Sex differences in sociodemographic, clinical, and laboratory variables in childhood asthma: A birth cohort study.

BACKGROUND: There are marked sex differences in the prevalence and severity of asthma, both during childhood and adulthood. There is a relative lack of comprehensive studies exploring sexdifferences in pediatric asthma cohorts. OBJECTIVE: To identify the most relevant sex differences in sociodemographic, clinical, and laboratory variables in a well-characterized large pediatric asthma cohort. METHODS: We performed a cross-sectional analysis of the Mayo Clinic Olmsted County Birth Cohort. In the full birth cohort, we used a natural language-processing algorithm based on the Predetermined Asthma Criteria for asthma ascertainment. In a stratified random sample of 300 children, we obtained additional pulmonary function tests and laboratory data. We identified the significant sex differences among available sociodemographic, clinical, and laboratory variables. RESULTS: Boys were more frequently diagnosed with having asthma than girls and were younger at the time of asthma diagnosis. There were no sex differences in relation to socioeconomic status. We identified a male predominance in the presence of a tympanostomy tube and a female predominance in the history of pneumonia. A higher percentage of boys had a forced expiratory volume in 1 second/forced vital capacity ratio less than 0.85. Blood eosinophilia and atopic sensitization were also more common in boys. Finally, boys had higher levels of serum periostin than girls. CONCLUSION: This study described significant sex differences in a large pediatric asthma cohort. Overall, boys had earlier and more severe asthma than girls. Differences in blood eosinophilia and serum periostin provide insights into possible mechanisms of the sex bias in childhood asthma.

MultiWD: Multi-label wellness dimensions in social media posts.

BACKGROUND: Halbert L. Dunn's concept of wellness is a multi-dimensional aspect encompassing social and mental well-being. Neglecting these dimensions over time can have a negative impact on an individual's mental health. The manual efforts employed in in-person therapy sessions reveal that underlying factors of mental disturbance if triggered, may lead to severe mental health disorders. OBJECTIVE: In our research, we introduce a fine-grained approach focused on identifying indicators of wellness dimensions and mark their presence in self-narrated human-writings on Reddit social media platform. DESIGN AND METHOD: We present the MultiWD dataset, a curated collection comprising 3281 instances, as a specifically designed and annotated dataset that facilitates the identification of multiple wellness dimensions in Reddit posts. In our study, we introduce the task of identifying wellness dimensions and utilize state-of-the-art classifiers to solve this multi-label classification task. RESULTS: Our findings highlights the best and comparative performance of fine-tuned large language models with fine-tuned BERT model. As such, we set BERT as a baseline model to tag wellness dimensions in a user-penned text with F1 score of 76.69. CONCLUSION: Our findings underscore the need of trustworthy and domain-specific knowledge infusion to develop more comprehensive and contextually-aware AI models for tagging and extracting wellness dimensions.

FedFSA: Hybrid and federated framework for functional status ascertainment across institutions.

INTRODUCTION: Patients' functional status assesses their independence in performing activities of daily living, including basic ADLs (bADL), and more complex instrumental activities (iADL). Existing studies have discovered that patients' functional status is a strong predictor of health outcomes, particularly in older adults. Depite their usefulness, much of the functional status information is stored in electronic health records (EHRs) in either semi-structured or free text formats. This indicates the pressing need to leverage computational approaches such as natural language processing (NLP) to accelerate the curation of functional status information. In this study, we introduced FedFSA, a hybrid and federated NLP framework designed to extract functional status information from EHRs across multiple healthcare institutions. METHODS: FedFSA consists of four major components: 1) individual sites (clients) with their private local data, 2) a rule-based information extraction (IE) framework for ADL extraction, 3) a BERT model for functional status impairment classification, and 4) a concept normalizer. The framework was implemented using the OHNLP Backbone for rule-based IE and open-source Flower and PyTorch library for federated BERT components. For gold standard data generation, we carried out corpus annotation to identify functional status-related expressions based on ICF definitions. Four healthcare institutions were included in the study. To assess FedFSA, we evaluated the performance of category- and institution-specific ADL extraction across different experimental designs. RESULTS: ADL extraction performance ranges from an F1-score of 0.907 to 0.986 for bADL and 0.825 to 0.951 for iADL across the four healthcare sites. The performance for ADL extraction with impairment ranges from an F1-score of 0.722 to 0.954 for bADL and 0.674 to 0.813 for iADL across four healthcare sites. For category-specific ADL extraction, laundry and transferring yielded relatively high performance, while dressing, medication, bathing, and continence achieved moderate-high performance. Conversely, food preparation and toileting showed low performance. CONCLUSION: NLP performance varied across ADL categories and healthcare sites. Federated learning using a FedFSA framework performed higher than non-federated learning for impaired ADL extraction at all healthcare sites. Our study demonstrated the potential of the federated learning framework in functional status extraction and impairment classification in EHRs, exemplifying the importance of a large-scale, multi-institutional collaborative development effort.

Arrhythmia Variant Associations and Reclassifications in the eMERGE-III Sequencing Study.

BACKGROUND: Sequencing Mendelian arrhythmia genes in individuals without an indication for arrhythmia genetic testing can identify carriers of pathogenic or likely pathogenic (P/LP) variants. However, the extent to which these variants are associated with clinically meaningful phenotypes before or after return of variant results is unclear. In addition, the majority of discovered variants are currently classified as variants of uncertain significance, limiting clinical actionability. METHODS: The eMERGE-III study (Electronic Medical Records and Genomics Phase III) is a multicenter prospective cohort that included 21 846 participants without previous indication for cardiac genetic testing. Participants were sequenced for 109 Mendelian disease genes, including 10 linked to arrhythmia syndromes. Variant carriers were assessed with electronic health record-derived phenotypes and follow-up clinical examination. Selected variants of uncertain significance (n=50) were characterized in vitro with automated electrophysiology experiments in HEK293 cells. RESULTS: As previously reported, 3.0% of participants had P/LP variants in the 109 genes. Herein, we report 120 participants (0.6%) with P/LP arrhythmia variants. Compared with noncarriers, arrhythmia P/LP carriers had a significantly higher burden of arrhythmia phenotypes in their electronic health records. Fifty-four participants had variant results returned. Nineteen of these 54 participants had inherited arrhythmia syndrome diagnoses (primarily long-QT syndrome), and 12 of these 19 diagnoses were made only after variant results were returned (0.05%). After in vitro functional evaluation of 50 variants of uncertain significance, we reclassified 11 variants: 3 to likely benign and 8 to P/LP. CONCLUSIONS: Genome sequencing in a large population without indication for arrhythmia genetic testing identified phenotype-positive carriers of variants in congenital arrhythmia syndrome disease genes. As the genomes of large numbers of people are sequenced, the disease risk from rare variants in arrhythmia genes can be assessed by integrating genomic screening, electronic health record phenotypes, and in vitro functional studies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier; NCT03394859.

Application of Natural Language Processing in Total Joint Arthroplasty: Opportunities and Challenges.

Total joint arthroplasty is becoming one of the most common surgeries within the United States, creating an abundance of analyzable data to improve patient experience and outcomes. Unfortunately, a large majority of this data is concealed in electronic health records only accessible by manual extraction, which takes extensive time and resources. Natural language processing (NLP), a field within artificial intelligence, may offer a viable alternative to manual extraction. Using NLP, a researcher can analyze written and spoken data and extract data in an organized manner suitable for future research and clinical use. This article will first discuss common subtasks involved in an NLP pipeline, including data preparation, modeling, analysis, and external validation, followed by examples of NLP projects. Challenges and limitations of NLP will be discussed, closing with future directions of NLP projects, including large language models.

External Validation of Natural Language Processing Algorithms to Extract Common Data Elements in THA Operative Notes.

BACKGROUND: Natural language processing (NLP) systems are distinctive in their ability to extract critical information from raw text in electronic health records (EHR). We previously developed three algorithms for total hip arthroplasty (THA) operative notes with rules aimed at capturing (1) operative approach, (2) fixation method, and (3) bearing surface using inputs from a single institution. The purpose of this study was to externally validate and improve these algorithms as a prerequisite for broader adoption in automated registry data curation. METHODS: The previous NLP algorithms developed at Mayo Clinic were deployed and refined on EHRs from OrthoCarolina, evaluating 39 randomly selected primary THA operative reports from 2018 to 2021. Operative reports were available only in PDF format, requiring conversion to "readable" text with Adobe software. Accuracy statistics were calculated against manual chart review. RESULTS: The operative approach, fixation technique, and bearing surface algorithms all demonstrated perfect accuracy of 100%. By comparison, validated performance at the developing center yielded an accuracy of 99.2% for operative approach, 90.7% for fixation technique, and 95.8% for bearing surface. CONCLUSION: NLP algorithms applied to data from an external center demonstrated excellent accuracy in delineating common elements in THA operative notes. Notably, the algorithms had no functional problems evaluating scanned PDFs that were converted to "readable" text by common software. Taken together, these findings provide promise for NLP applied to scanned PDFs as a source to develop large registries by reliably extracting data of interest from very large unstructured data sets in an expeditious and cost-effective manner.

Loci identified by a genome-wide association study of carotid artery stenosis in the eMERGE network.

Carotid artery atherosclerotic disease (CAAD) is a risk factor for stroke. We used a genome-wide association (GWAS) approach to discover genetic variants associated with CAAD in participants in the electronic Medical Records and Genomics (eMERGE) Network. We identified adult CAAD cases with unilateral or bilateral carotid artery stenosis and controls without evidence of stenosis from electronic health records at eight eMERGE sites. We performed GWAS with a model adjusting for age, sex, study site, and genetic principal components of ancestry. In eMERGE we found 1793 CAAD cases and 17,958 controls. Two loci reached genome-wide significance, on chr6 in LPA (rs10455872, odds ratio [OR] (95% confidence interval [CI]) = 1.50 (1.30-1.73), p = 2.1 × 10-8 ) and on chr7, an intergenic single nucleotide variant (SNV; rs6952610, OR (95% CI) = 1.25 (1.16-1.36), p = 4.3 × 10-8 ). The chr7 association remained significant in the presence of the LPA SNV as a covariate. The LPA SNV was also associated with coronary heart disease (CHD; 4199 cases and 11,679 controls) in this study (OR (95% CI) = 1.27 (1.13-1.43), p = 5 × 10-5 ) but the chr7 SNV was not (OR (95% CI) = 1.03 (0.97-1.09), p = .37). Both variants replicated in UK Biobank. Elevated lipoprotein(a) concentrations ([Lp(a)]) and LPA variants associated with elevated [Lp(a)] have previously been associated with CAAD and CHD, including rs10455872. With electronic health record phenotypes in eMERGE and UKB, we replicated a previously known association and identified a novel locus associated with CAAD.

An aberration detection-based approach for sentinel syndromic surveillance of COVID-19 and other novel influenza-like illnesses.

Coronavirus Disease 2019 has emerged as a significant global concern, triggering harsh public health restrictions in a successful bid to curb its exponential growth. As discussion shifts towards relaxation of these restrictions, there is significant concern of second-wave resurgence. The key to managing these outbreaks is early detection and intervention, and yet there is a significant lag time associated with usage of laboratory confirmed cases for surveillance purposes. To address this, syndromic surveillance can be considered to provide a timelier alternative for first-line screening. Existing syndromic surveillance solutions are however typically focused around a known disease and have limited capability to distinguish between outbreaks of individual diseases sharing similar syndromes. This poses a challenge for surveillance of COVID-19 as its active periods tend to overlap temporally with other influenza-like illnesses. In this study we explore performing sentinel syndromic surveillance for COVID-19 and other influenza-like illnesses using a deep learning-based approach. Our methods are based on aberration detection utilizing autoencoders that leverages symptom prevalence distributions to distinguish outbreaks of two ongoing diseases that share similar syndromes, even if they occur concurrently. We first demonstrate that this approach works for detection of outbreaks of influenza, which has known temporal boundaries. We then demonstrate that the autoencoder can be trained to not alert on known and well-managed influenza-like illnesses such as the common cold and influenza. Finally, we applied our approach to 2019-2020 data in the context of a COVID-19 syndromic surveillance task to demonstrate how implementation of such a system could have provided early warning of an outbreak of a novel influenza-like illness that did not match the symptom prevalence profile of influenza and other known influenza-like illnesses.

Delirium occurrence and association with outcomes in hospitalized COVID-19 patients.

Delirium is reported to be one of the manifestations of coronavirus infectious disease 2019 (COVID-19) infection. COVID-19 hospitalized patients are at a higher risk of delirium. Pathophysiology behind the association of delirium and COVID-19 is uncertain. We analyzed the association of delirium occurrence with outcomes in hospitalized COVID-19 patients, across all age groups, at Mayo Clinic hospitals.A retrospective study of all hospitalized COVID-19 patients at Mayo Clinic between March 1, 2020 and December 31, 2020 was performed. Occurrence of delirium and outcomes of mortality, length of stay, readmission, and 30-day mortality after hospital discharge were measured. Chi-square test, student t-test, survival analysis, and logistic regression analysis were performed to measure and compare outcomes of delirium group adjusted for age, sex, Charlson comorbidity score, and COVID-19 severity with no-delirium group.A total of 4351 COVID-19 patients were included in the study. Delirium occurrence in the overall study population was noted to be 22.4%. The highest occurrence of delirium was also noted in patients with critical COVID-19 illness severity. A statistically significant OR 4.35 (3.27-5.83) for in-hospital mortality and an OR 4.54 (3.25-6.38) for 30-day mortality after discharge in the delirium group were noted. Increased hospital length of stay, 30-day readmission, and need for skilled nursing facility on discharge were noted in the delirium group. Delirium in hospitalized COVID-19 patients is a marker for increased mortality and morbidity. In this group, outcomes appear to be much worse when patients are older and have a critical severity of COVID-19 illness.

Identification of asthma control factor in clinical notes using a hybrid deep learning model.

BACKGROUND: There are significant variabilities in guideline-concordant documentation in asthma care. However, assessing clinician's documentation is not feasible using only structured data but requires labor-intensive chart review of electronic health records (EHRs). A certain guideline element in asthma control factors, such as review inhaler techniques, requires context understanding to correctly capture from EHR free text. METHODS: The study data consist of two sets: (1) manual chart reviewed data-1039 clinical notes of 300 patients with asthma diagnosis, and (2) weakly labeled data (distant supervision)-27,363 clinical notes from 800 patients with asthma diagnosis. A context-aware language model, Bidirectional Encoder Representations from Transformers (BERT) was developed to identify inhaler techniques in EHR free text. Both original BERT and clinical BioBERT (cBERT) were applied with a cost-sensitivity to deal with imbalanced data. The distant supervision using weak labels by rules was also incorporated to augment the training set and alleviate a costly manual labeling process in the development of a deep learning algorithm. A hybrid approach using post-hoc rules was also explored to fix BERT model errors. The performance of BERT with/without distant supervision, hybrid, and rule-based models were compared in precision, recall, F-score, and accuracy. RESULTS: The BERT models on the original data performed similar to a rule-based model in F1-score (0.837, 0.845, and 0.838 for rules, BERT, and cBERT, respectively). The BERT models with distant supervision produced higher performance (0.853 and 0.880 for BERT and cBERT, respectively) than without distant supervision and a rule-based model. The hybrid models performed best in F1-score of 0.877 and 0.904 over the distant supervision on BERT and cBERT. CONCLUSIONS: The proposed BERT models with distant supervision demonstrated its capability to identify inhaler techniques in EHR free text, and outperformed both the rule-based model and BERT models trained on the original data. With a distant supervision approach, we may alleviate costly manual chart review to generate the large training data required in most deep learning-based models. A hybrid model was able to fix BERT model errors and further improve the performance.