# Theodore R Holford's research while affiliated with Yale-New Haven Hospital and other places

## Publications (414)

Article
Objective: Triple-crossover randomized controlled intervention trial to test whether reduced exposure to household NO2 or fine particles results in reduced symptoms among children with persistent asthma. Methods: Children (n = 126) aged 5-11 years with persistent asthma living in homes with gas stoves and levels of NO2 15 ppb or greater recruite...
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Introduction: A better understanding of how menthol cigarette flavoring and ENDS impact smoking initiation, cessation, and transitions between tobacco products could help elucidate the potential impact of a U.S. menthol ban on combustible tobacco products. Methods: A multistate transition model was applied to data on 23,232 adults from Waves 1-4...
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Importance Starting in 2022, the US Food and Drug Administration (FDA) plans to require all cigarette packages in the US to display graphic health warnings depicting health harms associated with smoking. The FDA originally planned to implement such warnings in 2012, but tobacco industry litigation delayed the effort. Objective To assess the estima...
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Background Knowing the true infected and symptomatic case fatality ratios (IFR and CFR) for COVID-19 is of high importance for epidemiological model projections. Early in the pandemic many locations had limited testing and reporting, so that standard methods for determining IFR and CFR required large adjustments for missed cases. We present an alte...
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In a population-based case control study of testicular germ cell tumors (TGCT), we reported a strong positive association between serum levels of Wolff's Group 1 (potentially estrogenic) polychlorinated biphenyl (PCBs) and risk of TGCT, and the observed associations were similar for both seminoma and non-seminoma. While the observed specific associ...
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The incidence rate of testicular germ cell tumors (TGCT) has continuously increased in Western countries over the last several decades. Some epidemiologic studies have reported that the endocrine disrupting polychlorinated biphenyls (PCBs) in serum may be associated with TGCT risk, but the evidence is inconsistent. Our goal was to investigate wheth...
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Purpose This study examines sociodemographic patterns of exclusive/dual/polytobacco use among U.S. high school students using multiple national surveys. Methods Using three national youth surveys (Population Assessment of Tobacco and Health [PATH] Wave 4 [2016–2017], 2017 Youth Risk Behavior Survey, and 2017 National Youth Tobacco Survey), we clas...
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Introduction Even prior to 2018, electronic nicotine delivery systems (ENDS) began to dramatically change the landscape of tobacco products and product use patterns in the USA. Methods Using a Markov multistate transition model accounting for complex survey design, transition rates between never, non-current, cigarette, ENDS and dual use states we...
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CYP-GUIDES (Cytochrome Psychotropic Genotyping Under Investigation for Decision Support) was a Randomized Controlled Trial (RCT) comparing 2 outcomes in hospitalized patients with major depressive disorder treated according to the patient's CYP2D6 genotype and functional status versus standard psychotropic therapy. The primary outcome was hospital...
Preprint
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Background. Knowing the true infected and symptomatic case fatality ratios (IFR and CFR) for COVID-19 is of high importance for epidemiological model projections. A large correction factor is usually applied for missed cases. For the United State reported CFR of 5.96%, the estimated IFR values are 10-50-fold lower, justified by early reported CFR v...
Article
CYP-GUIDES (Cytochrome Psychotropic Genotyping Under Investigation for Decision Support) is a randomized controlled trial (RCT) comparing 2 outcomes in hospitalized patients with major depressive disorder (MDD) treated according to the patient's CYP2D6 genotype and functional status versus standard psychotropic therapy. The primary outcome was hosp...
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A spatiotemporal calibration and resolution refinement model was fitted to calibrate nitrogen dioxide ($$\hbox {NO}_2$$) concentration estimates from the Community Multiscale Air Quality (CMAQ) model, using two sources of observed data on $$\hbox {NO}_2$$ that differed in their spatial and temporal resolutions. To refine the spatial resolution of t...
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Cohort or period components of trends can provide a rationale for new research or point to clues on the effectiveness of control strategies. Graphical display of trends guides models that quantify the experience of a population. In this paper, a method for smoothing rates by single year of age and year is developed and displayed to show the contrib...
Preprint
A spatiotemporal calibration and resolution refinement model was fitted to calibrate nitrogen dioxide (NO$_2$) concentration estimates from the Community Multiscale Air Quality (CMAQ) model, using two sources of observed data on NO$_2$ that differed in their spatial and temporal resolutions. To refine the spatial resolution of the CMAQ model estima...
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Background Patients treated for renal cell carcinoma (RCC) may be diagnosed with a metachronous, contralateral tumor. We evaluated the risks of contralateral tumor development using the Surveillance, Epidemiology, and End Results database. Methods Among RCC patients, we identified those with a metachronous, contralateral RCC diagnosed ≥1 year afte...
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Background: Tobacco control efforts implemented in the United States since the 1960s have led to considerable reductions in smoking and smoking-related diseases, including lung cancer. Objective: To project reductions in tobacco use and lung cancer mortality from 2015 to 2065 due to existing tobacco control efforts. Design: Comparative modelin...
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Incidence rates are an important population‐level disease risk measure. Cancer incidence data in the United States, which are collected by disease registries, have been spatiotemporally sparse. Back‐calculation methods can yield incidence estimates for a spatial domain by solving a convolution equation that relates mortality to incidence through su...
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Background Previous studies in the U.S. show higher smoking rates among those with lower levels of education attainment. Less is known about how these smoking patterns vary by birth cohort or how they may be driven by different demographic profiles across education groups. Furthermore, limited attention has been given to differences in smoking beha...
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Introduction Smoking remains the leading cause of preventable death in the USA but can be reduced through policy interventions. Computational models of smoking can provide estimates of the projected impact of tobacco control policies and can be used to inform public health decision making. We outline a protocol for simulating the effects of tobacco...
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Introduction US tobacco control policies to reduce cigarette use have been effective, but their impact has been relatively slow. This study considers a strategy of switching cigarette smokers to e-cigarette use (‘vaping’) in the USA to accelerate tobacco control progress. Methods A Status Quo Scenario, developed to project smoking rates and health...
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Objective Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods GWAS data on European Caucasians from the Interna...
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OBJECTIVE: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. METHODS: GWAS data on European Caucasians from the Intern...
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Introduction The public health impact of vaporized nicotine products (VNPs) such as e-cigarettes is unknown at this time. VNP uptake may encourage or deflect progression to cigarette smoking in those who would not have otherwise smoked, thereby undermining or accelerating reductions in smoking prevalence seen in recent years. Methods The public he...
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A revolution in our understanding of human health and disease has been launched by the sequencing of a prototypical human genome. To a large degree, this achievement represents the pinnacle of reductionist scientific thought, as having all genes dissected, one could in principle allow reconstitution of the organism. In contrast, the classical disci...
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Introduction: Characterizing smoking history patterns summarizes life course exposure for birth cohorts, essential for evaluating the impact of tobacco control on health. Limited attention has been given to patterns among African Americans.
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Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,95...
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Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,95...
Chapter
Age–period–cohort analysis refers to the interpretation of temporal trends in disease incidence or mortality rates in terms of the three time scales, age, calendar date (period), and year of birth (cohort). We present graphical and analytic methods for understanding trends in disease rates. A fundamental issue of identifiability arises in some mode...
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Evidence from a small number of studies suggests longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measuremen...
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Objective While the US Preventive Services Task Force has issued recommendations for lung cancer screening, its effectiveness at reducing lung cancer burden may vary at local levels due to regional variations in smoking behaviour. Our objective was to use an existing model to determine the impacts of lung cancer screening alone or in addition to in...
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Spatiotemporal calibration of output from deterministic models is an increasingly popular tool to more accurately and efficiently estimate the true distribution of spatial and temporal processes. Current calibration techniques have focused on a single source of data on observed measurements of the process of interest that are both temporally and sp...
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Introduction: The year 2014 marked the 50th Anniversary of the first Surgeon General’s Report. This paper estimates the effect of tobacco control policies in the US after the 1964 Surgeon General’s Report using the SimSmoke tobacco control simulation model. Methods: SimSmoke uses National Health Interview Survey (NHIS) data from 1965 through 2012...
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Background: More than half of the world's population lives in urban environments. Due to urban related factors (e.g. higher air pollution), urban residents may face higher risk of adverse health outcomes, while access to green space could benefit health. Purpose: We explored associations between urban and green land-use and birth weight. Method...
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Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.
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Background: No analytic epidemiological study has examined the relationship between use of muscle-building supplements (MBSs) and testicular germ cell cancer (TGCC) risk. Methods: We conducted a population-based case-control study including 356 TGCC cases and 513 controls from Connecticut and Massachusetts. Results: The odds ratio (OR) for eve...
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The impact of screening mammography on breast cancer incidence is difficult to disentangle from cohort- and age-related effects on incidence. We developed an age-period-cohort model of ductal carcinoma in situ (DCIS) and invasive breast cancer incidence in U.S. females using cancer registry data. Five functions were included in the model to estimat...
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Given the deleterious health effects associated with indoor air pollution (IAP), this study was conducted to evaluate an IAP intervention in rural areas in Gansu, one of the poorest provinces of China. We selected 371 rural households to take part in intervention measures including stove improvement and health education. Eight of 371 households wer...
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To measure serum levels of heavy metals in Chinese pregnant women and their newborns, and to evaluate the association of these metals with infant birth weight. We measured serum concentrations of lead (Pb), thallium (Tl), cadmium (Cd), selenium (Se), arsenic (As), nickle (Ni), vanadium (V), cobalt (Co), and mercury (Hg) in 81 mother-infant pairs us...
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A compartment model for cancer incidence and mortality is developed in which healthy subjects may develop cancer and subsequently die of cancer or another cause. In order to adequately represent the experience of a defined population, it is also necessary to allow for subjects who are diagnosed at death, as well as subjects who migrate and are subs...
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Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZ...
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Asthma affects 8–9% of pregnant women in the USA [1]. Since asthma exacerbations during pregnancy can lead to poor pulmonary function, hypoxia and other adverse health outcomes for the mother, fetus and neonate [2, 3], maintaining good control of asthma during pregnancy is recommended for the health of both mother and baby [4]. Reviews of the safet...
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Background In adolescents the temporal directionality to the asthma and adiposity association remains unclear. Asthma may be a consequence of obesity; however, asthma may increase adiposity.Objectives This study aimed to assess the associations between (i) baseline weight status and subsequent asthma and (ii) baseline asthma and subsequent weight s...
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Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk:...
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We propose a novel statistical framework by supplementing case–control data with summary statistics on the population at risk for a subset of risk factors. Our approach is to first form two unbiased estimating equations, one based on the case–control data and the other on both the case data and the summary statistics, and then optimally combine the...
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Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 pro...
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Typically available nitrogen dioxide ( $${\hbox {NO}}_{2}$$ ) measurements are either spatially representative but temporally sparse or temporally representative but spatially sparse. This article illustrates an approach for making use of the strengths of these two types of data to obtain pollution estimates that are representative both spatially a...
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Background: Little is known about the environmental and public health impact of unconventional natural gas extraction activities, including hydraulic fracturing, that occur near residential areas. Objectives: Our aim was to assess the relationship between household proximity to natural gas wells and reported health symptoms. Methods: We conducted a...
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Purpose: Genetic polymorphisms in DNA repair genes and hair dye use may both have a role in the development of non-Hodgkin lymphoma (NHL). We aimed to examine the interaction between variants in DNA repair genes and hair dye use with risk of NHL in a population-based case-control study of Connecticut women. Methods: We examined 24 single nucleot...
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In utero exposure to organochlorine pesticides (OCPs) is thought to be potentially harmful to fetal development. We aimed to investigate the associations of maternal and cord serum OCPs levels with infant birth weight in China. In this study, we measured serum levels of 18 OCPs in 81 mother–infant pairs, including DDT, hexachlorocyclohexanes (BHC),...
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Background Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.
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AimThe aim of this analysis was to examine the association between asthma and general and abdominal weight status, defined by age-specific and sex-specific cut-offs for body mass index (BMI) and waist circumference (WC) in adolescents.Methods Participants aged 12-19 years in the Young-HUNT (YH) Study (YH1 1995-1997: N=8,222; YH3 2006-2008: N=7,403)...
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Background The National Lung Screening Trial (NLST) demonstrated that in current and former smokers aged 55 to 74 years, with at least 30 pack-years of cigarette smoking history and who had quit smoking no more than 15 years ago, 3 annual computed tomography (CT) screens reduced lung cancer-specific mortality by 20% relative to 3 annual chest X-ray...
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We propose a novel two-step procedure to combine epidemiological data obtained from diverse sources with the aim to quantify risk factors affecting the probability that an individual develops certain disease such as cancer. In the first step we derive all possible unbiased estimating functions based on a group of cases and a group of controls each...
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Characterizing the smoking patterns for different birth cohorts is essential for evaluating the impact of tobacco control interventions and predicting smoking-related mortality, but the process of estimating birth cohort smoking histories has received limited attention. Smoking history summaries were estimated beginning with the 1890 birth cohort i...
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January 2014 marks the 50th anniversary of the first surgeon general's report on smoking and health. This seminal document inspired efforts by governments, nongovernmental organizations, and the private sector to reduce the toll of cigarette smoking through reduced initiation and increased cessation. To model reductions in smoking-related mortality...