Age, Sex, Health Insurance, and Race Associated With Increased Rate of Emergent Pediatric Gastrointestinal Procedures.

OBJECTIVES: Few studies have examined the role health disparities play in pediatric gastrointestinal (GI) procedures. We hypothesized that health disparity factors affect whether patients undergo an emergent versus nonemergent GI procedure. The aims were to characterize the existing pediatric population undergoing GI procedures at our institution and assess specific risk factors associated with emergent versus nonemergent care. METHODS: We retrospectively reviewed the medical records of 2110 patients undergoing GI procedures from January 2012 to December 2014. Emergent procedures were performed on an urgent inpatient basis. All other procedures were considered nonemergent. Health disparity factors analyzed included age, sex, insurance type, race, and language. Logistic regression analysis identified the odds of undergoing emergent procedures for each factor. RESULTS: Most study patients were boys (58.2%), primarily insured by Medicaid (63.8%), white (44.0%), and spoke English (91.7%). Ten percent of all patients had an emergent procedure. Logistic regression analysis showed significant odds ratios (P value) for ages 18 years older (2.16, 0.003), females (0.62, 0.001), commercial insurance users (0.49, <0.0001), African Americans (1.94, <0.0001), and other race (1.72, 0.039). CONCLUSIONS: Health disparities in age, sex, insurance, and race appear to exist in this pediatric population undergoing GI procedures. Patients older than 18 years, African Americans, and other races were significantly more likely to have an emergent procedure. Girls and commercial insurance users were significantly less likely to have an emergent procedure. More research is necessary to understand why these relations exist and how to establish appropriate interventions.

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose. METHODS: We explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung. RESULTS: We provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF. CONCLUSIONS: Our data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-of-mechanism trial of this agent is currently underway. TRIAL REGISTRATION NUMBER: NCT01725139, pre-clinical.

Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential ligand-binding properties and mediates biofilm formation.

The streptococcal antigen I/II (AgI/II)-family polypeptides are cell wall-anchored adhesins expressed by most indigenous oral streptococci. Proteins sharing 30-40% overall amino acid sequence similarities with AgI/II-family proteins are also expressed by Streptococcus pyogenes. The S. pyogenes M28_Spy1325 polypeptide (designated AspA) displays an AgI/II primary structure, with alanine-rich (A) and proline-rich (P) repeats flanking a V region that is projected distal from the cell. In this study it is shown that AspA from serotype M28 S. pyogenes, when expressed on surrogate host Lactococcus lactis, confers binding to immobilized salivary agglutinin gp-340. This binding was blocked by antibodies to the AspA-VP region. In contrast, the N-terminal region of AspA was deficient in binding fluid-phase gp-340, and L. lactis cells expressing AspA were not agglutinated by gp-340. Deletion of the aspA gene from two different M28 strains of S. pyogenes abrogated their abilities to form biofilms on saliva-coated surfaces. In each mutant strain, biofilm formation was restored by trans complementation of the aspA deletion. In addition, expression of AspA protein on the surface of L. lactis conferred biofilm-forming ability. Taken collectively, the results provide evidence that AspA is a biofilm-associated adhesin that may function in host colonization by S. pyogenes.

The Role of Health Disparities and Socioeconomic Status in Emergent Gastrointestinal Procedures.

Objectives: There is limited data describing the role of health disparity factors and socioeconomic status (SES) on emergent versus nonemergent gastrointestinal (GI) procedures within pediatrics. We aimed to characterize risk factors and determine the role of SES on emergent versus nonemergent GI care. We hypothesized that patients with lower SES incur higher risk of having emergent procedures performed. Methods: Retrospective chart review was performed between 2012 and 2016, with 2556 patient records reviewed. Demographic data and SES categories were determined. The majority of emergent procedures were performed on an inpatient basis. Health disparity factors analyzed included age, gender, insurance type, race, language, and SES using census tracts. Logistic regression analyses and paired t-tests were utilized. Results: Two hundred eighty-six (11.2%) patients had emergent GI procedures performed. Logistic regression (odds ratio [OR], confidence interval (95% CI)] showed patients from 6-11 to 12-17 years of age were less likely to seek emergent care than the youngest group [0.47, 0.33-0.66 and 0.61, 0.45-0.84]. Patients with Medicaid insurance [1.68, 1.27-2.26], African American or "other" race [2.07, 1.48-2.90 and 2.43, 1.77-3.36, respectively], as well as "other" language [2.1, 1.14-3.99] more often sought emergent care. Using geocoded data, we found that as SES increases by 1, emergent risk for procedures decreased by 2.9% (OR 0.97, p=0.045). Conclusions: Children with lower SES, at extremes of age (<5, >18 years), non-English or Spanish speaking and with Medicaid insurance are at higher risk of undergoing emergent GI procedures. This study gives us an opportunity to plan targeted interventions to improve access and quality of care.

Impact of Pre-Procedure Interventions on No-Show Rate in Pediatric Endoscopy.

Pediatric endoscopy has evolved into an indispensable tool in the diagnosis and management of gastrointestinal diseases in children. However, there is limited literature focusing on quality improvement initiatives in pediatric endoscopy. The primary goal of this project was to reduce the no-show rate in the pediatric endoscopy unit. Also, we aimed to improve patient and family satisfaction with the procedure by identifying opportunities for improvement. A checklist was designed based on the potential causes of no-show. The endoscopy nurse coordinator reviewed the checklist when scheduling the procedure to identify patients at high risk for non-compliance. Once a risk factor was identified, appropriate actions were taken. She also made a pre-procedure phone call as a reminder and to address any of these risks for non-compliance if present. A patient satisfaction survey was used to identify potential areas for improvement. The no-show rate decreased from an average of 7% in the pre-intervention phase to 2% in the post-intervention phase (p = 0.009). 91% of the patients/family recorded an overall satisfaction of 4 or 5 on a scale of 1-5 5 being best). Quality improvement strategies decreased the no-show rate in the pediatric endoscopy unit. A patient satisfaction survey helped in identifying areas for improvement.

Results From a Patient Experience Study in Pediatric Gastrointestinal Endoscopy.

OBJECTIVE: Gastrointestinal endoscopy in children has become a standard diagnostic and therapeutic modality. The aim of our study was to characterize the most memorable elements of the patient experience from the parent's and patient's perspective and determine ways to improve the overall quality of their experience. METHODS: Using a structured questionnaire, we conducted 47 phone interviews with families who had recently undergone gastrointestinal endoscopic procedures. RESULTS: Our study showed clear communication and mutual agreement on care decisions contributed to positive experiences. Inadequate communication of information regarding alternatives to the procedure and risk of complications during the informed consent discussion contributed to negative patient experiences. Standardization of postprocedure follow-up and timely communication of pathology findings also had potential for improvement. CONCLUSION: Our study revealed 2 areas for quality improvement interventions: The need to ensure that alternatives and complications are thoroughly discussed and the need for standardization of postprocedure follow-up.

The anti-fibrotic effect of inhibition of TGFß-ALK5 signalling in experimental pulmonary fibrosis in mice is attenuated in the presence of concurrent γ-herpesvirus infection.

TGFß-ALK5 pro-fibrotic signalling and herpesvirus infections have been implicated in the pathogenesis and exacerbation of pulmonary fibrosis. In this study we addressed the role of TGFß-ALK5 signalling during the progression of fibrosis in a two-hit mouse model of murine γ-herpesvirus 68 (MHV-68) infection on the background of pre-existing bleomycin-induced pulmonary fibrosis. Assessment of total lung collagen levels in combination with ex vivo micro-computed tomography (µCT) analysis of whole lungs demonstrated that MHV-68 infection did not enhance lung collagen deposition in this two-hit model but led to a persistent and exacerbated inflammatory response. Moreover, µCT reconstruction and analysis of the two-hit model revealed distinguishing features of diffuse ground-glass opacities and consolidation superimposed on pre-existing fibrosis that were reminiscent of those observed in acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). Virally-infected murine fibrotic lungs further displayed evidence of extensive inflammatory cell infiltration and increased levels of CCL2, TNFα, IL-1ß and IL-10. Blockade of TGFß-ALK5 signalling attenuated lung collagen accumulation in bleomycin-alone injured mice, but this anti-fibrotic effect was reduced in the presence of concomitant viral infection. In contrast, inhibition of TGFß-ALK5 signalling in virally-infected fibrotic lungs was associated with reduced inflammatory cell aggregates and increased levels of the antiviral cytokine IFNγ. These data reveal newly identified intricacies for the TGFß-ALK5 signalling axis in experimental lung fibrosis, with different outcomes in response to ALK5 inhibition depending on the presence of viral infection. These findings raise important considerations for the targeting of TGFß signalling responses in the context of pulmonary fibrosis.

Impact of Educational Cartoon on Pediatric Bowel Preparation Quality at Time of Colonoscopy.

OBJECTIVE: To evaluate if addition of educational cartoon to pediatric bowel preparation instructions improves the quality of bowel preparation and patient experience. METHODS: Patients were randomized to control group receiving standard bowel preparation instructions or intervention group receiving additional educational cartoon. To objectively rate bowel preparation, a blinded endoscopist completed numeric Ottawa score (0-14, with 0 being best). The family also completed a questionnaire rating the bowel preparation process. RESULTS: Data from 23 patients were analyzed. Mean Ottawa score in the intervention group compared with controls was not significantly different (mean scores 3.73 and 3.33, respectively; P = .384). Level of education was significantly correlated with better Ottawa score in the overall population (ρ = -.462, P = .026) and within the control group (ρ = -.658, P = .02). Both groups of patients reported positive experience with bowel preparation. CONCLUSION: There may be benefit to further investigation of this educational cartoon in parents with less than college level education or non-English-speaking families in larger population of patients.

The AgI/II family adhesin AspA is required for respiratory infection by Streptococcus pyogenes.

Streptococcus pyogenes (GAS) is a human pathogen that causes pharyngitis and invasive diseases such as toxic shock syndrome and sepsis. The upper respiratory tract is the primary reservoir from which GAS can infect new hosts and cause disease. The factors involved in colonisation are incompletely known however. Previous evidence in oral streptococci has shown that the AgI/II family proteins are involved. We hypothesized that the AspA member of this family might be involved in GAS colonization. We describe a novel mouse model of GAS colonization of the nasopharynx and lower respiratory tract to elucidate these interactions. We used two clinical M serotypes expressing AspA, and their aspA gene deletant isogenic mutants in experiments using adherence assays to respiratory epithelium, macrophage phagocytosis and neutrophil killing assays and in vivo models of respiratory tract colonisation and infection. We demonstrated the requirement for AspA in colonization of the respiratory tract. AspA mutants were cleared from the respiratory tract and were deficient in adherence to epithelial cells, and susceptible to phagocytosis. Expression of AspA in the surrogate host Lactococcus lactis protected bacteria from phagocytosis. Our results suggest that AspA has an essential role in respiratory infection, and may function as a novel anti-phagocytic factor.

The Chlamydomonas reinhardtii cia3 mutant lacking a thylakoid lumen-localized carbonic anhydrase is limited by CO2 supply to rubisco and not photosystem II function in vivo.

The Chlamydomonas reinhardtii cia3 mutant has a phenotype indicating that it requires high-CO(2) levels for effective photosynthesis and growth. It was initially proposed that this mutant was defective in a carbonic anhydrase (CA) that was a key component of the photosynthetic CO(2)-concentrating mechanism (CCM). However, more recent identification of the genetic lesion as a defect in a lumenal CA associated with photosystem II (PSII) has raised questions about the role of this CA in either the CCM or PSII function. To resolve the role of this lumenal CA, we re-examined the physiology of the cia3 mutant. We confirmed and extended previous gas exchange analyses by using membrane-inlet mass spectrometry to monitor(16)O(2),(18)O(2), and CO(2) fluxes in vivo. The results demonstrate that PSII electron transport is not limited in the cia3 mutant at low inorganic carbon (Ci). We also measured metabolite pools sizes and showed that the RuBP pool does not fall to abnormally low levels at low Ci as might be expected by a photosynthetic electron transport or ATP generation limitation. Overall, the results demonstrate that under low Ci conditions, the mutant lacks the ability to supply Rubisco with adequate CO(2) for effective CO(2) fixation and is not limited directly by any aspect of PSII function. We conclude that the thylakoid CA is primarily required for the proper functioning of the CCM at low Ci by providing an ample supply of CO(2) for Rubisco.