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  • 1.
    Asker, Lars
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Karlsson, Isak
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Papapetrou, Panagiotis
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Zhao, Jing
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Mining Candidates for Adverse Drug Interactions in Electronic Patient Records2014Ingår i: PETRA '14 Proceedings of the 7th International Conference on Pervasive Technologies Related to Assistive Environments, PETRA’14, New York: ACM Press, 2014Konferensbidrag (Refereegranskat)
    Abstract [en]

    Electronic patient records provide a valuable source of information for detecting adverse drug events. In this paper, we explore two different but complementary approaches to extracting useful information from electronic patient records with the goal of identifying candidate drugs, or combinations of drugs, to be further investigated for suspected adverse drug events. We propose a novel filter-and-refine approach that combines sequential pattern mining and disproportionality analysis. The proposed method is expected to identify groups of possibly interacting drugs suspected for causing certain adverse drug events. We perform an empirical investigation of the proposed method using a subset of the Stockholm electronic patient record corpus. The data used in this study consists of all diagnoses and medications for a group of patients diagnoses with at least one heart related diagnosis during the period 2008--2010. The study shows that the method indeed is able to detect combinations of drugs that occur more frequently for patients with cardiovascular diseases than for patients in a control group, providing opportunities for finding candidate drugs that cause adverse drug effects through interaction.

  • 2.
    Henriksson, Aron
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Zhao, Jing
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Dalianis, Hercules
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Modeling Electronic Health Records in Ensembles of Semantic Spaces for Adverse Drug Event Detection2015Ingår i: 2015 IEEE International Conference on Bioinformatics and Biomedicine: Proceedings / [ed] Jun (Luke) Huan et al., IEEE Computer Society, 2015, 343-350 s.Konferensbidrag (Refereegranskat)
    Abstract [en]

    Electronic health records (EHRs) are emerging as a potentially valuable source for pharmacovigilance; however, adverse drug events (ADEs), which can be encoded in EHRs by a set of diagnosis codes, are heavily underreported. Alerting systems, able to detect potential ADEs on the basis of patient- specific EHR data, would help to mitigate this problem. To that end, the use of machine learning has proven to be both efficient and effective; however, challenges remain in representing the heterogeneous EHR data, which moreover tends to be high- dimensional and exceedingly sparse, in a manner conducive to learning high-performing predictive models. Prior work has shown that distributional semantics – that is, natural language processing methods that, traditionally, model the meaning of words in semantic (vector) space on the basis of co-occurrence information – can be exploited to create effective representations of sequential EHR data, not only free-text in clinical notes but also various clinical events such as diagnoses, drugs and measurements. When modeling data in semantic space, an im- portant design decision concerns the size of the context window around an object of interest, which governs the scope of co- occurrence information that is taken into account and affects the composition of the resulting semantic space. Here, we report on experiments conducted on 27 clinical datasets, demonstrating that performance can be significantly improved by modeling EHR data in ensembles of semantic spaces, consisting of multiple semantic spaces built with different context window sizes. A follow-up investigation is conducted to study the impact on predictive performance as increasingly more semantic spaces are included in the ensemble, demonstrating that accuracy tends to improve with the number of semantic spaces, albeit not monotonically so. Finally, a number of different strategies for combining the semantic spaces are explored, demonstrating the advantage of early (feature) fusion over late (classifier) fusion. Ensembles of semantic spaces allow multiple views of (sparse) data to be captured (densely) and thereby enable improved performance to be obtained on the task of detecting ADEs in EHRs.

  • 3.
    Henriksson, Aron
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Zhao, Jing
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Dalianis, Hercules
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Modeling Heterogeneous Clinical Sequence Data in Semantic Space for Adverse Drug Event DetectionIngår i: IEEE International Conference on Data Science and Advanced Analytics (DSAA), IEEE conference proceedingsKonferensbidrag (Refereegranskat)
    Abstract [en]

    The enormous amounts of data that are continuously recorded in electronic health record systems offer ample opportunities for data science applications to improve healthcare. There are, however, challenges involved in using such data for machine learning, such as high dimensionality and sparsity, as well as an inherent heterogeneity that does not allow the distinct types of clinical data to be treated in an identical manner. On the other hand, there are also similarities across data types that may be exploited, e.g., the possibility of representing some of them as sequences. Here, we apply the notions underlying distributional semantics, i.e., methods that model the meaning of words in semantic (vector) space on the basis of co-occurrence information, to four distinct types of clinical data: free-text notes, on the one hand, and clinical events, in the form of diagnosis codes, drug codes and measurements, on the other hand. Each semantic space contains continuous vector representations for every unique word and event, which can then be used to create representations of, e.g., care episodes that, in turn, can be exploited by the learning algorithm. This approach does not only reduce sparsity, but also takes into account, and explicitly models, similarities between various items, and it does so in an entirely data-driven fashion. Here, we report on a series of experiments using the random forest learning algorithm that demonstrate the effectiveness, in terms of accuracy and area under ROC curve, of the proposed representation form over the commonly used bag-of-items counterpart. The experiments are conducted on 27 real datasets that each involves the (binary) classification task of detecting a particular adverse drug event. It is also shown that combining structured and unstructured data leads to significant improvements over using only one of them.

  • 4.
    Henriksson, Aron
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Zhao, Jing
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Dalianis, Hercules
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Ensembles of randomized trees using diverse distributed representations of clinical events2016Ingår i: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 16, 69Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Learning deep representations of clinical events based on their distributions in electronic health records has been shown to allow for subsequent training of higher-performing predictive models compared to the use of shallow, count-based representations. The predictive performance may be further improved by utilizing multiple representations of the same events, which can be obtained by, for instance, manipulating the representation learning procedure. The question, however, remains how to make best use of a set of diverse representations of clinical events – modeled in an ensemble of semantic spaces – for the purpose of predictive modeling. Methods: Three different ways of exploiting a set of (ten) distributed representations of four types of clinical events – diagnosis codes, drug codes, measurements, and words in clinical notes – are investigated in a series of experiments using ensembles of randomized trees. Here, the semantic space ensembles are obtained by varying the context window size in the representation learning procedure. The proposed method trains a forest wherein each tree is built from a bootstrap replicate of the training set whose entire original feature set is represented in a randomly selected set of semantic spaces – corresponding to the considered data types – of a given context window size. Results: The proposed method significantly outperforms concatenating the multiple representations of the bagged dataset; it also significantly outperforms representing, for each decision tree, only a subset of the features in a randomly selected set of semantic spaces. A follow-up analysis indicates that the proposed method exhibits less diversity while significantly improving average tree performance. It is also shown that the size of the semantic space ensemble has a significant impact on predictive performance and that performance tends to improve as the size increases. Conclusions: The strategy for utilizing a set of diverse distributed representations of clinical events when constructing ensembles of randomized trees has a significant impact on predictive performance. The most successful strategy – significantly outperforming the considered alternatives – involves randomly sampling distributed representations of the clinical events when building each decision tree in the forest.

  • 5.
    Karlsson, Isak
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Zhao, Jing
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Dimensionality Reduction with Random Indexing: An Application on Adverse Drug Event Detection using Electronic Health Records2014Ingår i: IEEE 27th International Symposium on Computer-Based Medical Systems, New York: IEEE Computer Society, 2014, 304-307 s.Konferensbidrag (Refereegranskat)
    Abstract [en]

    Although electronic health records (EHRs) have recently become an important data source for drug safety signals detection, which is usually evaluated in clinical trials, the use of such data is often prohibited by dimensionality and available computer resources. Currently, several methods for reducing dimensionality are developed, used and evaluated within the medical domain. While these methods perform well, the computational cost tends to increase with growing dimensionality. An alternative solution is random indexing, a technique commonly employed in text classification to reduce the dimensionality of large and sparse documents. This study aims to explore how the predictive performance of random forest is affected by dimensionality reduction through random indexing to predict adverse drug reactions (ADEs). Data are extracted from EHRs and the task is to predict whether or not a patient should be assigned an ADE related diagnosis code. Four different dimensionality settings are investigated and their sensitivity, specificity and area under ROC curve are reported for 14 data sets. The results show that for the investigated data sets, the predictive performance is not negatively affected by dimensionality reduction, however, the computational cost is significantly reduced. Therefore, this study concludes that applying random indexing on EHR data reduces the computational cost, while retaining the predictive performance.

  • 6.
    Karlsson, Isak
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Zhao, Jing
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Asker, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Predicting Adverse Drug Events by Analyzing Electronic Patient Records2013Ingår i: Artificial Intelligence in Medicine: 14th Conference on Artificial Intelligence in Medicine, AIME 2013. Proceedings / [ed] Niels Peek, Roque Marín Morales, Mor Peleg, Springer Berlin/Heidelberg, 2013, Vol. 7885, 125-129 s.Konferensbidrag (Refereegranskat)
    Abstract [en]

    Diagnosis codes for adverse drug events (ADEs) are sometimes missing from electronic patient records (EPRs). This may not only affect patient safety in the worst case, but also the number of reported ADEs, resulting in incorrect risk estimates of prescribed drugs. Large databases of electronic patient records (EPRs) are potentially valuable sources of information to support the identification of ADEs. This study investigates the use of machine learning for predicting one specific ADE based on information extracted from EPRs, including age, gender, diagnoses and drugs. Several predictive models are developed and evaluated using different learning algorithms and feature sets. The highest observed AUC is 0.87, obtained by the random forest algorithm. The resulting model can be used for screening EPRs that are not, but possibly should be, assigned a diagnosis code for the ADE under consideration. Preliminary results from using the model are presented.

  • 7. Löfström, Tuve
    et al.
    Zhao, Jing
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Linusson, Henrik
    Jansson, Karl
    Predicting Adverse Drug Events with Confidence2015Ingår i: Thirteenth Scandinavian Conference on Artificial Intelligence / [ed] Sławomir Nowaczyk, IOS Press, 2015, 88-97 s.Konferensbidrag (Refereegranskat)
    Abstract [en]

    This study introduces the conformal prediction framework to the task of predicting the presence of adverse drug events in electronic health records with an associated measure of statistically valid confidence. The imbalanced nature of the problem was addressed both by evaluating different machine learning algorithms, and by comparing different types of conformal predictors. A novel solution was also evaluated, where different underlying models, each model optimized towards one particular class, were combined into a single conformal predictor. This novel solution proved to be superior to previously existing approaches.

  • 8.
    Zhao, Jing
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Learning Predictive Models from Electronic Health Records2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The ongoing digitization of healthcare, which has been much accelerated by the widespread adoption of electronic health records, generates unprecedented amounts of clinical data in a readily computable form. This, in turn, affords great opportunities for making meaningful secondary use of clinical data in the endeavor to improve healthcare, as well as to support epidemiology and medical research. To that end, there is a need for techniques capable of effectively and efficiently analyzing large amounts of clinical data. While machine learning provides the necessary tools, learning effective predictive models from electronic health records comes with many challenges due to the complexity of the data. Electronic health records contain heterogeneous and longitudinal data that jointly provides a rich perspective of patient trajectories in the healthcare process. The diverse characteristics of the data need to be properly accounted for when learning predictive models from clinical data. However, how best to represent healthcare data for predictive modeling has been insufficiently studied. This thesis addresses several of the technical challenges involved in learning effective predictive models from electronic health records.

    Methods are developed to address the challenges of (i) representing heterogeneous types of data, (ii) leveraging the concept hierarchy of clinical codes, and (iii) modeling the temporality of clinical events. The proposed methods are evaluated empirically in the context of detecting adverse drug events in electronic health records. Various representations of each type of data that account for its unique characteristics are investigated and it is shown that combining multiple representations yields improved predictive performance. It is also demonstrated how the information embedded in the concept hierarchy of clinical codes can be exploited, both for creating enriched feature spaces and for decomposing the predictive task. Moreover, incorporating temporal information leads to more effective predictive models by distinguishing between event occurrences in the patient history. Both single-point representations, using pre-assigned or learned temporal weights, and multivariate time series representations are shown to be more informative than representations in which temporality is ignored. Effective methods for representing heterogeneous and longitudinal data are key for enhancing and truly enabling meaningful secondary use of electronic health records through large-scale analysis of clinical data.

  • 9.
    Zhao, Jing
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Temporal weighting of clinical events in electronic health records for pharmacovigilance2015Ingår i: 2015 IEEE International Conference on Bioinformatics and Biomedicine: Proceedings / [ed] Jun (Luke) Huan et al., IEEE Computer Society, 2015, 375-381 s.Konferensbidrag (Refereegranskat)
    Abstract [en]

    Electronic health records (EHRs) have recently been identified as a potentially valuable source for monitoring adverse drug events (ADEs). However, ADEs are heavily under- reported in EHRs. Using machine learning algorithms to automatically detect patients that should have had ADEs reported in their health records is an efficient and effective solution. One of the challenges to that end is how to take into account temporality when using clinical events, which are time stamped in EHRs, as features for machine learning algorithms to exploit. Previous research on this topic suggests that representing EHR data as a bag of temporally weighted clinical events is promising; however, how to assign weights in an optimal manner remains unexplored. In this study, nine different temporal weighting strategies are proposed and evaluated using data extracted from a Swedish EHR database, where the predictive performance of models constructed with the random forest learning algorithm is compared. Moreover, variable importance is analyzed to obtain a deeper understanding as to why a certain weighting strategy is favored over another, as well as which clinical events undergo the biggest changes in importance with the various weighting strategies. The results show that the choice of weighting strategy has a significant impact on the predictive performance for ADE detection, and that the best choice of weighting strategy depends on the target ADE and, specifically, on its dose-dependency.

  • 10.
    Zhao, Jing
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Henriksson, Aron
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Learning temporal weights of clinical events using variable importance2016Ingår i: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 16, nr Suppl. 2, 71Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Longitudinal data sources, such as electronic health records (EHRs), are very valuable for monitoring adverse drug events (ADEs). However, ADEs are heavily under-reported in EHRs. Using machine learning algorithms to automatically detect patients that should have had ADEs reported in their health records is an efficient and effective solution. One of the challenges to that end is how to take into account the temporality of clinical events, which are time stamped in EHRs, and providing these as features for machine learning algorithms to exploit. Previous research on this topic suggests that representing EHR data as a bag of temporally weighted clinical events is promising; however, the weights were in that case pre-assigned according to their time stamps, which is limited and potentially less accurate. This study therefore focuses on how to learn weights that effectively take into account the temporality and importance of clinical events for ADE detection. Methods: Variable importance obtained from the random forest learning algorithm is used for extracting temporal weights. Two strategies are proposed for applying the learned weights: weighted aggregation and weighted sampling. The first strategy aggregates the weighted clinical events from different time windows to form new features; the second strategy retains the original features but samples them by using their weights as probabilities when building each tree in the forest. The predictive performance of random forest models using the learned weights with the two strategies is compared to using pre-assigned weights. In addition, to assess the sensitivity of the weight-learning procedure, weights from different granularity levels are evaluated and compared. Results: In the weighted sampling strategy, using learned weights significantly improves the predictive performance, in comparison to using pre-assigned weights; however, there is no significant difference between them in the weighted aggregation strategy. Moreover, the granularity of the weight learning procedure has a significant impact on the former, but not on the latter. Conclusions: Learning temporal weights is significantly beneficial in terms of predictive performance with the weighted sampling strategy. Moreover, weighted aggregation generally diminishes the impact of temporal weighting of the clinical events, irrespective of whether the weights are pre-assigned or learned.

  • 11.
    Zhao, Jing
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Henriksson, Aron
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Asker, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Detecting Adverse Drug Events with Multiple Representations of Clinical Measurements2014Ingår i: 2014 IEEE International Conference on Bioinformatics and Biomedicine (BIBM): Proceedings, IEEE Computer Society, 2014, 536-543 s.Konferensbidrag (Refereegranskat)
    Abstract [en]

    Adverse drug events (ADEs) are grossly under-reported in electronic health records (EHRs). This could be mitigated by methods that are able to detect ADEs in EHRs, thereby allowing for missing ADE-specific diagnosis codes to be identified and added. A crucial aspect of constructing such systems is to find proper representations of the data in order to allow the predictive modeling to be as accurate as possible. One category of EHR data that can be used as indicators of ADEs are clinical measurements. However, using clinical measurements as features is not unproblematic due to the high rate of missing values and they can be repeated a variable number of times in each patient health record. In this study, five basic representations of clinical measurements are proposed and evaluated to handle these two problems. An empirical investigation using random forest on 27 datasets from a real EHR database with different ADE targets is presented, demonstrating that the predictive performance, in terms of accuracy and area under ROC curve, is higher when representing clinical measurements crudely as whether they were taken or how many times they were taken by a patient. Furthermore, a sixth alternative, combining all five basic representations, significantly outperforms using any of the basic representation except for one. A subsequent analysis of variable importance is also conducted with this fused feature set, showing that when clinical measurements have a high missing rate, the number of times they were taken by one patient is ranked as more informative than looking at their actual values. The observation from random forest is also confirmed empirically using other commonly employed classifiers. This study demonstrates that the way in which clinical measurements from EHRs are presented has a high impact for ADE detection, and that using multiple representations outperforms using a basic representation.

  • 12.
    Zhao, Jing
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Henriksson, Aron
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Asker, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Predictive modeling of structured electronic health records for adverse drug event detection2015Ingår i: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 15, nr SIArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The digitization of healthcare data, resulting from the increasingly widespread adoption of electronic health records, has greatly facilitated its analysis by computational methods and thereby enabled large-scale secondary use thereof. This can be exploited to support public health activities such as pharmacovigilance, wherein the safety of drugs is monitored to inform regulatory decisions about sustained use. To that end, electronic health records have emerged as a potentially valuable data source, providing access to longitudinal observations of patient treatment and drug use. A nascent line of research concerns predictive modeling of healthcare data for the automatic detection of adverse drug events, which presents its own set of challenges: it is not yet clear how to represent the heterogeneous data types in a manner conducive to learning high-performing machine learning models. Methods: Datasets from an electronic health record database are used for learning predictive models with the purpose of detecting adverse drug events. The use and representation of two data types, as well as their combination, are studied: clinical codes, describing prescribed drugs and assigned diagnoses, and measurements. Feature selection is conducted on the various types of data to reduce dimensionality and sparsity, while allowing for an in-depth feature analysis of the usefulness of each data type and representation. Results: Within each data type, combining multiple representations yields better predictive performance compared to using any single representation. The use of clinical codes for adverse drug event detection significantly outperforms the use of measurements; however, there is no significant difference over datasets between using only clinical codes and their combination with measurements. For certain adverse drug events, the combination does, however, outperform using only clinical codes. Feature selection leads to increased predictive performance for both data types, in isolation and combined. Conclusions: We have demonstrated how machine learning can be applied to electronic health records for the purpose of detecting adverse drug events and proposed solutions to some of the challenges this presents, including how to represent the various data types. Overall, clinical codes are more useful than measurements and, in specific cases, it is beneficial to combine the two.

  • 13.
    Zhao, Jing
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Henriksson, Aron
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Cascading Adverse Drug Event Detection in Electronic Health Records2015Ingår i: 2015 IEEE International Conference on Data Science and Advanced Analytics (DSAA): Proceedings, IEEE Computer Society, 2015Konferensbidrag (Refereegranskat)
    Abstract [en]

    The ability to detect adverse drug events (ADEs) in electronic health records (EHRs) is useful in many medical applications, such as alerting systems that indicate when an ADE-specific diagnosis code should be assigned. Automating the detection of ADEs can be attempted by applying machine learning to existing, labeled EHR data. How to do this in an effective manner is, however, an open question. The issues addressed in this study concern the granularity of the classification task: (1) If we wish to predict the occurrence of ADE, is it advantageous to conflate the various ADE class labels prior to learning, or should they be merged post prediction? (2) If we wish to predict a family of ADEs or even a specific ADE, can the predictive performance be enhanced by dividing the classification task into a cascading scheme: predicting first, on a coarse level, whether there is an ADE or not, and, in the former case, followed by a more specific prediction on which family the ADE belongs to, and then finally a prediction on the specific ADE within that particular family? In this study, we conduct a series of experiments using a real, clinical dataset comprising healthcare episodes that have been assigned one of eight ADE-related diagnosis codes and a set of randomly extracted episodes that have not been assigned any ADE code. It is shown that, when distinguishing between ADEs and non-ADEs, merging the various ADE labels prior to learning leads to significantly higher predictive performance in terms of accuracy and area under ROC curve. A cascade of random forests is moreover constructed to determine either the family of ADEs or the specific class label; here, the performance is indeed enhanced compared to directly employing a one-step prediction. This study concludes that, if predictive performance is of primary importance, the cascading scheme should be the recommended approach over employing a one-step prediction for detecting ADEs in EHRs.

  • 14.
    Zhao, Jing
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Henriksson, Aron
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Detecting Adverse Drug Events Using Concept Hierarchies of Clinical Codes2014Ingår i: 2014 IEEE International Conference on Healthcare Informatics: Proceedings, IEEE Computer Society, 2014, 285-293 s.Konferensbidrag (Refereegranskat)
    Abstract [en]

    Electronic health records (EHRs) provide a potentially valuable source of information for pharmacovigilance. However, adverse drug events (ADEs), which can be encoded in EHRs with specific diagnosis codes, are heavily under-reported. To provide more accurate estimates for drug safety surveillance, machine learning systems that are able to detect ADEs could be used to identify and suggest missing ADE-specific diagnosis codes. A fundamental consideration when building such systems is how to represent the EHR data to allow for accurate predictive modeling. In this study, two types of clinical code are used to represent drugs and diagnoses: the Anatomical Therapeutic Chemical Classification System (ATC) and the International Statistical Classification of Diseases and Health Problems (ICD). More specifically, it is investigated whether their hierarchical structure can be exploited to improve predictive performance. The use of random forests with feature sets that include only the original, low-level, codes is compared to using random forests with feature sets that contain all levels in the hierarchies. An empirical investigation using thirty datasets with different ADE targets is presented, demonstrating that the predictive performance, in terms of accuracy and area under ROC curve, can be significantly improved by exploiting codes on all levels in the hierarchies, compared to using only the low-level encoding. A further analysis is presented in which two strategies are employed for adding features level-wise according to the concept hierarchies: top-down, starting with the highest abstraction levels, and bottom-up, starting with the most specific encoding. The main finding from this subsequent analysis is that predictive performance can be kept at a high level even without employing the more specific levels in the concept hierarchies.

  • 15.
    Zhao, Jing
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Henriksson, Aron
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Kvist, Maria
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap. Karolinska Institute, Sweden.
    Asker, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Handling Temporality of Clinical Events for Drug Safety Surveillance2015Ingår i: AMIA Annual Symposium Proceedings, ISSN 1559-4076, Vol. 2015, 1371-1380 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using longitudinal data in electronic health records (EHRs) for post-marketing adverse drug event (ADE) detection allows for monitoring patients throughout their medical history. Machine learning methods have been shown to be efficient and effective in screening health records and detecting ADEs. How best to exploit historical data, as encoded by clinical events in EHRs is, however, not very well understood. In this study, three strategies for handling temporality of clinical events are proposed and evaluated using an EHR database from Stockholm, Sweden. The random forest learning algorithm is applied to predict fourteen ADEs using clinical events collected from different lengths of patient history. The results show that, in general, including longer patient history leads to improved predictive performance, and that assigning weights to events according to time distance from the ADE yields the biggest improvement.

  • 16.
    Zhao, Jing
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Karlsson, Isak
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Asker, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Applying Methods for Signal Detection in Spontaneous Reports to Electronic Patient Records2013Ingår i: Proceedings of the  19th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, Association for Computing Machinery (ACM), 2013Konferensbidrag (Refereegranskat)
    Abstract [en]

    Currently, pharmacovigilance relies mainly on disproportionality analysis of spontaneous reports. However, the analysis of spontaneous reports is concerned with several problems, such as reliability, under-reporting and insucient patient information. Longitudinal healthcare data, such as Electronic Patient Records (EPRs) in which comprehensive information of each patient is covered, is a complementary source of information to detect Adverse Drug Events (ADEs). A wide set of disproportionality methods has been developed for analyzing spontaneous reports to assess the risk of reported events being ADEs. This study aims to investigate the use of such methods for detecting ADEs when analyzing EPRs. The data used in this study was extracted from Stockholm EPR Corpus. Four disproportionality methods (proportional reporting rate, reporting odds ratio, Bayesian condence propagation neural network, and Gamma-Poisson shrinker) were applied in two dierent ways to analyze EPRs: creating pseudo spontaneous reports based on all observed drug-event pairs (event-level analysis) or analyzing distinct patients who experienced a drug-event pair (patient-level analysis). The methods were evaluated in a case study on safety surveillance of Celecoxib. The results showed that, among the top 200 signals, more ADEs were detected by the event-level analysis than by the patient-level analysis. Moreover, the event-level analysis also resulted in a higher mean average precision. The main conclusion of this study is that the way in which the disproportionality analysis is applied, the event-level or patient-level analysis, can have a much higher impact on the performance than which disproportionality method is employed.

  • 17.
    Zhao, Jing
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Papapetrou, Panagiotis
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Asker, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Boström, Henrik
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Learning from heterogeneous temporal data from electronic health records2017Ingår i: Journal of Biomedical Informatics, ISSN 1532-0464, E-ISSN 1532-0480, Vol. 65, 105-119 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Electronic health records contain large amounts of longitudinal data that are valuable for biomedical informatics research. The application of machine learning is a promising alternative to manual analysis of such data. However, the complex structure of the data, which includes clinical events that are unevenly distributed over time, poses a challenge for standard learning algorithms. Some approaches to modeling temporal data rely on extracting single values from time series; however, this leads to the loss of potentially valuable sequential information. How to better account for the temporality of clinical data, hence, remains an important research question. In this study, novel representations of temporal data in electronic health records are explored. These representations retain the sequential information, and are directly compatible with standard machine learning algorithms. The explored methods are based on symbolic sequence representations of time series data, which are utilized in a number of different ways. An empirical investigation, using 19 datasets comprising clinical measurements observed over time from a real database of electronic health records, shows that using a distance measure to random subsequences leads to substantial improvements in predictive performance compared to using the original sequences or clustering the sequences. Evidence is moreover provided on the quality of the symbolic sequence representation by comparing it to sequences that are generated using domain knowledge by clinical experts. The proposed method creates representations that better account for the temporality of clinical events, which is often key to prediction tasks in the biomedical domain.

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