Multicenter retrospective evaluation of magnetic resonance imaging in pediatric and congenital heart disease patients with cardiac implantable electronic devices.

BACKGROUND: Guidelines addressing magnetic resonance imaging (MRI) in patients with cardiac implantable electronic devices (CIEDs) provide algorithms for imaging pediatric and congenital heart disease (CHD) patients. Guideline acceptance varies by institution. Guidelines also do not support routine MRI scans in patients with epicardial or abandoned leads, common in pediatric and CHD patients. OBJECTIVE: The purpose of this study was to determine the incidence of MRI-related complications in pediatric and CHD patients with CIEDs, including epicardial and/or abandoned leads. METHODS: A multicenter retrospective review included patients with CIEDs who underwent any MRI between 2007 and 2022 at congenital cardiac centers. The primary outcome was any patient adverse event or clinically significant CIED change after MRI, defined as pacing lead capture threshold increase >0.5 V with output change, P- or R- wave amplitude decrease >50% with sensitivity change, or impedance change >50%. RESULTS: Across 14 institutions, 314 patients (median age 18.8 [1.3; 31.4] years) underwent 389 MRIs. There were 288 pacemakers (74%) and 87 implantable cardioverter-defibrillators (22%); 52% contained epicardial leads, and 14 (4%) were abandoned leads only. Symptoms or CIED changes occurred in 4.9% of MRI scans (6.1% of patients). On 9 occasions (2%), warmth or pain occurred. Pacing capture threshold or lead impedance changes occurred in 1.4% and 2.0% of CIEDs post-MRI and at follow-up. CONCLUSION: Our data provide evidence that MRIs can be performed in pediatric and CHD patients with CIEDs, including non-MRI-conditional CIEDs and epicardial and/or abandoned leads, with rare minor symptoms or CIED changes but no other complications.

Intracranial aneurysm and coarctation of the aorta: prevalence in the current era.

BACKGROUND: A 10% prevalence of intracranial aneurysms in patients with coarctation of the aorta has been described in a few studies. Our objective is to describe the rate of intracranial aneurysm detection in patients with coarctation of the aorta in the current era. We hypothesise that, with earlier detection and coarctation of the aorta intervention, the rate of intracranial aneurysm is lower than previously reported and screening imaging may only be warranted in older patients or patients with certain risk factors. METHODS: This is a retrospective study of 102 patients aged 13 years and older with coarctation who underwent brain computed tomography angiography, magnetic resonance imaging (MRI), or magnetic resonance angiography between January, 2000 and February, 2018. RESULTS: The median age of coarctation repair was 4.4 months (2 days-47 years) and the initial repair was primarily surgical (90.2%). There were 11 former smokers, 4 current smokers, and 13 patients with ongoing hypertension. Imaging modalities included computed tomography angiography (13.7%), MRI (41.2%), and magnetic resonance angiography (46.1%), performed at a median age of 33.3 years, 22.4 years, and 25 years, respectively. There were 42 studies performed for screening, 48 studies performed for neurologic symptoms, and 12 studies performed for both screening and symptoms. There were no intracranial aneurysms detected in this study. CONCLUSIONS: These results suggest that the rate of intracranial aneurysms may be lower than previously reported and larger studies should explore the risk of intracranial aneurysms in coarctation of the aorta in the current era.

Patient needs and preferences for herb-drug-disease interaction alerts: a structured interview study.

BACKGROUND: While complementary and alternative medicine (CAM) is commonly used in the United States and elsewhere, and hazardous interactions with prescription drugs can occur, patients do not regularly communicate with physicians about their CAM use. The objective of this study was to discover patient information needs and preferences for herb-drug-disease interaction alerts. METHODS: We recruited 50 people from several locations within the University of Utah Hospital to participate in this structured interview study. They were asked to provide their preferences for the herb-drug-disease interaction alerts. Qualitative methods were used to reveal the themes that emerged from the interviews. RESULTS: Most participants reported they had previously used, or they were currently using, CAM therapies. The majority had made the effort to inform their healthcare provider(s) about their CAM usage, although some had not. We found that most respondents were interested in receiving alerts and information about potential interactions. Many preferred to receive the alerts in a variety of ways, both in person and electronically. CONCLUSIONS: In addition to conventional medicine, many patients regularly use complementary and alternative therapies. And yet, communication between patients and providers about CAM use is not consistent. There is a demand for interventions in health care that provide timely, integrative communication support. Delivering the herb-drug-disease alerts through multiple channels could help meet critical patient information needs.

Regular Expression-Based Learning for METs Value Extraction.

Functional status as measured by exercise capacity is an important clinical variable in the care of patients with cardiovascular diseases. Exercise capacity is commonly reported in terms of Metabolic Equivalents (METs). In the medical records, METs can often be found in a variety of clinical notes. To extract METs values, we adapted a machine-learning algorithm called REDEx to automatically generate regular expressions. Trained and tested on a set of 2701 manually annotated text snippets (i.e. short pieces of text), the regular expressions were able to achieve good accuracy and F-measure of 0.89 and 0.86. This extraction tool will allow us to process the notes of millions of cardiovascular patients and extract METs value for use by researchers and clinicians.

Automated pictographic illustration of discharge instructions with Glyph: impact on patient recall and satisfaction.

OBJECTIVES: First, to evaluate the effect of standard vs pictograph-enhanced discharge instructions on patients' immediate and delayed recall of and satisfaction with their discharge instructions. Second, to evaluate the effect of automated pictograph enhancement on patient satisfaction with their discharge instructions. MATERIALS AND METHODS: Glyph, an automated healthcare informatics system, was used to automatically enhance patient discharge instructions with pictographs. Glyph was developed at the University of Utah by our research team. Patients in a cardiovascular medical unit were randomized to receive pictograph-enhanced or standard discharge instructions. Measures of immediate and delayed recall and satisfaction with discharge instructions were compared between two randomized groups: pictograph (n = 71) and standard (n = 73). RESULTS: Study participants who received pictograph-enhanced discharge instructions recalled 35% more of their instructions at discharge than those who received standard discharge instructions. The ratio of instructions at discharge was: standard = 0.04 ± 0.03 and pictograph-enhanced = 0.06 ± 0.03. The ratio of instructions at 1 week post discharge was: standard = 0.04 ± 0.02 and pictograph-enhanced 0.04 ± 0.02. Additionally, study participants who received pictograph-enhanced discharge instructions were more satisfied with the understandability of their instructions at 1 week post-discharge than those who received standard discharge instructions. DISCUSSION: Pictograph-enhanced discharge instructions have the potential to increase patient understanding of and satisfaction with discharge instructions. CONCLUSION: It is feasible to automatically illustrate discharge instructions and provide them to patients in a timely manner without interfering with clinical work. Illustrations in discharge instructions were found to improve patients' short-term recall of discharge instructions and delayed satisfaction (1-week post hospitalization) with the instructions. Therefore, it is likely that patients' understanding of and interaction with their discharge instructions is improved by the addition of illustrations.

Assessing Pictograph Recognition: A Comparison of Crowdsourcing and Traditional Survey Approaches.

BACKGROUND: Compared to traditional methods of participant recruitment, online crowdsourcing platforms provide a fast and low-cost alternative. Amazon Mechanical Turk (MTurk) is a large and well-known crowdsourcing service. It has developed into the leading platform for crowdsourcing recruitment. OBJECTIVE: To explore the application of online crowdsourcing for health informatics research, specifically the testing of medical pictographs. METHODS: A set of pictographs created for cardiovascular hospital discharge instructions was tested for recognition. This set of illustrations (n=486) was first tested through an in-person survey in a hospital setting (n=150) and then using online MTurk participants (n=150). We analyzed these survey results to determine their comparability. RESULTS: Both the demographics and the pictograph recognition rates of online participants were different from those of the in-person participants. In the multivariable linear regression model comparing the 2 groups, the MTurk group scored significantly higher than the hospital sample after adjusting for potential demographic characteristics (adjusted mean difference 0.18, 95% CI 0.08-0.28, P<.001). The adjusted mean ratings were 2.95 (95% CI 2.89-3.02) for the in-person hospital sample and 3.14 (95% CI 3.07-3.20) for the online MTurk sample on a 4-point Likert scale (1=totally incorrect, 4=totally correct). CONCLUSIONS: The findings suggest that crowdsourcing is a viable complement to traditional in-person surveys, but it cannot replace them.

Representation of Functional Status Concepts from Clinical Documents and Social Media Sources by Standard Terminologies.

Patient-reported functional status is widely recognized as an important patient-centered outcome that adds value to medical care, research, and quality improvement. Functional status outcomes are, however, not routinely or uniformly collected in the medical record, except in certain small patient populations (e.g. geriatrics, nursing home residents). To utilize patient reported functional status for clinical research and practice, we manually collected 2,763 terms from clinical records and social media sites and modeled them on the widely used Short Form-36 Health Survey. We then examined the coverage of the Unified Medical Language System (UMLS) for these functional status terms through automated mapping. Most terms (85.9%) did not have exact matches in the UMLS. The partial matches were prevalent, however, they typically did not capture the terms' exact semantics. Our study suggests that there is a need to extend existing standard terminologies to incorporate functional status terms used by patients and clinicians.

Evaluation of a pictograph enhancement system for patient instruction: a recall study.

OBJECTIVE: We developed a novel computer application called Glyph that automatically converts text to sets of illustrations using natural language processing and computer graphics techniques to provide high quality pictographs for health communication. In this study, we evaluated the ability of the Glyph system to illustrate a set of actual patient instructions, and tested patient recall of the original and Glyph illustrated instructions. METHODS: We used Glyph to illustrate 49 patient instructions representing 10 different discharge templates from the University of Utah Cardiology Service. 84 participants were recruited through convenience sampling. To test the recall of illustrated versus non-illustrated instructions, participants were asked to review and then recall a set questionnaires that contained five pictograph-enhanced and five non-pictograph-enhanced items. RESULTS: The mean score without pictographs was 0.47 (SD 0.23), or 47% recall. With pictographs, this mean score increased to 0.52 (SD 0.22), or 52% recall. In a multivariable mixed effects linear regression model, this 0.05 mean increase was statistically significant (95% CI 0.03 to 0.06, p<0.001). DISCUSSION: In our study, the presence of Glyph pictographs improved discharge instruction recall (p<0.001). Education, age, and English as first language were associated with better instruction recall and transcription. CONCLUSIONS: Automated illustration is a novel approach to improve the comprehension and recall of discharge instructions. Our results showed a statistically significant in recall with automated illustrations. Subjects with no-colleague education and younger subjects appeared to benefit more from the illustrations than others.

Differences in nationwide cohorts of acupuncture users identified using structured and free text medical records.

Integrative medicine including complementary and alternative medicine (CAM) has become more available through mainstream health providers. Acupuncture is one of the most widely used CAM therapies, though its efficacy for treating various conditions requires further investigation. To assist with such investigations, we set out to identify acupuncture patient cohorts using a nationwide clinical data repository. Acupuncture patients were identified using both structured data and unstructured free text notes: 44,960 acupuncture patients were identified using structured data consisting of CPT codes;. Using unstructured free text clinical notes, we trained a support vector classifier with 86% accuracy and was able to identify an additional 101,628 acupuncture patients not identified through structured data (a 226% increase). In addition, characteristics of the patients identified through structured and unstructured data were compared, which show differences in geographic locations and medical service usage patterns. Patients identified with structured data displayed a consistently higher use of the Veterans Health Administration (VHA) medical system.

The atypical histone macroH2A1.2 interacts with HER-2 protein in cancer cells.

Because HER-2 has been demonstrated in the nuclei of cancer cells, we hypothesized that it might interact with transcription factors that activate ERBB2 transcription. Macrohistone 2A1 (H2AFY; mH2A1) was found to interact with HER-2 in cancer cells that overexpress HER-2. Of the two human mH2A1 isoforms, mH2A1.2, but not mH2A1.1, interacted with HER-2 in human cancer cell lines. Overexpression of mH2A1.2, but not mH2A1.1, in cancer cells significantly increased HER-2 expression and tumorigenicity. Inhibition of HER-2 kinase activity diminished mH2A1 expression and mH2A1.2-induced ERBB2 transcription in cancer cells. Chromatin immunoprecipitation of mH2A1.2 in cancer cells stably transfected with mH2A1.2 showed enrichment of mH2A1.2 at the HER-2 promoter, suggesting a role for mH2A1.2 in driving HER-2 overexpression. The evolutionarily conserved macro domain of mH2A1.2 was sufficient for the interaction between HER-2 and mH2A1.2 and for mH2A1.2-induced ERBB2 transcription. Within the macro domain of mH2A1.2, a trinucleotide insertion (-EIS-) sequence not found in mH2A1.1 was essential for the interaction between HER-2 and mH2A1.2 as well as mH2A1.2-induced HER-2 expression and cell proliferation.

Conditional deletion of beta1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality.

Conditional deletion of beta1 integrins in the intestinal epithelium, unlike in epidermal and mammary epithelia, of mice does not result in decreased cell adhesion and proliferation, but instead causes a profound increase in epithelial proliferation with dysplasia and polypoid structures. The increased epithelial proliferation inhibited epithelial differentiation that caused severe malnutrition and early postnatal lethality. The striking similarities between beta1 integrin-deleted mice and neonatal mice with defective Hedgehog signaling led to the discovery that Hedgehog expression was markedly reduced in the former mice. beta1 integrins were found to drive the expression of Hedgehogs in intestinal epithelial cells in an HNF-3beta (Foxa2)-dependent fashion. The expression of Tcf-4, a transcription factor known to be required for intestinal epithelial stem cell proliferation, was increased and mislocalized in the intestinal epithelia of the beta1 integrin-deleted mice and in newborn mice treated with the Hedgehog signaling inhibitor cyclopamine. This study shows that beta1 integrins are key regulators of proliferation and homeostasis in the intestine and achieve this not through anchorage-dependent effects but by generating Hh expression and signaling.

Integrin alpha5/beta1 expression mediates HER-2 down-regulation in colon cancer cells.

HER-2 is constitutively activated and overexpressed in many cancers, and its inhibition in colon cancer cells diminishes tumorigenicity and induces apoptosis. Little is known about the regulation of HER-2 signaling in colon cancer cells. Integrin alpha5/beta1 expression is frequently lost in colorectal cancer cells compared with normal intestinal epithelium, and colon cancer cells lacking integrin alpha5/beta1 expression utilize HER-2 signaling for proliferation and tumorigenicity. Re-expression of integrin alpha5/beta1 in colon cancer cells abrogated their tumorigenicity, but how this occurs is not well known. Stable expression of integrin alpha5/beta1 in colon cancer cells with little or no detectable integrin alpha5/beta1 protein expression resulted in the post-transcriptional down-regulation of HER-2 protein. Integrin alpha5/beta1 was found to interact with HER-2, and the cytoplasmic domain of integrin alpha5/beta1 was sufficient to mediate HER-2 down-regulation. Integrin alpha5/beta1-mediated down-regulation of HER-2 was the result of increased lysosomal targeting. The inhibition of HER-2 signaling represents a potential mechanism by which integrin alpha5/beta1 exerts its tumor suppressor-like activity in colon cancer cells. These results also suggest that a novel function for integrin alpha5/beta1 is the control of HER-2 expression.

Effects of trastuzumab on epidermal growth factor receptor-dependent and -independent human colon cancer cells.

Little information is available as to the potential role of HER-2 as a therapeutic target in colon cancers, which express much fewer HER-2 receptors than breast cancer cells. Treatment of certain human colon cancer cell lines with the HER-2 inhibitory antibody mAb 4D5 demonstrated a role for HER-2 in mediating proliferation, apoptosis and tumorigenicity. However, only the cell lines that were dependent on autocrine EGFR-mediated cell proliferation were susceptible to the antiproliferative and antitumorigenic effects of HER-2 inhibition. The relative levels of HER-2, EGFR, HER-3 and HER-4 were not predictive of responsiveness to mAb 4D5. Treatment with HER-2 antibodies caused a decrease in HER-2 protein levels in all of the colon cancer cell lines and also significantly decreased EGFR levels but only in the EGFR-dependent cell lines. Treatment with mAb 4D5 caused the rapid ubiquitination and ligand-dependent downregulation of the EGFR in an EGFR-dependent colon cancer cell line. Treatment of athymic mice engrafted with EGFR-dependent colon cancer cells with mAb 4D5 caused tumor regression and a decrease in EGFR tyrosine phosphorylation in the tumor cells. EGFR-independent colon cancer cell xenografts were resistant to mAb 4D5 therapy. Combined inhibition of HER-2 and EGFR caused large areas of necrosis in EGFR-dependent colon cancer xenografts, suggesting a benefit of combined HER-2 and EGFR inhibitor therapy. Predicting clinical responsiveness of human colon cancer cells to anti-HER-2 and anti-EGFR therapy may require demonstration of EGFR tyrosine kinase dependency of the cells.

Nuclear factor kappaB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis.

The transcription factor nuclear factor kappaB (NFkappaB) is constitutively active in many types of cancercells and regulates the expression of several antiapoptotic genes. Previous studies demonstrated a role for the inhibition of NFkappaB in cancer therapyusing a transgenic approach in mice. We found that NFkappaB was transiently activated much greater than background constitutive levels during colon cancer cell readhesion, which rendered the readhering colon cancer cells exquisitely susceptible to apoptosis in the presence of soluble NFkappaB inhibitors. These compounds greatly reduced colon cancer cell implantation in an in vivo seeding model of metastasis. The ability of soluble NFkappaB inhibitors to significantly induce apoptosis of readherent colon cancer cells makes them prospective candidates for preventing colon cancer metastasis.