS: The Cardiovascular Health Study (CHS) is a longitudinal, population-based study of adults aged > or = 65 years. Recruitment began in 1989 with follow-up extending through June 2000 or death. Cox proportional hazard regression models were used to assess the association between beta-blocker therapy and all-cause mortality among 950 participants who developed new-onset CHF. RESULTS: beta-Blocker users (n = 157) were more likely than nonusers (n = 793) to have treated hypertension, clinical coronary artery disease, and valvular disease at the time of CHF diagnosis. Death occurred in 67 users and 446 nonusers during a median follow-up of 2.3 years. Compared with nonuse, use of beta-blockers was associated with a multivariable adjusted hazard ratio (HR) of 0.74 (95% CI 0.56-0.98) for all-cause mortality. Among the 520 participants who had left ventricular ejection fraction assessed within 90 days after CHF diagnosis, the risk for all cause mortality associated with beta-blocker use did not differ significantly between those with ejection fraction of < 40% and those with ejection fraction of > or = 40% (HR 0.56, 95% CI 0.27-1.13; HR 0.82, 95% CI 0.56-1.22, respectively; interaction P = .34). CONCLUSIONS: This observational study suggests that beta-blocker treatment is associated with a reduced risk of all-cause mortality among community-dwelling older adults with CHF.

Adrenergic beta-Antagonists↗