Unsupervised learning methods for identifying and evaluating disease clusters in electronic health records

Introduction Clustering algorithms are a class of algorithms that can discover groups of observations in complex data and are often used to identify subtypes of heterogeneous diseases in electronic health records (EHR). Evaluating clustering experiments for biological and clinical significance is a vital but challenging task due to the lack of consensus on best practices. As a result, the translation of findings from clustering experiments to clinical practice is limited. Aim The aim of this thesis was to investigate and evaluate approaches that enable the evaluation of clustering experiments using EHR. Methods We conducted a scoping review of clustering studies in EHR to identify common evaluation approaches. We systematically investigated the performance of the identified approaches using a cohort of Alzheimer's Disease (AD) patients as an exemplar comparing four different clustering methods (K-means, Kernel K-means, Affinity Propagation and Latent Class Analysis.). Using the same population, we developed and evaluated a method (MCHAMMER) that tested whether clusterable structures exist in EHR. To develop this method we tested several cluster validation indexes and methods of generating null data to see which are the best at discovering clusters. In order to enable the robust benchmarking of evaluation approaches, we created a tool that generated synthetic EHR data that contain known cluster labels across a range of clustering scenarios. Results Across 67 EHR clustering studies, the most popular internal evaluation metric was comparing cluster results across multiple algorithms (30% of studies). We examined this approach conducting a clustering experiment on AD patients using a population of 10,065 AD patients and 21 demographic, symptom and comorbidity features. K-means found 5 clusters, Kernel K means found 2 clusters, Affinity propagation found 5 and latent class analysis found 6. K-means 4 was found to have the best clustering solution with the highest silhouette score (0.19) and was more predictive of outcomes. The five clusters found were: typical AD (n=2026), non-typical AD (n=1640), cardiovascular disease cluster (n=686), a cancer cluster (n=1710) and a cluster of mental health issues, smoking and early disease onset (n=1528), which has been found in previous research as well as in the results of other clustering methods. We created a synthetic data generation tool which allows for the generation of realistic EHR clusters that can vary in separation and number of noise variables to alter the difficulty of the clustering problem. We found that decreasing cluster separation did increase cluster difficulty significantly whereas noise variables increased cluster difficulty but not significantly. To develop the tool to assess clusters existence we tested different methods of null dataset generation and cluster validation indices, the best performing null dataset method was the min max method and the best performing indices we Calinksi Harabasz index which had an accuracy of 94%, Davies Bouldin index (97%) silhouette score ( 93%) and BWC index (90%). We further found that when clusters were identified using the Calinski Harabasz index they were more likely to have significantly different outcomes between clusters. Lastly we repeated the initial clustering experiment, comparing 10 different pre-processing methods. The three best performing methods were RBF kernel (2 clusters), MCA (4 clusters) and MCA and PCA (6 clusters). The MCA approach gave the best results highest silhouette score (0.23) and meaningful clusters, producing 4 clusters; heart and circulatory( n=1379), early onset mental health (n=1761), male cluster with memory loss (n = 1823), female with more problem (n=2244). Conclusion We have developed and tested a series of methods and tools to enable the evaluation of EHR clustering experiments. We developed and proposed a novel cluster evaluation metric and provided a tool for benchmarking evaluation approaches in synthetic but realistic EHR

Conceptual graph-based knowledge representation for supporting reasoning in African traditional medicine

Although African patients use both conventional or modern and traditional healthcare simultaneously, it has been proven that 80% of people rely on African traditional medicine (ATM). ATM includes medical activities stemming from practices, customs and traditions which were integral to the distinctive African cultures. It is based mainly on the oral transfer of knowledge, with the risk of losing critical knowledge. Moreover, practices differ according to the regions and the availability of medicinal plants. Therefore, it is necessary to compile tacit, disseminated and complex knowledge from various Tradi-Practitioners (TP) in order to determine interesting patterns for treating a given disease. Knowledge engineering methods for traditional medicine are useful to model suitably complex information needs, formalize knowledge of domain experts and highlight the effective practices for their integration to conventional medicine. The work described in this paper presents an approach which addresses two issues. First it aims at proposing a formal representation model of ATM knowledge and practices to facilitate their sharing and reusing. Then, it aims at providing a visual reasoning mechanism for selecting best available procedures and medicinal plants to treat diseases. The approach is based on the use of the Delphi method for capturing knowledge from various experts which necessitate reaching a consensus. Conceptual graph formalism is used to model ATM knowledge with visual reasoning capabilities and processes. The nested conceptual graphs are used to visually express the semantic meaning of Computational Tree Logic (CTL) constructs that are useful for formal specification of temporal properties of ATM domain knowledge. Our approach presents the advantage of mitigating knowledge loss with conceptual development assistance to improve the quality of ATM care (medical diagnosis and therapeutics), but also patient safety (drug monitoring)

Automated COVID-19 Dialogue System Using a New Deep Learning Network

During the coronavirus disease 2019 (COVID-19) pandemic outbreak, it is necessary to apply social distancing measurements and search for an alternative to physical contact due to the spread of viral infection. The interest in task-oriented dialogue systems has grown remarkably in healthcare, using natural language in the dialogue between patients and doctors. However, the doctor’s advice is implicit and unclear in most conversations, and the patient may also be nervous when describing symptoms or may have difficulty describing them. Therefore, the patient’s description of symptoms is insufficient for a diagnosis by doctors. This study aims to provide suitable medical advice based on the patients’ symptoms during the conversation between doctors and patients by proposing a new deep learning method for automated medical dialogue systems. The model is based on an encoder and two stages of learning to make reliable decisions. The encoder extracts important words using text normalization, resulting in two vectors: symptom vectors and doctor utterance vectors. The symptom vectors are represented as a weighted bag-of-words feature. The first stage is used to cluster the patients’ utterances by applying Hopfield network while considering the semantic similarity, whereas the second stage extracts an implicit label as a template of advice using clustering. Additionally, the external evaluation model used the applied feedforward neural network classification algorithm using labels obtained in the second stage. The CovidDialog-English dataset is used to evaluate the model. The experimental results indicate the high performance of the feedforward neural network with an F1-score of 0.972 and presents a comparison of three clusters using the k-nearest neighbours and naïve Bayes-based models

The Language of Mental Illness

This paper surveys some philosophical issues with the language surrounding mental illness, but is especially focused on pejoratives relating to mental illness. I argue that though 'crazy' and similar mental illness-based epithets (MI-epithets) are not best understood as slurs, they do function to isolate, exclude, and marginalize members of the targeted group in ways similar to the harmfulness of slurs more generally. While they do not generally express the hate/contempt characteristic of weaponized uses of slurs, MI-epithets perpetuate epistemic injustice by portraying sufferers of mental illness as deserving minimal credibility. After outlining the ways in which these epithets can cause harm, I examine available legal and social remedies, and suggest that the best path going forward is to pursue a reclamation project rather than aiming to censure the use of MI-epithets

Identifying and evaluating clinical subtypes of Alzheimer's disease in care electronic health records using unsupervised machine learning

BACKGROUND: Alzheimer's disease (AD) is a highly heterogeneous disease with diverse trajectories and outcomes observed in clinical populations. Understanding this heterogeneity can enable better treatment, prognosis and disease management. Studies to date have mainly used imaging or cognition data and have been limited in terms of data breadth and sample size. Here we examine the clinical heterogeneity of Alzheimer's disease patients using electronic health records (EHR) to identify and characterise disease subgroups using multiple clustering methods, identifying clusters which are clinically actionable. METHODS: We identified AD patients in primary care EHR from the Clinical Practice Research Datalink (CPRD) using a previously validated rule-based phenotyping algorithm. We extracted and included a range of comorbidities, symptoms and demographic features as patient features. We evaluated four different clustering methods (k-means, kernel k-means, affinity propagation and latent class analysis) to cluster Alzheimer's disease patients. We compared clusters on clinically relevant outcomes and evaluated each method using measures of cluster structure, stability, efficiency of outcome prediction and replicability in external data sets. RESULTS: We identified 7,913 AD patients, with a mean age of 82 and 66.2% female. We included 21 features in our analysis. We observed 5, 2, 5 and 6 clusters in k-means, kernel k-means, affinity propagation and latent class analysis respectively. K-means was found to produce the most consistent results based on four evaluative measures. We discovered a consistent cluster found in three of the four methods composed of predominantly female, younger disease onset (43% between ages 42-73) diagnosed with depression and anxiety, with a quicker rate of progression compared to the average across other clusters. CONCLUSION: Each clustering approach produced substantially different clusters and K-Means performed the best out of the four methods based on the four evaluative criteria. However, the consistent appearance of one particular cluster across three of the four methods potentially suggests the presence of a distinct disease subtype that merits further exploration. Our study underlines the variability of the results obtained from different clustering approaches and the importance of systematically evaluating different approaches for identifying disease subtypes in complex EHR