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Publication Record


Assessing coronavirus disease 2019 (COVID-19) transmission to healthcare personnel: The global ACT-HCP case-control study.
Lentz RJ, Colt H, Chen H, Cordovilla R, Popevic S, Tahura S, Candoli P, Tomassetti S, Meachery GJ, Cohen BP, Harris BD, Talbot TR, Maldonado F
(2021) Infect Control Hosp Epidemiol 42: 381-387
MeSH Terms: Adult, Aged, COVID-19, Case-Control Studies, Female, Global Health, Humans, Infectious Disease Transmission, Patient-to-Professional, Logistic Models, Male, Middle Aged, Occupational Exposure, Personal Protective Equipment, Respiratory Protective Devices, Young Adult
Show Abstract · Added May 17, 2021
OBJECTIVE - To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection.
DESIGN - Case-control study.
SETTING - We collected data from international participants via an online survey.
PARTICIPANTS - In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study.
METHODS - Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases.
RESULTS - HCP infection was associated with non-aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04-1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1-16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2-0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4-0.7).
CONCLUSIONS - COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.
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Association of Genetic Risk of Obesity with Postoperative Complications Using Mendelian Randomization.
Robinson JR, Carroll RJ, Bastarache L, Chen Q, Mou Z, Wei WQ, Connolly JJ, Mentch F, Sleiman P, Crane PK, Hebbring SJ, Stanaway IB, Crosslin DR, Gordon AS, Rosenthal EA, Carrell D, Hayes MG, Wei W, Petukhova L, Namjou B, Zhang G, Safarova MS, Walton NA, Still C, Bottinger EP, Loos RJF, Murphy SN, Jackson GP, Kullo IJ, Hakonarson H, Jarvik GP, Larson EB, Weng C, Roden DM, Denny JC
(2020) World J Surg 44: 84-94
MeSH Terms: Adult, Body Mass Index, Female, Humans, Logistic Models, Male, Mendelian Randomization Analysis, Middle Aged, Obesity, Polymorphism, Single Nucleotide, Postoperative Complications, Retrospective Studies, Risk Factors
Show Abstract · Added March 24, 2020
BACKGROUND - The extent to which obesity and genetics determine postoperative complications is incompletely understood.
METHODS - We performed a retrospective study using two population cohorts with electronic health record (EHR) data. The first included 736,726 adults with body mass index (BMI) recorded between 1990 and 2017 at Vanderbilt University Medical Center. The second cohort consisted of 65,174 individuals from 12 institutions contributing EHR and genome-wide genotyping data to the Electronic Medical Records and Genomics (eMERGE) Network. Pairwise logistic regression analyses were used to measure the association of BMI categories with postoperative complications derived from International Classification of Disease-9 codes, including postoperative infection, incisional hernia, and intestinal obstruction. A genetic risk score was constructed from 97 obesity-risk single-nucleotide polymorphisms for a Mendelian randomization study to determine the association of genetic risk of obesity on postoperative complications. Logistic regression analyses were adjusted for sex, age, site, and race/principal components.
RESULTS - Individuals with overweight or obese BMI (≥25 kg/m) had increased risk of incisional hernia (odds ratio [OR] 1.7-5.5, p < 3.1 × 10), and people with obesity (BMI ≥ 30 kg/m) had increased risk of postoperative infection (OR 1.2-2.3, p < 2.5 × 10). In the eMERGE cohort, genetically predicted BMI was associated with incisional hernia (OR 2.1 [95% CI 1.8-2.5], p = 1.4 × 10) and postoperative infection (OR 1.6 [95% CI 1.4-1.9], p = 3.1 × 10). Association findings were similar after limitation of the cohorts to those who underwent abdominal procedures.
CONCLUSIONS - Clinical and Mendelian randomization studies suggest that obesity, as measured by BMI, is associated with the development of postoperative incisional hernia and infection.
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Real-world electronic health record identifies antimalarial underprescribing in patients with lupus nephritis.
Xiong WW, Boone JB, Wheless L, Chung CP, Crofford LJ, Barnado A
(2019) Lupus 28: 977-985
MeSH Terms: Adult, Aged, Antimalarials, Cohort Studies, Creatinine, Cross-Sectional Studies, Electronic Health Records, Female, Humans, Logistic Models, Lupus Erythematosus, Systemic, Lupus Nephritis, Male, Middle Aged, Severity of Illness Index, United States
Show Abstract · Added March 25, 2020
Antimalarials (AMs) reduce disease activity and improve survival in patients with systemic lupus erythematosus (SLE), but studies have reported low AM prescribing frequencies. Using a real-world electronic health record cohort, we examined if patient or provider characteristics impacted AM prescribing. We identified 977 SLE cases, 94% of whom were ever prescribed an AM. Older patients and patients with SLE nephritis were less likely to be on AMs. Current age (odds ratio = 0.97,  < 0.01) and nephritis (odds ratio = 0.16,  < 0.01) were both significantly associated with ever AM use after adjustment for sex and race. Of the 244 SLE nephritis cases, only 63% were currently on AMs. SLE nephritis subjects who were currently prescribed AMs were more likely to be followed by a rheumatologist than a nephrologist and less likely to have undergone dialysis or renal transplant (both  < 0.001). Non-current versus current SLE nephritis AM users had higher serum creatinine ( < 0.001), higher urine protein ( = 0.05), and lower hemoglobin levels ( < 0.01). As AMs reduce disease damage and improve survival in patients with SLE, our results demonstrate an opportunity to target future efforts to improve prescribing rates among multi-specialty providers.
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Serum Metabolites and Cardiac Death in Patients on Hemodialysis.
Hu JR, Grams ME, Coresh J, Hwang S, Kovesdy CP, Guallar E, Rhee EP, Shafi T
(2019) Clin J Am Soc Nephrol 14: 747-749
MeSH Terms: Aged, Death, Female, Humans, Ketone Bodies, Logistic Models, Male, Metabolomics, Middle Aged, Renal Dialysis
Added August 13, 2020
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Early onset oral tongue squamous cell carcinoma: Associated factors and patient outcomes.
Campbell BR, Sanders CB, Netterville JL, Sinard RJ, Rohde SL, Langerman A, Mannion K, Kim YJ, Murphy BA, Lewis JS, Warner JL, Smith DK, Lang Kuhs KA
(2019) Head Neck 41: 1952-1960
MeSH Terms: Adult, Age of Onset, Aged, Carcinoma, Squamous Cell, Combined Modality Therapy, Female, Health Behavior, Humans, Incidence, Logistic Models, Male, Middle Aged, Proportional Hazards Models, Risk Factors, Survival Rate, Tobacco, Smokeless, Tongue Neoplasms
Show Abstract · Added March 20, 2020
BACKGROUND - Incidence of oral tongue squamous cell carcinoma (OTC) is rising among those under age 50 years. The etiology is unknown.
METHODS - A total of 395 cases of OTC diagnosed and/or treated at Vanderbilt University Medical Center between 2000 and 2017 were identified. Of those, 113 (28.6%) were early onset (age < 50 years). Logistic regression was used to identify factors associated with early onset OTC. Cox proportional hazards models evaluated survival and recurrence.
RESULTS - Compared to typical onset patients, patients with early onset OTC were more likely to receive multimodality treatment (surgery and radiation; adjusted odds ratio [aOR], 2.7; 95% confidence interval [CI], 1.2-6.3) and report a history of snuff use (aOR, 5.4; 95% CI, 1.8-15.8) and were less likely to report a history of cigarette use (aOR, 0.5; 95% CI, 0.2-0.9). Early onset patients had better overall survival (adjusted hazard ratio, 0.6).
CONCLUSIONS - This is the largest study to evaluate factors associated with early onset OTC and the first to report an association with snuff.
© 2019 Wiley Periodicals, Inc.
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Association Between Red Blood Cell Distribution Width and Outcomes of Open Airway Reconstruction Surgery in Adults.
Xie DX, Rehman SC, Francis DO, Netterville JL, Garrett CG, Gelbard A, Lipscomb B, Wootten CT
(2019) JAMA Otolaryngol Head Neck Surg 145: 210-215
MeSH Terms: Adult, Aged, Erythrocyte Indices, Female, Humans, Laryngostenosis, Logistic Models, Male, Middle Aged, Reconstructive Surgical Procedures, Retrospective Studies, Tracheal Stenosis, Treatment Outcome
Show Abstract · Added July 30, 2020
Importance - Airway reconstruction for adults with laryngotracheal stenosis (LTS) is directed toward improving airway caliber to mitigate the patient's dyspnea and achieve prosthesis-free breathing (ie, without tracheostomy, intraluminal stent, or T-tube). Despite the importance of preoperative risk stratification to minimize postoperative complications, consensus on an objective predictive algorithm for open airway reconstruction is lacking.
Objective - To determine whether the ability to achieve a prosthesis-free airway in adults after open airway reconstruction is associated with red blood cell distribution width (RDW) at the time of surgery.
Design, Setting, and Participants - Case series study investigating 92 consecutive patients 18 years and older with laryngotracheal stenosis who underwent open airway reconstruction at a US tertiary care hospital from January 1, 2006, to January 1, 2017.
Main Outcomes and Measures - The main outcome was a prosthesis-free airway (absence of tracheostomy, intraluminal stent, or T-tubes) at last follow-up. Multivariate logistic regression modeling was used to identify independent factors associated with this outcome.
Results - Of the 92 patients who met inclusion criteria, the median (interquartile range) age was 44 (33.0-60.3) years; 50 (53%) were female, and 82 (89%) were white. In all, 74 patients (80%) were prosthesis free at the last follow-up (mean, 833 days; 95% CI, 10-4229 days). In multivariate analyses, airway decannulation was significantly correlated with reduced RDW (odds ratio [OR], 0.40; 95% CI, 0.19-0.84) and the absence of posterior glottic stenosis (OR, 0.12; 95% CI, 0.04-0.37).
Conclusions and Relevance - These data suggest that surgical success in open airway reconstruction is significantly associated with RDW and whether the patient had posterior glottic stenosis. The RDW is a routine laboratory parameter that may provide some insight to the preoperative probability of prosthesis removal, facilitate risk stratification, promote informed patient decision making, and optimize health care resource management.
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White matter differences between essential tremor and Parkinson disease.
Juttukonda MR, Franco G, Englot DJ, Lin YC, Petersen KJ, Trujillo P, Hedera P, Landman BA, Kang H, Donahue MJ, Konrad PE, Dawant BM, Claassen DO
(2019) Neurology 92: e30-e39
MeSH Terms: Aged, Anisotropy, Cohort Studies, Diffusion Tensor Imaging, Essential Tremor, Female, Humans, Image Processing, Computer-Assisted, Leukoencephalopathies, Logistic Models, Male, Middle Aged, Parkinson Disease
Show Abstract · Added June 22, 2019
OBJECTIVE - To assess white matter integrity in patients with essential tremor (ET) and Parkinson disease (PD) with moderate to severe motor impairment.
METHODS - Sedated participants with ET (n = 57) or PD (n = 99) underwent diffusion tensor imaging (DTI) and fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values were computed. White matter tracts were defined using 3 well-described atlases. To determine candidate white matter regions that differ between ET and PD groups, a bootstrapping analysis was applied using the least absolute shrinkage and selection operator. Linear regression was applied to assess magnitude and direction of differences in DTI metrics between ET and PD populations in the candidate regions.
RESULTS - Fractional anisotropy values that differentiate ET from PD localize primarily to thalamic and visual-related pathways, while diffusivity differences localized to the cerebellar peduncles. Patients with ET exhibited lower fractional anisotropy values than patients with PD in the lateral geniculate body ( < 0.01), sagittal stratum ( = 0.01), forceps major ( = 0.02), pontine crossing tract ( = 0.03), and retrolenticular internal capsule ( = 0.04). Patients with ET exhibited greater radial diffusivity values than patients with PD in the superior cerebellar peduncle ( < 0.01), middle cerebellar peduncle ( = 0.05), and inferior cerebellar peduncle ( = 0.05).
CONCLUSIONS - Regionally, distinctive white matter microstructural values in patients with ET localize to the cerebellar peduncles and thalamo-cortical visual pathways. These findings complement recent functional imaging studies in ET but also extend our understanding of putative physiologic features that account for distinctions between ET and PD.
© 2018 American Academy of Neurology.
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Phenome-wide association study identifies dsDNA as a driver of major organ involvement in systemic lupus erythematosus.
Barnado A, Carroll RJ, Casey C, Wheless L, Denny JC, Crofford LJ
(2019) Lupus 28: 66-76
MeSH Terms: Adult, Autoantibodies, Biomarkers, Cohort Studies, DNA, Electronic Health Records, Female, Genome-Wide Association Study, Humans, Logistic Models, Lupus Erythematosus, Systemic, Male, Middle Aged, Phenotype, Severity of Illness Index
Show Abstract · Added March 25, 2020
In systemic lupus erythematosus (SLE), dsDNA antibodies are associated with renal disease. Less is known about comorbidities in patients without dsDNA or other autoantibodies. Using an electronic health record (EHR) SLE cohort, we employed a phenome-wide association study (PheWAS) that scans across billing codes to compare comorbidities in SLE patients with and without autoantibodies. We used our validated algorithm to identify SLE subjects. Autoantibody status was defined as ever positive for dsDNA, RNP, Smith, SSA and SSB. PheWAS was performed in antibody positive vs. negative SLE patients adjusting for age and race and using a false discovery rate of 0.05. We identified 1097 SLE subjects. In the PheWAS of dsDNA positive vs. negative subjects, dsDNA positive subjects were more likely to have nephritis ( p = 2.33 × 10) and renal failure ( p = 1.85 × 10). After adjusting for sex, race, age and other autoantibodies, dsDNA was independently associated with nephritis and chronic kidney disease. Those patients negative for dsDNA, RNP, SSA and SSB negative subjects were all more likely to have billing codes for sleep, pain and mood disorders. PheWAS uncovered a hierarchy within SLE-specific autoantibodies with dsDNA having the greatest impact on major organ involvement.
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Relationship between very low low-density lipoprotein cholesterol concentrations not due to statin therapy and risk of type 2 diabetes: A US-based cross-sectional observational study using electronic health records.
Feng Q, Wei WQ, Chung CP, Levinson RT, Sundermann AC, Mosley JD, Bastarache L, Ferguson JF, Cox NJ, Roden DM, Denny JC, Linton MF, Edwards DRV, Stein CM
(2018) PLoS Med 15: e1002642
MeSH Terms: Adult, Case-Control Studies, Cholesterol, LDL, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Electronic Health Records, Female, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Risk Factors, United States, Young Adult
Show Abstract · Added April 2, 2019
BACKGROUND - Observations from statin clinical trials and from Mendelian randomization studies suggest that low low-density lipoprotein cholesterol (LDL-C) concentrations may be associated with increased risk of type 2 diabetes mellitus (T2DM). Despite the findings from statin clinical trials and genetic studies, there is little direct evidence implicating low LDL-C concentrations in increased risk of T2DM.
METHODS AND FINDINGS - We used de-identified electronic health records (EHRs) at Vanderbilt University Medical Center to compare the risk of T2DM in a cross-sectional study among individuals with very low (≤60 mg/dl, N = 8,943) and normal (90-130 mg/dl, N = 71,343) LDL-C levels calculated using the Friedewald formula. LDL-C levels associated with statin use, hospitalization, or a serum albumin level < 3 g/dl were excluded. We used a 2-phase approach: in 1/3 of the sample (discovery) we used T2DM phenome-wide association study codes (phecodes) to identify cases and controls, and in the remaining 2/3 (validation) we identified T2DM cases and controls using a validated algorithm. The analysis plan for the validation phase was constructed at the time of the design of that component of the study. The prevalence of T2DM in the very low and normal LDL-C groups was compared using logistic regression with adjustment for age, race, sex, body mass index (BMI), high-density lipoprotein cholesterol, triglycerides, and duration of care. Secondary analyses included prespecified stratification by sex, race, BMI, and LDL-C level. In the discovery cohort, phecodes related to T2DM were significantly more frequent in the very low LDL-C group. In the validation cohort (N = 33,039 after applying the T2DM algorithm to identify cases and controls), the risk of T2DM was increased in the very low compared to normal LDL-C group (odds ratio [OR] 2.06, 95% CI 1.80-2.37; P < 2 × 10-16). The findings remained significant in sensitivity analyses. The association between low LDL-C levels and T2DM was significant in males (OR 2.43, 95% CI 2.00-2.95; P < 2 × 10-16) and females (OR 1.74, 95% CI 1.42-2.12; P = 6.88 × 10-8); in normal weight (OR 2.18, 95% CI 1.59-2.98; P = 1.1× 10-6), overweight (OR 2.17, 95% CI 1.65-2.83; P = 1.73× 10-8), and obese (OR 2.00, 95% CI 1.65-2.41; P = 8 × 10-13) categories; and in individuals with LDL-C < 40 mg/dl (OR 2.31, 95% CI 1.71-3.10; P = 3.01× 10-8) and LDL-C 40-60 mg/dl (OR 1.99, 95% CI 1.71-2.32; P < 2.0× 10-16). The association was significant in individuals of European ancestry (OR 2.67, 95% CI 2.25-3.17; P < 2 × 10-16) but not in those of African ancestry (OR 1.09, 95% CI 0.81-1.46; P = 0.56). A limitation was that we only compared groups with very low and normal LDL-C levels; also, since this was not an inception cohort, we cannot exclude the possibility of reverse causation.
CONCLUSIONS - Very low LDL-C concentrations occurring in the absence of statin treatment were significantly associated with T2DM risk in a large EHR population; this increased risk was present in both sexes and all BMI categories, and in individuals of European ancestry but not of African ancestry. Longitudinal cohort studies to assess the relationship between very low LDL-C levels not associated with lipid-lowering therapy and risk of developing T2DM will be important.
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Photoperiod during maternal pregnancy and lifetime depression in offspring.
Devore EE, Chang SC, Okereke OI, McMahon DG, Schernhammer ES
(2018) J Psychiatr Res 104: 169-175
MeSH Terms: Adult, Antidepressive Agents, Cohort Studies, Depression, Female, Humans, Logistic Models, Maternal Exposure, Middle Aged, Nurses, Photoperiod, Pregnancy, Pregnancy Trimester, Second, Prenatal Exposure Delayed Effects, Psychiatric Status Rating Scales, Suicide, United States
Show Abstract · Added March 18, 2020
Experimental studies indicate that perinatal light exposure has enduring effects on affective behaviors in rodents; however, insufficient research has explored this hypothesis in humans. We examined photoperiod (i.e., day length) metrics during maternal pregnancy in relation to lifetime depression in the longitudinal Nurses' Health Study (NHS) and NHS II. 160,723 participants reported birth date and birth state (used to derive daily photoperiod based on published mathematical equations), and clinician-diagnosed depression and antidepressant use throughout adulthood. Logistic regression was used to estimate odds ratios (OR) (and 95% confidence intervals [CI]) for depression (defined as clinician diagnosis and antidepressant use) across quintiles of two exposures during maternal pregnancy: 1) total photoperiod (total number of daylight hours) and 2) differences between minimum/maximum photoperiod; each trimester of pregnancy was examined separately. Total photoperiod during maternal pregnancy was not associated with depression overall or by trimester of pregnancy. However, larger differences between minimum/maximum photoperiod during maternal pregnancy were related to lower odds of depression (multivariable [MV]-adjusted OR: 0.86, 95% CI: 0.83, 0.90 comparing extreme quintiles of exposure; p-trend<0.0001); this association appeared specific to the second trimester of pregnancy (MV-adjusted p-trends = 0.03, <0.0001, and 0.3 across the three trimesters, respectively). In addition, birth at higher latitude (where larger differences in minimum/maximum photoperiod exist) was associated with a significant reduction in the lifetime risk of depression. These findings are consistent with an emerging hypothesis in which perinatal light exposure may influence risk of depression, and they might be understood through the conceptual framework of adaptive developmental plasticity.
Copyright © 2018 Elsevier Ltd. All rights reserved.
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