Data quality in European primary care research databases. Report of a workshop held in London September 2013

Primary care research databases provide a significant resource for health services and epidemiological research. However since data are recorded primarily for clinical care their suitability for research may vary widely according to the research application or recording practices of individual general practitioners. A methodological approach for characterising data quality is required. We describe a one-day workshop entitled “Towards a common protocol for measuring and monitoring data quality in European primary care research databases”. Researchers, database experts and clinicians were invited to give their perspectives on data quality and to exchange ideas on what data quality metrics should be made available to researchers. We report the main outcomes of this workshop, including a summary of the presentations and discussions and suggested way forward

A pragmatic approach for measuring data quality in primary care databases

There is currently no widely recognised methodology for undertaking data quality assessment in electronic health records used for research. In an attempt to address this, we have developed a protocol for measuring and monitoring data quality in primary care research databases, whereby practice-based data quality measures are tailored to the intended use of the data. Our approach was informed by an in-depth investigation of aspects of data quality in the Clinical Practice Research Datalink Gold database and presentations of the results to data users. Although based on a primary care database, much of our proposed approach would be equally applicable to other health care databases

Exploiting the potential of large databases of electronic health records for research using rapid search algorithms and an intuitive query interface.

Objective: UK primary care databases, which contain diagnostic, demographic and prescribing information for millions of patients geographically representative of the UK, represent a significant resource for health services and clinical research. They can be used to identify patients with a specified disease or condition (phenotyping) and to investigate patterns of diagnosis and symptoms. Currently, extracting such information manually is time-consuming and requires considerable expertise. In order to exploit more fully the potential of these large and complex databases, our interdisciplinary team developed generic methods allowing access to different types of user. Materials and methods: Using the Clinical Practice Research Datalink database, we have developed an online user-focused system (TrialViz), which enables users interactively to select suitable medical general practices based on two criteria: suitability of the patient base for the intended study (phenotyping) and measures of data quality. Results: An end-to-end system, underpinned by an innovative search algorithm, allows the user to extract information in near real-time via an intuitive query interface and to explore this information using interactive visualization tools. A usability evaluation of this system produced positive results. Discussion: We present the challenges and results in the development of TrialViz and our plans for its extension for wider applications of clinical research. Conclusions: Our fast search algorithms and simple query algorithms represent a significant advance for users of clinical research databases

PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance

Aberrant activation of embryonic signaling pathways is frequent in pancreatic ductal adenocarcinoma (PDA), making developmental regulators therapeutically attractive. Here we demonstrate diverse functions for pancreatic and duodenal homeobox 1 (PDX1), a transcription factor indispensable for pancreas development, in the progression from normal exocrine cells to metastatic PDA. We identify a critical role for PDX1 in maintaining acinar cell identity, thus resisting the formation of pancreatic intraepithelial neoplasia (PanIN)-derived PDA. Upon neoplastic transformation, the role of PDX1 changes from tumor-suppressive to oncogenic. Interestingly, subsets of malignant cells lose PDX1 expression while undergoing epithelial-to-mesenchymal transition (EMT), and PDX1 loss is associated with poor outcome. This stage-specific functionality arises from profound shifts in PDX1 chromatin occupancy from acinar cells to PDA. In summary, we report distinct roles of PDX1 at different stages of PDA, suggesting that therapeutic approaches against this potential target need to account for its changing functions at different stages of carcinogenesis. These findings provide insight into the complexity of PDA pathogenesis and advocate a rigorous investigation of therapeutically tractable targets at distinct phases of PDA development and progression

Small Gene Networks: Finding Optimal Models Small Gene Networks: Finding Optimal Models

Genetic networks help in identifying interactions between genes, and provide information about the function role of individual genes in the cellular system. In this thesis, we have employed a Bayesian framework to learn network structures from microarray data, and implemented an algorithm that uses dynamic programming to find the optimal gene network model for a small number of genes. To test its performance, we applied the method to two distinctive synthetic datasets. ROC graphs were used to evaluate the effects of noise and a small number of samples, features that are known to be characteristic of gene expression datasets. Results showed significant improvements when the numbers of samples in a dataset were increased. The effect of adding noise to the data gave unexpected results and requires further analysis. The method was finally applied to a real microarray dataset, and led to biologically plausible results

Chemometric guided isolation of new triterpenoid saponins as acetylcholinesterase inhibitors from Achyranthes bidentata Blume

Achyranthes bidentata Blume is an annual herb widely used as functional food and for ethnomedicinal purposes in Traditional Chinese medicine. Its seeds are widely used as cereal grain substitutes due to their excellent nutritional composition and health benefits. In current study, chemical profiling with chemometric guided approach was adopted for the tentative identification of fifty-six compounds based on UPLC-IM-Q-TOF-MS/MS analysis. Chemometric guided approach also led to the isolation of two previously undescribed triterpenoid saponins, named as, achyranosides A-B (1-2) along with three known compounds (3-5) from water fraction of A. bidentata seeds. The structure elucidation of isolated molecules was done by using NMR, HR-ESI-MS, FT-IR and GC-FID techniques. Chikusetsusaponin IVa (5) exhibited most promising inhibition (IC50 values of 63.72 µM) of acetylcholinesterase in vitro with mixed type of AChE inhibition in enzyme kinetic studies. Additionally, in-silico studies disclosed the underlying molecular interactions and binding free energy between ligands and the binding sites. The current study demonstrated the effectiveness of chemometric guided integrated approach for the phytochemical exploration and isolation of new oleanane-type triterpenoid saponins from A. bidentata seeds

Male preponderance in HIV seropositive patients with mucocutaneous complaints in a tertiary care hospital in North India

Objective: A panorama of mucocutaneous manifestations is seen at every stage of HIV. This study was done to study the sex prevalence in HIV/AIDS patients with mucocutaneous disorders. Methods: A total of 1 000 HIV seropositive patients attending Skin-STD clinic, Govt. Medical College, Amritsar, for any dermatologic complaints were studied in respect to the sex group preponderance. Results: Males constituted the majority as 75.6% while females were 24.4%. Conclusions: Women, in most of the cases, get infected from their spouses, who have acquired infection through extramarital sexual contact. HIV infection in female patients increases the risk of HIV transmission to neonates and infants, thus further spreading the HIV in a community. So it is very crucial to initiate early preventive measures to reduce HIV burden

Self assembled monolayers of Octadecyltrichlorosilane for dielectric materials

Treatment of surfaces to change the interaction of fluids with them is a critical step in constructing useful microfluidics devices, especially those used in biological applications. Selective modification of inorganic materials such as Si, SiO2 and Si3N4 is of great interest in research and technology. We evaluated the chemical formation of OTS self-assembled monolayers on silicon substrates with different dielectric materials. Our investigations were focused on surface modification of formerly used common dielectric materials SiO2, Si3N4 and a-poly. The improvement of wetting behaviour and quality of monolayer films were characterized using Atomic force microscope, Scanning electron microscope, Contact angle goniometer, Raman spectroscopy and X-ray photoelectron spectroscopy ( XPS) monolayer deposited oxide surface