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Featured researches published by Bernhard Fassl.


Pediatrics | 2012

The Joint Commission Children’s Asthma Care Quality Measures and Asthma Readmissions

Bernhard Fassl; Flory L. Nkoy; Bryan L. Stone; Rajendu Srivastava; Tamara D. Simon; Derek A. Uchida; Karmella Koopmeiners; Tom Greene; Lawrence J. Cook; Christopher G. Maloney

BACKGROUND AND OBJECTIVES: The Joint Commission introduced 3 Children’s Asthma Care (CAC 1–3) measures to improve the quality of pediatric inpatient asthma care. Validity of the commission’s measures has not yet been demonstrated. The objectives of this quality improvement study were to examine changes in provider compliance with CAC 1–3 and associated asthma hospitalization outcomes after full implementation of an asthma care process model (CPM). METHODS: The study included children aged 2 to 17 years who were admitted to a tertiary care children’s hospital for acute asthma between January 1, 2005, and December 31, 2010. The study was divided into 3 periods: preimplementation (January 1, 2005–December 31, 2007), implementation (January 1, 2008–March 31, 2009), and postimplementation (April 1, 2009–December 31, 2010) periods. Changes in provider compliance with CAC 1–3 and associated changes in hospitalization outcomes (length of stay, costs, PICU transfer, deaths, and asthma readmissions within 6 months) were measured. Logistic regression was used to control for age, gender, race, insurance type, and time. RESULTS: A total of 1865 children were included. Compliance with quality measures before and after the CPM implementation was as follows: 99% versus 100%, CAC-1; 100% versus 100%, CAC-2; and 0% versus 87%, CAC-3 (P < .01). Increased compliance with CAC-3 was associated with a sustained decrease in readmissions from an average of 17% to 12% (P = .01) postimplementation. No change in other outcomes was observed. CONCLUSIONS: Implementation of the asthma CPM was associated with improved compliance with CAC-3 and with a delayed, yet significant and sustained decrease in hospital asthma readmission rates, validating CAC-3 as a quality measure. Due to high baseline compliance, CAC-1 and CAC-2 are of questionable value as quality measures.


The Journal of Pediatrics | 2013

Fluticasone propionate pharmacogenetics: CYP3A4*22 polymorphism and pediatric asthma control

Chris Stockmann; Bernhard Fassl; Roger Gaedigk; Flory L. Nkoy; Derek A. Uchida; Steven Monson; Christopher A. Reilly; J. Steven Leeder; Garold S. Yost; Robert M. Ward

OBJECTIVE To determine the relationship between allelic variations in genes involved in fluticasone propionate (FP) metabolism and asthma control among children with asthma managed with inhaled FP. STUDY DESIGN The relationship between variability in asthma control scores and genetic variation in drug metabolism was assessed by genotyping 9 single nucleotide polymorphisms in the CYP3A4, CYP3A5, and CYP3A7 genes. Genotype information was compared with asthma control scores (0=well controlled to 15=poorly controlled), determined using a questionnaire modified from the National Heart Lung and Blood Institutes Expert Panel 3 guidelines. RESULTS Our study cohort comprised 734 children with asthma (mean age, 8.8±4.3 years) and was predominantly male (61%) and non-Hispanic white (53%). More than one-half of the children (56%; n=413) were receiving an inhaled glucocorticoid daily, with FP the most frequently prescribed agent (65%). Among the children receiving daily FP, single nucleotide polymorphisms in CYP3A5 and CYP3A7 were not associated with asthma control scores. In contrast, asthma control scores were significantly improved in the 20 children (7%) with the CYP3A4*22 allele (median, 3; range, 0-6) compared with the 201 children without the CYP3A4*22 allele (median, 4; range, 0-15; P=.02). The presence of CYP3A4*22 was associated with improved asthma control scores by 2.1 points (95% CI, 0.5-3.8). CONCLUSION The presence of CYP3A4*22, which is associated with decreased hepatic CYP3A4 expression and activity, was accompanied by improved asthma control in the FP-treated children. Decreased CYP3A4 activity may improve asthma control with inhaled FP.


Pediatrics | 2008

Quality of Care for Children Hospitalized With Asthma

Flory L. Nkoy; Bernhard Fassl; Tamara D. Simon; Bryan L. Stone; Rajendu Srivastava; Per H. Gesteland; Gena M. Fletcher; Christopher G. Maloney

OBJECTIVES. The goals were (1) to identify evidence-based clinical process measures that are appropriate, feasible, and reliable for assessing the quality of inpatient asthma care for children and (2) to evaluate provider compliance with these measures. METHODS. Key asthma quality measures were identified by using a modified Rand appropriateness method, combining a literature review of asthma care evidence with a consensus panel. The feasibility and reliability of obtaining these measures were determined through manual chart review. Provider compliance with these measures was evaluated through retrospective manual chart review of data for 252 children between 2 and 17 years of age who were admitted to a tertiary care childrens hospital in 2005 because of asthma exacerbations. RESULTS. Nine appropriate, feasible, reliable, clinical process measures of inpatient asthma care were identified. Provider compliance with these measures was as follows: acute asthma severity assessment at admission, 39%; use of systemic corticosteroid therapy, 98%; use of oral (not intravenous) systemic corticosteroid therapy, 87%; use of ipratropium bromide restricted to <24 hours after admission, 71%; use of albuterol delivered with a metered-dose inhaler (not nebulizer) for children >5 years of age, 20%; documented chronic asthma severity assessment, 22%; parental participation in an asthma education class, 33%; written asthma action plan, 5%; scheduled follow-up appointment with the primary care provider at discharge, 22%. CONCLUSIONS. Nine appropriate, feasible, reliable, clinical process measures of inpatient asthma care were identified. Provider compliance across these measures was highly variable but generally low. Our study highlights opportunities for improvement in the provision of asthma care for hospitalized children. Future studies are needed to confirm these findings in other inpatient settings.


Pediatrics | 2015

Improving Pediatric Asthma Care and Outcomes Across Multiple Hospitals

Flory L. Nkoy; Bernhard Fassl; Bryan L. Stone; Derek A. Uchida; Joseph M. Johnson; Carolyn Reynolds; Karen Valentine; Karmella Koopmeiners; Eun H. Kim; Lucy A. Savitz; Christopher G. Maloney

BACKGROUND AND OBJECTIVES: Gaps exist in inpatient asthma care. Our aims were to assess the impact of an evidence-based care process model (EB-CPM) 5 years after implementation at Primary Childrens Hospital (PCH), a tertiary care facility, and after its dissemination to 7 community hospitals. METHODS: Participants included asthmatics 2 to 17 years admitted at 8 hospitals between 2003 and 2013. The EB-CPM was implemented at PCH between January 2008 and March 2009, then disseminated to 7 community hospitals between January and June 2011. We measured compliance using a composite score (CS) for 8 quality measures. Outcomes were compared between preimplementation and postimplementation periods. Confounding was addressed through multivariable regression analyses. RESULTS: At PCH, the CS increased and remained at >90% for 5 years after implementation. We observed sustained reductions in asthma readmissions (P = .026) and length of stay (P < .001), a trend toward reduced costs (P = .094), and no change in hospital resource use, ICU transfers, or deaths. The CS also increased at the 7 community hospitals, reaching 80% to 90% and persisting >2 years after dissemination, with a slight but not significant readmission reduction (P = .119), a significant reduction in length of stay (P < .001) and cost (P = .053), a slight increase in hospital resource use (P = .032), and no change in ICU transfers or deaths. CONCLUSIONS: Our intervention resulted in sustained, long-term improvement in asthma care and outcomes at the tertiary care hospital and successful dissemination to community hospitals.


American Journal of Respiratory Cell and Molecular Biology | 2015

Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma

Cassandra E. Deering-Rice; Darien Shapiro; Erin G. Romero; Chris Stockmann; Tatjana Bevans; Quang M. Phan; Bryan L. Stone; Bernhard Fassl; Flory L. Nkoy; Derek A. Uchida; Robert M. Ward; John M. Veranth; Christopher A. Reilly

Inhaled irritants activate transient receptor potential ankyrin-1 (TRPA1), resulting in cough, bronchoconstriction, and inflammation/edema. TRPA1 is also implicated in the pathogenesis of asthma. Our hypothesis was that particulate materials activate TRPA1 via a mechanism distinct from chemical agonists and that, in a cohort of children with asthma living in a location prone to high levels of air pollution, expression of uniquely sensitive forms of TRPA1 may correlate with reduced asthma control. Variant forms of TRPA1 were constructed by mutating residues in known functional elements and corresponding to single-nucleotide polymorphisms in functional domains. TRPA1 activity was studied in transfected HEK-293 cells using allyl-isothiocynate, a model soluble electrophilic agonist; 3,5-ditert butylphenol, a soluble nonelectrophilic agonist and a component of diesel exhaust particles; and insoluble coal fly ash (CFA) particles. The N-terminal variants R3C and R58T exhibited greater, but not additive, activity with all three agonists. The ankyrin repeat domain-4 single nucleotide polymorphisms E179K and K186N exhibited decreased response to CFA. The predicted N-linked glycosylation site residues N747A and N753A exhibited decreased responses to CFA, which were not attributable to differences in cellular localization. The pore-loop residue R919Q was comparable to wild-type, whereas N954T was inactive to soluble agonists but not CFA. These data identify roles for ankyrin domain-4, cell surface N-linked glycans, and selected pore-loop domain residues in the activation of TRPA1 by insoluble particles. Furthermore, the R3C and R58T polymorphisms correlated with reduced asthma control for some children, which suggest that TRPA1 activity may modulate asthma, particularly among individuals living in locations prone to high levels of air pollution.


Pediatrics | 2013

Longitudinal Validation of a Tool for Asthma Self-Monitoring

Flory L. Nkoy; Bryan L. Stone; Bernhard Fassl; Derek A. Uchida; Karmella Koopmeiners; Sarah Halbern; Eun H. Kim; Allison Wilcox; Jian Ying; Tom Greene; David M. Mosen; Michael N. Schatz; Christopher G. Maloney

OBJECTIVES: To establish longitudinal validation of a new tool, the Asthma Symptom Tracker (AST). AST combines weekly use of the Asthma Control Test with a color-coded graph for visual trending. METHODS: Prospective cohort study of children age 2 to 18 years admitted for asthma. Parents or children (n = 210) completed baseline AST assessments during hospitalization, then over 6 months after discharge. Concurrent with the first 5 AST assessments, the Asthma Control Questionnaire (ACQ) was administered for comparison. RESULTS: Test–retest reliability (intraclass correlation) was moderate, with a small longitudinal variation of AST measurements within subjects during follow-ups. Internal consistency was strong at baseline (Cronbach’s α 0.70) and during follow-ups (Cronbach’s α 0.82–0.90). Criterion validity demonstrated a significant correlation between AST and ACQ scores at baseline (r = −0.80, P < .01) and during follow-ups (r = −0.64, −0.72, −0.63, and −0.69). The AST was responsive to change over time; an increased ACQ score by 1 point was associated with a decreased AST score by 2.65 points (P < .01) at baseline and 3.11 points (P < .01) during follow-ups. Discriminant validity demonstrated a strong association between decreased AST scores and increased oral corticosteroid use (odds ratio 1.13, 95% confidence interval, 1.10–1.16, P < .01) and increased unscheduled acute asthma visits (odds ratio 1.23, 95% confidence interval, 1.18–1.28, P < .01). CONCLUSIONS: The AST is reliable, valid, and responsive to change over time, and can facilitate ongoing monitoring of asthma control and proactive medical decision-making in children.


Journal of Biological Chemistry | 2016

Characterization of Transient Receptor Potential Vanilloid-1 (TRPV1) Variant Activation by Coal Fly Ash Particles and Associations with Altered Transient Receptor Potential Ankyrin-1 (TRPA1) Expression and Asthma

Cassandra E. Deering-Rice; Chris Stockmann; Erin G. Romero; Zhenyu Lu; Darien Shapiro; Brian L. Stone; Bernhard Fassl; Flory L. Nkoy; Derek A. Uchida; Robert M. Ward; John M. Veranth; Christopher A. Reilly

Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of transient receptor potential vanilloid-1 (TRPV1) would be uniquely responsive to insoluble coal fly ash compared with the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1-I315M and -T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles due to reduced translation of protein and an apparent role for Ile-585 in activation by particles. In HEK-293 cells, I585V had an inhibitory effect on wild-type TRPV1 expression, activation, and internalization/agonist-induced desensitization. In normal human bronchial epithelial cells, IL-8 secretion in response to coal fly ash treatment was reduced for cells heterozygous for TRPV1-I585V. Finally, both the I315M and I585V variants were associated with worse asthma symptom control with the effects of I315M manifesting in mild asthma and those of the I585V variant manifesting in severe, steroid-insensitive individuals. This effect may be due in part to increased transient receptor potential ankyrin-1 (TRPA1) expression by lung epithelial cells expressing the TRPV1-I585V variant. These findings suggest that specific molecular interactions control TRPV1 activation by particles, differential activation, and desensitization of TRPV1 by particles and/or other agonists, and cellular changes in the expression of TRPA1 as a result of I585V expression could contribute to variations in asthma symptom control.


Hospital pediatrics | 2018

Neighborhood Deprivation and Childhood Asthma Outcomes, Accounting for Insurance Coverage

Flory L. Nkoy; Bryan L. Stone; Andrew J. Knighton; Bernhard Fassl; Joseph M. Johnson; Christopher G. Maloney; Lucy A. Savitz

OBJECTIVES Collecting social determinants data is challenging. We assigned patients a neighborhood-level social determinant measure, the area of deprivation index (ADI), by using census data. We then assessed the association between neighborhood deprivation and asthma hospitalization outcomes and tested the influence of insurance coverage. METHODS A retrospective cohort study of children 2 to 17 years old admitted for asthma at 8 hospitals. An administrative database was used to collect patient data, including hospitalization outcomes and neighborhood deprivation status (ADI scores), which were grouped into quintiles (ADI 1, the least deprived neighborhoods; ADI 5, the most deprived neighborhoods). We used multivariable models, adjusting for covariates, to assess the associations and added a neighborhood deprivation status and insurance coverage interaction term. RESULTS A total of 2270 children (median age 5 years; 40.6% girls) were admitted for asthma. We noted that higher ADI quintiles were associated with greater length of stay, higher cost, and more asthma readmissions (P < .05 for most quintiles). Having public insurance was independently associated with greater length of stay (β: 1.171; 95% confidence interval [CI]: 1.117-1.228; P < .001), higher cost (β: 1.147; 95% CI: 1.093-1.203; P < .001), and higher readmission odds (odds ratio: 1.81; 95% CI: 1.46-2.24; P < .001). There was a significant deprivation-insurance effect modification, with public insurance associated with worse outcomes and private insurance with better outcomes across ADI quintiles (P < .05 for most combinations). CONCLUSIONS Neighborhood-level ADI measure is associated with asthma hospitalization outcomes. However, insurance coverage modifies this relationship and needs to be considered when using the ADI to identify and address health care disparities.


International journal of critical illness and injury science | 2018

An evidence-based approach to evaluation and management of the febrile child in Indian emergency department

Prerna Batra; Neha Thakur; Prashant Mahajan; Reena Patel; Narendra Rai; Nitin Trivedi; Bernhard Fassl; Binita R. Shah; Abhijeet Saha; Marie M. Lozon; Rockefeller Oteng; Dheeraj Shah; Sagar Galwankar

Fever is the most common complaint for a child to visit hospital. Under the aegis of INDO-US Emergency and Trauma Collaborative, Pediatric Emergency Medicine chapter of Academic College of Emergency Experts in India developed evidence-based consensus for evaluation and management of febrile child in emergency department. An extensive literature search and further online communication of the group led to the development of a detailed approach for the evaluation and management of individual conditions associated with fever. To develop an approach to individual conditions presenting with fever, that is, best suited to the epidemiology prevalent in India. The algorithmic approach given by the group describes in details the evaluation and management of specialized and individual conditions like fever and immunocompromised state, fever with localizing signs that include fever with seizures, cough, ear discharge, loose stools, rash and dysuria; fever without localization with epidemiological evidence supporting diagnosis such as malaria, enteric fever and dengue; and fever without any localization and no epidemiological evidence supporting the diagnosis.


Indian Pediatrics | 2017

Consensus guidelines on evaluation and management of the febrile child presenting to the emergency department in India

Prashant Mahajan; Prerna Batra; Neha Thakur; Reena Patel; Narendra Rai; Nitin Trivedi; Bernhard Fassl; Binita R. Shah; Marie M. Lozon; Rockerfeller A. Oteng; Abhijeet Saha; Dheeraj Shah; Sagar Galwankar; Trauma Collaborative

JustificationIndia, home to almost 1.5 billion people, is in need of a country-specific, evidence-based, consensus approach for the emergency department (ED) evaluation and management of the febrile child.ProcessWe held two consensus meetings, performed an exhaustive literature review, and held ongoing web-based discussions to arrive at a formal consensus on the proposed evaluation and management algorithm. The first meeting was held in Delhi in October 2015, under the auspices of Pediatric Emergency Medicine (PEM) Section of Academic College of Emergency Experts in India (ACEE-INDIA); and the second meeting was conducted at Pune during Emergency Medical Pediatrics and Recent Trends (EMPART 2016) in March 2016. The second meeting was followed with futher e-mail-based discussions to arrive at a formal consensus on the proposed algorithm.ObjectiveTo develop an algorithmic approach for the evaluation and management of the febrile child that can be easily applied in the context of emergency care and modified based on local epidemiology and practice standards.RecommendationsWe created an algorithm that can assist the clinician in the evaluation and management of the febrile child presenting to the ED, contextualized to health care in India. This guideline includes the following key components: triage and the timely assessment; evaluation; and patient disposition from the ED. We urge the development and creation of a robust data repository of minimal standard data elements. This would provide a systematic measurement of the care processes and patient outcomes, and a better understanding of various etiologies of febrile illnesses in India; both of which can be used to further modify the proposed approach and algorithm.

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