Toward a Reference Architecture for Intelligent Systems in Clinical Care

A Software Architecture for Precision Medicine

Intelligent systems in clinical care leverage the latest innovations in machine learning, real-time data stream mining, visual analytics, natural language processing, ontologies, production rule systems, and cloud computing to provide clinicians with the best knowledge and information at the point of care for effective clinical decision making. In this post, I propose a unified open reference architecture that combines all these technologies into a hybrid cognitive system for clinical decision support. Indeed, truly intelligent systems are capable of reasoning. The goal is not to replace clinicians, but instead to provide them with cognitive support during clinical decision making. Furthermore, Intelligent Personal Assistants (IPAs) such as Apple's Siri, Google's Google Now, and Microsoft's Cortana have raised our expectations on how intelligent systems interact with users through voice and natural language.

In the strict sense of the term, a reference architecture should be abstracted away from concrete technology implementation. However in order to enable a better understanding of the proposed approach, I take liberty in explaining how available open source software can be used to realize the intent of the architecture. There is an urgent need for an open and interoperable architecture which can be deployed across devices and platforms. Unfortunately, this is not the case today with solutions like Apple's HealthKit and ResearchKit.

The specific open source software mentioned in this post can be substituted with other tools which provide similar capabilities. The following diagram is a depiction of the architecture (click to enlarge).

 

Clinical Data Sources

Clinical data sources are represented on the left of the architecture diagram. Examples include electronic medical record systems (EMR) commonly used in routine clinical care, clinical genome databases, genome variant knowledge bases, medical imaging databases, data from medical devices and wearable sensors, and unstructured data sources such as biomedical literature databases. The approach implements the Lambda Architecture enabling both batch and real-time data stream processing and mining.

Predictive Modeling, Real-Time Data Stream Mining, and Big Data Genomics

The back-end provides various tools and frameworks for advanced analytics and decision management. The analytics workbench includes tools for creating predictive models and data streaming mining. The decision management workbench includes a production rule system (providing seamless integration with clinical events and processes) and an ontology editor.

The incoming clinical data likely meet the Big Data criteria of volume, velocity, and variety (this is particularly true for physiological time series from wearable sensors). Therefore, specialized frameworks for large scale cluster computing like Apache Spark are used to analyze and process the data. Statistical computing and Machine Learning tools like R are used here as well. The goal is knowledge and patterns discovery using Machine Learning model builders like Decision Trees, k-Means Clustering, Logistic Regression, Support Vector Machines (SVMs), Bayesian Networks, Neural Networks, and the more recent Deep Learning techniques. The latter hold great promise in applications such as Natural Language Processing (NLP), medical image analysis, and speech recognition.

These Machine Learning algorithms can support diagnosis, prognosis, simulation, anomaly detection, care alerting, and care planning. For example, anomaly detection can be performed at scale using the k-means clustering machine learning algorithm in Apache Spark. In addition, Apache Spark allows the implementation of the Lambda Architecture and can also be used for genome Big Data analysis at scale.

In another post titled How Good is Your Crystal Ball?: Utility, Methodology, and Validity of Clinical Prediction Models, I discuss quantitative measures of performance for clinical prediction models.

Visual Analytics

Visual Analytics tools like D3.js, rCharts, ploty, googleVis, ggplot2, and ggvis can help obtain deep insight for effective understanding, reasoning, and decision making through the visual exploration of massive, complex, and often ambiguous data. Of particular interest is Visual Analytics of real-time data streams like physiological time series. As a multidisciplinary field, Visual Analytics combines several disciplines such as human perception and cognition, interactive graphic design, statistical computing, data mining, spatio-temporal data analysis, and even Art. For example, similar to Minard's map of the Russian Campaign of 1812-1813 (see graphic below), Visual Analytics can help in comparing different interventions and care pathways and their respective clinical outcomes over a certain period of time by displaying causes, variables, comparisons, and explanations.

Production Rule System, Ontology Reasoning, and NLP

The architecture also includes a production rule engine and an ontology editor (Drools and Protégé respectively). This is done in order to leverage existing clinical domain knowledge available from clinical practice guidelines (CPGs) and biomedical ontologies like SNOMED CT.  This approach complements machine learning algorithms' probabilistic approach to clinical decision making under uncertainty. The production rule system can translate CPGs into executable rules which are fully integrated with clinical processes (workflows) and events. The ontologies can provide automated reasoning capabilities for decision support.

NLP includes capabilities such as:

• Text classification, text clustering, document and passage retrieval, text summarization, and more advanced clinical question answering (CQA) capabilities which can be useful for satisfying clinicians' information needs at the point of care; and
• Named entity recognition (NER) for extracting concepts from clinical notes.

The data tier supports the efficient storage of large amounts of time series data and is implemented with tools like Cassandra and HBase. The system can run in the cloud, for example using the Amazon Elastic Compute Cloud (EC2). For real-time processing of distributed data streams, cloud-based solutions like Amazon Kinesis and Lambda can be used.

 

Clinical Decision Services

The clinical decision services provide intelligence at the point of care typically using deployed predictive models, clinical rules, text mining outputs, and ontology reasoners. For example, Machine Learning algorithms can be exported in predictive markup language (PMML) format for run-time scoring based on the clinical data of individual patients, enabling what is referred to as Personalized Medicine. Clinical decision services include:

• Diagnosis and prognosis
• Simulation
• Anomaly detection 
• Data visualization
• Information retrieval (e.g., clinical question answering)
• Alerts and reminders
• Support for care planning processes.

The clinical decision services can be deployed in the cloud as well. Other clinical systems can consume these services through a SOAP or REST-based web service interface (using the HL7 vMR and DSS specifications for interoperability) and single sign-on (SSO) standards like SAML2 and OpenID Connect.

Intelligent Personal Assistants (IPAs)

Clinical decision services can also be delivered to patients and clinicians through IPAs. IPAs can accept inputs in the form of voice, images, and user's context and respond in natural language. IPAs are also expanding to wearable technologies such as smart watches and glasses. The precision of speech recognition, natural language processing, and computer vision is improving rapidly with the adoption of Deep Learning techniques and tools. Accelerated hardware technologies like GPUs and FPGAs are improving the performance and reducing the cost of deploying these systems at scale.

Hexagonal, Reactive, and Secure Architecture

Intelligent Health IT systems are not just capable of discovering knowledge and patterns in data. They are also scalable, resilient, responsive, and secure. To achieve these objectives, several architectural patterns have emerged during the last few years:

• Domain Driven Design (DDD) puts the emphasis on the core domain and domain logic and recommends a layered architecture (typically user interface, application, domain, and infrastructure) with each layer having well defined responsibilities and interfaces for interacting with other layers. Models exist within "bounded contexts". These "bounded contexts" communicate with each other typically through messaging and web services using HL7 standards for interoperability.


• The Hexagonal Architecture defines "ports and adapters" as a way to design, develop, and test an application in a way that is independent of the various clients, devices, transport protocols (HTTP, REST, SOAP, MQTT, etc.), and even databases that could be used to consume its services in the future. This is particularly important in the era of the Internet of Things in healthcare.


• Microservices consist in decomposing large monolithic applications into smaller services following good old principles of service-oriented design and single responsibility to achieve modularity, maintainability, scalability, and ease of deployment (for example, using Docker).


• CQRS/ES: Command Query Responsibility Segregation (CQRS) and Event Sourcing (ES) are two architectural patterns which consist in the use of event-driven messaging and an Event Store for separating commands (write-side) from queries (read-side) relying on the principle of Eventual Consistency. CQRS/ES can be implemented in combination with microservices to deliver new capabilities such as temporal queries, behavioral analysis, complex audit logs, and real-time notifications and alerts.


• Functional Programming: Functional Programming languages like Scala have several benefits that are particularly important for applying Machine Learning algorithms on large data sets. Like functions in mathematics, functions in Scala have no side effects. This provides referential transparency. Machine Learning algorithms are in fact based on Linear Algebra and Calculus. Scala supports high-order functions as well. Variables are immutable witch greatly simplifies concurrency. For all those reasons, Machine Learning libraries like Apache Mahout have embraced Scala, moving away from the Java MapReduce paradigm.


• Reactive Architecture: The Reactive Manifesto makes the case for a new breed of applications called "Reactive Applications". According to the manifesto, the Reactive Application architecture allows developers to build "systems that are event-driven, scalable, resilient, and responsive."  Leading frameworks that support Reactive Programming include Akka and RxJava. The latter is a library for composing asynchronous and event-based programs using observable sequences. RxJava is a Java port (with a Scala adaptor) of the original Rx (Reactive Extensions) for .NET created by Erik Meijer.
  
  Based on the Actor Model and built in Scala, Akka is a framework for building highly concurrent, asynchronous, distributed, and fault tolerant event-driven applications on the JVM. Akka offers location transparency, fault tolerance, asynchronous message passing, and a non-deterministic share-nothing architecture. Akka Cluster provides a fault-tolerant decentralized peer-to-peer based cluster membership service with no single point of failure or single point of bottleneck.
  
  Also built with Scala, Apache Kafka is a scalable message broker which provides high-throughput, fault-tolerance, built-in partitioning, and replication  for processing real-time data streams. In the reference architecture, the ingestion layer is implemented with Akka and Apache Kafka.

• Web Application Security: special attention is given to security across all layers, notably the proper implementation of authentication, authorization, encryption, and audit logging. The implementation of security is also driven by deep knowledge of application security patterns, threat modeling, and enforcing security best practices (e.g., OWASP Top Ten and CWE/SANS Top 25 Most Dangerous Software Errors) as part of the continuous delivery process.

An Interface that Works across Devices and Platforms

The front-end uses a Mobile First approach and a Single Page Application (SPA) architecture with Javascript-based frameworks like AngularJS to create very responsive user experiences. It also allows us to bring the following software engineering best practices to the front-end:

• Dependency Injection
• Test-Driven Development (Jasmine, Karma, PhantomJS)
• Package Management (Bower or npm)
• Build system and Continuous Integration (Grunt or Gulp.js)
• Static Code Analysis (JSLint and JSHint), and 
• End-to-End Testing (Protractor). 

For mobile devices, Apache Cordova can be used to access native functions when desired. The main goal is to provide a user interface that works across devices and platforms such as iOS, Android, and Windows Phone.

Interoperability

Interoperability will always be a key requirement in clinical systems. Interoperability is needed between all players in the healthcare ecosystem including providers, payers, labs, knowledge artifact developers, quality measure developers, and public health agencies like the CDC. These standards exist today and are implementation-ready. However, only health IT buyers have the leverage to demand interoperability from their vendors.

Standards related to clinical decision support (CDS) include:

• The HL7 Fast Healthcare Interoperability Resources (FHIR)
• The HL7 virtual Medical Record (vMR)
• The HL7 Decision Support Services (DSS) specification
• The HL7 CDS Knowledge Artifact specification
• The DMG Predictive Model Markup Language (PMML) specification.

Overcoming Barriers to Adoption

In a previous post, I discussed a practical approach to addressing challenges to the adoption of clinical decision support (CDS) systems.

Single Sign-On (SSO) for Cloud-based SaaS Applications

Single Sign-On (SSO) is a key capability for Software as a Service (SaaS) applications particularly when there is a need to integrate with existing enterprise applications. In the enterprise world dominated by SOAP-based web services, security has been traditionally achieved with standards like WS-Security, WS-SecurityPolicy, WS-SecureConversation, WS-Trust, XML Encryption, XML Signatures, the WS-Security SAML Token Profile, and XACML.

During the last few years, the popularity of Web APIs, mobile technology, and Cloud-based software services has led to the emergence of light-weight security standards in support of the new REST/JSON paradigm with specifications like OAuth2 and OpenID Connect.

In this post, I discuss the state of the art in standards for SSO.

SAML2 Web SSO Profile

SAML2 Web SSO Profile (not to be confused with the WS-Security SAML Token Profile mentioned earlier) is not a new standard. It was approved as an OASIS standard in 2005. SAML2 Web SSO Profile is still today a force to reckon with when it comes to enabling SSO within the enterprise. In a post titled SAML vs OAuth: Which One Should I Use?, Anil Saldhana, former Lead Identity Management Architect at Red Hat offered the following suggestions:

• If your usecase involves SSO (when at least one actor or participant is an enterprise), then use SAML.
• If your usecase involves providing access (temporarily or permanent) to resources (such as accounts, pictures, files etc), then use OAuth.
• If you need to provide access to a partner or customer application to your portal, then use SAML.
• If your usecase requires a centralized identity source, then use SAML  (Identity provider).
• If your usecase involves mobile devices, then OAuth2 with some form of Bearer Tokens is appropriate.

Salesforce.com who is arguably the leader in cloud-based SaaS services supports SAML2 Web SSO Profile as one of its main SSO mechanisms (see the Salesforce Single Sign-On Implementation Guide). The Google Apps platform supports SAML2 Web SSO Profile as well.

Federal Identity, Credential, and Access Management (FICAM), a US Federal Government initiative has selected SAML2 Web SSO Profile for the purpose of Level of Assurance (LOA) 1 to 4 as defined by the NIST Special Publication 800-62-2 (see ICAM SAML 2.0 Web Browser SSO Profile). This is significant given the challenges associated with identity federation at the scale of a large organization like the US federal government.

SAML bindings specify underlying transport protocols including:

• HTTP Redirect Binding
• HTTP POST Binding
• HTTP Artifact Binding
• SAML SOAP Binding.

SAML profiles define how the SAML assertions, protocols, and bindings are combined to support particular usage scenarios. The Web Browser SSO Profile and the Single Logout Profile are the most commonly used profiles.

Identity Provider (idP) initiated SSO with POST binding is one the most popular implementations (see diagram below from the OASIS SAML Technical Overview for a typical authentication flow).

The SAML2 Web SSO ecosystem is very mature, cross-platform, and scalable. There are a number of open source implementations available as well. However, things are constantly changing in technology and identity federation is no exception. At the Cloud Identity Summit in 2012, Craig Burton, a well known analyst in the identity space declared:

 SAML is the Windows XP of Identity. No funding. No innovation. People still use it. But it has no future. There is no future for SAML. No one is putting money into SAML development. No one is writing new SAML code. SAML is dead.

 Craig Burton further clarified his remarks by saying:

SAML is dead does not mean SAML is bad. SAML is dead does not mean SAML isn’t useful. SAML is dead means SAML is not the future.

At the time, this provoked a storm in the Twitterverse because of the significant investments that have been made by enterprise customers to implement SAML2 for SSO. 

WS-Federation

There is an alternative to SAML2 Web SSO Profile called WS-Federation which is supported in Microsoft products like Active Directory Federation Services (ADFS), Windows Identity Foundation (WIF), and Azure Active Directory. Microsoft has been a strong promoter of WS-Federation and has implemented WS-Federation in several products. There is also a popular open source identity server on the .NET platform called Thinktecture IdentityServer v2 which also supports WS-Federation.

For enterprise SSO scenarios between business partners exclusively using Microsoft products and development environment, WS-Federation could be a serious contender. However, SAML2 is more widely supported and implemented outside of the Microsoft world. For example, Salesforce.com and Google Apps do not support WS-Federation for SSO. Note that Microsoft ADFS implements the SAML2 Web SSO Profile in addition to WS-Federation.

OpenID Connect

OpenID Connect is a simple identity layer on top of OAuth2. It has been ratified by the OpenID Foundation in February 2014 but has been in development for several years. Nat Sakimura's Dummy’s guide for the Difference between OAuth Authentication and OpenID is a good resource for understanding the difference between OpenID, OAuth2, and OpenID Connect. In particular, it explains why OAuth2 alone is not strictly an authentication standard. The following diagram from the OpenID Connect specification represents the components of the OpenID Connect stack (click to enlarge).

Also note that OAuth2 tokens can be JSON Web Token (JWT) or SAML assertions.

The following is the basic flow as defined in the OpenID Connect specification:

1. The RP (Client) sends a request to the OpenID Provider (OP).
2. The OP authenticates the End-User and obtains authorization.
3. The OP responds with an ID Token and usually an Access Token.
4. The RP can send a request with the Access Token to the UserInfo Endpoint.
5. The UserInfo Endpoint returns Claims about the End-User.

There are two subsets of the Core functionality with corresponding implementer’s guides:

• Basic Client Implementer’s Guide –for a web-based Relying Party (RP) using the OAuth code flow
• Implicit Client Implementer’s Guide – for a web-based Relying Party using the OAuth implicit flow

OpenID Connect is particularly well-suited for modern applications which offer RESTful Web APIs,  support JSON payloads, run on mobile devices, and are deployed to the Cloud. Despite being a relatively new standard, OpenID Connect also boasts an impressive list of implementations across platforms. It is already supported by big players like Google, Microsoft, PayPal, and Salesforce.  In particular, Google is consolidating all federated sign-in support onto the OpenID Connect standard. Open Source OpenID Connect Identity Providers include the Java-based OpenAM and the .Net-based Thinktecture Identity Server v3.

From WS* to JW* and JOSE

As can be seen from the diagram above, a complete identity federation ecosystem based on OpenID Connect will also require standards for representing security assertions, digital signatures, encryption, and cryptographic keys. These standards include:

• JSON Web Token (JWT)
• JSON Web Signature (JWS)
• JSON Web Encryption (JWE)
• JSON Web Key (JWK)
• JSON Web Algorithms (JWA).

There is a new acronym for these emerging JSON-based identity and security protocols: JOSE which stands for Javascript Object Signing and Encryption. It is also the name of the IETF Working Group developing JWS, JWE, and JWK. A Java-based open source implementation called jose4j is available.

Access Control with the User Managed Access (UMA)

According to the UMA Core specification,

User-Managed Access (UMA) is a profile of OAuth 2.0. UMA defines how resource owners can control protected-resource access by clients operated by arbitrary requesting parties, where the resources reside on any number of resource servers, and where a centralized authorization server governs access based on resource owner policy.

In the UMA protocol, OpenID Connect provides federated SSO and is also used to convey user claims to the authorization server. In a previous post titled Patient Privacy at Web Scale, I discussed the application of UMA to the challenges of patient privacy.

Ontologies for Addiction and Mental Disease: Enabling Translational Research and Clinical Decision Support

In a previous post titled Why do we need ontologies in healthcare applications, I elaborated on what ontologies are and why they are different from information models of data structures like relational database schemas and XML schemas commonly used in healthcare informatics applications. In this post, I discuss two interesting applications of ontology engineering related to addiction and mental disease treatment. The first is the use of ontologies for achieving semantic interoperability in  translational research. The second is the use of ontologies for modeling complex medical knowledge in clinical practice guidelines (CPGs) for the purpose of automated reasoning during execution in clinical decision support systems (CDS) at the point of care.

Why Semantic Interoperability is needed in biomedical translational research?

In order to accelerate the discovery of new effective therapeutics for mental health and addiction treatment, there is a need to integrate data across disciplines spanning biomedical research and clinical care delivery [1]. For example, linking data across disciplines can facilitate a better understanding of treatment response variability among patients in addiction treatment. These disciplines include:

• Genetics, the study of genes.
• Chemistry, the study of chemical compounds including substances of abuse like heroin.
• Neuroscience, the study of the nervous system and the brain (addiction is a chronic disease of the brain)
• Psychiatry which is focused on the diagnosis, treatment, and prevention of addiction and mental disorders.

Each of these disciplines has its own terminology or controlled vocabularies. In the clinical domain for example, DSM5 and RrxNorm are used for documenting clinical care. In biomedical research, several ontologies have been developed over the last few years including:

• The Gene Ontology (GO)
• The Chemical Entities of Biological Interest Ontology (CHEBI)
• NeuroLex, an OWL ontology covering major domains of neuroscience: anatomy, cell, subcellular, molecule, function, and dysfunction.

To facilitate semantic interoperability between these ontologies, there are best practices established by the Open Biomedical Ontology (OBO) community. An example of best practice is the use of an upper-level ontology called the Basic Formal Ontology (BFO) which acts as a common foundational ontology upon which  new ontologies can be created. OBO ontologies and principles are available on the OBO Foundry web site.

Among the ontologies available on the OBO Foundry is the Mental Functioning Ontology (MF) [2, 3]. The MF is being developed as a collaboration between the University of Geneva in Switzerland and the University at Buffalo in the United States. The project also includes a Mental Disease Ontology (MD) which extends the MF and the Ontology for General Medical Science (OGMS). The Basic Formal Ontology (BFO) is an upper-level ontology for both the MF and the OGMS. The picture below is a view of the class hierarchy of the MD showing details of the class "Paranoid Schizophrenia" in the right pane of the windows of the beta release of Protege 5, an open source ontology development environment (click on the image to enlarge it).

The following is a tree view of the "Mental Disease Course" class (click on the image to enlarge it):

Ontology constructs defined by the OWL2 language can help establish common semantics (meaning) and relationships between entities across domains. These constructs provide automated inferencing capabilities such as equivalence (e.g., owl:sameAs and owl:equivalentClass) and subsumption (e.g., rdfs:subClassOf) relationships between entities.

In addition, publishing data sources following Linked Open Data (LOD) principles and semantic search using federated SPARQL queries can help answer new research questions. Another application is semantic annotation for natural language processing (NLP) applications.

 

Ontologies as knowledge representation formalism for clinical decision support (CDS)

As knowledge representation formalism, ontologies are well suited for modeling complex medical knowledge and can facilitate reasoning during the automated execution of clinical practice guidelines (CPGs) and Care Pathways (CPs) based on patient data at the point of care. Several approaches to modelling CPGs and CPs have been proposed in the past including PROforma, HELEN, EON, GLIF, PRODIGY, and SAGE. However, the lack of free and open source tooling has been a major impediment to a wide adoption of these knowledge representation formalisms. OWL has the advantage of being a widely implemented W3C Recommendation with available mature open source  tools.

In practice, the medical knowledge contained in CPGs can be manually translated into IF-THEN statements in most programming languages. Executable CDS rules (like other complex types of business rules) can be implemented with a production rule engine using forward chaining. This is the approach taken by OpenCDS and some large scale CDS implementations in real world healthcare delivery settings. This allows CDS software developers to externalize the medical knowledge contained in clinical guidelines in the form of declarative rules as opposed to embedding that knowledge in procedural code. Many viable open source business rule management systems (BRMS) are available today and provide capabilities such as a rule authoring user interface, a rules repository, and a testing environment.

However, production rule systems have a limitation. They do not scale because they require writing a rule for each clinical concept code (there are more than 311,000 active concepts in SNOMED CT alone). An alternative is to exploit the class hierarchy in an ontology so that subclasses of a given superclass can inherit the clinical rules that are applicable to the superclass (this is called subsumption). In addition to subsumption, an OWL ontology also support reasoning with description logic (DL) axioms [4].

An ontology designed for a clinical decision support (CDS) system can integrate the clinical rules from a CPG, a domain ontology like the Mental Disorder (MD) ontology, and the patient medical record from an EHR database in order to provide inferences in the form of treatment recommendations at the point of care. The OWL API [5] facilitates the integration of ontologies into software applications. It supports inferencing using reasoners like Pellet and HermiT. OWL2 reasoning capabilites can be enhanced with rules represented in SWRL (Semantic Web Rule Language) which is implemented by reasoners like Pellet as well as the Protege OWL development environement. In addition to inferencing, another benefit of an OWL-based approach is transparency: the CDS system can provide an explanation or justification of how it arrives at the treatment recommendations.

Nonetheless, these approaches are not mutually exclusive: a production rule system can be integrated with business processes, ontologies, and predictive analytics models. Predictive analytics models provide a probabilistic approach to treatment recommendations to assist in the clinical decision making process.

References

[1]  Janna Hastings, Werner Ceusters, Mark Jensen, Kevin Mulligan and Barry Smith. Representing mental functioning: Ontologies for mental health and disease. Proceedings of the Mental Functioning Ontologies workshop of ICBO 2012, Graz, Austria.

[2]  Ceusters, W. and Smith, B. (2010a). Foundations for a realist ontology of mental disease. Journal of Biomedical Semantics, 1(1), 10.

[3] Hastings, J., Smith, B., Ceusters, W., and Mulligan, K. (2012). The mental functioning ontology. http://code.google.com/p/mental-functioning-ontology/, last accessed August 24, 2014

[4] Sesen MB, Peake MD, Banares-Alcantara R, Tse D, Kadir T, Stanley R, Gleeson F, Brady M. 2014 Lung Cancer Assistant: a hybrid clinical decision support application for lung cancer care. J. R. Soc. Interface 11: 20140534.

[5] Matthew Horridge, Sean Bechhofer. The OWL API: A Java API for OWL Ontologies Semantic Web Journal 2(1), Special Issue on Semantic Web Tools and Systems, pp. 11-21, 2011.

Natural Language Processing (NLP) for Clinical Decision Support: A Practical Approach

A significant portion of the electronic documentation of clinical care is captured in the form of unstructured narrative text like psychotherapy and progress notes. Despite the big push to adopt structured data entry (as required by the Meaningful Use incentive program for example), many clinicians still like to document care using free narrative text. The advantage of using narrative text as opposed to coded entries is that narrative text can tell the story of the patient and the care provided particularly in complex cases. My opinion is that free narrative text should be used to complement coded entries when necessary to capture relevant information.

Furthermore, medical knowledge is expanding very rapidly. For example, PubMed has more than 24 millions citations for biomedical literature from MEDLINE, life science journals, and online books. It is impossible for the human brain to keep up with that amount of knowledge. These unstructured sources of knowledge contain the scientific evidence that is required for effective clinical decision making in what is referred to as Evidence-Based Medicine (EBM).

In this blog, I discuss two practical applications of Natural Language Processing (NLP). The first is the use of NLP tools and techniques to automatically extract clinical concepts and other insight from clinical notes for the purpose of providing treatment recommendations in Clinical Decision Support (CDS) systems. The second is the use of text analytics techniques like clustering and summarization for Clinical Question Answering (CQA).

The emphasis of this post is on a practical approach using freely available and mature open source tools as opposed to an academic or theoretical approach. For a theoretical treatment of the subject, please refer to the book Speech and Language Processing by Daniel Jurafsky and James Martin.

Clinical NLP with Apache cTAKES

Based on the Apache Unstructured Information Management Architecture (UIMA) framework and the Apache OpenNLP natural language processing toolkit, Apache cTAKES provides a modular architecture utilizing both rule-based and machine learning techniques for information extraction from clinical notes. cTAKES can extract named entities (clinical concepts) from clinical notes in plain text or HL7 CDA format and map these entities to various dictionaries including the following Unified Medical Language System (UMLS) semantic types: diseases/disorders, signs/symptoms, anatomical sites, procedures, and medications.

cTAKES includes the following key components which can be assembled to create processing pipelines:

• Sentence boundary detector based on the OpenNLP Maximum Entropy (ME) sentence detector.
• Tokenizor
• Normalizer using the National Library of Medicine's Lexical Variant Generation (LVG) tool
• Part-of-speech (POS) tagger
• Shallow parser
• Named Entity Recognition (NER) annotator using dictionary look-up to UMLS concepts and semantic types. The Drug NER can extract drug entities and their attributes such as dosage, strength, route, etc.
• Assertion module which determines the subject of the statement (e.g., is the subject of the statement the patient or a parent of the patient) and whether a named entity or event is negated (e.g., does the presence of the word "depression" in the text implies that the patient has depression).

Apache cTAKES 3.2 has added YTEX, a set of extensions developed at Yale University which provide integration with MetaMap, semantic similarity, export to Machine Learning packages like Weka and R, and feature engineering.

The following diagram from the Apache cTAKES Wiki provides an overview of these components and their dependencies (click to enlarge):

Source: Apache cTAKES wiki

Massively Parallel Clinical Text Analytics in the Cloud with GATECloud

The General Architecture for Text Engineering (GATE) is a mature, comprehensive, and open source text analytics platform. GATE is a family of tools which includes:

• GATE Developer: an integrated development environment (IDE) for language processing components with a comprehensive set of available plugins called CREOLE (Collection of REusable Objects for Language Engineering). 
• GATE Embedded: an object library for embedding services developed with GATE Developer into third-party applications.
• GATE Teamware: a collaborative semantic annotation environment based on a workflow engine for creating manually annotated corpora for applying machine learning algorithms. 
• GATE Mímir: the "Multi-paradigm Information Management Index and Repository" which supports a multi-paradigm approach to index and search over text, ontologies, and semantic metadata.
• GATE Cloud: a massively parallel clinical text analytics platform (Platform as a Service or PaaS) built on the Amazon AWS Cloud.

What makes GATE particularly attractive is the recent addition of GATECloud.net PaaS which can boost the productivity of people involved in large scale text analytics tasks.

 

Clustering, Classification, Text Summarization, and Clinical Question Answering (CQA)

 

An unsupervised machine learning approach called Clustering can be used to classify large volumes of medical literature into groups (clusters) based on some similarity measure (such as the Euclidean distance). Clustering can be applied at the document, search result, and word/topic levels. Carrot2 and Apache Mahout are open source projects that provide several methods for document clustering. For example, the Latent Dirichlet Allocation learning algorithm in Apache Mahout automatically clusters words into topics and documents into mixtures of topics. Other clustering algorithms in Apache Mahout include: Canopy, Mean-Shift, Spectral, K-Means and Fuzzy K-Means. Apache Mahout is part of the Hadoop ecosystem and can therefore scale to very large volumes of unstructured text.

Document classification essentially consists in assigning predefined set of labels to documents. This can be achieved through supervised machine learning algorithms. Apache Mahout implements the Naive Bayes classifier.

Text summarization techniques can be used to present succinct and clinically relevant evidence to clinicians at the point of care. MEAD (http://www.summarization.com/mead/) is an open source project that implements multiple summarization algorithms. In the biomedical domain, SemRep is a program that extracts semantic predications (subject-relation-object triples) from biomedical free text. Subject and object arguments of each predication are concepts from the UMLS Metathesaurus and the relation is from the UMLS Semantic Network (e.g., TREATS, Co-OCCURS_WITH). The SemRep summarization provides a short summary of these concepts and their semantic relations.

AskHermes (Help clinicians to Extract and aRrticulate Multimedia information for answering clinical quEstionS) is a project that attempts to implement these techniques in the clinical domain. It allows clinicians to enter questions in natural language and uses the following unstructured information sources: MEDLINE abstracts, PubMed Central full-text articles, eMedicine documents, clinical guidelines, and Wikipedia articles.

The processing pipeline in AskHermes includes the following: Question Analysis, Related Questions Extraction, Information Retrieval, Summarization and Answer Presentation. AskHermes performs question classification using MMTx (MetaMap Technology Transfer) to map keywords to UMLS concepts and semantic types. Classification is achieved through supervised machine learning algorithms such as Support Vector Machine (SVM) and conditional random fields (CFRs). Summarization and answer presentation are based on clustering techniques. AskHermes is powered by open source components including: JBoss Seam, Weka, Mallet , Carrot2 , Lucene/Solr, and WordNet (a lexical database for the English language).

Enabling Scalable Realtime Healthcare Analytics with Apache Spark

Modern and massively parallel computing platforms can process humongous amounts of data in real time to obtain actionable insights for effective clinical decision making. In this blog, I discuss an emerging Big Data platform called Apache Spark and its application to remote real-time healthcare monitoring using data from medical devices and wearable sensors. The goal is to provide effective remote care for an increasingly aging population as well as public health surveillance.

The Apache Spark Framework

Apache Spark has emerged during the last couple of years as an innovative platform for Big Data and in-memory cluster computing capable of running programs up to 100x faster than traditional Hadoop MapReduce. Apache Spark is written in Scala, a functional programming language (see my previous post titled Navigating in Scala land). Spark also offers a Java and a Python APIs. The Scala API allows developers to interact with Spark by using very concise and expressive Scala code.

The Spark stack also includes the following integrated tools:

• Spark SQL which allows relational queries expressed in SQL, HiveQL, or Scala to be executed using Spark through a data abstraction called SchemaRDD. Supported data sources include Parquet files (a columnar storage format for Hadoop), JSON datasets, or data stored in Apache Hive.


• Spark Streaming which enables fault-tolerant stream processing of live data streams. Data can be ingested from many sources like Kafka, Flume, Twitter, ZeroMQ or plain old TCP sockets. The ingested data can be directly processed with Spark built-in Machine Learning algorithms.


• MLlib (Machine Learning Library) provides a library of practical Machine Learning algorithms including support vector machines (SVM), logistic regression, decision trees, naive Bayes, and k-means clustering.


• GraphX which provides graph-parallel computation for graph-analytics application like social networks.

Apache Spark can also play nicely with other frameworks within the Hadoop ecosystem. For example, it can run standalone or on a Hadoop 2's YARN cluster manager, on Amazon EC2 or a Mesos cluster manager. Spark can also read data from HFDS, HBase, Cassandra or any other Hadoop data source. Other noteworthy integrations include:

• SparkR, an R package allowing the use of Spark from R, a very popular open source software environment for statistical computing with more that 5800 packages including Machine Learning packages; and


• H2O-Sparkling which provides an integration with the H2O platform through in-memory sharing with Tachyon, a memory-centric distributed file system for data sharing across cluster frameworks. This allows Spark applications to leverage advanced distributed Machine Learning algorithms supported by the H2O platform like emerging Deep Learning algorithms.

 

Wearable Sensors for Remote Healthcare Monitoring 

Three factors are contributing to the availability of massive amounts of clinical data: the rising adoption of EHRs by providers thanks in part to the Meaningful Use incentive program; the increasing use of medical devices including wearable sensors used by patients outside of healthcare facilities; and medical knowledge (for example in the form of medical research literature).

One promising area in Healthcare Informatics where Big Data architectures like the one provided by Apache Spark can make a difference is in applications using data from wearable health monitoring sensors for anomaly detection, care alerting, diagnosis, care planning, and prediction. For example, anomaly detection can be performed at scale using the k-means clustering machine learning algorithm in Spark.

These sensors and devices are part of a larger trend called the "Internet of Things". They enable new capabilities such as remote health monitoring for personalized medicine and chronic care management for an increasingly aging population as well as public health surveillance for outbreaks and epidemics.

Wearable sensors can collect vital signs data like weight, temperature, blood pressure (BP), heart rate (HR), blood glucose (BG), respiratory rate (RR), electrocardiogram (ECG), oxygen saturation (SpO2), and Photoplethysmography (PPG). Spark Streaming can be used to perform real-time stream processing on sensors data and the data can be processed and analyzed using the Machine Learning algorithms available in MLlib and the other integrated frameworks like R and H2O. What makes Spark particularly suitable for this type of applications is that sensor data meet the Big Data criteria of volume, velocity, and variety.

Researchers predict that internet use on mobile phones will increase 20-fold in Africa in the next five years. The number of mobile subscriptions in sub-Saharan Africa is expected to reach 635 millions by the end of this year. This unprecedented level of connectivity (fueled in part by the historical lack of land line infrastructure) provides opportunities for effective public health surveillance and disease management in the developing world.

Apache Spark is the type of open source computing infrastructure that is needed for distributed, scalable, and real-time healthcare analytics for reducing healthcare costs and improving outcomes.

Building business sustainability: why Agile needs Lean Startup principles?

In his book on leadership titled On Becoming a Leader, Warren Bennis wrote: "Managers do things right while leaders do the right thing". This quote can help explain why Agile needs Lean Startup principles.

Toward Product Leadership

Lean Startup is about Product Leadership. In business, the ultimate goal of the enterprise is to eventually generate revenue and profit and that requires having enough customers who are willing to pay for a product or service. This is the key to sustainability in a free market system. The concept of the Lean Startup was first introduced by Eric Ries in his book titled: The Lean Startup: How Today's Entrepreneurs Use Continuous Innovation to Create Radically Successful Businesses. Steve Blank wrote an article in the Harvard Business Review last year titled: Why the Lean Start-Up Changes Everything.

Agile is about the management of Product Development. When applied properly using techniques such as Test Automation and Continuous Delivery, Agile (and its various flavors like XP, Scrum, or Kanban) is a proven methodology for successful software delivery. However, a purely ceremonial approach (daily standup, sprint planning, review, retrospective, story pointing, etc.) may not yield best results.

Having the best software developers in town and building a well-designed and well-tested software on time and under budget will not necessarily translate into market success and business growth and sustainability. So what is the missing piece? How do we ensure that Agile is delivering a product that users are willing to buy? How do we know that the software itself and the many features that we work hard to implement every sprint are actually going to be needed, paid for, and used by our customers?

How Agile projects can become big failed experiments

Agile promotes the use of cross-functional teams that include business users, subject matter experts (SMEs), software developers, and testers. There is also the role of Product Owner in Agile teams. The Product Owner and the business users help the team define and prioritize backlog items. The issue is that most of the time, neither the Product Owner nor the business users are the people who are actually going to sign a check or use their credit card to buy the product. This is the case when the product will be marketed and sold to the market at large. Implementing the wrong design and building the wrong product can be very costly to the enterprise. So the result is that the design and the features that are being implemented by the development team are just assumptions and hypotheses (by so called experienced experts and product visionaries) that have never been validated. Not surprisingly, many Agile projects have become big failed experiments.

Untested assumptions and hypotheses

What we call vision and strategy are often just untested assumptions and hypotheses. Yet, we invest significant time and resources pursuing those ideas. A deep understanding (acquired through lengthy industry experience) of the business, customers' pain points, regulatory environment, and the competitive landscape will not always produce the correct assumptions about a product. This is because the pace of change has accelerated dramatically over the last two decades.

Traditional management processes and tools like strategic planning and the Balanced Scorecard do not always provide a framework for validating those assumptions. Even newer management techniques like the Blue Ocean Strategy taught by business schools to MBA candidates contain significant elements of risk and uncertainty when confronted with the brutal reality of the marketplace.

This reminds me of my days in aviation training. Aviation operations are characterized by a high level of planning. The Flight Plan contains details about the departure time, route, estimated time enroute, fuel onboard, cruising altitude, airspeed, destination, alternate airports, etc. However, pilots are also trained to respond effectively to uncertainty. Examples of these critical decision points are the well known "Go/No Go" decision during takeoff and the "Go-Around" during the final approach to landing. According to the Flight Safety Foundation, a lack of go-arounds is the number one risk factor in approach and landing accidents and the number one cause of "runway excursions".

The following is how the FAA Airplane Flying Handbook describes the go-around:

The assumption that an aborted landing is invariably the consequence of a poor approach, which in turn is due to insufficient experience or skill, is a fallacy. The go-around is not strictly an emergency procedure. It is a normal maneuver that may at times be used in an emergency situation. Like any other normal maneuver, the go-around must be practiced and perfected.

 

Applying Lean Startup engineering Principles

A software development culture that tolerates risk-taking and failure as a source of rapid learning and growth is actually a good thing. The question is how do we perform fail-safe experiments early and often to validate our assumptions and hypotheses about customers' pain points and the business model (how money is made), quickly learn from those experiments, and pivot to new ideas and new experiments until we get the product right? The traditional retrospective in Agile usually involves discussion about what went wrong and how we can improve with a focus on the activities performed by team members. The concept of pivot in Lean Startup engineering is different. The pivot is about being responsive to customer feedback and demands in order to build a sustainable and resilient product and business. The pivot has significant implications on the architecture, design, and development of a product. As Peter Senge wrote in his book titled The Fifth Discipline: The Art and Practice of the The Learning Organization:

The only sustainable competitive advantage is an organization's ability to learn faster than the competition.

The Lean Startup recipe is to create Minimum Viable Products (MVPs) that are tested early and often with future customers of the product. An MVP can be created through rapid prototyping or by incrementally delivering new product features through Continuous Delivery, while leveraging cloud-based capabilities such as a Platform as a Service (PaaS) to remain lean. Testing MVPs requires the team (including software developers) to get out of their cubicles or workstations and meet with customers face-to-face whenever possible to obtain direct feedback and validation. MVPs can also be tested through analytics, A/B testing, or end-user usability testing. Actionable metrics like the System Usability Scale (SUS) should be collected during these fail-safe experiments and subsequently analyzed.

These fail-safe experiments allows the Product Owner and team to refine the product vision and business model through validated learning. Lean Startup principles are not just for startups. They can also make a big difference in established enterprises where resource constraints combined with market competition and uncertainty can render the traditional strategic planning exercise completely useless.

Navigating in Scala Land

In a previous post titled Toward Polyglot Programming on the Java Virtual Machine (JVM), I described my preliminary  exploration of the other languages and frameworks on the JVM including Groovy, Gradle, Grails, Scala, Akka, Clojure, and the Play Framework. I made the switch from Maven to Gradle, a Groovy-based build language that combines the best of Ant and Maven. I was seduced by the scaffolding capabilities of Grails, but decided to make the jump to Scala and functional programming. So I have been navigating in Scala land recently. In this post, I described my journey.

I am still learning, but I can tell you that I never had so much fun learning a new programming language. It probably has something to do with the use of pure mathematical functions in Scala. I did spend a year studying pure mathematics at the University of Abomey-Calavi after graduating from high school. My first exposure to functional programming was with XSLT and XQuery and I very much enjoyed programming without side effects when using those languages. XSLT 3.0 is a fully-fledged functional programming language with support for functions as first class values and high-order functions. XQuery 3.0 is a typed functional language for processing and querying XML data.


Scala is a complex and ambitious language as it supports both object-oriented and functional programming. When I started to learn Scala, I took the wrong directions several times and had to make several U-turns. So the following steps have been effective for me:

• The Coursera class Functional Programming Principles in Scala taught by Martin Odersky (the designer of Scala) is a good place to start. It explains the motivations behind Scala and emphasizes its mathematical and functional nature without trying to map pre-existing knowledge (of Java or Python, or any other language) to Scala. This is a refreshing approach because Scala is a different language although it can interoperate with Java. A good companion to this course is the book Programming in Scala: A Comprehensive Step-by-Step Guide, 2nd Edition by Martin Odersky, Lex Spoon and Bill Venners.


• If you're a Java programmer moving to Scala, then the book Scala for the Impatient by Cay S. Horstmann would be a good reference. 


• If you're interested in building a web application in Scala, then I would recommend the book Play for Scala by Peter Hilton, Erik Bakker and Francisco Canedo. Scala and Play come with their own ecosystem of tools. This includes a Scala-based build system called sbt (simple build tool), testing tools (like Spec2 and ScalaTest), IDEs (Eclipse-based Scala IDE and IntelliJ), database drivers (like ReactiveMongo and Slick), and authentication/authorization (SecureSocial and Deadbolt). Play has first-class support for JSON and REST, supports asynchronous responses (based on the concepts of "Future" and "Promise"), reactive programming with Akka, caching, iteratees (for processing large streams of data), and real-time push-based technologies like WebSockets and Server-Sent Events.


• A this point, if you decide to dive into the deep waters of Scala, you might want to consider learning Reactive Programming and purely functional data structures. 


• There is a second Scala course at Coursera titled Principles of Reactive Programming taught by Martin Odersky, Erik Meijer, and Roland Kuhn. The Reactive Manifesto makes the case for a new breed of applications called "Reactive Applications". According to the manifesto, the Reactive Application architecture allows developers to build "systems that are event-driven, scalable, resilient, and responsive."  In Scala land, there are currently two leading frameworks that support Reactive Programming: Akka and RxJava. The latter is a library for composing asynchronous and event-based programs using observable sequences. RxJava is a Java port (with a Scala adaptor) of the original Rx (Reactive Extensions) for .NET created by Erik Meijer. Based on the Actor Model, Akka is a framework for building highly concurrent, asynchronous, distributed, and fault tolerant event-driven applications on the JVM (it supports both Java and Scala).


• For purely functional data structures, there is a Scala-based library called Scalaz. The book Functional Programming in Scala by Paul Chiusano and Rúnar Bjarnason is a good resource for exploring Scalaz.


• Readers of this blog probably know that I am a proponent of Domain Driven Design (DDD) in building complex software systems. So I have been investigated how DDD principles can be implemented with a functional and reactive approach. Vaughn Vernon recently presented a podcast on Reactive DDD with Scala and Akka. In a post titled Functional Patterns in Domain Modeling - Anemic Models and Compositional Domain Behaviors, Debasish Ghosh provides an interesting perspective on the subject of anemic domain models in DDD done within a functional programming language as opposed to an object-oriented one.


• For me, Big Data is real, not just a buzzword. I believe in analyzing humongous amounts of data to find hidden patterns and obtain insight for solving complex problems. Dean Wampler called copious data, the killer app for functional programming. Scalding by Twitter can be used for writing MapReduce jobs in Scala. Apache Spark which is written in Scala can run Machine Learning programs up to 100x faster than Hadoop MapReduce in memory. A talk titled Why Spark is the Next Top Compute Model by Dean Wampler explains why Spark has emerged as the most likely replacement for MapReduce in Hadoop applications.

Improving the quality of mental health and substance use treatment: how can Informatics help?

According to the 2012 National Survey on Drug Use and Health, an estimated 43.7 million adults aged 18 or older in the United States had mental illness in the past year. This represents 18.6 percent of all adults in this country. Among those 43.7 million adults, 19.2 percent (8.4 million adults) met criteria for a substance use disorder (i.e., illicit drug or alcohol dependence or abuse). In 2012, an estimated 9.0 million adults (3.9 percent) aged 18 or older had serious thoughts of suicide in the past year.

Mental health and substance use are often associated with other issues such as:

• Co-morbidity involving other chronic diseases like HIV, hepatitis, diabetes, and cardiovascular disease.


• Overdose and emergency care utilization.


• Social issues like incarceration, violence, homelessness, and unemployment.

It is now well established that addiction is a chronic disease of the brain and should be treated as such from a health and social policy standpoint.

The regulatory framework

• The Affordable Care Act (ACA) requires non-grandfathered health plans in the individual and small group markets to provide essential health benefits (EHBs) including mental health and substance use disorder benefits.  


• Starting in 2014, insurers can no longer deny coverage because of a pre-existing mental health condition.


• The ACA requires health plans to cover recommended evidence-based prevention and screening services including depression screening for adults and adolescents and behavioral assessments for children.


• On November 8, 2013, HHS and the Departments of Labor and Treasury released the final rules implementing the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 (MHPAEA). 


• Not all behavioral health specialists are eligible to the Meaningful Use EHR Incentive program created by the Health Information Technology for Economic and Clinical Health Act (HITECH) of 2009.

 

Implementing Clinical Practice Guidelines (CPGs) with Clinical Decision Support (CDS) systems

 

Clinical Decision Support (CDS) can help address key challenges in mental health and substance use treatment such as:

• Shortages and high turnover in the addiction treatment workforce.


• Insufficient or lack of adequate clinician education in mental health and addiction medicine.


• Lack of implementation of available evidence-based clinical practice guideline (CPGs) in mental health and addiction medicine.

For example, there are a number of scientifically validated CPGs for the Medication Assisted Treatment (MAT) of opioid addiction using methadone or buprenorphine. These evidence-based CPGs can be translated into executable CDS rules using business rule engines. These executable clinical rules should also be seamlessly integrated with clinical workflows.

The complexity and costs inherent in capturing the medical knowledge in clinical guidelines and translating that knowledge into executable code remains an impediment to the widespread adoption of CDS software. Therefore, there is a need for standards that facilitate the sharing and interchange of CDS knowledge artifacts and executable clinical guidelines. The ONC Health eDecision Initiative has published specifications to support the interoperability of CDS knowledge artifacts and services.

Ontologies as knowledge representation formalism are well suited for modeling complex medical knowledge and can facilitate reasoning during the automated execution of clinical guidelines based on patient data at the point of care.

The typical Clinical Practice Guideline (CPG) is 50 to 150 pages long. Clinical Decision Support (CDS) should also include other forms of cognitive aid such as Electronic Checklists, Data Visualization, Order Sets, and Infobuttons.

The issues of human factors and usability of CDS systems as well as CDS integration with clinical workflows have been the subject of many research projects in healthcare informatics. The challenge is to be bring these research findings into the practice of developing clinical systems software.

Learning from Data

Learning what works and what does not work in clinical practice is important for building a learning health system. This can be achieved by incorporating the results of Comparative Effectiveness Research (CER) and Patient-Centered Outcome Research (PCOR) into CDS systems. Increasingly, outcomes research will be performed using observational studies (based on real world clinical data) which are recognized as complementary to randomized control trials (RCTs). For example, CER and PCOR can help answer questions about the comparative effectiveness of pharmacological and  psychotherapeutic interventions in mental health and substance abuse treatment. This is a form of Practice-Based Evidence (PBE) that is necessary to close the evidence loop.

Three factors are contributing to the availability of massive amounts of clinical data: the rising adoption of EHRs by providers (thanks in part to the Meaningful Use incentive program), medical devices (including those used by patients outside of healthcare facilities), and medical knowledge (for example in the form of medical research literature). Massively parallel  computing platforms such as Apache Hadoop or Apache Spark can process humongous amounts of data (including in real time) to obtain actionable insights for effective clinical decision making.

The use of predictive modeling for personalized medicine (based on statistical computing and machine learning techniques) is becoming a common practice in healthcare delivery as well. These models can predict the health risk of patients (for pro-active care) based on their individual health profiles and can also help predict which treatments are more likely to lead to positive outcomes.

Embedding Visual Analytics capabilities into CDS systems can help clinicians obtain deep insight for effective understanding, reasoning, and decision making through the visual exploration of massive, complex, and often ambiguous data. For example, Visual Analytics can help in comparing different interventions and care pathways and their respective clinical outcomes for a patient or population of patients over a certain period of time through the vivid showing of causes, variables, comparisons, and explanations.

Genomics of Addiction and Personalized Medicine

Advances in genomics and pharmacogenomics are helping researchers understand treatment response variability among patients in addiction treatment. Clinical Decision Support (CDS) systems can also be used to provide cognitive support to clinicians in providing genetically guided treatment interventions.

Quality Measurement for Mental Health and Substance Use Treatment

An important implication of the shift from a fee-for-service to a value-based healthcare delivery model is that existing process measures and the regulatory requirements to report them are no longer sufficient.

Patient-reported outcomes (PROs) and patient-centered measures include essential metrics such as mortality, functional status, time to recovery, severity of side effects, and remission (depression remission at six and twelve months). These measures should take into account the values, goals, and wishes of the patient. Therefore patient-centered outcomes should also include the patient's own evaluation of the care received.

Another issue to be addressed is the lack of data elements in Electronic Medical Record (EMR) systems for capturing, reporting, and analyzing PROs. This is the key to accountability and quality improvement in mental health and substance use treatment.

Using Natural Language Processing (NLP) for the automated processing of clinical narratives

Electronic documentation in mental health and substance use treatment is often captured in the form of narrative text such as psychotherapy notes. Natural Language Processing (NLP) and machine learning tools and techniques (such as named entity recognition) can be used to extract clinical concepts and other insight from clinical notes.

Another area of interest is Clinical Question Answering (CQA) that would allow clinicians to ask questions in natural language and extract clinical answers from very large amounts of unstructured sources of medical knowledge. PubMed has more than 23 millions citations for biomedical literature from MEDLINE, life science journals, and online books. It is impossible for the human brain to keep up with that amount of knowledge.

Computer-Based Cognitive Behavioral Therapy (CCBT) and mHealth

According to a report published last year by the California HealthCare Foundation and titled The Online Couch: Mental Health Care on the Web:

"Computer-based cognitive behavioral therapy (CCBT) cost-effectively leverages the Internet for coaching patterns in self-driven or provider-assisted programs. Technological advances have enabled computer systems designed to replicate aspects of cognitive behavior therapy for a growing range of mental health issues".

An example of a successful nationwide adoption of CCBT is the online behavioral therapy site Beating the Blues in the United Kingdom which has been proven to help patients suffering from anxiety and mild to moderate depression. Beating the Blues has been recommended for use in the NHS by the National Institute for Health and Clinical Excellence (NICE).

In addition, there is growing evidence to support the efficacy of mobile health (mHealth) technologies for supporting patent engagement and activation in health behavior change (e.g., smoking cessation).

 

Technologies in support of a Collaborative Care Model

There is sufficient evidence to support the efficacy of the collaborative care model (CCM) in the treatment of chronic mental health and substance use conditions.The CCM is based on the following principles:

• Coordinated care involving a multi-disciplinary care team.


• Longitudinal care plan as the backbone of care coordination.


• Co-location of primary care and mental health and substance use specialists.


• Case management by a Care Manager. 

Implementing an effective collaborative care model will require a new breed of advanced clinical collaboration tools and capabilities such as:

• Conversations and knowledge sharing using tools like video conferencing for virtual two-way face-to-face communication between clinicians (see my previous post titled Health IT Innovations for Care Coordination).


• Clinical content management and case management tools.


• File sharing and syncing allowing the longitudinal care plan to be synchronized and shared among all members of the care team.


• Light-weight and simple clinical data exchange standards and protocols for content, transport, security, and privacy. 

 

Patient Consent and Privacy

Because of the stigma associated with mental health and substance use, it is important to give patients control over the sharing of their medical record. Patients consent should be obtained about what type information is shared, with whom, and for what purpose. The patient should also have access to an audit trail of all data exchange-related events. Current paper-based consent processes are inefficient and lack accountability. Web-based consent management applications facilitate the capture and automated enforcement of patient consent directives (see my previous post titled Patient privacy at web scale).

Toward Polyglot Programming on the JVM

In my previous post titled Treating Javascript as a first class language, I wrote about how the Java Virtual Machine (JVM) is evolving with new languages and frameworks like Groovy, Grails, Scala, Akka, and the Play Framework. In this post, I report on my experience in learning and evaluating these emerging technologies and their roles in the Java ecosystem.

A KangaRoo on the JVM

On a previous project, I used Spring Roo to jumpstart the software development process. Spring Roo was created by Ben Alex, an Australian engineer who is also the creator of Spring Security. Spring Roo was a big productivity boost and generated a significant amount of code and configuration based on the specification of the domain model. Spring Roo automatically generated the following:

• The domain entities with support for JPA annotations.
• Repository and service layers. In addition to JPA, Spring Roo also supports NoSQL persistence for MongoDB based on the Spring Data repository abstraction.
• A web layer with Spring MVC controllers and JSP views with support for Tiles-based layout, theming, and localization. The JSP views were subsequently replaced with a combination of Thymeleaf (a next generation server-side HTML5 template engine) and Twitter Boostrap to support a Responsive Web Design (RWD) approach. Roo also supports GWT and JSF.
• REST and JSON remoting for all domain types.
• Basic configuration for Spring Security, Spring Web Flow, Spring Integration, JMS, Email, and Apache Solr.
• Entity mocking, automatic generation of test data ("Data on Demand"),  in-container integration testing, and end-to-end Selenium integration tests.
• A Maven build file for the project and full integration with Spring STS.
• Deployment to Cloud Foundry.

Roo also supports other features such as database reverse engineering and Ajax . Another benefit of using Roo is that it helped enforce Spring best practices and other architectural concerns such as proper application layering.

For my future projects, I am looking forward to taking developer's productivity and innovation to the next level. There are several criteria in my mind:

• Being able to do more with less. This means being able to write code that is concise, expressive, requires less configuration and boilerplate coding, and is easier to understand and maintain (particularly for difficult concerns like concurrency which is a key factor in scalability).
• Interoperability with the Java language and being able to run on the JVM, so that I can take advantage of the larger and rich Java ecosystem of tools and frameworks.
• Lastly, my interest in responsive, massively scalable, and fault-tolerant systems has picked up recently.

Getting Groovy

Maven has been a very powerful build system for several projects that I have worked on. My goal now is to support continuous delivery pipelines as a pattern for achieving high quality software. Large open source projects like Hibernate, Spring, and Android have already moved to Gradle. Gradle builds are written in a Groovy DSL and are more concise than Maven POM files which are based on a more verbose XML syntax. Gradle supports Java, Groovy, and Scala out-of-the box. It also has other benefits like incremental builds, multi-project builds, and plugins for other essential development tools like Eclipse, Jenkins, SonarQube, Ivy, and Artifactory.

Grails is a full-stack framework based on Groovy, leveraging its concise syntax (which includes Closures), dynamic language programming, metaprogramming, and DSL support. The core principle of Grails is "convention over configuration". Grails also integrates well with existing and popular Java projects like Spring Security, Hibernate, and Sitemesh. Roo generates code at development time and makes use of AOP. Grails on the other hand generates code at run-time, allowing the developer to do more with less code. The scaffolding mechanism is very similar in Roo and Grails.

Grails has its own view technology called Groovy Server Pages (GSP) and its own ORM implementation called Grails Object Relational Mapping (GORM) which uses Hibernate under the hood. There is also decent support for REST/JSON and URL routing to controller actions. This makes it easy to use Grails together with Javascript MVC frameworks like AngularJS in creating more responsive user experiences based on the Single Page Application (SPA) architectural pattern.

There are many factors that can influence the decision to use Roo vs. Grails (e.g., the learning curve associated with Groovy and Grails for a traditional Java team). There is also a new high-productivity framework called Spring Boot that is emerging as part of the soon to be released Spring Framework 4.0.

Becoming Reactive

I am also interested in massively scalable and fault-tolerant systems. This is no longer a requirement solely for big internet players like Google, Twitter, Yahoo, and LinkedIn that need to scale to millions of users. These requirements (including response time and up time) are also essential in mission-critical applications such as healthcare.

The recently published "Reactive Manifesto" makes the case for a new breed of applications called "Reactive Applications". According to the manifesto, the Reactive Application architecture allows developers to build "systems that are event-driven, scalable, resilient, and responsive." That is the premise of the other two prominent languages on the JVM: Scala and Clojure. They are based on a different programming paradigm (than traditional OOP) called Functional Programming that is becoming very popular in the multi-core era.

Twitter uses Scala and has open-sourced some of their internal Scala resources like "Effective Scala" and "Scala School". One interesting framework based on Scala is Akka, a concurrency framework built on the Actor Model.

The Play Framework 2 is a full-stack web application framework based on Scala which is currently used by LinkedIn (which has over 225 millions registered users worldwide). In addition to its elegant design, Play's unique benefits include:

• An embedded Java NIO (New I/O) non-blocking server based on JBoss Netty, providing the ability to call collaborating services asynchronously without relying on thread pools to handle I/O. This new breed of servers is called "Evented Servers" (NodeJS is another implementation) as opposed to the old "Threaded Servers". Older frameworks like Spring MVC use a threaded and synchronous approach which is more difficult to scale.
• The ability to make changes to the source code and just refresh the browser page to see the changes (this is called hot reload).
• Type-safe Scala templates (errors are displayed in the browser during development).
• Integrated support for Akka which provides (among other benefits) fault-tolerance, the ability to quickly recover from failure.
• Asynchronous responses (based on the concepts of "Future" and "Promise" also found in AngularJS), caching, iteratees (for processing large streams of data), and support for real-time push-based technologies like WebSockets and Server-Sent Events.

The biggest challenge in moving to Scala is that the move to Functional Programming can be a significant learning curve for developers with a traditional OOP background in Java. Functional Programming is not new. Languages like Lisp and Haskell are functional programming languages. More recently, XML processing languages like XSLT and XQuery have adopted functional programming ideas.

Bringing Clojure to the JVM

Clojure is a dialect of LISP and a dynamically-type functional programming language which compiles to JVM bytecode. Clojure supports multithreaded programming and immutable data structures. One interesting application of Clojure is Incanter, a statistical computing and data visualization environment enabling big data analysis on the JVM.

Treating Javascript as a first-class language

With the emergence of the Single Page Application (SPA) architecture as an approach to creating more fluid and responsive user experiences in the browser, Javascript is gaining prominence as a platform for modern application development. Paypal, a large online payment service, announced recently that it has achieved significant performance and productivity gains by shifting its server-side development from Java to Javascript. From a software architecture and development perspective, what do expressions like "Javascript as a first-class language" or "Javascript as a platform" actually mean?

Let's consider a well-established first-class language and platform like Java. By the way, I still consider Java a strong and safe bet for developing applications. What makes Java strong is not just the language, but the rich ecosystem of free and open source tools and frameworks built around it (e.g., Eclipse, Tomcat, JBoss Application Server, Drools, Maven, Jenkins, Solr, Hibernate, Spring, Hadoop to name just a few). The JVM is evolving with new languages and frameworks like Groovy, Grails, Clojure, Scala, Akka, and the Play Framework which aim to enhance developer's productivity. It is also well-known that big internet companies like Twitter have achieved significant gains in performance, scalability, and other architectural concerns by shifting a lot of back-end code from Ruby on Rails to the JVM. There are a number of architectural patterns and software development practices that have been adopted over the years in successfully building quality Java applications. These include:

• Design patterns such as the Gang of Four (GoF), Dependency Injection, Model View Controller (MVC), Enterprise Integration Patterns (EIP), Domain Driven Design (DDD), and modularity patterns like those based on OSGi.
• Test-Driven Development (TDD) using tools like JUnit, TestNG, Mockito (mocking), Cucumber-JVM (for behavior-driven development or BDD), and Selenium (for automated end-to-end testing).
• Build tools like Maven and Gradle.
• Static analysis with tools like FindBugs, Checkstyle, PMD, and Sonar.
• Continuous integration and delivery with tools like Jenkins.
• Performance testing with JMeter.
• Web application vulnerability testing with Burp.

As we move to a rich client application paradigm based on Javascript and the Single Page Application (SPA) architecture, it is clear that Javascript can no longer be considered a toy language for front-end developers and so we need to bring the same engineering discipline to Javascript. As I said previously, the JVM remains my platform of choice for back-end development. For example, I find that AngularJS (a client-side Javascript MVC framework) works well with Spring back-end capabilities (like Spring Security and REST support in Spring MVC, HATEOAS, or Grail). However, I also keep an eye on server-side Javascript frameworks like Node.js.

The good news is that the community is coming up with patterns, tools, and practices that are helping elevate Javascript to the status of first-class language. The following is a list of patterns and tools that I find interesting and promising so far:

• Javascript design patterns including the application of the GoFs to Javascript. The MVC and Dependency Injection patterns are both implemented in AngularJS, my favorite Javascript MVC framework. There are also modularity patterns like Asyncronous Module Definition (AMD) supported by RequireJS.
• Functional programming support in Javascript (e.g., higher-order functions and closures) is emerging as a best practice in writing quality Javascript code. 
• Behavior-Driven Development (BDD) testing with Jasmine.
• Static analysis with Javascript code quality tools like JSLint and JSHint.
• Build with Grunt, a Javascript task runner.
• Karma, a test runner for Javascript.
• Protractor, an end-to-end test framework built on top of Selenium WedDriverJS.
• Single Page Applications are subject to common web application vulnerabilities like Cookie Snooping, Cross-Site Scripting (XSS), Cross-Site Request Forgery (CSRF), and JSON Injection. Security is mainly the responsibility of the server, although client-side frameworks like AngularJS also provide some features to enhance the security of Single Page Applications.

Health IT Innovations for Care Coordination

The Business Case

According to an article by Bodenheimer et al. published in the January/February 2009 issue of Health Affairs and titled Confronting The Growing Burden Of Chronic Disease: Can The U.S. Health Care Workforce Do The Job?:

In 2005, 133 million americans were living with at least one chronic condition. In 2020, this number is expected to grow to 157 million. In 2005, sixty-three million people had multiple chronic illnesses, and that number will reach eighty-one million in 2020. 

Patients with co-morbidities are typically treated by multiple clinicians working for different healthcare organizations. Care Coordination is necessary for the effective treatment of these patients and reducing costs. Effective Care Coordination can reduce the number of redundant tests and procedures, hospital admissions and readmissions, medical errors, and patient safety issues related to the lack of medication reconciliation. 

According to a paper by Dennison and Hugues published in the Journal of Cardiovascular Nursing and titled Progress in Prevention Imperative to Improve Care Transitions for Cardiovascular Patients, direct communication between the hospital and primary care setting occurred only 3 percent of the time. According to the same paper, at discharge, a summary was provided only 12 percent of the time, and this occurrence remained poor at 4 weeks post-discharge, with only 51 percent of practitioners providing a summary. The paper concluded that this standard affected quality of care in 25 percent of follow-up visits.

Health Information Exchanges (HIEs) and emerging delivery models like the Accountable Care Organization (ACO) and the Patient-Centered Medical Home (PCMH) were designed to promote care coordination. However, according to an article by Furukawa et al. published in the August 2013 issue of Health Affairs and titled Hospital Electronic Health Information Exchange Grew Substantially In 2008–12:

In 2012, 51 percent of hospitals exchanged clinical information with unaffiliated ambulatory care providers, but only 36 percent exchanged information with other hospitals outside the organization. . . . In 2012 more than half of hospitals exchanged laboratory results or radiology reports, but only about one-third of them exchanged clinical care summaries or medication lists with outside providers.                      

Furthermore, the financial sustainability of many HIEs remains an issue. According to another article by Adler-Milstein et al. published in the same issue of Health Affairs and titled Operational Health Information Exchanges Show Substantial Growth, But Long-Term Funding Remains A Concern, "74 percent of health information exchange efforts report struggling to develop a sustainable business model".  

There are other obstacles to care coordination including the existing fee-for-service healthcare delivery model (as opposed to a value-based model), the lack of interoperability between healthcare information systems, and the lack of adoption of effective collaboration tools.

According to a report by the Institute of Medicine (IOM) titled  The Healthcare Imperative: Lowering Costs and Improving Outcomes, a program designed to improve care coordination could result in national annual savings of $240.1 billions.

What Can We Learn From High Risk Operations in Other Industries?

Similar breakdowns in communication during shift handovers have also been observed in risky operating environments, sometimes with devastating consequences. In the aerospace industry, human factors research and training have played an important role in successfully addressing the issue. A research paper by Parke and Mishkin titled Best Practices in Shift Handover Communication: Mars Exploration Rover Surface Operations included the following recommendations:

• Two-way Communication, Preferably Face-to-Face. . . . Two-way communication enables the incoming worker to ask questions and rephrase the material to be handed over, so as to expose these differences [in mental model].



• Face-to-Face Handovers with Written Support. Face-to-face handovers are improved if they are supported by structured written material—e.g., a checklist of items to convey, and/or a position log to review. 



• Content of Handover Captures Intent. Handover communication works best if it captures problems, hypotheses, and intent, rather than simply lists what occurred.

While the logistics of healthcare delivery does not always permit physical face-to-face communication between clinicians during transitions of care, the web has seen an explosion in online collaboration tools. Innovative organizations have embraced these technologies giving rise to a new breed of enterprise software known as Enterprise 2.0 or Social Enterprise Software. This new breed of software is not only social, but also mobile, and cloud-based.

Care Coordination in the Health Enterprise 2.0

• Collaborative Authoring of a Longitudinal Care Plan. From a content perspective, the Care Plan is the backbone of Care Coordination. The Care Plan should be comprehensive and standardized (similar to the checklist in aerospace operations). It should include problems, medications, orders, results, care goals (taking into consideration the patient's wishes and values), care team members and their responsibilities, and actual patient outcomes (e.g., functional status). Clinical Decision Support (CDS) tools can be used to dynamically generate a basic Care Plan based on the patient's specific clinical data. This basic Care Plan can be used by members of the care team to build a more elaborate Longitudinal Care Plan. CDS tools can also automatically generate alerts and reminders for the care team.



• Communication and Collaboration using Enterprise 2.0 Software.  These tools should be used to enable collaboration between all members of the care team which include not only clinicians, but also non-clinician caregivers, and the patient herself. Beyond email, these tools allow conversations and knowledge sharing through instant messaging, video conferencing (for virtual two-way face-to-face communication), content management, file syncing (allowing the longitudinal care plan to be synchronized and shared among all members of the care team), search, and enterprise social networking (because clinical work is a social activity like most human activities). A providers directory should make it easy for users to find a specific provider and all their contact information based on search criteria such as location, specialty, knowledge, experience, and telephone number.



• Light Weight Standards and Protocols for Content, Transport, Security, and Privacy. The foundation standards are: REST, JSON, OAuth2, and OpenID Connect. An emerging approach that could really help put patients in control of the privacy of their electronic medical record is the OAuth2.0-based User-Managed Access (UMA) Protocol of the Kantara Initiative (see my previous post titled Patient Privacy at Web Scale). Initiatives like the ONC-sponsored RESTful Health Exchange (RHEX) project and the HL7 Fast Healthcare Interoperability Resources (FHIR) hold great promise.



• Case Management Tools. They are typically used by Nurse Practionners (Case Managers) in Medical Homes, a concept popularized by the Patient-Centered Medical Home healthcare delivery model to coordinate care. These tools integrate various capabilities such as risk stratification (using predictive modeling) to identify at-risk patients, content management (check-in, check-out, versioning), workflows (human tasks), communication, business rule engine, and case reporting/analytics capabilities.