Publications by authors named "David E Brown"

11 Publications

  • Page 1 of 1

Cefiderocol for the Treatment of Adult and Pediatric Patients with Cystic Fibrosis and Achromobacter xylosoxidans Infections.

Clin Infect Dis 2020 Dec 13. Epub 2020 Dec 13.

Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA.

Treatment options for Achromobacter xylosoxidans are limited. Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses. Pre-treatment in vitro resistance was seen in 3/8 cases. Clinical response occurred after 11/12 treatment courses. However, microbiologic relapse was observed after 11/12 treatment courses, notably without emergence of resistance.
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http://dx.doi.org/10.1093/cid/ciaa1847DOI Listing
December 2020

Comparison of multichannel and single-channel wrist-based devices with polysomnography to measure sleep in children and adolescents.

J Clin Sleep Med 2021 Apr;17(4):645-652

Department of Exercise Science, University of South Carolina, Columbia, South Carolina.

Study Objectives: To compare sleep parameters produced by the Fitbit Charge 3 (Fitbit) and Actigraph GT9X accelerometer (Actigraph) to polysomnography in children and adolescents.

Methods: Participants (n = 56, ages 9.2 ± 3.3 years) wore a Fitbit and an Actigraph on their nondominant wrist concurrently with polysomnography during an overnight observation at a children's sleep laboratory. Total sleep time, sleep efficiency, wake after sleep onset, sleep onset, and sleep offset were extracted from the Fitabase and Actilife software packages, respectively, with the Sadeh algorithm. Bland-Altman plots were used to assess the agreement between wearable devices and polysomnography.

Results: Seventy-nine percent of participants were diagnosed with OSA. Compared with polysomnography, the Fitbit and the Actigraph underestimated total sleep time by 6.1 minutes (absolute mean bias [AMB] = 27.7 minutes) and 31.5 minutes (AMB = 38.2 minutes), respectively. The Fitbit overestimated sleep efficiency by 3.0% (AMB = 6.3%), and the Actigraph underestimated sleep efficiency by 12.9% (AMB = 13.2%). The Fitbit overestimated wake after sleep onset by 18.8 minutes (AMB = 23.9 minutes), and the Actigraph overestimated wake after sleep onset by 56.1 minutes (AMB = 54.7 minutes). In addition, the Fitbit and the Actigraph underestimated sleep onset by 1.2 minutes (AMB = 13.9 minutes) and 10.2 minutes (AMB = 18.1 minutes), respectively. Finally, the Fitbit and the Actigraph overestimated sleep offset by 6.0 minutes (AMB = 12.0 minutes) and 10.5 minutes (AMB = 12.6 minutes). Linear regression indicated significant trends, with the Fitbit underestimating wake after sleep onset and sleep efficiency at higher values.

Conclusions: The Fitbit provided comparable and in some instances better sleep estimates with polysomnography compared to the Actigraph. Findings support the use of multichannel devices to measure sleep in children and adolescents. Additional studies are needed in healthy children over several nights and in free-living settings.
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http://dx.doi.org/10.5664/jcsm.8980DOI Listing
April 2021

The Cost-Effectiveness of Platelet-Rich Plasma Compared With Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis.

Arthroscopy 2020 12 25;36(12):3072-3078. Epub 2020 Jul 25.

OrthoNebraska, Omaha, Nebraska, U.S.A.

Purpose: To examine the cost-effectiveness of a series (total of 3 injections) of intra-articular platelet-rich plasma (PRP) injections in comparison to that of hyaluronic acid (HA) viscosupplementation for the treatment of symptomatic knee osteoarthritis.

Methods: Outcome data regarding the use of PRP or HA injections for the treatment of symptomatic knee osteoarthritis were determined from the highest-quality data (Level I) available in the literature until 2015. Health utility values were then derived from these high-quality data. Costs were determined by examining typical charges for patients undergoing a series of either PRP or HA injections for the treatment of this condition at a large private orthopaedic practice. These health utility values and costs were used to create an expected-value decision analysis model.

Results: The results of the model revealed that the cost per quality-adjusted life-year (QALY) of a series of PRP injections was $8,635.23/QALY and that of a series of HA injections was $5,331.75/QALY. A series of PRP injections was associated with a higher initial cost than a series of HA injections (difference, $1,433.67); however, PRP was also more effective (higher utility value) than HA by 0.11 QALYs (0.69 vs 0.58, P = .0062) at 1 year. The incremental cost-effectiveness ratio of the use of PRP injections as opposed to HA was $12,628.15/QALY.

Conclusions: Although a series of either PRP ($8,635.23/QALY) or HA ($5,331.75/QALY) injections for the treatment of symptomatic knee osteoarthritis would be considered cost-effective (cost per QALY < $50,000), PRP injections were not more cost-effective than HA injections. However, PRP was significantly more effective at 1 year, and being associated with an incremental cost-effectiveness ratio of $12,628.15/QALY when compared with HA, a series of PRP injections should be considered a reasonable and acceptable alternative to HA injections for the treatment of symptomatic knee osteoarthritis.

Level Of Evidence: Level II, economic and decision analysis of Level I studies.
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http://dx.doi.org/10.1016/j.arthro.2020.07.027DOI Listing
December 2020

Combining bacteriophages with cefiderocol and meropenem/vaborbactam to treat a pan-drug resistant Achromobacter species infection in a pediatric cystic fibrosis patient.

Pediatr Pulmonol 2020 11 20;55(11):2990-2994. Epub 2020 Jul 20.

Department of Pharmacy, Division of Pediatric Infectious Diseases, Prisma Health Children's Hospital - Midlands, Columbia, South Carolina.

Cystic fibrosis is associated with significant morbidity and early mortality due to recurrent acute and chronic lung infections. The chronic use of multiple antibiotics without pathogen eradication increases the possibility of extensive drug resistance or even pan-drug resistance (PDR). It is imperative that new or alternative treatment options be explored. We present a clinical case of a 10-year-old female cystic fibrosis patient, infected with a PDR Achromobacter spp. She was treated with cefiderocol, meropenem/vaborbactam, and bacteriophage therapy (Ax2CJ45ϕ2) during two separate admissions in an attempt to clear her infection and restore baseline pulmonary function. The Centers for Disease Control and Prevention confirmed antibiotic susceptibilities, which showed resistance to both cefiderocol and meropenem/vaborbactam. However, after using all three agents concomitantly during the second treatment course, our patient's pulmonary function improved dramatically, and the Achromobacter spp. could not be isolated from sputum samples obtained 8 and 16 weeks after completion of therapy. Overall, the treatment regimen consisting of cefiderocol, meropenem/vaborbactam, and bacteriophage was safe and well-tolerated in our patient.
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http://dx.doi.org/10.1002/ppul.24945DOI Listing
November 2020

Exploring knowledge and perceptions of palliative care to inform integration of palliative care education into cystic fibrosis care.

Pediatr Pulmonol 2018 09 3;53(9):1218-1224. Epub 2018 Jun 3.

Departments of Psychiatry and Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

Background: Individuals with cystic fibrosis (CF) face the challenges of managing a chronic, progressive disease. While palliative care is a standard of care in serious illnesses, there are no guidelines for its incorporation into CF care. Patients with CF, caregivers, and CF care providers may lack knowledge about palliative care and perceive barriers to integrated care.

Objectives: To: 1) explore knowledge and perceptions of palliative care among patients with CF, caregivers, and CF care providers; 2) solicit opinions about incorporating palliative care into routine CF care; and 3) solicit recommendations for CF-specific palliative care education for patients and caregivers.

Methods: We conducted semi-structured interviews with adult patients with CF, parents of adolescents with CF, and CF care providers to assess knowledge and perceptions of palliative care. Discussion included suggestions for palliative care education and integration into CF care. The sample was characterized using summary statistics. Key themes were identified using qualitative content analysis.

Results: Ten patients with CF, ten parents, and eight CF care providers participated. Many had minimal knowledge of palliative care and endorsed the association with end of life as a barrier to palliative care, but after learning more about palliative care, thought it could be helpful, and should be introduced earlier.

Conclusions: In this single center study, many patients with CF, caregivers, and providers lacked knowledge about palliative care. These findings warrant replication in a larger, multisite study to inform palliative care educational interventions as a step toward consistent integration of palliative care into routine CF care.
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http://dx.doi.org/10.1002/ppul.24073DOI Listing
September 2018

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia.

Ann Am Thorac Soc 2013 Dec;10(6):574-81

1 Department of Pediatrics.

Rationale: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized.

Objectives: To use a standard protocol for measuring nNO to establish a disease-specific cutoff value at one site, and then validate at six other sites.

Methods: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD.

Measurements And Main Results: At the lead site, nNO values in PCD (mean ± standard deviation, 20.7 ± 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 ± 118.8; 125.5-867.0 nl/min), asthma (267.8 ± 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 ± 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 ± 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD.

Conclusions: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.
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http://dx.doi.org/10.1513/AnnalsATS.201305-110OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960971PMC
December 2013

Respiratory syncytial virus morbidity and outpatient palivizumab dosing in South Carolina, 2004-2009.

South Med J 2012 Aug;105(8):399-404

Palmetto Health University of South Carolina, University of South Carolina Arnold School of Public Health, USA.

Objective: Respiratory syncytial virus (RSV) has been identified as an important cause of lower respiratory tract disease in infants. In patients at high risk, prevention is attempted through immunoprophylaxis with palivizumab. In 2008, as a result of revisions to the American Academy of Pediatrics' guidelines, South Carolina Medicaid reduced the number of approved palivizumab doses from six to five. This study attempted to determine whether the reduction of approved doses would affect hospitalization and emergency department visits and to characterize dose administration.

Methods: We obtained data for all South Carolina Medicaid reimbursed births from November 2004 through March 2009. For each RSV season, infants who should have received palivizumab were identified. Rates of outpatient palivizumab dosing and hospitalizations and emergency department visits because of RSV also were identified.

Results: In the seasons sampled, 1956 infants met eligibility criteria for our study. Infants younger than 29 weeks' gestation received 34% to 48% of their total eligible palivizumab doses, whereas infants 29 to 31 weeks' gestation received 36% to 46% of their doses. The rate of emergency department visits and inpatient admissions because of RSV did not differ significantly across years.

Discussion: In evaluating our primary outcome, there was no increase in hospitalizations or emergency department visits. Overall, we did note a poor dosing rate in all of the groups. A statistically significant decline in dosing per eligible month was noted following the dose reductions. Despite solid evidence of the benefits of palivizumab in high-risk groups, we are doing an inadequate job of dosing these patients.

Conclusions: We believe adherence to current recommendations for palivizumab dosing is suboptimal in preterm infants insured by the South Carolina Medicaid program. Healthcare professionals must work harder to identify and follow-up with patients who qualify for palivizumab dosing, including infants who meet criteria for a second season.
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http://dx.doi.org/10.1097/SMJ.0b013e31825ea57dDOI Listing
August 2012

Cost-effectiveness analysis of autologous chondrocyte implantation: a comparison of periosteal patch versus type I/III collagen membrane.

Am J Sports Med 2012 Jun 5;40(6):1252-8. Epub 2012 Apr 5.

Department of Orthopaedic Surgery and Rehabilitation, University of Nebraska Medical Center, 981080 Nebraska Medical Center, Omaha, NE 68198-1080, USA.

Background: Autologous chondrocyte implantation (ACI) involves the use of a periosteal patch (ACI-P) as a cover for transplanted chondrocytes. Theoretically, this periosteal patch provides mesenchymal stem cells and growth factors that encourage chondrocyte development/differentiation. However, there is a significant rate of graft hypertrophy with the use of periosteum compared with using a type I/III collagen patch (ACI-C). This type I/III collagen patch, although not approved by the United States Food and Drug Administration for ACI, has been used extensively in Europe and in an "off-label" nature in the United States as a cover during ACI.

Purpose: To examine the cost effectiveness of ACI and determine whether ACI-C is more cost effective than ACI-P.

Study Design: Economic and decision analysis; Level of evidence, 2.

Methods: Outcome data and complication rates from patients undergoing ACI (ACI-P and ACI-C) were derived from the best evidence in the literature. Costs were determined by examining the typical patient charges undergoing ACI at a local orthopaedic hospital. The costs, results, and complication rates were used to develop a decision analysis model comparing ACI-P to ACI-C.

Results: The cost of ACI-P was $66,752 and for ACI-C was $66,939.50 ($187.50 difference). The cost per quality-adjusted life year (QALY) for ACI-P was $9466 compared with $9243 for ACI-C. Sensitivity analysis was performed regarding the additional cost of the type I/III collagen patch ($780) in ACI-C as well as the rate of graft hypertrophy after ACI-P (25%). This analysis revealed that the cost of the type I/III collagen patch would have to reach $1721, or the rate of graft hypertrophy after ACI-P reduced to almost 11%, before ACI-P became more cost effective than ACI-C.

Conclusion: This cost-effectiveness analysis reveals that, while both ACI-P and ACI-C are cost effective, ACI-C is slightly more cost effective than ACI-P. This is likely secondary to the significant rate of patch-related complications associated with ACI-P, which is significantly reduced with ACI-C. Although the model is very sensitive to differences in outcomes between ACI-P and ACI-C, there is no high-quality evidence to suggest that there is a significant difference between the two. Thus, ACI-P becomes more cost effective if the cost of the type I/III collagen membrane is significantly increased or if the rate of graft hypertrophy after ACI-P were to be markedly reduced.
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http://dx.doi.org/10.1177/0363546512441586DOI Listing
June 2012

Primary ciliary dyskinesia in Amish communities.

J Pediatr 2010 Jun 29;156(6):1023-1025. Epub 2010 Mar 29.

Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. Electronic address:

Primary ciliary dyskinesia is an autosomal recessive multigenic disease that results in impaired mucociliary clearance. We have diagnosed 9 subjects with primary ciliary dyskinesia from geographically dispersed Amish communities, on the basis of clinical characteristics and ciliary ultrastructural defects. Despite consanguinity, affected individuals had evidence of genetic heterogeneity.
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http://dx.doi.org/10.1016/j.jpeds.2010.01.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875274PMC
June 2010

Early lung disease in young children with primary ciliary dyskinesia.

Pediatr Pulmonol 2008 May;43(5):514-6

Department of Pediatrics, Division of Pulmonology, University of North Carolina, Chapel Hill, North Carolina, USA.

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease in which ciliary dysfunction leads to chronic lung, sinus, and middle ear disease. PCD is often not diagnosed until late childhood due to its presumed rarity and the technical expertise necessary for diagnosis; as such, little is known about lung disease in young children with PCD. We report on 3 young children with PCD who had evidence of lung disease on infant pulmonary function testing, bronchoscopy, and/or computed tomography (CT) of the chest before 3 years of age.
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http://dx.doi.org/10.1002/ppul.20792DOI Listing
May 2008

Workforce development for older youth.

New Dir Youth Dev 2006 (111):91-104, 10-1

District of Columbia's Department of Youth Rehabilitation Services, USA.

The challenges facing youth who are disconnected from our nation's employment and education systems are expansive. Research has suggested that youth services and supports that are grounded in a developmental approach not only help young people avoid self-destructive behavior, but also enable them to acquire the academic and work-readiness skills and personal attributes that employers seek. In 1995, the National Youth Employment Coalition and its members established the Promising and Effective Practices Network (PEPNet) to identify the key elements of quality youth programs and develop tools that would help organizations establish, connect to, and promote quality programs. PEPNet represents a standards framework that captures the key elements common to successful programs that connect youth to jobs, careers, and education. This chapter provides some insights into the current practices that have been implemented to facilitate older youth's transition to the workforce and highlights the supports youth need for successful adulthood, citizenship, and career pursuits.
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http://dx.doi.org/10.1002/yd.185DOI Listing
February 2007