PICU Up!: Impact of a Quality Improvement Intervention to Promote Early Mobilization in Critically Ill Children.

OBJECTIVE: To determine the safety and feasibility of an early mobilization program in a PICU. DESIGN: Observational, pre-post design. SETTING: PICU in a tertiary academic hospital in the United States. PATIENTS: Critically ill pediatric patients admitted to the PICU. INTERVENTION: This quality improvement project involved a usual-care baseline phase, followed by a quality improvement phase that implemented a multicomponent, interdisciplinary, and tiered activity plan to promote early mobilization of critically ill children. MEASUREMENTS AND MAIN RESULTS: Data were collected and analyzed from July to August 2014 (preimplementation phase) and July to August 2015 (postimplementation). The study sample included 200 children 1 day through 17 years old who were admitted to the PICU and had a length of stay of at least 3 days. PICU Up! implementation led to an increase in occupational therapy consultations (44% vs 59%; p = 0.034) and physical therapy consultations (54% vs 66%; p = 0.08) by PICU day 3. The median number of mobilizations per patient by PICU day 3 increased from 3 to 6 (p < 0.001). More children engaged in mobilization activities after the PICU Up! intervention by PICU day 3, including active bed positioning (p < 0.001), and ambulation (p = 0.04). No adverse events occurred as a result of early mobilization activities. The most commonly reported barriers to early mobilization after PICU Up! implementation was availability of appropriate equipment. The program was positively received by PICU staff. CONCLUSIONS: Implementation of a structured and stratified early mobilization program in the PICU was feasible and resulted in no adverse events. PICU Up! increased physical therapy and occupational therapy involvement in the children's care and increased early mobilization activities, including ambulation. A bundled intervention to create a healing environment in the PICU with structured activity may have benefits for short- and long-term outcomes of critically ill children.

Feeding methods for infants with single ventricle physiology are associated with length of stay during stage 2 surgery hospitalization.

BACKGROUND: Tube feedings are often needed to achieve the growth and nutrition goals associated with decreased morbidity and mortality in patients with single ventricle anatomy. Variability in feeding method through the interstage period has been previously described, however, comparable information following stage 2 palliation is lacking. OBJECTIVES: To identify types of feeding methods following stage 2 palliation and their influence on length of stay. DESIGN: Secondary analysis of the National Pediatric Cardiology Quality Improvement Collaborative registry was performed on 932 patients. Demographic data, medical characteristics, postoperative complications, type of feeding method, and length of stay for stage 2 palliation were analyzed. RESULTS: Type of feeding method remained relatively unchanged during hospitalization for stage 2 palliation. Gastrostomy tube fed only patients were the oldest at time of surgery (182.7 ± 57.7 days, P < .001) and had the lowest weight-for-age z scores at admission (-1.6 ± 1.4, P < .001). Oral + gastrostomy tube groups had the longest median bypass times (172.5 minutes, P = .001) and longest length of stay (median 12 days, P < .001). Multivariable modeling revealed that feeding by tube only (P < .001), oral + tube feeding (P ≤ .001), reintubation (P < .001), and prolonged intubation (P < .001) were associated with increased length of stay. Neither age (P = .156) nor weight-for-age z score at admission (P = .066) was predictive of length of stay. CONCLUSIONS: Feeding methods established at admission for stage 2 palliation are not likely to change by discharge. Length of stay is more likely to be impacted by tube feeding and intubation history than age or weight-for-age z score at admission. Better understanding for selection of feeding methods and their impact on patient outcomes is needed to develop evidence-based guidelines to decrease variability in clinical practice patterns and provide appropriate counseling to caregivers.

Financial and Health Impacts of Multidisciplinary Aerodigestive Care.

OBJECTIVES: (1) Analyze upstream and downstream activity before and after enrollment with the Multidisciplinary Pediatric Aerodigestive Care Team (MPACT). (2) Identify potential demand for MPACT services with ICD-9 data. STUDY DESIGN: Retrospective review of financial claims data. SETTING: Tertiary care children's center. SUBJECTS: Pediatric patients (0-18 years old) enrolled with MPACT (pediatric otolaryngology, gastroenterology, pulmonary, speech-language pathology). METHODS: Case mix data from fiscal years (FYs) 2010-2013 were analyzed for primary, secondary, and tertiary ICD-9 codes in 4 aerodigestive diagnostic categories (ADCs): dysphagia, chronic cough, gastroesophageal disease, and chronic pulmonary disease/asthma. Inclusion criteria included patients <18 years old, seen by MPACT, with FY2010-FY2013 case mix data and ≥2 ADCs. Unique outpatient and inpatient encounters and associated charges were evaluated to determine upstream and downstream activity trends. RESULTS: Of the 126 patients meeting inclusion criteria, 55 (44%) had ≥3 ADCs, and 11 (9%) had 4. These 126 patients received outpatient care during 3068 unique encounters. Outpatient total charges were $282,102 before and $744,542 after MPACT intervention. Eighty-six (68%) patients received inpatient care during 423 unique encounters. Inpatient charges were $4,257,137 before and $2,872,849 after MPACT enrollment. Overall, a net reduction of $921,848 in total charges, $7316 per MPACT patient, was noted. FY2010-FY2014 data identified an additional 1728 pediatric patients with ≥2 ADCs not enrolled in MPACT. CONCLUSION: A cohort of children with aerodigestive disease experienced a shift from inpatient to outpatient care with an overall 20% reduction in patient charges when the years before and after MPACT enrollment were compared. Available ICD-9 data suggest potential demand for MPACT services.

Interdisciplinary pediatric aerodigestive care and reduction in health care costs and burden.

IMPORTANCE: Children with complex respiratory and gastrointestinal disorders frequently require care from multiple pediatric subspecialists. Interdisciplinary pediatric aerodigestive clinic centers have been established at several pediatric tertiary care centers in the United States. Their effectiveness is unknown. OBJECTIVE: To determine whether an interdisciplinary approach to pediatric aerodigestive disorders reduces health care costs and burden. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review for the first 125 unique pediatric patients (median age, 1.51 years) seen at the Pediatric Aerodigestive Center (PAC) for aerodigestive disorders between June 2010 and August 2013 for a total of 163 outpatient clinical encounters. The PAC is an academic pediatric tertiary care center where specialists in gastroenterology, otolaryngology, pulmonology, and speech-language pathology provide interdisciplinary evaluation during a single clinic encounter and combined operative management when indicated. INTERVENTIONS: Interdisciplinary evaluation and treatment of pediatric aerodigestive disorders. MAIN OUTCOMES AND MEASURES: Number of operative procedures and estimated hospital charges related to combining clinic encounters and operative procedures. RESULTS: During the initial visit, each of the 125 patients received a mean (SD) of 2.9 (0.8) of a potential 4 services. Estimating per-encounter visit costs for gas, parking, and facility fees, we found that the average cost savings per family per PAC visit was $182. Evaluation under anesthesia was recommended for 85 patients (68%), resulting in 267 operative procedures performed by participating services during 158 encounters with general anesthesia. Thus, 109 episodes of anesthesia were avoided (41% reduction), reducing the risks of anesthesia and related care costs ($1985 per avoided episode). CONCLUSIONS AND RELEVANCE: Coordination of interdisciplinary care in the PAC resulted in a reduction of hospital charges realized through reduction in clinic- and anesthesia-related visits. Reductions in episodes of anesthesia may also reduce neurocognitive risks associated with multiple anesthetic exposures. Other nontangible benefits associated with the coordination of care, such as caregiver satisfaction, warrant further study.

Gastrointestinal complications after stage I Norwood versus hybrid procedures.

BACKGROUND: Patients undergoing palliation for hypoplastic left heart syndrome are at risk for gastrointestinal complications including necrotizing enterocolitis, gastroesophageal reflux, and intolerance to oral feeding. Few data exist comparing these outcomes between patients undergoing the Norwood and hybrid procedures. METHODS: Forty-three patients with hypoplastic left heart syndrome or variants underwent 50 Norwood (n = 34) or hybrid (n = 16) procedures (2004 to 2011). Routine preoperative assessments included flexible fiberoptic laryngoscopy and oral feeding evaluations. Examinations were repeated postoperatively with modified barium swallows. A retrospective review was conducted to examine the incidence, causes, and consequences of gastrointestinal complications. RESULTS: In 18 of 50 cases (38%), patients were tolerating full oral feeding at discharge; abnormal preoperative feeding evaluation predicted the inability to feed orally (p < 0.002, positive predictive value 100%). Hybrid and Norwood patients had a similar incidence of vocal fold palsy (20.0% versus 34.5%, p = 0.3), and inability to feed orally at discharge (67.5% versus 56.3%, p = not significant). Both groups had a high incidence. Postoperative abnormalities were common, namely, abnormal oral feeding evaluations (70.7%) or modified barium swallows (81.8%). Predictors of abnormal postoperative examinations included noncardiac congenital anomalies (p = 0.08), preoperative mechanical ventilation (p = 0.01), and younger age (p = 0.01). Grade IIA/IIB necrotizing enterocolitis was more common among patients having hybrid procedures (26.7%, versus 2.9%, p = 0.01). CONCLUSIONS: Gastrointestinal complications are common after initial palliation of patients with hypoplastic left heart syndrome. Preoperative and perioperative factors play a significant role. Despite a more "limited" intervention, patients undergoing hybrid procedures remain at high risk for feeding issues, commonly leading to a prolonged hospital course. Close attention and proactive management are essential to optimize the nutritional status in these patients.

Structure and stereochemistry of new cytotoxic clerodane diterpenoids from the bark of Casearia lucida from the Madagascar rainforest.

Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the bark of Casearia lucida resulted in the isolation of 11 new clerodane diterpenes, namely, casearlucins A-K (1-11), and three known clerodane diterpenoids, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (12), rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-methoxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (13), and rel-(2S,5R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (14). The structures of compounds 1-11 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. All compounds exhibited cytotoxicity activity against the A2780 ovarian cancer cell line, but none of the six compounds selected for testing in multiple cell lines showed significant selectivity.

Synthesis and biological evaluation of C-3'NH/C-10 and C-2/C-10 modified paclitaxel analogues.

Concurrent modifications on the C-3'NH/C-10, and C-2/C-10 positions on paclitaxel were carried out as a way of investigating possible synergistic effects. The biological activities of these analogues were evaluated in both a microtubule assembly assay and human ovarian cancer (A2780) and prostate cancer (PC3) cytotoxicity assay. In some cases the doubly modified analogues were more active than would have been predicted based on the activity of the singly modified analogues, indicating probable synergistic effects.

Isolation and absolute configuration of ent-Halimane diterpenoids from Hymenaea courbaril from the Suriname rain forest.

Bioactivity-directed fractionation of a methanol extract of Hymenaea courbaril afforded the three new diterpenoids (13R)-13-hydroxy-1(10),14-ent-halimadien-18-oic acid (1), (2S,13R)-2,13-dihydroxy-1(10),14-ent-halimadien-18-oic acid (2), and (13R)-2-oxo-13-hydroxy-1(10),14-ent-halimadien-18-oic acid (3). The configurations of these compounds were determined from X-ray crystallography of 1, circular dichroism of 2 and 3, and spectral studies of prepared derivatives. Compound 1 exhibited weak cytotoxicity toward the 1138 mutant yeast strain and the A2780 human ovarian cancer cell line.

A new triterpene saponin from Pittosporum viridiflorum from the Madagascar rainforest.

A novel triterpenoid saponin, pittoviridoside (1), which possesses an unusual 2,3,4-trisubstituted glycosidic linkage, has been isolated from Pittosporum viridiflorum using the engineered yeast strains 1138, 1140, 1353, and Sc-7 for bioactivity-guided fractionation. The structure of this compound was determined to be 3-O-[beta-D-glucopyranosyl(1-->2)]-[alpha-D-arabinopyranosyl(1-->3)],[alpha-l-arabinofuranosyl(1-->4)-beta-D-glucuronopyranosyl-21-angeloyl-22-senecioylolean-12-en-3beta,15alpha,16alpha,21beta,22alpha,28-hexol by spectral, chemical, and GC analyses. This compound showed weak cytotoxicity against the A2780 human ovarian cancer cell line.

A novel cytotoxic guttiferone analogue from Garcinia macrophylla from the Suriname rainforest.

Bioassay-guided fractionation of the EtOAc extract of the twigs of Garcinia macrophylla from Suriname produced the known benzophenone, guttiferone A (1), and a new guttiferone analogue, guttiferone G (2). Friedelin was also isolated. The structures of compounds 1 and 2 were elucidated using 1D and 2D NMR spectroscopy. Compounds 1 and 2 were weakly cytotoxic in the A2780 human ovarian cell line, with IC (50) values of 6.8 and 8.0 microg/mL, respectively.

Bioactive saponins from Acacia tenuifolia from the suriname rainforest.

Bioassay-guided fractionation of the MeOH extract of Acacia tenuifolia using the engineered yeast strains 1138, 1140, 1353, and Sc7 as the bioassay tool resulted in the isolation of the three new saponins 3, 5, and 6 and the three known saponins 1, 2, and 4. The structures of the new compounds were established on the basis of HRMS, 1D and 2D NMR spectral data on the intact saponins, and GC-MS analyses of the sugars. Compounds 1,2 and 5,6 showed cytotoxicity against mammalian cell lines.