Indiana Network For Patient Care Research Articles

Ondansetron blocks wild-type and p.F503L variant small-conductance Ca2+-activated K+ channels.

Apamin-sensitive small-conductance Ca2+-activated K+ (SK) current ( IKAS) is encoded by Ca2+-activated K+ channel subfamily N ( KCNN) genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT syndrome (diLQTS), we screened for KCNN variants among patients with diLQTS, determined the properties of heterologously expressed wild-type (WT) and variant KCNN channels, and determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS. We searched 2,306,335 records in the Indiana Network for Patient Care and found 11 patients with diLQTS who had DNA available in the Indiana Biobank. DNA sequencing discovered a heterozygous KCNN2 variant (p.F503L) in a 52-yr-old woman presenting with corrected QT interval prolongation at baseline (473 ms) and further corrected QT interval lengthening (601 ms) after oral administration of ondansetron. That patient was also heterozygous for the p.S38G and p.P2835S variants of the QT-controlling genes KCNE1 and ankyrin 2, respectively. Patch-clamp experiments revealed that the p.F503L KCNN2 variant heterologously expressed in human embryonic kidney (HEK)-293 cells augmented Ca2+ sensitivity, increasing IKAS density. The fraction of total F503L-KCNN2 protein retained in the membrane was higher than that of WT KCNN2 protein. Ondansetron at nanomolar concentrations inhibited WT and p.F503L SK2 channels expressed in HEK-293 cells as well as native SK channels in ventricular cardiomyocytes. Ondansetron-induced IKAS inhibition was also demonstrated in Langendorff-perfused murine hearts. In conclusion, the heterozygous p.F503L KCNN2 variant increases Ca2+ sensitivity and IKAS density in transfected HEK-293 cells. Ondansetron at therapeutic (i.e., nanomolar) concentrations is a potent IKAS blocker. NEW & NOTEWORTHY We showed that ondansetron, a 5-HT3 receptor antagonist, blocks small-conductance Ca2+-activated K+ (SK) current. Ondansetron may be useful in controlling arrhythmias in which increased SK current is a likely contributor. However, its SK-blocking effects may also facilitate the development of drug-induced long QT syndrome.

Estimating causal log-odds ratio using the case-control sample and its application in the pharmaco-epidemiology study.

One important goal in pharmaco-epidemiology studies is to understand the causal relationship between drug exposures and their clinical outcomes, including adverse drug events. In order to achieve this goal, however, we need to resolve several challenges. Most of pharmaco-epidemiology data are observational and confounding is largely present due to many co-medications. The pharmaco-epidemiology study data set is often sampled from large medical record databases using a matched case-control design, and it may not be representative of the original patient population in the medical record databases. Data analysis method needs to handle a large sample size that cannot be handled using existing statistical analysis packages. In this paper, we tackle these challenges both methodologically and computationally. We propose a conditional causal log-odds ratio (OR) definition to characterize causal effects of drug exposures on a binary adverse drug event adjusting for individual level confounders. Using a case-control design, we present a propensity score estimation using only case samples and we provide sufficient conditions for the consistency of the estimation of the causal log-odds ratio using case-based propensity scores. Computationally, we implement a principle component analysis to reduce high-dimensional confounders. Extensive simulation studies are performed to demonstrate superior performance of our method to existing methods. Finally, we apply the proposed method to analyze drug-induced myopathy data sampled from a de-identified subset of medical record database (close to 5 million patient records), The Indiana Network for Patient Care. Our method identified 70 drug-induced myopathy (p < 0.05) out 72 drugs, which have myoathy side effects on their FDA drug labels. These 70 drugs include three statins who are known for their myopathy side effects.

Noncompaction cardiomyopathy and heterotaxy syndrome

Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by compact and trabecular layers of the left ventricular myocardium. This cardiomyopathy may occur with congenital heart disease (CHD). Single cases document co-occurrence of LVNC and heterotaxy, but no data exist regarding the prevalence of this association. This study sought to determine whether a non-random association of LVNC and heterotaxy exists by evaluating the prevalence of LVNC in patients with heterotaxy.In a retrospective review of the Indiana Network for Patient Care, we identified 172 patients with heterotaxy (69 male, 103 female). Echocardiography and cardiac magnetic resonance imaging results were independently reviewed by two cardiologists to ensure reproducibility of LVNC. A total of 13/172 (7.5%) patients met imaging criteria for LVNC. The CHD identified in this subgroup included atrioventricular septal defects [11], dextrocardia [10], systemic and pulmonary venous return abnormalities [7], and transposition of the great arteries [5]. From this subgroup, 61% (n=8) of the patients developed arrhythmias; and 61% (n=8) required medical management for chronic heart failure.This study indicates that LVNC has increased prevalence among patients with heterotaxy when compared to the general population (0.014–1.3%) suggesting possible common genetic mechanisms. Interestingly, mice with a loss of function of Scrib or Vangl2 genes showed abnormal compaction of the ventricles, anomalies in cardiac looping, and septation defects in previous studies. Recognition of the association between LVNC and heterotaxy is important for various reasons. First, the increased risk of arrhythmias demonstrated in our population. Secondly, theoretical risk of thromboembolic events remains in any LVNC population. Finally, many patients with heterotaxy undergo cardiac surgery (corrective and palliative) and when this is associated with LVNC, patients should be presumed to incur a higher peri-operative morbidity based on previous studies. Further research will continue to determine long-term and to corroborate genetic pathways.

Demographic, clinical, and outcomes characteristics associated with screening colonoscopy in colorectal cancer patients.

554 Background: Screening colonoscopy has well established role in CRC prevention. Factors associated with underutilization of screening colonoscopy, and how underutilization affects the CRC outcomes is unclear. We conducted a retrospective study with an aim to identify demographic, clinical and outcome characteristics associated with screening colonoscopy in patients with CRC. Methods: The Indiana Network for Patient Care (INPC) was used to identify patients diagnosed with CRC between 2001-2015. The INPC is the largest and longest tenured clinical data warehouse of the Indiana Health Information Exchange in the USA. Patient demographic (age, race, gender, median household income, insurance type, geographical location), clinical (BMI, year of diagnosis, stage, tumor location, CEA, surgery, chemotherapy, comorbidity) and outcome characteristics were obtained. Only patients who had colonoscopy prior to diagnosis were included, and divided those who received screening colonoscopy versus diagnostic colonoscopy. Chi-square was used for univariate analysis. Multivariate logistic regression was used to model the association of colonoscopy with overall mortality, and CRC-specific mortality. Results: A total of 1546 patients were identified, of which 361 (23.3%) and 1185 (76.6%) had screening and diagnostic colonoscopy, respectively. On univariate analyses, older age, female gender, Caucasian race, lower BMI and lack of insurance, were significantly associated with screening colonoscopy (P &lt; 0.05). Additionally, patients receiving screening colonoscopy had higher likelihood to undergo surgery and receive chemotherapy (P &lt; 0.05). Multivariate analyses adjusted for age, gender, race, surgery, chemotherapy and insurance status showed that screening colonoscopy (as compared with diagnostic colonoscopy) is associated with a 38% lower odds of overall mortality (adjusted OR = 0.62, 95% CI, 0.46-0.83, p &lt; 0.001), and 68% lower odds of CRC-specific mortality (adjusted OR = 0.32, 95% CI, 0.19-0.51, p &lt; 0.001). Conclusions: Screening colonoscopy is associated with decreased odds of overall and CRC-specific mortality and individuals with older age are more likely to receive it.

Gallbladder Ejection Fraction Is Unrelated to Gallbladder Pathology in Children and Adolescents.

Biliary dyskinesia is a common diagnosis that frequently results in cholecystectomy. In adults, most clinicians use a cut off value for the gallbladder ejection fraction (GBEF) of <35% to define the disease. This disorder is not well characterized in children. Our aim was to determine the relation between GBEF and gallbladder pathology using a large statewide medical record repository. We obtained records from all patients of 21 years and younger who underwent hepatic iminodiacetic acid (HIDA) testing within the Indiana Network for Patient Care from 2004 to 2013. GBEF results were obtained from radiology reports using data mining techniques. Age, sex, race, and insurance status were obtained for each patient. Any gallbladder pathology obtained subsequent to an HIDA scan was also obtained and parsed for mention of cholecystitis, cholelithiasis, or cholesterolosis. We performed mixed effects logistic regression analysis to determine the influence of age, sex, race, insurance status, pathologist, and GBEF on the presence of these histologic findings. Two thousand eight hundred forty-one HIDA scans on 2558 patients were found. Of these, 310 patients had a full-text gallbladder pathology report paired with the HIDA scan. GBEF did not correlate with the presence of gallbladder pathology (cholecystitis, cholelithiasis, or cholesterolosis) when controlling for age, sex, race, insurance status, and pathologist using a mixed effects model. Hypokinetic gallbladders are no more likely to have gallbladder pathology than normal or hyperkinetic gallbladders in the setting of a patient with both a HIDA scan and a cholecystectomy. Care should be used when interpreting the results of HIDA scans in children and adolescents.

Triamterene Enhances the Blood Pressure Lowering Effect of Hydrochlorothiazide in Patients with Hypertension.

Triamterene, because of its potassium-sparing properties, is frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the cortical collecting duct, triamterene reduces potassium secretion, thus reducing the risk of hypokalemia. Whether triamterene has an independent effect on blood pressure (BP) has not been well studied. To determine if triamterene provides an effect to further lower BP in patients treated with HCTZ. We conducted an observational study using electronic medical record data from the Indiana Network for Patient Care. Participants were 17,291 patients with the diagnosis of hypertension between 2004 and 2012. BP was the primary outcome. We compared the BP between patients who were taking HCTZ, with and without triamterene, either alone or in combination with other antihypertensive medications, by using a propensity score analysis. For each medication combination, we estimated the propensity score (i.e., probability) of a patient receiving triamterene using a logistic regression model. Patients with similar propensity scores were stratified into subclasses and BP was compared between those taking triamterene or not within each subclass; the effect of triamterene was then assessed by combining BP differences estimated from all subclasses. The mean systolic BP in the triamterene + HCTZ group was 3.8 mmHg lower than in the HCTZ only group (p < 0.0001); systolic BP was similarly lower for patients taking triamterene with other medication combinations. Systolic BP reduction was consistently observed for different medication combinations. The range of systolic BP reduction was between 1 and 4 mm Hg, depending on the concurrently used medications. In the present study, triamterene was found to enhance the effect of HCTZ to lower BP. In addition to its potassium-sparing action, triamterene's ability to lower BP should also be considered.

Preparing a collection of radiology examinations for distribution and retrieval.

Clinical documents made available for secondary use play an increasingly important role in discovery of clinical knowledge, development of research methods, and education. An important step in facilitating secondary use of clinical document collections is easy access to descriptions and samples that represent the content of the collections. This paper presents an approach to developing a collection of radiology examinations, including both the images and radiologist narrative reports, and making them publicly available in a searchable database. The authors collected 3996 radiology reports from the Indiana Network for Patient Care and 8121 associated images from the hospitals' picture archiving systems. The images and reports were de-identified automatically and then the automatic de-identification was manually verified. The authors coded the key findings of the reports and empirically assessed the benefits of manual coding on retrieval. The automatic de-identification of the narrative was aggressive and achieved 100% precision at the cost of rendering a few findings uninterpretable. Automatic de-identification of images was not quite as perfect. Images for two of 3996 patients (0.05%) showed protected health information. Manual encoding of findings improved retrieval precision. Stringent de-identification methods can remove all identifiers from text radiology reports. DICOM de-identification of images does not remove all identifying information and needs special attention to images scanned from film. Adding manual coding to the radiologist narrative reports significantly improved relevancy of the retrieved clinical documents. The de-identified Indiana chest X-ray collection is available for searching and downloading from the National Library of Medicine (http://openi.nlm.nih.gov/).

Database queries for hospitalizations for acute congestive heart failure: flexible methods and validation based on set theory

Electronic health records databases are increasingly used for identifying cohort populations, covariates, or outcomes, but discerning such clinical 'phenotypes' accurately is an ongoing challenge. We developed a flexible method using overlapping (Venn diagram) queries. Here we describe this approach to find patients hospitalized with acute congestive heart failure (CHF), a sampling strategy for one-by-one 'gold standard' chart review, and calculation of positive predictive value (PPV) and sensitivities, with SEs, across different definitions. We used retrospective queries of hospitalizations (2002-2011) in the Indiana Network for Patient Care with any CHF ICD-9 diagnoses, a primary diagnosis, an echocardiogram performed, a B-natriuretic peptide (BNP) drawn, or BNP >500 pg/mL. We used a hybrid between proportional sampling by Venn zone and over-sampling non-overlapping zones. The acute CHF (presence/absence) outcome was based on expert chart review using a priori criteria. Among 79,091 hospitalizations, we reviewed 908. A query for any ICD-9 code for CHF had PPV 42.8% (SE 1.5%) for acute CHF and sensitivity 94.3% (1.3%). Primary diagnosis of 428 and BNP >500 pg/mL had PPV 90.4% (SE 2.4%) and sensitivity 28.8% (1.1%). PPV was <10% when there was no echocardiogram, no BNP, and no primary diagnosis. 'False positive' hospitalizations were for other heart disease, lung disease, or other reasons. This novel method successfully allowed flexible application and validation of queries for patients hospitalized with acute CHF.

Measuring the impact of a health information exchange intervention on provider-based notifiable disease reporting using mixed methods: a study protocol.

BackgroundHealth information exchange (HIE) is the electronic sharing of data and information between clinical care and public health entities. Previous research has shown that using HIE to electronically report laboratory results to public health can improve surveillance practice, yet there has been little utilization of HIE for improving provider-based disease reporting. This article describes a study protocol that uses mixed methods to evaluate an intervention to electronically pre-populate provider-based notifiable disease case reporting forms with clinical, laboratory and patient data available through an operational HIE. The evaluation seeks to: (1) identify barriers and facilitators to implementation, adoption and utilization of the intervention; (2) measure impacts on workflow, provider awareness, and end-user satisfaction; and (3) describe the contextual factors that impact the effectiveness of the intervention within heterogeneous clinical settings and the HIE.Methods/DesignThe intervention will be implemented over a staggered schedule in one of the largest and oldest HIE infrastructures in the U.S., the Indiana Network for Patient Care. Evaluation will be conducted utilizing a concurrent design mixed methods framework in which qualitative methods are embedded within the quantitative methods. Quantitative data will include reporting rates, timeliness and burden and report completeness and accuracy, analyzed using interrupted time-series and other pre-post comparisons. Qualitative data regarding pre-post provider perceptions of report completeness, accuracy, and timeliness, reporting burden, data quality, benefits, utility, adoption, utilization and impact on reporting workflow will be collected using semi-structured interviews and open-ended survey items. Data will be triangulated to find convergence or agreement by cross-validating results to produce a contextualized portrayal of the facilitators and barriers to implementation and use of the intervention.DiscussionBy applying mixed research methods and measuring context, facilitators and barriers, and individual, organizational and data quality factors that may impact adoption and utilization of the intervention, we will document whether and how the intervention streamlines provider-based manual reporting workflows, lowers barriers to reporting, increases data completeness, improves reporting timeliness and captures a greater portion of communicable disease burden in the community.

Data for drugs available through low-cost prescription drug programs are available through pharmacy benefit manager and claims data

BackgroundObservational data are increasingly being used for pharmacoepidemiological, health services and clinical effectiveness research. Since pharmacies first introduced low-cost prescription programs (LCPP), researchers have worried that data about the medications provided through these programs might not be available in observational data derived from administrative sources, such as payer claims or pharmacy benefit management (PBM) company transactions.MethodWe used data from the Indiana Network for Patient Care to estimate the proportion of patients with type 2 diabetes to whom an oral hypoglycemic agent was dispensed. Based on these estimates, we compared the proportions of patients who received medications from chains that do and do not offer an LCPP, the proportion trend over time based on claims data from a single payer, and to proportions estimated from the Medical Expenditure Panel Survey (MEPS).ResultsWe found that the proportion of patients with type 2 diabetes who received oral hypoglycemic medications did not vary based on whether the chain that dispensed the drug offered an LCPP or over time. Additionally, the rates were comparable to those estimated from MEPS.ConclusionResearchers can be reassured that data for medications available through LCPPs continue to be available through administrative data sources.

Enhancing laboratory report contents to improve outpatient management of test results

In today's environment, providers are extremely time-constrained. Assembling relevant contextual data to make decisions on laboratory results can take a significant amount of time from the day. The Regenstrief Institute has created a system which leverages data within Indiana Health Information Exchange's (IHIE's) repository, the Indiana Network for Patient Care (INPC), to provide well-organized and contextual information on returning laboratory results to outpatient providers. The system described here uses data extracted from INPC to add historical test results, medication-dispensing events, visit information, and clinical reminders to traditional laboratory result reports. These "Enhanced Laboratory Reports" (ELRs) are seamlessly delivered to outpatient practices connected through IHIE via the DOCS4DOCS clinical messaging service. All practices, including those without electronic medical record systems, can receive ELRs. In this paper, the design and implementation issues in creating this system are discussed, and generally favorable preliminary results of attitudes by providers towards ELRs are reported.

An Empiric Modification to the Probabilistic Record Linkage Algorithm Using Frequency-Based Weight Scaling

ObjectiveTo incorporate value-based weight scaling into the Fellegi-Sunter (F–S) maximum likelihood linkage algorithm and evaluate the performance of the modified algorithm. BackgroundBecause healthcare data are fragmented across many healthcare systems, record linkage is a key component of fully functional health information exchanges. Probabilistic linkage methods produce more accurate, dynamic, and robust matching results than rule-based approaches, particularly when matching patient records that lack unique identifiers. Theoretically, the relative frequency of specific data elements can enhance the F–S method, including minimizing the false-positive or false-negative matches. However, to our knowledge, no frequency-based weight scaling modification to the F–S method has been implemented and specifically evaluated using real-world clinical data. MethodsThe authors implemented a value-based weight scaling modification using an information theoretical model, and formally evaluated the effectiveness of this modification by linking 51,361 records from Indiana statewide newborn screening data to 80,089 HL7 registration messages from the Indiana Network for Patient Care, an operational health information exchange. In addition to applying the weight scaling modification to all fields, we examined the effect of selectively scaling common or uncommon field-specific values. ResultsThe sensitivity, specificity, and positive predictive value for applying weight scaling to all field-specific values were 95.4, 98.8, and 99.9%, respectively. Compared with nonweight scaling, the modified F–S algorithm demonstrated a 10% increase in specificity with a 3% decrease in sensitivity. ConclusionBy eliminating false-positive matches, the value-based weight modification can enhance the specificity of the F–S method with minimal decrease in sensitivity.

The Indiana Network For Patient Care: A Working Local Health Information Infrastructure

The Indiana Network for Patient Care (INPC) is a local health information infrastructure (LHII) that includes information from the five major hospital systems (fifteen separate hospitals), the county and state public health departments, and Indiana Medicaid and RxHub and that carries 660 million separate results. It provides cross-institutional access to physicians in emergency rooms and hospitals based on patient-physician proximity or on hospital credentialing. The network includes and delivers laboratory, radiology, dictation, and other documents to a majority of Indianapolis office practices. The INPC began operation seven years ago and is one of the first and best examples of an LHII.

The Indiana Network for Patient Care

Presented in this article is the Indiana Network for Patient Care, an integrated citywide medical record system that promotes health quality by enabling efficient access to clinical information. It begins with a description of the system's infrastructure, which includes an explanation of how the system accomplishes data integration. This is followed by a series of descriptions and rationales behind the many clinical applications that interface these data. In doing so, some of the factors that we feel contribute to the success of the system are illustrated.

Electronic laboratory reporting: barriers, solutions and findings.

Electronic laboratory reporting can improve surveillance for notifiable conditions. Building on standards for message structure and content, we have implemented an electronic laboratory reporting system by building on the infrastructure created for the Indiana Network for Patient Care (INPC). The system has proven reliable in delivering results and scalable to multiple laboratories over 36 months of use. In April 2000, the system identified over 1,000 cases of notifiable conditions from the laboratories at four different laboratories. Our experience in developing the system has highlighted the need for improved compliance with HL7 result message formats by the laboratory information systems and more structured reporting of results for tests such as microbiology including consistent use of the abnormal flag.