Rho Federal Systems Division

Chapel Hill, NC, United States

Rho Federal Systems Division

Chapel Hill, NC, United States

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Brennan D.C.,University of Washington | Kopetskie H.A.,Rho Federal Systems Division | Sayre P.H.,Immune Tolerance Network | Alejandro R.,University of Miami | And 6 more authors.
American Journal of Transplantation | Year: 2016

We report the long-term follow-up of the efficacy and safety of islet transplantation in seven type 1 diabetic subjects from the United States enrolled in the multicenter international Edmonton Protocol who had persistent islet function after completion of the Edmonton Protocol. Subjects were followed up to 12 years with serial testing for sustained islet allograft function as measured by C-peptide. All seven subjects demonstrated continued islet function longer than a decade from the time of first islet transplantation. One subject remained insulin independent without the need for diabetic medications or supplemental transplants. One subject who was insulin-independent for over 8 years experienced graft failure 10.9 years after the first islet transplant. The remaining six subjects demonstrated continued islet function upon trial completion, although three had received a supplemental islet transplant each. At trial completion, five subjects were receiving insulin and two remained insulin independent, although one was treated with liraglutide. The median hemoglobin A1c was 6.3% (45 mmol/mol). All subjects experienced progressive decline in the C-peptide/glucose ratio. No patients experienced severe hypoglycemia, opportunistic infection, or lymphoma. Thus, although the rate and duration of insulin independence was low, the Edmonton Protocol was safe in the long term. Alternative approaches to islet transplantation are under investigation. Copyright © 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.


Salo P.M.,U.S. National Institutes of Health | Arbes Jr. S.J.,Rho Federal Systems Division | Jaramillo R.,Social and Scientific Systems | Calatroni A.,Rho Federal Systems Division | And 8 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014

Background Allergic sensitization is an important risk factor for the development of atopic disease. The National Health and Nutrition Examination Survey (NHANES) 2005-2006 provides the most comprehensive information on IgE-mediated sensitization in the general US population. Objective We investigated clustering, sociodemographic, and regional patterns of allergic sensitization and examined risk factors associated with IgE-mediated sensitization. Methods Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Participants aged 1 year or older (n = 9440) were tested for serum specific IgEs (sIgEs) to inhalant and food allergens; participants 6 years or older were tested for 19 sIgEs, and children aged 1 to 5 years were tested for 9 sIgEs. Serum samples were analyzed by using the ImmunoCAP System. Information on demographics and participants' characteristics was collected by means of questionnaire. Results Of the study population aged 6 years and older, 44.6% had detectable sIgEs, whereas 36.2% of children aged 1 to 5 years were sensitized to 1 or more allergens. Allergen-specific IgEs clustered into 7 groups that might have largely reflected biological cross-reactivity. Although sensitization to individual allergens and allergen types showed regional variation, the overall prevalence of sensitization did not differ across census regions, except in early childhood. In multivariate modeling young age, male sex, non-Hispanic black race/ethnicity, geographic location (census region), and reported pet avoidance measures were most consistently associated with IgE-mediated sensitization. Conclusions The overall prevalence of allergic sensitization does not vary across US census regions, except in early life, although allergen-specific sensitization differs based on sociodemographic and regional factors. Biological cross-reactivity might be an important but not the sole contributor to the clustering of allergen-specific IgEs. © 2014 American Academy of Allergy, Asthma and Immunology.


Busse W.W.,University of Wisconsin - Madison | Morgan W.J.,University of Arizona | Gergen P.J.,National Institute of Allergy and Infectious Diseases | Mitchell H.E.,Rho Federal Systems Division | And 13 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based therapy in achieving greater disease control. METHODS: We enrolled inner-city children, adolescents, and young adults with persistent asthma in a randomized, double-blind, placebo-controlled, parallel-group trial at multiple centers to assess the effectiveness of omalizumab, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for 60 weeks, and the primary outcome was symptoms of asthma. RESULTS: Among 419 participants who underwent randomization (at which point 73% had moderate or severe disease), omalizumab as compared with placebo significantly reduced the number of days with asthma symptoms, from 1.96 to 1.48 days per 2-week interval, a 24.5% decrease (P<0.001). Similarly, omalizumab significantly reduced the proportion of participants who had one or more exacerbations from 48.8 to 30.3% (P<0.001). Improvements occurred with omalizumab despite reductions in the use of inhaled glucocorticoids and long-acting beta-agonists. CONCLUSIONS: When added to a regimen of guidelines-based therapy for inner-city children, adolescents, and young adults, omalizumab further improved asthma control, nearly eliminated seasonal peaks in exacerbations, and reduced the need for other medications to control asthma. (Funded by the National Institute of Allergy and Infectious Diseases and Novartis; ClinicalTrials.gov number, NCT00377572.) Copyright © 2011 Massachusetts Medical Society.


Herold K.C.,Yale University | Gitelman S.E.,University of California at San Francisco | Ehlers M.R.,Immune Tolerance Network | Gottlieb P.A.,Aurora University | And 9 more authors.
Diabetes | Year: 2013

Trials of immune therapies in new-onset type 1 diabetes (T1D) have shown success, but not all subjects respond, and the duration of response is limited. Our aim was to determine whether two courses of teplizumab, an Fc receptor-nonbinding anti-CD3 monoclonal antibody, reduces the decline in C-peptide levels in patients with T1D 2 years after disease onset. We also set out to identify characteristics of responders. We treated 52 subjects with new-onset T1D with teplizumab for 2 weeks at diagnosis and after 1 year in an open-label, randomized, controlled trial. In the intent to treat analysis of the primary end point, patients treated with teplizumab had a reduced decline in C-peptide at 2 years (mean 20.28 nmol/L [95% CI 20.36 to 20.20]) versus control (mean 20.46 nmol/L [95% CI 20.57 to 20.35]; P = 0.002), a 75% improvement. The most common adverse events were rash, transient upper respiratory infections, headache, and nausea. In a post hoc analysis we characterized clinical responders and found that metabolic (HbA1c and insulin use) and immunologic features distinguished this group from those who did not respond to teplizumab. We conclude that teplizumab treatment preserves insulin production and reduces the use of exogenous insulin in some patients with new-onset T1D. Metabolic and immunologic features at baseline can identify a subgroup with robust responses to immune therapy. © 2013 by the American Diabetes Association.


Du Toit G.,King's College London | Roberts G.,University of Southampton | Sayre P.H.,University of California at San Francisco | Bahnson H.T.,Rho Federal Systems Division | And 11 more authors.
New England Journal of Medicine | Year: 2015

Background: The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy. Methods: We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test - one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age. Results: Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P = 0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy. Conclusions: The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. Copyright © 2015 Massachusetts Medical Society. All rights reserved.


Toit G.D.,King's College London | Sayre P.H.,University of California at San Francisco | Roberts G.,University of Southampton | Sever M.L.,University of California at San Francisco | And 10 more authors.
New England Journal of Medicine | Year: 2016

BACKGROUND In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanutconsumption group), as compared with those who had avoided peanuts (peanutavoidance group). METHODS At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age. RESULTS We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P = 0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)-specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio. CONCLUSIONS Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longerterm effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846.). © 2016 Massachusetts Medical Society.


Huskins W.C.,Mayo Medical School | Huckabee C.M.,Rho Federal Systems Division | O'Grady N.P.,U.S. National Institutes of Health | Murray P.,U.S. National Institutes of Health | And 8 more authors.
New England Journal of Medicine | Year: 2011

Background Intensive care units (ICUs) are high-risk settings for the transmission of methicillinresistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). Methods In a cluster-randomized trial, we evaluated the effect of surveillance for MRSA and VRE colonization and of the expanded use of barrier precautions (intervention) as compared with existing practice (control) on the incidence of MRSA or VRE colonization or infection in adult ICUs. Surveillance cultures were obtained from patients in all participating ICUs; the results were reported only to ICUs assigned to the intervention. In intervention ICUs, patients who were colonized or infected with MRSA or VRE were assigned to care with contact precautions; all the other patients were assigned to care with universal gloving until their discharge or until surveillance cultures obtained at admission were reported to be negative. Results During a 6-month intervention period, there were 5434 admissions to 10 intervention ICUs, and 3705 admissions to 8 control ICUs. Patients who were colonized or infected with MRSA or VRE were assigned to barrier precautions more frequently in intervention ICUs than in control ICUs (a median of 92% of ICU days with either contact precautions or universal gloving [51% with contact precautions and 43% with universal gloving] in intervention ICUs vs. a median of 38% of ICU days with contact precautions in control ICUs, P<0.001). In intervention ICUs, health care providers used clean gloves, gowns, and hand hygiene less frequently than required for contacts with patients assigned to barrier precautions; when contact precautions were specified, gloves were used for a median of 82% of contacts, gowns for 77% of contacts, and hand hygiene after 69% of contacts, and when universal gloving was specified, gloves were used for a median of 72% of contacts and hand hygiene after 62% of contacts. The mean (±SE) ICU-level incidence of events of colonization or infection with MRSA or VRE per 1000 patient-days at risk, adjusted for baseline incidence, did not differ significantly between the intervention and control ICUs (40.4±3.3 and 35.6±3.7 in the two groups, respectively; P = 0.35). Conclusions The intervention was not effective in reducing the transmission of MRSA or VRE, although the use of barrier precautions by providers was less than what was required. (Funded by the National Institute of Allergy and Infectious Diseases and others; STAR ICU ClinicalTrials.gov number, NCT00100386.) © 2011 Massachusetts Medical Society.


Teach S.J.,George Washington University | Gergen P.J.,National Institute of Allergy and Infectious Diseases | Szefler S.J.,University of Colorado at Denver | Mitchell H.E.,Rho Federal Systems Division | And 10 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background Asthma exacerbations remain common, even in children and adolescents, despite optimal medical management. Identification of host risk factors for exacerbations is incomplete, particularly for seasonal episodes. Objective We sought to define host risk factors for asthma exacerbations unique to their season of occurrence. Methods This is a retrospective analysis of patients aged 6 to 20 years who comprised the control groups of the Asthma Control Evaluation study and the Inner City Anti-IgE Therapy for Asthma study. Univariate and multivariate models were constructed to determine whether patients' demographic and historical factors, allergic sensitization, fraction of exhaled nitric oxide values, spirometric measurements, asthma control, and treatment requirements were associated with seasonal exacerbations. Results The analysis included 400 patients (54.5% male; 59.0% African American; median age, 13 years). Exacerbations occurred in 37.5% of participants over the periods of observation and were most common in the fall (28.8% of participants). In univariate analysis impaired pulmonary function was significantly associated with greater odds of exacerbations for all seasons, as was an exacerbation in the previous season for all seasons except spring. In multivariate analysis exacerbation in the previous season was the strongest predictor in fall and winter, whereas a higher requirement for inhaled corticosteroids was the strongest predictor in spring and summer. The multivariate models had the best predictive power for fall exacerbations (30.5% variance attributed). Conclusions Among a large cohort of inner-city children with asthma, patients' risk factors for exacerbation vary by season. Thus information on individual patients might be beneficial in strategies to prevent these seasonal events. © 2015 American Academy of Allergy, Asthma & Immunology.


Nair N.,Emory University | Kourbatova E.,Emory University | Poole K.,Rho Federal Systems Division | Huckabee C.M.,Rho Federal Systems Division | And 4 more authors.
Infection Control and Hospital Epidemiology | Year: 2011

background. The multicenter, cluster-randomized Strategies to Reduce Transmission of Antimicrobial Resistant Bacteria in Intensive Care Units (STAR*ICU) trial was performed in 18 U.S. adult intensive care units (ICUs). It evaluated the effectiveness of infection control strategies to reduce the transmission of methicillin-resistant Staphylococcus aureus (MRSA) colonization and/or infection. Our study objective was to examine the molecular epidemiology of MRSA and assess the prevalence and risk factors for community acquired (CA)-MRSA genotype nasal carriage at the time of ICU admission. methods. Selected MRSA isolates were subjected to molecular typing using pulsed-field gel electrophoresis. results. Of 5,512 ICU patient admissions in the STAR*ICU trial during the intervention period, 626 (11%) had a nares sample culture result that was positive for MRSA. A total of 210 (34%) of 626 available isolates were selected for molecular typing by weighted random sampling. Of 210 patients, 123 (59%) were male; mean age was 63 years. Molecular typing revealed that 147 isolates (70%) were the USA100 clone, 26 (12%) were USA300, 12 (6%) were USA500, 8 (4%) were USA800, and 17 (8%) were other MRSA genotypes. In a multivariate analysis, patients who were colonized with a CA-MRSA genotype (USA300, USA400, or USA1000) were less likely to have been hospitalized during the previous 12 months (PR [prevalence ratio], 0.39 [95% confidence interval (CI), 0.21-0.73]) and were less likely to be older (PR, 0.97 [95% CI, 0.95-0.98] per year) compared with patients who were colonized with a healthcare-associated (HA)-MRSA genotype. conclusion. CA-MRSA genotypes have emerged as a cause of MRSA nares colonization among patients admitted to adult ICUs in the United States. During the study period (2006), the predominant site of CA-MRSA genotype acquisition appeared to be in the community. © 2011 by The Society for Healthcare Epidemiology of America. All rights reserved.


News Article | February 22, 2017
Site: www.eurekalert.org

Healthy human skin is alive with bacteria. In fact, there are more microorganisms living in and on the human body than there are human cells. Most can live on the human skin without harming the host, but in some people bacteria can negatively alter their health, maybe even become life-threatening. University of California San Diego School of Medicine researchers screened 10,000 colonies of bacteria found on the epidermis to determine how many had antimicrobial properties and at what rate these are found on healthy and non-healthy skin. In a paper published February 22 in Science Translational Medicine, the team reports isolating and growing good bacteria that produce antimicrobial peptides and successfully transplanting it to treat patients with the most common type of eczema, known as atopic dermatitis. "We discovered antimicrobial peptides produced by bacteria commonly found on healthy human skin. These novel antimicrobials have selective activity against pathogenic bacteria, but do not harm other commensal bacteria that have a beneficial effect to us," said Teruaki Nakatsuji, PhD, project scientist in the Department of Dermatology at UC San Diego School of Medicine and first author. The team tested if bacteria normally found on human skin, including Staphylococcus hominis and Staphylococcus epidermis, defend against Staphylococcus aureus -- a pathogenic bacteria that aggravates skin conditions like atopic dermatitis. When S. aureus becomes antibiotic resistant it is known as methicillin-resistant Staphylococcus aureus or MRSA. It is a leading cause of death resulting from infection in the United States. "We discovered that healthy people have many bacteria producing previously undiscovered antimicrobial peptides, but when you look at the skin of people with atopic dermatitis, their bacteria are not doing the same thing. They have the wrong type of bacteria," said Richard Gallo, MD, PhD, professor and chair of the Department of Dermatology at UC San Diego School of Medicine. "After isolating the good bacteria and growing it, we were able to transplant it back to people who were deficient in it and it had an immediate impact by reducing the amount of S. aureus on the skin." According to the National Eczema Association, nearly 18 million people in the United States are plagued with atopic dermatitis, the most common form of eczema, which normally appears as a rash on arms, legs and cheeks. The first tests were done in animal models where S. aureus was eliminated by transplanting good bacteria to the area where S. aureus was found. Success with these models led to a small phase I clinical trial in which an individual's good bacteria with antimicrobial activity was grown, formulated in a skin cream and applied once to the forearm of the eczema patient infected by S. aureus. The phase I trial was intended only to test for safety and efficacy, but every patient treated in this way exhibited a significant decrease in S. aureus on their skin. "We now have a rational therapeutic approach for atopic dermatitis by using bacterial transplant technology," said Gallo. "It appears that people with this disorder will need to have it reapplied because their body does not naturally promote the growth of these organisms. The good thing is this is easy to do because it's just a cream." A phase II clinical trial is just beginning to evaluate whether prolonged application of one of the most potent good bacteria from human skin can provide long-term protection against S. aureus and improve atopic dermatitis. "Using a natural antibiotic produced by the skin microbiome is superior to current pharmaceutical approaches because the bacteriotherapy does not kill protective bacteria strains," said Nakatsuji. "Antibiotic resistance is not likely to occur because the bacteria therapy is attacking pathogens by multiple different ways at once." According to researchers, the microbiome is clearly associated with disease but cause and effect had not been established. This study reveals one of the chemicals that normal skin bacteria make to help humans fight off infection or an imbalance in the skin microflora. Co-authors include: Tiffany H. Chen, Saisindhu Narala, Kimberly A. Chun, Aimee M. Two, Tong Yun, Faiza Shafiq, Paul F. Kotol, Amina Bouslimani, Alexey V. Melnik, Haythem Latif, Ji-Nu Kim, Pieter C. Dorrestein, Karsten Zengler, Tissa R. Hata, UC San Diego; Alexandre Lockhart, Keli Artis, Gloria David, Rho Federal Systems Division, Inc.; Patricia Taylor, Joanne Streib, Donald Y. M. Leung, National Jewish Health; Alex Grier, and Steven R. Gill, University of Rochester. Disclosure: Teruaki Nakatsuji and Richard L. Gallo are co-inventors of UC San Diego technology related to the bacterial antimicrobial peptides discussed, and Gallo is a cofounder, consultant, chair of the scientific advisory board and holds equity in MatriSys Bioscience, a company that is developing skin bacteriotherapy.

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