Large language models in medicine: the potentials and pitfalls

Large language models (LLMs) have been applied to tasks in healthcare, ranging from medical exam questions to responding to patient questions. With increasing institutional partnerships between companies producing LLMs and healthcare systems, real world clinical application is coming closer to reality. As these models gain traction, it is essential for healthcare practitioners to understand what LLMs are, their development, their current and potential applications, and the associated pitfalls when utilized in medicine. This review and accompanying tutorial aim to give an overview of these topics to aid healthcare practitioners in understanding the rapidly changing landscape of LLMs as applied to medicine

TrueImage: A Machine Learning Algorithm to Improve the Quality of Telehealth Photos

Telehealth is an increasingly critical component of the health care ecosystem, especially due to the COVID-19 pandemic. Rapid adoption of telehealth has exposed limitations in the existing infrastructure. In this paper, we study and highlight photo quality as a major challenge in the telehealth workflow. We focus on teledermatology, where photo quality is particularly important; the framework proposed here can be generalized to other health domains. For telemedicine, dermatologists request that patients submit images of their lesions for assessment. However, these images are often of insufficient quality to make a clinical diagnosis since patients do not have experience taking clinical photos. A clinician has to manually triage poor quality images and request new images to be submitted, leading to wasted time for both the clinician and the patient. We propose an automated image assessment machine learning pipeline, TrueImage, to detect poor quality dermatology photos and to guide patients in taking better photos. Our experiments indicate that TrueImage can reject 50% of the sub-par quality images, while retaining 80% of good quality images patients send in, despite heterogeneity and limitations in the training data. These promising results suggest that our solution is feasible and can improve the quality of teledermatology care.Comment: 12 pages, 5 figures, Preprint of an article published in Pacific Symposium on Biocomputing \c{opyright} 2020 World Scientific Publishing Co., Singapore, http://psb.stanford.edu

Towards Reliable Dermatology Evaluation Benchmarks

Benchmark datasets for digital dermatology unwittingly contain inaccuracies that reduce trust in model performance estimates. We propose a resource-efficient data cleaning protocol to identify issues that escaped previous curation. The protocol leverages an existing algorithmic cleaning strategy and is followed by a confirmation process terminated by an intuitive stopping criterion. Based on confirmation by multiple dermatologists, we remove irrelevant samples and near duplicates and estimate the percentage of label errors in six dermatology image datasets for model evaluation promoted by the International Skin Imaging Collaboration. Along with this paper, we publish revised file lists for each dataset which should be used for model evaluation. Our work paves the way for more trustworthy performance assessment in digital dermatology.Comment: Link to the revised file lists: https://github.com/Digital-Dermatology/SelfClean-Revised-Benchmark

Development and Clinical Evaluation of an AI Support Tool for Improving Telemedicine Photo Quality

Telemedicine utilization was accelerated during the COVID-19 pandemic, and skin conditions were a common use case. However, the quality of photographs sent by patients remains a major limitation. To address this issue, we developed TrueImage 2.0, an artificial intelligence (AI) model for assessing patient photo quality for telemedicine and providing real-time feedback to patients for photo quality improvement. TrueImage 2.0 was trained on 1700 telemedicine images annotated by clinicians for photo quality. On a retrospective dataset of 357 telemedicine images, TrueImage 2.0 effectively identified poor quality images (Receiver operator curve area under the curve (ROC-AUC) =0.78) and the reason for poor quality (Blurry ROC-AUC=0.84, Lighting issues ROC-AUC=0.70). The performance is consistent across age, gender, and skin tone. Next, we assessed whether patient-TrueImage 2.0 interaction led to an improvement in submitted photo quality through a prospective clinical pilot study with 98 patients. TrueImage 2.0 reduced the number of patients with a poor-quality image by 68.0%.Comment: 24 pages, 7 figure

Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling 19,149 SCC cases and 680,049 controls. We discover eight novel loci associated with SCC, confirm all previously associated loci, and perform fine mapping of causal variants. The novel SNPs occur within skin-specific regulatory elements and implicate loci involved in cancer development, immune regulation, and keratinocyte differentiation in SCC susceptibility

Pathway analysis of genome-wide data improves warfarin dose prediction

Background: Many genome-wide association studies focus on associating single loci with target phenotypes. However, in the setting of rare variation, accumulating sufficient samples to assess these associations can be difficult. Moreover, multiple variations in a gene or a set of genes within a pathway may all contribute to the phenotype, suggesting that the aggregation of variations found over the gene or pathway may be useful for improving the power to detect associations. Results: Here, we present a method for aggregating single nucleotide polymorphisms (SNPs) along biologically relevant pathways in order to seek genetic associations with phenotypes. Our method uses all available genetic variants and does not remove those in linkage disequilibrium (LD). Instead, it uses a novel SNP weighting scheme to down-weight the contributions of correlated SNPs. We apply our method to three cohorts of patients taking warfarin: two European descent cohorts and an African American cohort. Although the clinical covariates and key pharmacogenetic loci for warfarin have been characterized, our association metric identifies a significant association with mutations distributed throughout the pathway of warfarin metabolism. We improve dose prediction after using all known clinical covariates and pharmacogenetic variants in VKORC1 and CYP2C9. In particular, we find that at least 1% of the missing heritability in warfarin dose may be due to the aggregated effects of variations in the warfarin metabolic pathway, even though the SNPs do not individually show a significant association. Conclusions: Our method allows researchers to study aggregative SNP effects in an unbiased manner by not preselecting SNPs. It retains all the available information by accounting for LD-structure through weighting, which eliminates the need for LD pruning

Towards Transparency in Dermatology Image Datasets with Skin Tone Annotations by Experts, Crowds, and an Algorithm

While artificial intelligence (AI) holds promise for supporting healthcare providers and improving the accuracy of medical diagnoses, a lack of transparency in the composition of datasets exposes AI models to the possibility of unintentional and avoidable mistakes. In particular, public and private image datasets of dermatological conditions rarely include information on skin color. As a start towards increasing transparency, AI researchers have appropriated the use of the Fitzpatrick skin type (FST) from a measure of patient photosensitivity to a measure for estimating skin tone in algorithmic audits of computer vision applications including facial recognition and dermatology diagnosis. In order to understand the variability of estimated FST annotations on images, we compare several FST annotation methods on a diverse set of 460 images of skin conditions from both textbooks and online dermatology atlases. We find the inter-rater reliability between three board-certified dermatologists is comparable to the inter-rater reliability between the board-certified dermatologists and two crowdsourcing methods. In contrast, we find that the Individual Typology Angle converted to FST (ITA-FST) method produces annotations that are significantly less correlated with the experts' annotations than the experts' annotations are correlated with each other. These results demonstrate that algorithms based on ITA-FST are not reliable for annotating large-scale image datasets, but human-centered, crowd-based protocols can reliably add skin type transparency to dermatology datasets. Furthermore, we introduce the concept of dynamic consensus protocols with tunable parameters including expert review that increase the visibility of crowdwork and provide guidance for future crowdsourced annotations of large image datasets

Chapter 7: Pharmacogenomics

<div><p>There is great variation in drug-response phenotypes, and a “one size fits all” paradigm for drug delivery is flawed. Pharmacogenomics is the study of how human genetic information impacts drug response, and it aims to improve efficacy and reduced side effects. In this article, we provide an overview of pharmacogenetics, including pharmacokinetics (PK), pharmacodynamics (PD), gene and pathway interactions, and off-target effects. We describe methods for discovering genetic factors in drug response, including genome-wide association studies (GWAS), expression analysis, and other methods such as chemoinformatics and natural language processing (NLP). We cover the practical applications of pharmacogenomics both in the pharmaceutical industry and in a clinical setting. In drug discovery, pharmacogenomics can be used to aid lead identification, anticipate adverse events, and assist in drug repurposing efforts. Moreover, pharmacogenomic discoveries show promise as important elements of physician decision support. Finally, we consider the ethical, regulatory, and reimbursement challenges that remain for the clinical implementation of pharmacogenomics.</p> </div

Chapter 7: Pharmacogenomics.

There is great variation in drug-response phenotypes, and a "one size fits all" paradigm for drug delivery is flawed. Pharmacogenomics is the study of how human genetic information impacts drug response, and it aims to improve efficacy and reduced side effects. In this article, we provide an overview of pharmacogenetics, including pharmacokinetics (PK), pharmacodynamics (PD), gene and pathway interactions, and off-target effects. We describe methods for discovering genetic factors in drug response, including genome-wide association studies (GWAS), expression analysis, and other methods such as chemoinformatics and natural language processing (NLP). We cover the practical applications of pharmacogenomics both in the pharmaceutical industry and in a clinical setting. In drug discovery, pharmacogenomics can be used to aid lead identification, anticipate adverse events, and assist in drug repurposing efforts. Moreover, pharmacogenomic discoveries show promise as important elements of physician decision support. Finally, we consider the ethical, regulatory, and reimbursement challenges that remain for the clinical implementation of pharmacogenomics

Drug discovery.

<p>Pharmacogenomics can be used at multiple steps along the drug discovery pipeline to minimize costs, as well as increase throughput and safety. First, association and expression methods (as well as pathway analysis) can be used to identify potential gene targets for a given disease. Cheminformatics can then be used to narrow the number of targets to be tested biochemically, as well as identifying potential polypharmacological factors that could contribute to adverse events. After initial trials (including animal models and Phase I trials), pharmacogenomics can identify variants that may potentially affect dosing and efficacy. This information can then be used in designing a larger Phase III clinical trial, excluding “non-responding” and targeting the drug towards those more likely to respond favorably.</p