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Top Manuscripts

Top Epidemiology Manuscripts

The following 10 papers were selected from over 500 new publications during the 2014-15 academic year. They represent the breadth and impact of work in the Department of Epidemiology. These manuscripts were published in journals of high scientific impact and most received significant attention in the lay press. They are all first or senior authored by epidemiology faculty, thus demonstrate scientific leadership in the field.

Early-pregnancy vitamin D deficiency and risk of preterm birth subtypes

Lisa M. Bodnar
Bodnar LM, Platt RW, Simhan HN. "Early-pregnancy vitamin D deficiency and risk of preterm birth subtypes." Obstetrics and Gynecology. 2015 Feb; 125 (2):439-47. PMCID: PMC4304969. PMID: 25569002. doi: 10.1097/AOG.0000000000000621.

We used data from a large cohort of births at Magee-Womens Hospital to estimate the association between maternal vitamin D status and risk of preterm birth. We found that the confounder-adjusted risk of preterm birth was highest when serum 25-hydroxyvitamin D was less than 50 nmol/L, declined as 25-hydroxyvitamin D increased to approximately 90 nmol/L, and then plateaued. Findings were similar for spontaneous or medically indicated preterm birth and preterm birth at less than 34 weeks of gestation. Our data as well as several large extant epidemiologic studies provide a key element of justification for the conduct of a randomized clinical trial of vitamin D supplementation in pregnancy.

Effect of vitamin E supplementation on HDL function by Haptoglobin genotype in type 1 diabetes: Results from the HapE randomized crossover pilot trial

Tina Costacou
Costacou T, Levy AP, Miller RG, Snell-Bergeon J, Asleh R, Farbstein D, Fickley CE, Pambianco G, de la Vega R, Evans RW, Orchard TJ. "Effect of vitamin E supplementation on HDL function by Haptoglobin genotype in type 1 diabetes: Results from the HapE randomized crossover pilot trial." In press, Acta Diabetologica. 2015. DOI: 10.1007/s00592-015-0770-8.

In investigating mechanisms for the increased CAD risk associated with the Hp 2-2 genotype, we showed that HDL function worsens with the number of Hp 2 alleles in type 1 diabetes. Moreover, results from our pilot randomized crossover trial suggest that α-tocopherol supplementation improves HDL function in Hp 2-2 carriers but appears to adversely affect lipid peroxides and lipoprotein subfractions among Hp 1 allele carriers. These findings, which require replication in a full pharmacogenetic trial, may partially explain the null or harmful effects observed with antioxidant supplementation in previously conducted trials.

Incidence of head and neck squamous cell carcinoma among subjects at high risk for lung cancer: results from the Pittsburgh Lung Screening Study

Brenda Diergaarde
Dixit R, Weissfeld JL, Wilson DO, Balogh P, Sufka P, Siegfried JM, Grandis JR, and Diergaarde B. "Incidence of head and neck squamous cell carcinoma among subjects at high risk for lung cancer: results from the Pittsburgh Lung Screening Study." Cancer. 2015 Jan 5. doi: 10.1002/cncr.29189. [Epub ahead of print]. PMID: 25559556, PMCID: PMC4409462

Earlier detection and diagnosis of head and neck squamous cell carcinoma (HNSCC) should lead to improved outcomes. However, no effective screening strategy has been identified to date. Given the current recommendations for lung cancer screening and because cigarette smoking is also one of the primary risk factors for head and neck cancer, we hypothesized that it would be useful to screen subjects targeted for lung cancer screening for HNSCC as well. As a first step, we used data from the Pittsburgh Lung Screening Study and the Surveillance, Epidemiology, and End Results (SEER) program of the NCI to evaluate whether incident HNSCC cases are more common among those targeted for lung cancer screening than in the general U.S. population. Results from our study provide a rationale for offering head and neck cancer screening along with computed tomography screening for lung cancer. Randomized controlled trials that assess the effectiveness of adding examination of the head and neck area to lung cancer screening programs are warranted.

The Pittsburgh Fatigability scale for older adults: development and validation

Nancy W Glynn
Glynn NW, Santanasto AJ, Simonsick EM, Boudreau RM, Beach SR, Schulz R, Newman AB. "The Pittsburgh Fatigability scale for older adults: development and validation." Journal of The American Geriatrics Society. 2015 Jan; 63 (1):130-5. PMID: 25556993. doi: 10.1111/jgs.13191.

This paper describes the development of the Pittsburgh Fatigability Scale (PFS) and establish its reliability, concurrent validity against two measures of performance fatigability, and its convergent validity for mobility, physical function, and fitness.  The scale development sample included 1,013 individuals aged 60 and older from two registries; validation sample: 483 adults aged 60 and older from the Baltimore Longitudinal Study of Aging.  The PFS showed strong internal consistency (Cronbach’s alpha 0.88) and excellent test–retest reliability (intraclass correlation 0.86). In the validation sample, PFS scores, adjusted for age, sex, and race, were greater for those with high performance fatigability, slow gait speed, worse physical function, and lower fitness, with differences between high and low fatigability ranging from 3.2 to 5.1 points (P < .001). The 10-item PFS physical fatigability score is a valid and reliable measure of perceived fatigability in older adults and can serve as an adjunct to performance-based fatigability measures for identifying older adults at risk of mobility limitation in clinical and research settings.

The impact of lifestyle intervention on sedentary time in individuals at high risk of diabetes

Andrea M Kriska
Rockette-Wagner B, Kriska A, Edelstein S, Venditti Em, Reddy D, Bray G, Carrion-Peterson ML, Dabelea D, Rubon R, Delahanty LM, Florez H, Franks PW, Montez M, for the Diabetes Prevention Program Research Group. "The impact of lifestyle intervention on sedentary time in individuals at high risk of diabetes." Diabetologia. 2015 Jun;58(6):1198-202.

We recently published a manuscript examining sedentary behaviour in 3,234 overweight adults at high risk for diabetes from the Diabetes Prevention Program (DPP). Our results demonstrated that the DPP lifestyle intervention, already shown to be successful at increasing moderate intensity activity, was also successful at reducing sedentary time. Additionally, for participants in all treatment arms, the risk of developing diabetes increased approximately 3.4% for each reported hour per day of TV watching after adjustment for age, sex, treatment arm and time-dependent leisure physical activity. This association was reduced when time-dependent weight was added to the model (to a 2.1% increased risk of developing diabetes per hour of watching TV, which was not statistically significant).

White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes

Karen Nunley
Nunley KA, Ryan CM, Orchard TJ, Aizenstein HJ, Jennings JR, Ryan J, Zgibor JC, Boudreau RM, Costacou T, Maynard JD, Miller RG, Rosano C. "White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes." Neurology. 2015 May 19;84(20):2062-9. PMID: 25904692

Severity and volume of white matter hyperintensities (WMHs) and infarcts were quantified in 97 patients with childhood-onset type 1 diabetes mellitus (T1DM) (mean age and duration: 50 and 41 years) and compared with 81 non-T1DM adults of similar age (mean age: 48 years), concurrent with cognitive and health-related measures. Childhood-onset T1DM patients had had more severe WMHs and slower information processing: digit symbol substitution, # correct: 54.9 (13.6) vs 65.7 (10.9); pegboard, seconds: 88.6 (34.2) vs 66.0 (9.9) independent of age, education, or other factors (p<0.0001).  WMHs were associated with slower information processing in both groups; adjusting for WMHs attenuated the group differences (13% for digit symbol, 11% for pegboard). Among T1DM patients, prevalent neuropathies and smoking tripled the odds of high WMH burden, independent of age or disease duration. WMHs were not associated with blood pressure or hyperglycemia. Clinically relevant WMHs are evident earlier among middle-aged patients with childhood-onset T1DM. Brain imaging in patients with T1DM who have cognitive difficulties, especially those with neuropathies, may help uncover cerebral microvascular damage.

Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis

Jean B Nachega
Uthman OA, Okwundu C, Gbenga K, Volmink JA, Dowdy DW, Zumla A, Nachega JB. "Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis." Annals of Internal Medicine. 2015 Jul 9. (in press).

In a meta-analysis of randomized controlled trials Drs. Uthman (Assistant Professor, Warwick University, UK), Nachega (Associate Professor of Medicine and Epidemiology, Pitt GSPH and Senior Author of the paper) and Colleagues investigated the optimal timing of initiating antiretroviral therapy (ART) in 4568 HIV-infected adults patients with newly diagnosed Tuberculosis (TB). Concurrent TB and HIV treatments can challenging due to overlapping side effects, non-adherence due pill burden and drug-drug interactions. The found that early initiation (within 2 weeks after initiation TB treatment) improves survival in those with CD4+ T-cell counts <0.050 x 109cells/L , although this is associated with a two-fold increase in the frequency of TB-Immune Reconstitution Inflammatory Syndrome (TB-IRIS). In patients with higher CD4+ T-cell counts between 0.050 and 0.220 x 109cells/L, evidence was insufficient to support or refute a survival benefit. Their study also included important recent trial findings which suggest that ART can be deferred to after the end of 6-month TB treatment in patients with CD4+ T-cell counts >0.220 x 109cells/L. The authors recommends that existing clinical guidelines should be updated to consider this new evidence which supports a less rigid approach emphasizing issues such as clinical presentation and calling for additional analyses from existing cohorts or trials to inform the CD4+ T-cell counts threshold at which the survival benefit associated with early ART begins to attenuate as well as cost-effectiveness data among patients initiating ART at aCD4+ T-cell counts >0.050 x 109cells/L. 

Continuous decline in mortality from coronary heart disease in Japan despite a continuous and marked rise in total cholesterol: Japanese experience after the Seven Countries Study

Akira Sekikawa
Sekikawa A, Miyamoto Y, Miura K, Nishimura K, Willcox BJ, Masaki KH, Rodriguez B, Tracy RP, Okamura T, Kuller LH. "Continuous decline in mortality from coronary heart disease in Japan despite a continuous and marked rise in total cholesterol: Japanese experience after the Seven Countries Study." Int J Epidemiol. 2015 Jul 16. pii: dyv143. [Epub ahead of print] PMID: 26182938

This paper described trends in mortality from coronary heart disease and total cholesterol as well as other risk factors since 1980, highlighting the trends in Japan contrasting those in other selected developed countries, i.e., Australia, Canada, France, Spain, Sweden, the UK, and the US. Age-adjusted mortality from coronary heart disease continuously declined between 1980 and 2007 in all these countries. The decline in age-adjusted mortality from coronary heart disease was accompanied by a constant fall in total cholesterol except for Japan where total cholesterol continuously rose. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries. The observations may suggest some protective factors unique to Japanese in Japan.

Fine particulate matter and the risk of autism spectrum disorder

Evelyn O Talbott
Talbott EO, Arena VC, Rager JR, Clougherty JE, Michanowicz DR, Sharma RK, Stacy SL. "Fine particulate matter and the risk of autism spectrum disorder." Environ Res. 2015 May 6;140:414-420. doi: 10.1016/j.envres.2015.04.021. [Epub ahead of print]
PMID: 25957837.

Recent studies have suggested that air pollution, including PM2.5, may play a role in the onset of Childhood autism. We investigated the association between prenatal and early childhood exposure to fine particulate matter (PM2.5) and risk for childhood ASD for six counties in SW PA from 2005-2009. A land use regression (LUR) model was used to create PM2.5 estimates for 217 ASD cases and 226 controls for key developmental time periods. Autism cases  were  more likely to live in areas with higher levels of PM2.5 specifically  for pre-pregnancy through year two with an increased risk after adjusting for potential confounders  (OR=1.51, 95% CI=1.01-2.26).

A systematic review of barriers to data sharing in public health

Wilbert Van Panhuis
Van Panhuis WG, Paul P, Emerson C, Grefenstette J, Wilder R, Herbst AJ, Heymann D, Burke DS. "A systematic review of barriers to data sharing in public health." BMC Public Health. 2014; 5(14):1144.

In the current information age, the use of data has become essential for decision making in public health from the local to global level. Despite a global commitment to the use and sharing of public health data, this can be challenging in reality. We conducted a systematic literature review and found 20 potential barriers to data sharing in public health in six categories: technical, motivational, economic, political, legal and ethical. The simultaneous effect of multiple interacting barriers has limited advances in public health data sharing. A systematic framework towards solutions will be essential to accelerate the use of valuable information for the global good.

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