Publications

Human studies are one of the most valuable sources of knowledge in biomedical research, but data about their design and results are currently widely dispersed in siloed systems. Federation of these data is needed to facilitate large-scale data analysis to realize the goals of evidence-based medicine. The Human Studies Database project has developed an informatics infrastructure for federated query of human studies databases, using a generalizable approach to ontology-based data access. Our approach has three main components. First, the Ontology of Clinical Research (OCRe) provides the reference semantics. Second, a data model, automatically derived from OCRe into XSD, maintains semantic synchrony of the underlying representations while facilitating data acquisition using common XML technologies. Finally, the Query Integrator issues queries distributed over the data, OCRe, and other ontologies such as SNOMED in BioPortal. We report on a demonstration of this infrastructure on data acquired from institutional systems and from ClinicalTrials.gov.

An abstraction network is an auxiliary network of nodes and links that provides a compact, high-level view of an ontology. Such a view lends support to ontology orientation, comprehension, and quality-assurance efforts. A methodology is presented for deriving a kind of abstraction network, called a partial-area taxonomy, for the Ontology of Clinical Research (OCRe). OCRe was selected as a representative of ontologies implemented using the Web Ontology Language (OWL) based on shared domains. The derivation of the partial-area taxonomy for the Entity hierarchy of OCRe is described. Utilizing the visualization of the content and structure of the hierarchy provided by the taxonomy, the Entity hierarchy is audited, and several errors and inconsistencies in OCRe's modeling of its domain are exposed. After appropriate corrections are made to OCRe, a new partial-area taxonomy is derived. The generalizability of the paradigm of the derivation methodology to various families of biomedical ontologies is discussed.

Alcohol withdrawal is a common clinical condition that has a variety of complications and morbidities. The manifestations can range from mild agitation to withdrawal seizures and delirium tremens. The treatments for alcohol withdrawal include benzodiazepines, anticonvulsants, beta-blockers and antihypertensives. Although benzodiazepines are presently a first-line therapy, there is controversy regarding the efficacies of these medications compared with others. Treatment protocols often involve one of two contrasting approaches: symptom-triggered versus fixed-schedule dosing of benzodiazepines. We describe these protocols in our review and examine the data supporting symptom-triggered dosing as the preferred method for most patients in withdrawal.The Clinical Institute Withdrawal Assessment for Alcohol scoring system for alcohol withdrawal streamlines care, optimizes patient management, and is the best scale available for withdrawal assessment. Quality improvement implications for inpatient management of alcohol withdrawal include increasing training for signs of withdrawal and symptom recognition, adding new hospital protocols to employee curricula, and ensuring manageable patient-to-physician and patient-to-nurse ratios.

Atrial fibrillation (AF) is the commonest cardiac rhythm disorder worldwide, affecting 1% of the general population. It is estimated that up to 16 million people in the US will suffer from the arrhythmia by 2050. AF is an independent stroke risk factor and associated with more severe strokes. For six decades, warfarin has been the only truly effective therapy to protect against stroke for patients with atrial fibrillation. Despite the proven worth of warfarin, its limitations have seen reluctance amongst physicians and patients to utilise this efficacious agent. This has meant that substantial numbers of patients are either unprotected against stroke or suboptimally protected with antiplatelet therapy. Contemporary well-validated stroke risk factor schemes (CHA(2)DS(2)-VASc) now permit rapid but comprehensive evaluation of a patient's risk for thromboembolism, allowing better identification of low-risk patients who do not require antithrombotic therapy, and whilst for those with ≥1 stroke risk factors require formal oral anticoagulation. Aspirin has been proven to be inferior to anticoagulation, and is not free of bleeding risk. We also have simple scores to easily evaluate a patient's risk of haemorrhage (e.g. HAS-BLED). The emergence of new oral anticoagulants should further improve stroke prevention in AF, and they successfully negotiate many of the hurdles to oral anticoagulation generated by warfarin's limitations. Monitoring, reversal, and perioperative management are areas which require further investigation to enhance our ability to safely and effectively utilise the new agents.

BACKGROUND

The primary treatment endpoint for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is HBeAg seroconversion; however, data on the durability of response are inconsistent.

GOALS

Our goal was to investigate the rate of recurrent viremia after HBeAg seroconversion and subsequent discontinuation of therapy.

METHODS

We retrospectively studied 88 consecutive Asian American patients who achieved HBeAg seroconversion [loss of HBeAg and development of antibody to HBeAg (anti-HBe)] among 458 HBeAg-positive patients who received oral antiviral therapy at 3 US clinics between March 1998 and November 2010. Recurrent viremia was defined as reappearance of detectable serum hepatitis B virus DNA (>100 IU/mL) on 2 consecutive laboratory tests from previously undetectable levels.

RESULTS

Antiviral medications used at the time of HBeAg seroconversion included: lamivudine (23%), adefovir (34%), entecavir (36%), tenofovir (4%), and combination therapy (3%). Antiviral therapy was continued after HBeAg seroconversion in 49 patients (group I) and discontinued in the other 39 patients after consolidation therapy [median=12 months (range, 1 to 55 mo)] (group II). No patients in group I experienced recurrent viremia, whereas 90% in group II did. Elevated alanine aminotransferase also occurred in 38% of group II patients [median peak alanine aminotransferase 249 IU/mL (range, 93 to 1070 IU/mL)].

CONCLUSIONS

Despite consolidation therapy, almost all patients who discontinued therapy after achieving HBeAg seroconversion and complete viral suppression experienced recurrent viremia, and close to half also experienced biochemical flares. HBeAg seroconversion does not seem to be a durable treatment endpoint for many patients, and they should be monitored carefully for virologic relapse and biochemical flares if antiviral therapy is withdrawn.