Chronic Cough: Characterizing and Quantifying Burden in Adults Using a Nationwide Electronic Health Records Database.

Chronic cough is a common condition; until recently, no International Classification of Diseases (ICD) code for chronic cough existed; therefore, the true scope and burden of chronic cough is unclear. Using established algorithms, we examined chronic cough patients and their risk profiles, recurrent cough episodes, and subsequent 1-year health care utilization in the nationwide Cerner EHR data resource, compared with those with acute cough. An ICD-based algorithm was applied to the Cerner Health Facts EHR database to derive a phenotype of chronic cough defined as three ICD-based "cough" encounters 14-days apart over a 56-to-120-day period from 2015 to 2017. Demographics, comorbidities, and outcomes (1-year outpatient, emergency, and inpatient encounters) were collected for the chronic cough cohort and acute cough cohort. The chronic cough cohort was 61.5% female, 70.4% white, and 15.2% African American, with 13.7% being of Asian, Native American, or unknown race. Compared with the acute cough cohort, chronic cough patients were more likely to be older, female, and have chronic pulmonary disease, obesity, and depression. Predictors of recurrent chronic cough were older age and race. Those with chronic cough had more outpatient (2.48 ± 2.10 vs. 1.48 ± 0.99; SMD = 0.94), emergency (1.90 ± 2.26 vs. 1.23 ± 0.68; SMD = 0.82), and inpatient (1.11 ± 0.36 vs. 1.05 ± 0.24, SMD = 0.24) encounters compared with acute cough. While EHR-based data may provide a useful resource to identify chronic cough phenotypes, supplementary data approaches and screening methods for chronic cough can further identify the scope of the problem.

Standardized Health data and Research Exchange (SHaRE): promoting a learning health system.

Aggregate de-identified data from electronic health records (EHRs) provide a valuable resource for research. The Standardized Health data and Research Exchange (SHaRE) is a diverse group of US healthcare organizations contributing to the Cerner Health Facts (HF) and Cerner Real-World Data (CRWD) initiatives. The 51 facilities at the 7 founding organizations have provided data about more than 4.8 million patients with 63 million encounters to HF and 7.4 million patients and 119 million encounters to CRWD. SHaRE organizations unmask their organization IDs and provide 3-digit zip code (zip3) data to support epidemiology and disparity research. SHaRE enables communication between members, facilitating data validation and collaboration as we demonstrate by comparing imputed EHR module usage to actual usage. Unlike other data sharing initiatives, no additional technology installation is required. SHaRE establishes a foundation for members to engage in discussions that bridge data science research and patient care, promoting the learning health system.

Aligning EHR Data for Pediatric Leukemia With Standard Protocol Therapy.

PURPOSE: Children with acute lymphoblastic leukemia (ALL) are treated according to risk-based protocols defined by the Children's Oncology Group (COG). Alignment between real-world clinical practice and protocol milestones is not widely understood. Aggregate deidentified electronic health record (EHR) data offer a useful resource to evaluate real-world clinical practice. METHODS: A cohort of children with ALL was identified in the Cerner Health Facts deidentified aggregate EHR data. Manual review identified candidate procedural milestones. Automated methods were developed to classify likely standard-risk precursor B-cell ALL patients. Milestone procedures were adjusted relative to initiation of therapy and then aligned to the COG protocols for standard induction therapy. RESULTS: We identified 7,728 patients with pediatric ALL with 188,187 encounters. Records for lumbar punctures (LP) and bone marrow biopsies were frequently present in the data and were appropriate targets to evaluate guideline performance. Alluvial graph analysis of 14 health systems indicated that none of the systems have data from all three COG-recommended lumbar procedures for all patients but alignment demonstrated that most systems test at the recommended times. CONCLUSION: Source-system variation introduces inconsistency and incompleteness into aggregate EHR data. Data visualization was helpful in characterizing and interpreting the data. Health systems with patients meeting the inclusion criteria demonstrated strong alignment with the recommended milestones for LP. Large-scale aggregate EHR data are useful to evaluate alignment of recommended versus actual clinical milestones in support of treating children with ALL. This work can inform other guideline and protocol driven care.

Molecular Determinants of Enterotoxigenic Escherichia coli Heat-Stable Toxin Secretion and Delivery.

Enterotoxigenic Escherichia coli (ETEC), a heterogeneous diarrheal pathovar defined by production of heat-labile (LT) and/or heat-stable (ST) toxins, causes substantial morbidity among young children in the developing world. Studies demonstrating a major burden of ST-producing ETEC have focused interest on ST toxoids for ETEC vaccines. We examined fundamental aspects of ST biology using ETEC strain H10407, which carries estH and estP genes encoding STh and STp, respectively, in addition to eltAB genes responsible for LT. Here, we found that deletion of estH significantly diminished cyclic GMP (cGMP) activation in target epithelia, while deletion of estP had a surprisingly modest impact, and a dual estH estP mutant was not appreciably different from the estH mutant. However, we noted that either STh or STp recombinant peptides stimulated cGMP production and that the loss of estP was compensated by enhanced estH transcription. We also found that the TolC efflux protein was essential for toxin secretion and delivery, providing a potential avenue for efflux inhibitors in treatment of acute diarrheal illness. In addition, we demonstrated that the EtpA adhesin is required for optimal delivery of ST and that antibodies against either the adhesin or STh significantly impaired toxin delivery and cGMP activation in target T84 cells. Finally, we used FLAG epitope fusions to demonstrate that the STh propeptide sequence is secreted by ETEC, potentially providing additional epitopes for antibody neutralization. These studies collectively extend our understanding of ETEC pathogenesis and potentially inform additional avenues to mitigate disease by these common diarrheal pathogens.

A novel microwave sensor for real-time online monitoring of roll compacts of pharmaceutical powders online--a comparative case study with NIR.

Control of particulate processes is hard to achieve because of the ease with which powders tend to segregate. Thus, proper sensing methods must be employed to ensure content uniformity during operation. The role of sensing schemes becomes even more critical while operating the process continuously as measurements are essential for implementation of feedback control (Austin et al. 2013. J Pharm Sci 102(6):1895-1904; Austin et al. 2014. Anal Chim Acta 819:82-93). A microwave sensor was developed and shown to be effective in online measurement of active pharmaceutical ingredient (API) concentration in a powder blend. During powder transport and hopper storage before processing, powder blends may segregate and cause quality deviations in the subsequent tableting operation. Therefore, it is critical to know the API concentration in the ribbons as the content uniformity is fixed once the ribbon is processed. In this study, a novel microwave sensor was developed that could provide measurement of a roller compacted ribbon's API concentration online, along with its density and moisture content. The results indicate that this microwave sensor is capable of increased accuracy compared with a commercially available near-IR probe for the determination of content uniformity and density in roller compacted ribbons online.