Association of Enrollment in an Aerodigestive Clinic With Reduced Hospital Stay for Children With Special Health Care Needs.

Importance: Children with special health care needs (CSHCN) have disproportionate health care utilization. Previous studies have demonstrated that a primary medical home improves health care outcomes for this population. Objective: To elucidate if enrollment in a multidisciplinary aerodigestive clinic improves outcomes and reduces health care costs by decreasing admissions and inpatient days. Design, Setting, and Participants: A retrospective medical record review of 113 patients with aerodigestive disorders enrolled in a pediatric multidisciplinary clinic from June 2009 to December 2013 was performed. Of the 113 particpants, 58 (51.3%) were male, 59 (52.2%) had a tracheostomy, and 90 (80.5%) had a gastrostomy tube during their enrollment period. Patient ages at enrollment ranged from 0 to 20 years, with 59 (52.2%) ranging from 0 to 5 years, 23 (20.4%) ranging from 6 to 10 years, 18 (15.9%) ranging from 11 to 15 years, and 13 (11.5%) being 16 years or older. Admissions data before and after enrollment in a pediatric multidisciplinary clinic were examined. Main Outcomes and Measures: The main outcomes studied were changes in admissions and inpatient days before and after enrollment. Financial data were also examined to determine the reduction in technical direct cost. Results: The admissions data for 113 children were analyzed. No significant difference in number of admissions per year was seen with enrollment with a median difference of -0.30 admissions per year (range, -10.6 to 6.7 admissions per year; 95% CI, -3.5 to 2.9). However, there was a significant decrease seen in inpatient days per year following enrollment, with a median decrease of 4.1 inpatient days per year (range, -80 to 283.3 inpatient days per year; 95% CI, 0.33 to 91.0). When examining aerodigestive admissions alone, the median number of aerodigestive hospital days avoided per patient was 0.57 days per month, or 6.8 days per year, representing a 70% reduction in technical direct cost. Conclusions and Relevance: These findings indicate that for children with special health care needs, enrollment in a multidisciplinary aerodigestive clinic may improve health care outcomes by decreasing technical direct cost by 70% and significantly decreasing patient hospital days by an estimated 1 week per year. Furthermore, coordinated aerodigestive care in a medical home setting may lower health care expenditures from a systems-based perspective.

Approach to treating cystic fibrosis pulmonary exacerbations varies widely across US CF care centers.

There is no standard definition of a CF pulmonary exacerbation universally accepted by clinicians. We aimed to investigate the variability of clinical practice among US CF clinicians in the diagnosis and treatment of exacerbations. Using clinical vignettes, we examined if variation in the identification and treatment of CF exacerbations is common, if practice patterns differ between CF care centers and what clinical factors determine treatment. Twenty-eight clinical cases were developed by varying five clinical factors. Participants were given four options for treatment of the patient described in each vignette. Cases were sent via email to a convenience sample of 112 CF clinicians from 13 US CF centers, with 109 clinicians participating (97.3%). 2,792 of the 3,052 cases received a response (91.5%). ANOVA demonstrated variation in rater scores was explained by case scenario and by care center (P < 0.0001). Examining the frequency of each treatment strategy demonstrated no absolute treatment consensus for any given scenario and variability within and between care centers. Direct logistic regression revealed that systemic symptoms (OR = 5.95), decreased O(2) saturation (OR = 4.99) and decreased FEV(1) (OR = 3.78) had a greater effects on the decision to treat a case with IV antibiotics than increased cough/sputum (OR = 2.19) and crackles present on physical examination (OR = 2.10). Similar findings were demonstrated with a cluster analysis. There was surprising variation in the identification and treatment of pulmonary exacerbations by CF clinicians. Variation was present between CF Centers, within each CF center and at the individual clinician level. This study provides additional evidence for the need of a standard definition for a CF pulmonary exacerbation.

Improving care at cystic fibrosis centers through quality improvement.

Quality improvement (QI) using a clinical microsystems approach provides cystic fibrosis (CF) centers the opportunity to make a significant positive impact on the health of their patients. The availability of center-specific outcomes data and the support of the Cystic Fibrosis Foundation are important advantages for these quality improvement efforts. This article illustrates how the clinical microsystems methodology can improve care delivery and outcomes by describing the gradual application of quality improvement principles over the past 5 years by the CF team at the Lewis Walker Cystic Fibrosis Center at Akron Children's Hospital in Akron, Ohio. Using the example of a project to improve the pulmonary function of the pediatric patients at our center as a framework, we describe the QI process from the initial team-building phase, through the assessment of care processes, standardization of care, and developing a culture of continuous improvement. We outline how enthusiastic commitment from physician leadership, clinical managers and central administration, the availability of coaches, and an appreciation of the importance of measurement, patient involvement, communication, and standardization are critical components for successful process improvement.

Statin-mediated correction of STAT1 signaling and inducible nitric oxide synthase expression in cystic fibrosis epithelial cells.

The expression of the inducible form of nitric oxide synthase (NOS2) is reduced in cystic fibrosis (CF) epithelium despite the presence of aggressive inflammation. A potential mechanism for reduced NOS2 expression in CF is diminished signal transducer and activator of transcription-1 (STAT1) activity, possibly due to an increase in expression of protein inhibitor of activated STAT1 (PIAS1). Previous evidence also suggests that NOS2 expression can be negatively regulated by increased activation of the GTPase RhoA, leading to the hypothesis that CF-related increases in PIAS1 expression and altered STAT1 signaling may be mediated by Rho GTPase function. Consistent with this hypothesis, data demonstrate increased expression of RhoA in two models of CF epithelium with a proportional increase in the active GTP-bound RhoA. Mouse embryonic fibroblasts null for p190B Rho GTPase-activating protein exhibit increased RhoA protein content and activation, similar to what is observed in CF models, and also exhibit CF-like alterations in STAT1 regulation, including decreased STAT1 activation, increased PIAS1 protein expression, and reduced NOS2 induction, implicating RhoA-mediated signaling in CF-related STAT1 alterations. Inhibition of the Rho GTPase pathway at the level of isoprenoid/cholesterol synthesis with mevastatin reduces PIAS1 expression, increases STAT1 activation, and restores NOS2 expression in models of CF epithelium, suggesting that pharmacological inhibition of the isoprenoid synthesis/Rho GTPase pathway may represent a potential avenue for therapeutic intervention for CF.

Mechanisms of NOS2 regulation by Rho GTPase signaling in airway epithelial cells.

The aberrant dysregulation of the inducible form of nitric oxide synthase (NOS2) is thought to play a role in many inflammatory disorders including cystic fibrosis (CF). The complex regulation of NOS2 expression is the subject of intense investigation, and one intriguing regulatory pathway known to influence NOS2 expression is the Rho GTPase cascade. We examined NOS2 regulation in response to inflammatory cytokines in a human alveolar epithelial cell line treated with inhibitors of different upstream and downstream components of the Rho GTPase pathway to better define potential signaling mechanisms. Statin-mediated 3-hydroxy-3-methylglutaryl-CoA reductase inhibition increased cytokine-dependent activation of the NOS2 promoter, reversible by the addition of geranylgeranyl pyrphosphate. However, inhibition of Rho-associated kinase (ROCK) with Y-27632 resulted in a decrease in NOS2 promoter activity, yet an increase in NOS2 mRNA and protein levels. Our results suggest that prenylation events influence NOS2 promoter activity independently of the Rho GTPase pathway and that Rho GTPase signaling mediated through ROCK suppresses NOS2 production downstream of promoter function at the message and protein level.