Identification of molecular signatures of cystic fibrosis disease status with plasma-based functional genomics.

Although cystic fibrosis (CF) is attributed to dysfunction of a single gene, the relationships between the abnormal gene product and the development of inflammation and progression of lung disease are not fully understood, which limits our ability to predict an individual patient's clinical course and treatment response. To better understand CF progression, we characterized the molecular signatures of CF disease status with plasma-based functional genomics. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with plasma samples from CF patients ( n = 103) and unrelated, healthy controls ( n = 31). Gene expression levels were measured with an Affymetrix microarray (GeneChip Human Genome U133 Plus 2.0). Peripheral blood samples from a subset of the CF patients ( n = 40) were immunophenotyped by flow cytometry, and the data were compared with historical data for age-matched healthy controls ( n = 351). Plasma samples from another subset of CF patients ( n = 56) and healthy controls ( n = 16) were analyzed by multiplex enzyme-linked immunosorbent assay (ELISA) for numerous cytokines and chemokines. Principal component analysis and hierarchical clustering of induced transcriptional data revealed disease-specific plasma-induced PBMC profiles. Among 1,094 differentially expressed probe sets, 51 genes were associated with pancreatic sufficient status, and 224 genes were associated with infection with Pseudomonas aeruginosa. The flow cytometry and ELISA data confirmed that various immune modulators are relevant contributors to the CF molecular signature. This study provides strong evidence for distinct molecular signatures among CF patients. An understanding of these molecular signatures may lead to unique molecular markers that will enable more personalized prognoses, individualized treatment plans, and rapid monitoring of treatment response.

Development of a Standardized Clinical Assessment and Management Plan for Pediatric Acute Respiratory Distress Syndrome.

Pediatric acute respiratory distress syndrome (PARDS) is one of the most challenging patient populations for a clinician to manage with mortality between 8 and 31%. The project was designed to identify patients with PARDS, implement management guidelines with the goal of standardizing practice. Our objectives were to describe the development and implementation of a protocolized approach to identify patients with PARDS and institute ventilator management guidelines. Patients who met criteria for moderate or severe PARDS as per the Pediatric Acute Lung Injury Consensus Conference (PALICC) definitions were identified using the best practice alert (BPA) in the electronic health record (EHR). Patients who did not meet exclusion criteria qualified for management using the Standardized Clinical Assessment and Management Plan (SCAMP), a quality improvement (QI) methodology with iterative cycles. The creation of a BPA enabled identification of patients with PARDS. With our second cycle, the number of false BPA alerts due to incorrect data decreased from 66.7 (68/102) to 29.2% (19/65; p < 0.001) and enrollment increased from 48.3 (14/29) to 73.2% (30/41; p = 0.03). Evaluation of our statistical process control chart (SPC) demonstrated a shift in the adherence with the tidal volume guideline. Overall, we found that SCAMP methodology, when used in the development of institutional PARDS management guidelines, allows for development of a process to aid identification of patients and monitor adherence to management guidelines. This should eventually allow assessment of impact of deviations from clinical practice guidelines.

Providers' assessment of a novel interactive health information technology in a pediatric intensive care unit.

OBJECTIVE: To explore perceptions of critical care providers about a novel collaborative inpatient health information technology (HIT) in a pediatric intensive care unit (PICU) setting. METHODS: This cross-sectional, concurrent mixed methods study was conducted in the PICU of a large midwestern children's hospital. The technology, the Large Customizable Interactive Monitor (LCIM), is a flat panel touch screen monitor that displays validated patient information from the electronic health record. It does not require a password to login and is available in each patient's room for viewing and interactive use by physicians, nurses, and families. Quantitative data were collected via self-administered, standardized surveys, and qualitative data via in-person, semistructured interviews between January and April 2015. Data were analyzed using descriptive statistics and inductive thematic analysis. RESULTS: The qualitative analysis showed positive impacts of the LCIM on providers' workflow, team interactions, and interactions with families. Providers reported concerns regarding perceived patient information overload and associated anxiety and burden for families. Sixty percent of providers thought that LCIM was useful for their jobs at different levels, and almost 70% of providers reported that LCIM improved information sharing and communication with families. The average overall satisfaction score was 3.4 on a 0 to 6 scale, between "a moderate amount" and "pretty much." DISCUSSION AND CONCLUSION: This study provides new insight into collaborative HIT in the inpatient pediatric setting and demonstrates that using such technology has the potential to improve providers' experiences with families and just-in-time access to EHR information in a format more easily shared with families.

Impact of Computerized Order Entry to Pharmacy Interface on Order-Infusion Pump Discrepancies.

Background. The ability of safety technologies to decrease errors, harm, and risk to patients has yet to be demonstrated consistently. Objective. To compare discrepancies between medication and intravenous fluid (IVF) orders and bedside infusion pump settings within a pediatric intensive care unit (PICU) before and after implementation of an interface between computerized physician order entry (CPOE) and pharmacy systems. Methods. Within a 72-bed PICU, medication and IVF orders in the CPOE system and bedside infusion pump settings were collected. Rates of discrepancy were calculated and categorized by type. Results were compared to a study conducted prior to interface implementation. Expansion of PICU also occurred between study periods. Results. Of 455 observations, discrepancy rate decreased for IVF (p = 0.01) compared to previous study. Overall discrepancy rate for medications was unchanged; however, medications infusing without an order decreased (p < 0.01), and orders without corresponding infusion increased (p < 0.05). Conclusions. Following implementation of an interface between CPOE and pharmacy systems, fewer discrepancies between IVF orders and infusion pump settings were observed. Discrepancies for medications did not change, and some types of discrepancies increased. In addition to interface implementation, changes in healthcare delivery and workflow related to ICU expansion contributed to observed changes.

Circadian rhythm of salivary cortisol in infants with congenital heart disease.

Children with congenital heart disease (CHD) have associated extracardiac co-morbidities at the time of surgery and during ongoing growth and development. Perioperative events include disrupted glucose homeostasis, capillary leak, and fluid retention. The hypothalamic-pituitary-adrenal (HPA) axis has an important role in homeostasis in that the secretion of cortisol contributes to the response to stress, glucose regulation, blood volume control, and immune regulation. We investigated the diurnal rhythm of the HPA axis in infants with CHD by measuring salivary cortisol in the morning (0600-0900 h-circadian peak) and evening (2100-2400 h-circadian nadir). Twenty-nine infants aged 12 weeks to 1 year were included: 16 with acyanotic disease (SpO2 ≥ 90 %) and 13 with cyanotic disease (SpO2 < 90 %). Morning salivary cortisol was similar between the two groups [acyanotic 7.0 nmol/L (1.8-23.1); cyanotic 9.7 nmol/L (0.9-15.6); p = 0.68]. Evening salivary cortisol was similar between the two groups [acyanotic 0.9 nmol/L (0.2-8.5); cyanotic 1.4 nmol/L (0.5-14.9); p = 0.32]. Both cyanotic and acyanotic groups demonstrated an intact diurnal rhythm. In conclusion, chronic hypoxia secondary to cyanotic CHD does not affect the circadian rhythm of the HPA axis. By 12 weeks of age, infants with hypoxia secondary to cyanotic CHD have a normal cortisol diurnal rhythm.

Discrepancies between medication orders and infusion pump programming in a paediatric intensive care unit.

BACKGROUND: Errors and the incorrect use of medications are significant sources of risk and harm to children in US hospitals. The risk associated with medication infusions has led to recommendations for the adoption of technologies including computer order physician entry (CPOE) and 'smart' infusion pumps despite a paucity of evidence demonstrating the ability of these technologies to reduce harm to paediatric inpatients. OBJECTIVE: To measure discrepancies between medication orders for infusions entered into a CPOE system and the medication being infused as measured by the programmed settings of the smart infusion pump within a paediatric intensive care unit. METHODS: This study used a prospective, observational design in a 30-bed paediatric intensive care unit. Data were simultaneously collected from the medication orders in the CPOE system and the bedside smart infusion pumps by trained observers. Analysis consisted of a line-by-line comparison of order observation data with the pump observation data. CONCLUSIONS: Of 296 observations of medication infusions and 231 observations of intravenous fluid infusions, the frequency of discrepancies between orders entered and pumps programming ranged from 24.3% for observed medications to 42.4% for observed fluids. Anti-infectives (100%), concentrated electrolytes (46.7%) and anticoagulants (46.2%) were associated with greatest discrepancy between orders and programmed doses.