A case study evaluating the portability of an executable computable phenotype algorithm across multiple institutions and electronic health record environments.

Electronic health record (EHR) algorithms for defining patient cohorts are commonly shared as free-text descriptions that require human intervention both to interpret and implement. We developed the Phenotype Execution and Modeling Architecture (PhEMA, http://projectphema.org) to author and execute standardized computable phenotype algorithms. With PhEMA, we converted an algorithm for benign prostatic hyperplasia, developed for the electronic Medical Records and Genomics network (eMERGE), into a standards-based computable format. Eight sites (7 within eMERGE) received the computable algorithm, and 6 successfully executed it against local data warehouses and/or i2b2 instances. Blinded random chart review of cases selected by the computable algorithm shows PPV ≥90%, and 3 out of 5 sites had >90% overlap of selected cases when comparing the computable algorithm to their original eMERGE implementation. This case study demonstrates potential use of PhEMA computable representations to automate phenotyping across different EHR systems, but also highlights some ongoing challenges.

Quality of EHR data extractions for studies of preterm birth in a tertiary care center: guidelines for obtaining reliable data.

BACKGROUND: The use of Electronic Health Records (EHR) has increased significantly in the past 15 years. This study compares electronic vs. manual data abstractions from an EHR for accuracy. While the dataset is limited to preterm birth data, our work is generally applicable. We enumerate challenges to reliable extraction, and state guidelines to maximize reliability. METHODS: An Epic™ EHR data extraction of structured data values from 1,772 neonatal records born between the years 2001-2011 was performed. The data were directly compared to a manually-abstracted database. Specific data values important to studies of perinatology were chosen to compare discrepancies between the two databases. RESULTS: Discrepancy rates between the EHR extraction and the manual database were calculated for gestational age in weeks (2.6 %), birthweight (9.7 %), first white blood cell count (3.2 %), initial hemoglobin (11.9 %), peak total and direct bilirubin (11.4 % and 4.9 %), and patent ductus arteriosus (PDA) diagnosis (12.8 %). Using the discrepancies, errors were quantified in both datasets using chart review. The EHR extraction errors were significantly fewer than manual abstraction errors for PDA and laboratory values excluding neonates transferred from outside hospitals, but significantly greater for birth weight. Reasons for the observed errors are discussed. CONCLUSIONS: We show that an EHR not modified specifically for research purposes had discrepancy ranges comparable to a manually created database. We offer guidelines to minimize EHR extraction errors in future study designs. As EHRs become more research-friendly, electronic chart extractions should be more efficient and have lower error rates compared to manual abstractions.

Pediatric chronic pancreatitis is associated with genetic risk factors and substantial disease burden.

OBJECTIVE: To determine the clinical presentation, diagnostic variables, risk factors, and disease burden in children with chronic pancreatitis. STUDY DESIGN: We performed a cross-sectional study of data from the International Study Group of Pediatric Pancreatitis: In Search for a Cure, a registry of children with acute recurrent pancreatitis and chronic pancreatitis. Between-group differences were compared using Wilcoxon rank-sum test. RESULTS: Among 170 subjects in the registry, 76 (45%) had chronic pancreatitis; 57% were female, 80% were white; median age at diagnosis was 9.9 years. Pancreatitis-predisposing genetic mutations were identified in 51 (67%) and obstructive risk factors in 25 (33%). Toxic/metabolic and autoimmune factors were uncommon. Imaging demonstrated ductal abnormalities and pancreatic atrophy more commonly than calcifications. Fifty-nine (77%) reported abdominal pain within the past year; pain was reported as constant and receiving narcotics in 28%. Children with chronic pancreatitis reported a median of 3 emergency department visits and 2 hospitalizations in the last year. Forty-seven subjects (70%) missed 1 day of school in the past month as the result of chronic pancreatitis; 26 (34%) missed 3 or more days. Children reporting constant pain were more likely to miss school (P = .002), visit the emergency department (P = .01), and experience hospitalizations (P = .03) compared with children with episodic pain. Thirty-three children (43%) underwent therapeutic endoscopic retrograde pancreatography; one or more pancreatic surgeries were performed in 30 (39%). CONCLUSIONS: Chronic pancreatitis occurs at a young age with distinct clinical features. Genetic and obstructive risk factors are common, and disease burden is substantial.

"Collection of a lifetime: a practical approach to developing a longitudinal collection of women's healthcare biological samples".

OBJECTIVE: The objective is to develop a biorepository of samples that represent all stages of a women's life. Importantly, our goal is to collect longitudinal physical specimens as well as the associated short and long-term clinical information. STUDY DESIGN: The Women's Health Tissue Repository was established to encompass four tissue banks: Well Women Tissue Bank, Reproductive Endocrinology and Infertility Tissue Bank, Maternal Fetal Tissue Bank, and the long-established Gynecologic Malignancies Tissue Bank. Based on their health status, women being seen in Women's Health at the University of Iowa are recruited to contribute samples and grant access to their electronic medical record to the biorepository. Samples are coded, processed, and stored for use by investigators. RESULTS: The Maternal Fetal Tissue Bank was the first expansion of our department's biobanking efforts. Approximately 75% of the women approached consent to participate in the Maternal Fetal Tissue Bank. Enrollment has steadily increased. Samples have been used for over 20 projects in the first 3 years and are critical to 7 funded grants and 3 patent applications. CONCLUSION: Patient samples with corresponding clinical data are initially important to women's health research. Our model demonstrates that many research projects by faculty, fellows, and residents have benefited from the existence of the Women's Health Tissue Repository. While challenging to achieve, longitudinal sampling allows for the greatest opportunity to study normal and pathological changes throughout all phases of a women's life, including pregnancy. This bank facilitates and accelerates the development of novel research, technologies, and possible therapeutic options in women's health. The establishment of more longitudinal biorepositories based on our model would enhance women's health research.

Design and implementation of INSPPIRE.

OBJECTIVES: Acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are rare and poorly understood diseases in children. Better understanding of these disorders can only be accomplished via a multicenter, structured, data collection approach. METHODS: The International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) consortium was created to investigate the epidemiology, etiologies, pathogenesis, natural history, and outcomes of pediatric ARP and CP. Patient and physician questionnaires were developed to capture information on demographics, medical history, family and social history, medications, hospitalizations, risk factors, diagnostic evaluation, treatments, and outcome information. Information collected in paper questionnaires was then transferred into Research Electronic Data Capture (REDCap), tabulated, and analyzed. RESULTS: The administrative structure of the INSPPIRE consortium was established, and National Institutes of Health funding was obtained. A total of 14 sites (10 in the United States, 2 in Canada, and 2 overseas) participated. Questionnaires were amended and updated as necessary, followed by changes made into the REDCap database. Between September 1, 2012 and August 31, 2013, a total of 194 children were enrolled into the study: 54% were girls, 82% were non-Hispanic, and 72% were whites. CONCLUSIONS: The INSPPIRE consortium demonstrates the feasibility of building a multicenter patient registry to study the rare pediatric diseases, ARP and CP. Analyses of collected data will provide a greater understanding of pediatric pancreatitis and create opportunities for therapeutic interventional studies that would not otherwise be possible without a multicenter approach.

Up regulation of the GRP-78 and GADD-153 and down regulation of Bcl-2 proteins in primary glomerular diseases: a possible involvement of the ER stress pathway in glomerulonephritis.

The role of endoplasmic reticulum (ER) stress in kidney diseases is not well elucidated. Fifty patients with primary glomerular diseases (PGD): minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN), and crescentic glomerulonephritis, n = 10 (each group) were enrolled. MCD, FSGS, and MGN patients were sub-grouped as nonproliferative glomerulonephritis (NPGN) and MPGN, RPGN as proliferative glomerulonephritis (PGN). Glucose regulated proteins (GRP-78), growth arrest and DNA damage inducible proteins (GADD-153), and Bcl-2 protein expression was analyzed by Western blotting, immunofluorescence and immunohistochemistry in the kidney biopsy. Up regulation of GADD-153, GRP-78, with more pronounced expression in PGN vs. NPGN (P < 0.05) and down regulation of Bcl-2 proteins was observed in the GN (PGD excluding MCD) as compared to MCD (P < 0.05). Our results suggest that renal injury in PGD is associated with ER stress and ER stress may be involved in the rapid progression of PGN to renal failure.