Lee Wheless’s research while affiliated with Vanderbilt University and other places

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Publications (81)


Frequency and timing of multiple skin cancer development in five cohorts
  • Article

February 2025

Journal of the American Academy of Dermatology

Lee Wheless

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Kai-Ping Liao

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Siwei Zheng

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[...]

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Mackenzie R. Wehner

The impact of imprecise case definitions in electronic health record research: a melanoma case-study from the Million Veteran Program

January 2025

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1 Read

Archives of Dermatological Research

Cases for a disease can be defined broadly using diagnostic codes, or narrowly using gold-standard confirmation that often is not available in large administrative datasets. These different definitions can have significant impacts on the results and conclusions of studies. We conducted this study to assess how using melanoma phecodes versus histologic confirmation for invasive or in situ melanoma impacts the results of a genome-wide association study (GWAS) using the Million Veteran Program. Melanoma status was determined three ways: (1) by the presence of two or more phecodes, (2) histologically-confirmed invasive melanoma, and (3) histologically-confirmed melanoma in situ. We conducted a GWAS for variants with minor allele frequencies of 1% or greater. There were 45,665 cases in the phecode cohort, 5364 cases in the confirmed invasive melanoma cohort, and 4792 cases in the confirmed melanoma in situ cohort. There were 20,457 variants significant at the genome-wide level in the phecode cohort, 2582 in the invasive melanoma cohort, and 1989 in the melanoma in situ cohort. Most of the variants identified in the phecode cohort did not replicate in the histologically-confirmed cohorts. The different case definitions led to large differences in sample size and variants associated at the genome-wide level. Unvalidated and imprecise case definitions can lead to less accurate results. Investigators should use validated phenotypes when gold-standard definitions are not available.





Characteristics of patients in the MVP cohort included in this study.for use under a CC0 license.
No Increased Risk of Major Adverse Cardiovascular Events following Nicotinamide Exposure
  • Preprint
  • File available

September 2024

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46 Reads

IMPORTANCE Nicotinamide metabolites have recently been implicated in increased risk of major cardiovascular events (MACE). Supportive data about clinical risk of MACE for nicotinamide users is lacking. OBJECTIVE To determine whether nicotinamide use results in an increase of MACE. DESIGN, SETTING, PARTICIPANTS Retrospective cohort study of two patient cohorts, Vanderbilt University Medical Center (VUMC) and Military Veteran Program (MVP). The risk of MACE in patients exposed to nicotinamide was compared to the risk of MACE in unexposed patients. In the VUMC cohort, 1228 patients were exposed to nicotinamide based on keyword entry for “nicotinamide” or “niacinamide” and hand-review of charts, while 253 were unexposed but had documented recommendation for use. In the MVP cohort, there were 1594 with exposure to nicotinamide propensity score matched to 2694 without exposure. EXPOSURES The primary exposure for the VUMC cohort was a confirmed exposure to nicotinamide in chart review. The primary exposure for the MVP cohort was medication entry for “nicotinamide” or “niacinamide”. MAIN OUTCOME(S) AND MEASURE(S) The primary outcome was development of MACE based on a validated phenotype. RESULTS Between both cohorts, 6039 patients were included, of whom 5125 were male with a mean age of 63.2 years. Neither cohort had significant differences in mean age, sex, race and ethnicity between the nicotinamide exposed and unexposed groups. In the VUMC cohort, there was no significant association between nicotinamide exposure and the primary outcome of MACE (HR 0.76, 95% CI 0.46 – 1.25, p = 0.28). MACE prior to nicotinamide exposure was strongly associated with subsequent MACE (HR 9.01, 95% CI 5.90 – 13.70, p < 0.001). In the MVP cohort, we adjusted for MACE risk factors as potential confounding variables and saw no significant association between nicotinamide exposure and MACE (HR 1.00 95% CI 0.75 – 1.32), while history of prior MACE remained strongly associated with subsequent MACE (HR 9.50, 95% CI 6.38 – 14.1). CONCLUSIONS AND RELEVANCE In this retrospective cohort study of 6039 adults from two different patient populations, we found no increased risk of MACE in patients with nicotinamide exposure.

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Citations (44)


... CSCC. Larger and longer follow-up data are necessary to fully assess the effect of belatacept on CSCC prevalence post-SOT[68]. ...

Reference:

Cutaneous Squamous Cell Carcinoma in Patients with Solid-Organ-Transplant-Associated Immunosuppression
De novo belatacept does not reduce the rate of skin cancer in renal transplant recipients compared to standard therapy
  • Citing Article
  • June 2024

Journal of the American Academy of Dermatology

... However, using triangulation, the totality of evidence of cancer in humans strongly supports a causal interpretation. These lines of evidence included a monotonic increase in risk with increasing voriconazole exposure in the most robust study, 8 evidence derived from gene-drug interaction that informs risk specific to the phototoxic metabolite voriconazole N-oxide, 9 and the occurrence of SCC even in children exposed to the agent. ...

Voriconazole metabolism is associated with the number of skin cancers per patient

Archives of Dermatological Research

... 23 Individuals with late-onset SLE may be subject to greater organ damage and higher mortality than those diagnosed with SLE earlier in life. 5,6,[24][25][26][27][28] Our findings highlight the heterogeneous disease trajectories of older adults with SLE as perceived by the patients themselves. As patient and clinician perceptions of SLE disease activity and health status concerns may be discordant, 29,30 and age-related bias has been identified among healthcare professionals in other clinical contexts, 31 these data underscore the importance of eliciting the patient's perception of their disease course to ensure optimal management. ...

Comparison of late-onset and non-late-onset systemic lupus erythematosus individuals in a real-world electronic health record cohort

... F-statistic is an effective tool for assessing the strength of associations between SNPs and exposure and can reduce the bias caused by weak IVs. F-statistic is calculated as "F = (β 2 / standard error 2 )" when F-statistic > 10 indicates that SNPs are reliable [39]. In addition, the F-statistic is closely related to the degree of interpretation for phenotype by sample size (N), the number of instrumental variables (k), and genetic variation (R 2 ). ...

Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk

JAMA Network Open

... We tested associations with two phenotypes: CKD and T2D. To phenotype individuals, ICD-9 and ICD-10 codes were mapped to PhecodeX if they had at least two separate instances of an ICD code 49 . The Phecodes used were as follows: CKD = GU_582.2, ...

Next-generation phenotyping: introducing phecodeX for enhanced discovery research in medical phenomics

Bioinformatics

... Further evidence in support of the ion channel hypothesis comes from a recent human genetics study demonstrating that the N264K substitution in the protein sequence of APOL1 both decreased APOL1 ion flux and reduced kidney disease incidence in APOL1 G2 carriers 36 . ...

Genetic Inhibition of APOL1 Pore-Forming Function Prevents APOL1-Mediated Kidney Disease

Journal of the American Society of Nephrology

... In practice, ML applications are mainly focused on the use of consolidated databases containing heterogeneous information, for which traditional statistical techniques have limited applicability (PAIXÃO et al., 2022). ML algorithms have already been widely adopted across various fields, including banking systems for fraud detection (LOPES, 2019), internet search engines (CARVALHO, 2012), video surveillance systems (MOITINHO & BENICASA, 2023), data security (HENKE et al., 2018), robotics (RYBCZAK et al., 2024), and in medicine for diagnosis and prognosis (GROSSARTH et al, 2023). In the medical field, with the digitization of medical records, laboratory tests, and imaging exams, there has been a significant growth in databases, which are prime sources for applying ML techniques aimed at disease prevention, early diagnosis, and treatment (PAIXÃO et al., 2022). ...

Recent Advances in Melanoma Diagnosis and Prognosis Using Machine Learning Methods

Current Oncology Reports

... Several studies reported the application of ChatGPT in generating medical articles, such as literature reviews, case studies, and research summaries [4]. Researchers have also employed ChatGPT for data extraction, interpretation, and visualization in systematic reviews and meta-analyses. ...

On the cusp: Considering the impact of artificial intelligence language models in healthcare
  • Citing Article
  • March 2023

Med

... A study conducted by physicians involved generating medical questions classified by difficulty and then comparing the accuracy of ChatGPTgenerated answers. The results showed that ChatGPT provided largely accurate information to multiple medical questions, as judged by academic physician specialists (Johnson et al. 2023). Likewise, the data from this study showed that ChatGPT had an increased similarity score for Autism and ADHD. ...

Assessing the Accuracy and Reliability of AI-Generated Medical Responses: An Evaluation of the Chat-GPT Model

... A previous report indicated that PCP prophylaxis was continued until the day patients with rheumatic diseases were prescribed ≤ 15 mg/day of PSL; half of these patients had SLE [14]. According to a study using administrative claim data on patients with SLE, 14% of patients overall were on PCP prophylaxis, while 74% of patients with ≥ 20 mg of PSL were on PCP prophylaxis [15]. Similar to a previous report, our study found that 20% of all patients received PCP prophylaxis and 68% of those on ≥ 20 mg of PSL. ...

Rates of Pneumocystis jirovecii pneumonia and prophylaxis prescribing patterns in a large electronic health record cohort of patients with systemic lupus erythematosus
  • Citing Article
  • October 2022

Seminars in Arthritis and Rheumatism