PillHarmonics: An Orchestrated Pharmacogenetics Medication Clinical Decision Support Service.

OBJECTIVES: Pharmacogenetics (PGx) is increasingly important in individualizing therapeutic management plans, but is often implemented apart from other types of medication clinical decision support (CDS). The lack of integration of PGx into existing CDS may result in incomplete interaction information, which may pose patient safety concerns. We sought to develop a cloud-based orchestrated medication CDS service that integrates PGx with a broad set of drug screening alerts and evaluate it through a clinician utility study. METHODS: We developed the PillHarmonics service for implementation per the CDS Hooks protocol, algorithmically integrating a wide range of drug interaction knowledge using cloud-based screening services from First Databank (drug-drug/allergy/condition), PharmGKB (drug-gene), and locally curated content (drug-renal/hepatic/race). We performed a user study, presenting 13 clinicians and pharmacists with a prototype of the system's usage in synthetic patient scenarios. We collected feedback via a standard questionnaire and structured interview. RESULTS: Clinician assessment of PillHarmonics via the Technology Acceptance Model questionnaire shows significant evidence of perceived utility. Thematic analysis of structured interviews revealed that aggregated knowledge, concise actionable summaries, and information accessibility were highly valued, and that clinicians would use the service in their practice. CONCLUSION: Medication safety and optimizing efficacy of therapy regimens remain significant issues. A comprehensive medication CDS system that leverages patient clinical and genomic data to perform a wide range of interaction checking and presents a concise and holistic view of medication knowledge back to the clinician is feasible and perceived as highly valuable for more informed decision-making. Such a system can potentially address many of the challenges identified with current medication-related CDS.

Visualization of Patient-Generated Health Data: A Scoping Review of Dashboard Designs.

BACKGROUND: Patient-centered clinical decision support (PC CDS) aims to assist with tailoring decisions to an individual patient's needs. Patient-generated health data (PGHD), including physiologic measurements captured frequently by automated devices, provide important information for PC CDS. The volume and availability of such PGHD is increasing, but how PGHD should be presented to clinicians to best aid decision-making is unclear. OBJECTIVES: Identify best practices in visualizations of physiologic PGHD, for designing a software application as a PC CDS tool. METHODS: We performed a scoping review of studies of PGHD dashboards that involved clinician users in design or evaluations. We included only studies that used physiologic PGHD from single patients for usage in decision-making. RESULTS: We screened 468 titles and abstracts, 63 full-text papers, and identified 15 articles to include in our review. Some research primarily sought user input on PGHD presentation; other studies garnered feedback only as a side effort for other objectives (e.g., integration with electronic health records [EHRs]). Development efforts were often in the domains of chronic diseases and collected a mix of physiologic parameters (e.g., blood pressure and heart rate) and activity data. Users' preferences were for data to be presented with statistical summaries and clinical interpretations, alongside other non-PGHD data. Recurrent themes indicated that users desire longitudinal data display, aggregation of multiple data types on the same screen, actionability, and customization. Speed, simplicity, and availability of data for other purposes (e.g., documentation) were key to dashboard adoption. Evaluations were favorable for visualizations using common graphing or table formats, although best practices for implementation have not yet been established. CONCLUSION: Although the literature identified common themes on data display, measures, and usability, more research is needed as PGHD usage grows. Ensuring that care is tailored to individual needs will be important in future development of clinical decision support.

Leveraging the Multidisciplinary Tumor Board for Dissemination of Evidence-Based Recommendations on the Staging and Treatment of Gastric Cancer: A Pilot Study.

BACKGROUND: Compliance with evidence-based treatment guidelines for gastric cancer across the United States is poor. This pilot study aimed to create and evaluate a change package for disseminating information on the staging and treatment of gastric cancer during multidisciplinary tumor boards and for identifying barriers to implementation. METHODS: The change package included a 10-min video, a brief knowledge assessment, and a discussion guide. Commission on Cancer-accredited sites that perform gastrectomy were invited to participate. Participants completed the Organizational Readiness for Implementing Change (ORIC) scale (range, 12-60) and scales to measure the feasibility, acceptability, and appropriateness (score range, 4-20). Semi-structured interviews were conducted to further define inner and outer setting barriers. RESULTS: Seven centers participated in the study. A total of 74 participants completed the pre-video knowledge assessment, and 55 participants completed the post-video assessment. The recommendations found to be most controversial were separate staging laparoscopy and modified D2 lymphadenectomy. Sum scores were calculated for acceptability (mean, 17.43 ± 2.51) appropriateness (mean, 16.86 ± 3.24), and feasibility (mean, 16.14 ± 3.07) of the change package. The ORIC scores (mean, 46.57 ± 8.22) correlated with responses to the open-ended questions. The key barriers identified were patient volume, skills in the procedures, and attitudes and beliefs. CONCLUSIONS: The change package was moderately to highly feasible, appropriate, and acceptable. The activity identified specific recommendations for gastric cancer care that are considered controversial and local barriers to implementation. Future efforts could focus on building skills and knowledge as well as the more difficult issue of attitudes and beliefs.

"Closing the loop": a mixed-methods study about resident learning from outcome feedback after patient handoffs.

Background Learning patient outcomes is recognized as crucial for ongoing refinement of clinical decision-making, but is often difficult in fragmented care with frequent handoffs. Data on resident habits of seeking outcome feedback after handoffs are lacking. Methods We performed a mixed-methods study including (1) an analysis of chart re-access rates after handoffs performed using access logs of the electronic health record (EHR); and (2) a web-based survey sent to internal medicine (IM) and emergency medicine (EM) residents about their habits of and barriers to learning the outcomes of patients after they have handed them off to other teams. Results Residents on ward rotations were often able to re-access charts of patients after handoffs, but those on EM or night admitting rotations did so <5% of the time. Among residents surveyed, only a minority stated that they frequently find out the outcomes of patients they have handed off, although learning outcomes was important to both their education and job satisfaction. Most were not satisfied with current systems of learning outcomes of patients after handoffs, citing too little time and lack of reliable patient tracking systems as the main barriers. Conclusions Despite perceived importance of learning outcomes after handoffs, residents cite difficulty with obtaining such information. Systematically providing feedback on patient outcomes would meet a recognized need among physicians in training.

Developing a Semantic Model to Describe Physical Activity Data.

The importance of data in the social and behavioral domains to biomedical research is increasing, but ensuring the reusability of such data through standardization is not a trivial task. To start addressing this challenge, we developed a semantic model of the physical activity domain by reviewing 302 physical activity questions collected from standardized questionnaires and public data repositories. Our semantic model is comprised of activity keywords, qualifiers, response measures and context. We identified three types of contexts: active lifestyle, physical capacity, and environment. The majority (94%) of the 204 activity keywords extracted from the 302 questions were mapped to the UMLS Metathesaurus. Preliminary evaluation of our model with 309 additional activity questions showed that the majority of the questions were related to one of the three context categories. We also noted the need to expand context categories to incorporate the questions assessing psychological aspects of dealing with physical activities.

Clinical criteria to screen for inpatient diagnostic errors: a scoping review.

Diagnostic errors are common and costly, but difficult to detect. "Trigger" tools have promise to facilitate detection, but have not been applied specifically for inpatient diagnostic error. We performed a scoping review to collate all individual "trigger" criteria that have been developed or validated that may indicate that an inpatient diagnostic error has occurred. We searched three databases and screened 8568 titles and abstracts to ultimately include 33 articles. We also developed a conceptual framework of diagnostic error outcomes using real clinical scenarios, and used it to categorize the extracted criteria. Of the multiple criteria we found related to inpatient diagnostic error and amenable to automated detection, the most common were death, transfer to a higher level of care, arrest or "code", and prolonged length of hospital stay. Several others, such as abrupt stoppage of multiple medications or change in procedure, may also be useful. Validation for general adverse event detection was done in 15 studies, but only one performed validation for diagnostic error specifically. Automated detection was used in only two studies. These criteria may be useful for developing diagnostic error detection tools.

Understanding data requirements of retrospective studies.

BACKGROUND AND OBJECTIVE: Usage of data from electronic health records (EHRs) in clinical research is increasing, but there is little empirical knowledge of the data needed to support multiple types of research these sources support. This study seeks to characterize the types and patterns of data usage from EHRs for clinical research. MATERIALS AND METHODS: We analyzed the data requirements of over 100 retrospective studies by mapping the selection criteria and study variables to data elements of two standard data dictionaries, one from the healthcare domain and the other from the clinical research domain. We also contacted study authors to validate our results. RESULTS: The majority of variables mapped to one or to both of the two dictionaries. Studies used an average of 4.46 (range 1-12) data element types in the selection criteria and 6.44 (range 1-15) in the study variables. The most frequently used items (e.g., procedure, condition, medication) are often available in coded form in EHRs. Study criteria were frequently complex, with 49 of 104 studies involving relationships between data elements and 22 of the studies using aggregate operations for data variables. Author responses supported these findings. DISCUSSION AND CONCLUSION: The high proportion of mapped data elements demonstrates the significant potential for clinical data warehousing to facilitate clinical research. Unmapped data elements illustrate the difficulty in developing a complete data dictionary.

Pentoxifylline attenuates pulmonary inflammation and neutrophil activation in experimental acute pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) is associated with a systemic inflammatory response. Pentoxifylline (PTX) has been shown to attenuate neutrophil activation and end-organ injury in shock states such as hemorrhage and sepsis. We hypothesized that PTX would down-regulate AP-induced lung injury. METHODS: Sprague-Dawley rats underwent catheterization of the pancreatic duct. Acute pancreatitis (n = 7) and AP/PTX animals (n = 7) received a retrograde infusion of 3.5% sodium taurocholate and intravenous treatment with normal saline or normal saline and PTX (25 mg/kg), respectively. Pulmonary neutrophil degranulation and sequestration were determined by zymography and detection of myeloperoxidase. Nuclear factor kappa B and mitogen-activated protein kinase phosphorylation was determined by Western blot. Cytokine-induced neutrophil chemoattractant was quantified by enzyme linked immunosorbent assay. RESULTS: Pulmonary histologic injury scores were attenuated in the AP/PTX group (P < 0.05). Plasma amylase levels remained unchanged. Pentoxifylline produced a significant decline in myeloperoxidase content and matrix metalloproteinase activity (P < 0.05). The increase in the phosphorylation of pulmonary nuclear factor kappa B, p38 mitogen-activated protein kinase, and extracellular-related signal kinase 1/2 observed after AP was not demonstrated with PTX (P < 0.05). Pentoxifylline supplementation reduced pulmonary cytokine-induced neutrophil chemoattractant levels by 50% (P < 0.05). CONCLUSIONS: Pentoxifylline significantly attenuated histologic lung injury, pulmonary neutrophil activity, and proinflammatory signaling in a severe model of AP. Therefore, PTX may serve as an adjunct for the treatment of the inflammatory complications of severe AP.

Hypertonic saline and pentoxifylline attenuates gut injury after hemorrhagic shock: the kinder, gentler resuscitation.

BACKGROUND: We have previously demonstrated that postshock resuscitation with Hypertonic saline and Pentoxifylline (HSPTX) attenuates pulmonary and histologic gut injury when compared with Ringer's lactate (RL). In this study, we hypothesized that the decrease in gut injury observed with HSPTX is associated with the attenuation of inducible nitric oxide synthase (iNOS) activity and production of ileal proinflammatory mediators after hemorrhagic shock. METHODS: In a rat model of hemorrhagic shock, resuscitation was conducted with RL (32 mL/kg; n = 7) or HSPTX (4 mL/kg 7.5% NaCl + PTX 25 mg/kg; n = 7). Sham animals that did not undergo shock were also studied. Four hours after resuscitation, the terminal ileum was collected for evaluation of nitrite, tumor necrosis factor (TNF)-alpha, Interleukin (IL)-6, and cytokine-induced neutrophil chemoattractant (CINC) by enzyme immunoassay. Heme oxygenase-1 (HO-1), iNOS, cytoplasmic inhibitor of kappa B (Ikappa B) phosphorylation, and nuclear factor (NF)kappa B p65 nuclear translocation were determined by Western blot. RESULTS: HSPTX resuscitation resulted in a 49% decrease in iNOS when compared with RL (p < 0.05). Similar results were obtained when examining nitrite (882 +/- 59 vs. 1,435 +/- 177 micromol/L; p < 0.01), and HO-1 content (p < 0.05). RL resuscitation resulted in markedly higher levels of TNF-alpha (83 +/- 27 vs. 9 +/- 5 pg/mL; p < 0.01), IL-6 (329 +/- 58 vs. 118 +/- 43 pg/mL; p < 0.05), and CINC (0.43 +/- .06 vs. 0.19 +/- .08 ng/mL; p < 0.05) than HSPTX. The increase in cytokines observed with RL was also associated with an increase in I-kappaB phosphorylation (p < 0.01) and NF-kappaB p65 nuclear translocation (p < 0.001). CONCLUSION: The attenuation in gut injury after postshock resuscitation with HSPTX is associated with downregulation of iNOS activity and subsequent proinflammatory mediator synthesis. HSPTX has the potential to be a superior resuscitation fluid with significant immunomodulatory properties.

Patient factors and operating room resuscitation predict mortality in traumatic abdominal aortic injury: a 20-year analysis.

BACKGROUND: Injuries to the abdominal aorta are rare and remain one of the most lethal causes of early death in trauma. The purposes of this study were to identify primary predictors of mortality and to examine the impact of a well-established operating room resuscitation protocol on survival in patients with traumatic aortic injury. METHODS: A 20-year retrospective review was performed of medical records and autopsy reports of trauma patients admitted with confirmed injury to the abdominal aorta. Data on patient demographics, admission characteristics, operative findings, and the initial location of resuscitation were collected. The main outcome measure was death. RESULTS: Abdominal aortic injuries were diagnosed in 60 patients. Their average age was 26.5 years, and the mean transport time was 10 minutes. The overall mortality rate (MR) was 73%. With the exclusion of 18 patients considered dead on arrival, the MR decreased to 61%. The mechanism of injury was blunt in 20% (MR 92%) and penetrating in 80% (MR 68%). Acidosis, defined as a pH <7.2 (MR 81%) or a base deficit >10 (MR 77%), was a predictor of death (P < .0001). Patients resuscitated directly in the operating room had a significantly lower MR (40%) than those resuscitated in the trauma room (MR 78%; P < .02). The lack of retroperitoneal tamponade (P < .02), the presence of associated intra-abdominal injuries (P < .001), and the location of aortic injury at the subdiaphragmatic (18%; MR 90%) or suprarenal location (37%; MR 71%; P < .005) at exploration resulted in significantly higher patient mortality. Surgical management consisted of primary repair in 26, end-to-end repair in 1, interposition graft in 8, or patch in 1. Resuscitative thoracotomy was performed in 27 patients (45%), with an overall MR of 92%. CONCLUSION: Despite advances in fluid resuscitation, operative strategy, and transport during the past 20 years, the mortality of traumatic injury to the abdominal aorta remains high. Shock, acidosis, suprarenal aortic injury, and a lack of retroperitoneal tamponade all independently contribute to mortality and should raise the suspicion for a potentially lethal aortic injury in a severely injured patient. Rapid identification and resuscitation in the operating room may therefore be the only factors to improve current survival rates in such devastating injuries.