12 results on '"Jocelyn Voell"'
Search Results
2. Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study
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Eddie Sullivan, John H. Beigel, Jocelyn Voell, Richard T. Davey, Kanakatte Raviprakash, Parag Kumar, Jin An Jiao, Hua Wu, and Thomas C. Luke
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0301 basic medicine ,myalgia ,medicine.medical_specialty ,business.industry ,Renal function ,Common cold ,medicine.disease ,Placebo ,law.invention ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,Infectious Diseases ,Randomized controlled trial ,Tolerability ,law ,Internal medicine ,medicine ,medicine.symptom ,business ,Adverse effect - Abstract
Summary Background Middle East respiratory syndrome (MERS) is a severe respiratory illness with an overall mortality of 35%. There is no licensed or proven treatment. Passive immunotherapy approaches are being developed to prevent and treat several human medical conditions where alternative therapeutic options are absent. We report the safety of a fully human polyclonal IgG antibody (SAB-301) produced from the hyperimmune plasma of transchromosomic cattle immunised with a MERS coronavirus vaccine. Methods We did a phase 1 double-blind, placebo-controlled, single-dose escalation trial at the National Institutes of Health Clinical Center. We recruited healthy participants aged 18–60 years who had normal laboratory parameters at enrolment, a body-mass index of 19–32 kg/m 2 , and a creatinine clearance of 70 mL/min or more, and who did not have any chronic medical problems that required daily oral medications, a positive rheumatoid factor (≥15 IU/mL), IgA deficiency ( Findings Between June 2, 2016, and Jan 4, 2017, we screened 43 participants, of whom 38 were eligible and randomly assigned to receive SAB-301 (n=28) or placebo (n=10). 97 adverse events were reported: 64 adverse events occurred in 23 (82%) of 28 participants receiving SAB-301 (mean 2·3 adverse events per participant). 33 adverse events occurred in all ten participants receiving placebo (mean 3·3 adverse events per participant). The most common adverse events were headache (n=6 [21%] in participants who received SAB-301 and n=2 [20%] in those receiving placebo), albuminuria (n=5 [18%] vs n=2 [20%]), myalgia (n=3 [11%] vs n=1 [10%]), increased creatine kinase (n=3 [11%] vs 1 [10%]), and common cold (n=3 [11%] vs n=2 [20%]). There was one serious adverse event (hospital admission for suicide attempt) in one participant who received 50 mg/kg of SAB-301. The area under the concentration–time curve (AUC) in the 50 mg/kg dose (27 498 μg × days per mL) is comparable to the AUC that was associated with efficacy in a preclinical model. Interpretation Single infusions of SAB-301 up to 50 mg/kg appear to be safe and well tolerated in healthy participants. Human immunoglobulin derived from transchromosomic cattle could offer a new platform technology to produce fully human polyclonal IgG antibodies for other medical conditions. Funding National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Biomedical Advanced Research and Development Authority.
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- 2018
3. Safety, tolerability, and pharmacokinetics of radavirsen (AVI-7100), an antisense oligonucleotide targeting influenza a M1/M2 translation
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Jianbo Zhang, John H. Beigel, Richard T. Davey, Michael Wong, Kristina M Brooks, Parag Kumar, Patrick L. Iversen, Alison E. Heald, Jocelyn Voell, and Paula Muñoz
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0301 basic medicine ,Pharmacology ,Proteinuria ,business.industry ,Safety tolerability ,Placebo ,03 medical and health sciences ,030104 developmental biology ,Tolerability ,Pharmacokinetics ,Antisense oligonucleotides ,Cohort ,medicine ,Pharmacology (medical) ,medicine.symptom ,business ,Adverse effect - Abstract
SummaryAims To assess the safety, tolerability, and pharmacokinetics (PK) of radavirsen following single ascending doses and multiple doses given as IV infusions in healthy adults. Methods A Phase 1 safety and pharmacokinetic (PK) study of radavirsen was performed in healthy volunteers. The study was divided into 2 parts. The first was a single-ascending dose study of 5 cohorts of 8 subjects each, randomized 6:2 to receive single intravenous doses of radavirsen ranging from 0.5 to 8 mg/kg or placebo. The second was a multiple dose study of 16 subjects randomized 12:4 to receive 8 mg/kg or placebo once daily for 5 days. Results 66 subjects were screened and 56 subjects were dosed between 2013 and 2015. At least one adverse event occurred in 31/42 (74%) who received radavirsen, and 13/14 (93%) receiving placebo. The most common adverse events were headache and proteinuria, and were similar among those receiving radavirsen or placebo. Single dose PK demonstrated relatively linear and dose-proportional increases in maximal concentration and area-under-the-concentration-time curve (AUC0-24). At 8 mg/kg in the multiple dose cohort, the Day 4 geometric mean AUC0-24 was 57.9 μg*h/mL. Conclusion Single infusions of radavirsen up to 8 mg/kg, and multi-dosing at 8 mg/kg once daily for 5 days, appear to be safe and well-tolerated in healthy subjects. The multi-dose Day 4 AUC0-24 this study is comparable to the AUC which was associated with protection from viral infection in a preclinical ferret influenza model. Further evaluation of radavirsen for the treatment of influenza infections is warranted.
- Published
- 2017
4. Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study
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John H Beigel, Pablo Tebas, Marie-Carmelle Elie-Turenne, Ednan Bajwa, Todd E Bell, Charles B Cairns, Shmuel Shoham, Jaime G Deville, Eric Feucht, Judith Feinberg, Thomas Luke, Kanakatte Raviprakash, Janine Danko, Dorothy O'Neil, Julia A Metcalf, Karen King, Timothy H Burgess, Evgenia Aga, H Clifford Lane, Michael D Hughes, Richard T Davey, Joseph Quinn, Yan Jiang, Robyn Hoelle, Nicole Iovine, Robert Shawn Wills, Socorro Pata, Monique Huggins, Belinda Manukian, Carrie Holland, Kelsey Brait, Taylor Hunt, Christopher Stowell, Amy Slater, Mary Townsends, Eugenia B Quackenbush, Yara A Park, Paul Gaither Jordan, Cherie Blanchet, Kevin Chronowski, Kathleen Alvarez, Darin Ostrander, Terry Woessner, Sandra Thoman, James Lin, Alyssa Ziman, Kavita Shankar, Tom Blok, Don Batts, Bob Beck, Gail Massey, Carol Bradley, Patricia Carey, Jenifer Baer, Eva Moore Whitehead, Sharon Kohrs, Robert Giulitto, Christina Schofield, Mary Fairchok, Susan Chambers, Cindy Baker, null RN, Michelle Parker, Marta Harshbarger, M Hong Nguyen, Mary Ellen Carey, Julie Paronish, Frank Cornell, Jim Cramer, Diana Lynn Pakstis, Michael G Ison, Richard Wunderink, Marshall Glesby, Kirsis Ham, Valery Hughes, Melissa Cushing, Cheryl Goss, Joanne Grenade, Pauline K Park, Lena M Napolitano, Krishnan Raghavendran, Robert C Hyzy, Robertson Davenport, Kristin Brierley, Theresa Downs, Michelle Ng Gong, Joan Uehlinger, Michael Lin, Janice Fritsche, Tondria Green, Bruce McLeod, Deena Patel, Mary F Bavaro, Robert Deiss, Carolyn Brandt, Stephanie Cammarata, Allan Kremp, Karine Hollis-Perry, Tahaniyat Lalani, Susan Banks, Jacqueline Johnson, Jason Maguire, Janet McNiff, Leslie E Rigg, Anuradha Ganesan, Irma Barahona, Steven Spencer, David Stagliano, Timothy Burgess, Daniel Talmor, Monique Mohammed, Valerie Banner-Goodspeed, Robert Salata, Robert Finberg, Jennifer Wang, Karen Longtine, Jaclyn Longtine, Mellissa O'Neil, Philippe R Bauer, Ognjen Gajic, Suanne M Weist, Jonathan Sevransky, Mona Brown, John Roback, John Oropello, Bridget Twohig, Jeffrey Jhang, Rahgu Seethala, Wilbur H Chen, Magali Fontaine, Kapil Saharia, Jennifer Husson, Roberta DeBiasi, Jurran L Wilson, Valli Ree Criss, Jocelyn Voell, Susan Leitman, James Wade Atkins, Hemaxi Patel, Traci Paige, Cathy Cantilena, Donald Siegel, Faye DeMuth, Craig H Fletcher, J Peter R Pelletier, Hassan Alnuaimat, and Michelle Pourde
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Mechanical ventilation ,Pediatrics ,medicine.medical_specialty ,Respiratory rate ,business.industry ,medicine.medical_treatment ,Hazard ratio ,medicine.disease ,law.invention ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Randomized controlled trial ,law ,Clinical endpoint ,Medicine ,030212 general & internal medicine ,business ,Adverse effect ,Stroke - Abstract
Summary Background Influenza causes substantial morbidity and mortality despite available treatments. Anecdotal reports suggest that plasma with high antibody titres to influenza might be of benefit in the treatment of severe influenza. Methods In this randomised, open-label, multicentre, phase 2 trial, 29 academic medical centres in the USA assessed the safety and efficacy of anti-influenza plasma with haemagglutination inhibition antibody titres of 1:80 or more to the infecting strain. Hospitalised children and adults (including pregnant women) with severe influenza A or B (defined as the presence of hypoxia or tachypnoea) were randomly assigned to receive either two units (or paediatric equivalent) of anti-influenza plasma plus standard care, versus standard care alone, and were followed up for 28 days. The primary endpoint was time to normalisation of patients' respiratory status (respiratory rate of ≤20 breaths per min for adults or age-defined thresholds of 20–38 breaths per min for children) and a room air oxygen saturation of 93% or more. This study is registered with ClinicalTrials.gov, number NCT01052480. Findings Between Jan 13, 2011, and March 2, 2015, 113 participants were screened for eligibility and 98 were randomly assigned from 20 out of 29 participating sites. Of the participants with confirmed influenza (by PCR), 28 (67%) of 42 in the plasma plus standard care group normalised their respiratory status by day 28 compared with 24 (53%) of 45 participants on standard care alone (p=0·069). The hazard ratio (HR) comparing plasma plus standard care with standard care alone was 1·71 (95% CI 0·96–3·06). Six participants died, one (2%) from the plasma plus standard care group and five (10%) from the standard care group (HR 0·19 [95% CI 0·02–1·65], p=0·093). Participants in the plasma plus standard care group had non-significant reductions in days in hospital (median 6 days [IQR 4–16] vs 11 days [5–25], p=0·13) and days on mechanical ventilation (median 0 days [IQR 0–6] vs 3 days [0–14], p=0·14). Fewer plasma plus standard care participants had serious adverse events compared with standard care alone recipients (nine [20%] of 46 vs 20 [38%] of 52, p=0·041), the most frequent of which were acute respiratory distress syndrome (one [2%] vs two [4%] patients) and stroke (one [2%] vs two [4%] patients). Interpretation Although there was no significant effect of plasma treatment on the primary endpoint, the treatment seemed safe and well tolerated. A phase 3 randomised trial is now underway to further assess this intervention. Funding National Institute of Allergy and Infectious Diseases, US National Institutes of Health.
- Published
- 2017
5. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine
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Meng Shi, Jay W. Hooper, Nelson L. Michael, Shon Remich, James E. Moon, Judie B. Alimonti, Nicole M. Van Deusen, Paula Muñoz, Jocelyn Voell, Richard T. Davey, Barney S. Graham, Peter Silvera, Zonghui Hu, Linda L. Jagodzinski, H. Clifford Lane, Ramiro L. Gutierrez, Yan Zhou, Matthew D. Josleyn, Amy R. Castellano, John H. Beigel, Steven A. Kwilas, Patrick S. Twomey, Daphne A. Stanley, Kirsten S. Smith, Charles J. Link, Brian K. Martin, Kristopher M. Paolino, Wang Jing, W. Jay Ramsey, Holly R. Hack, Jason W. Bennett, Jason A. Regules, Olivier Tshiani Mbaya, Richard C. Ruck, Sheila A. Peel, Stephen J. Thomas, Nancy J. Sullivan, Julie E. Ledgerwood, Thomas P. Monath, and Meagan L. Wisniewski
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Adult ,Male ,0301 basic medicine ,viruses ,Enzyme-Linked Immunosorbent Assay ,Viremia ,Vesicular stomatitis Indiana virus ,Antibodies, Viral ,Vaccines, Attenuated ,medicine.disease_cause ,Article ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Viral Envelope Proteins ,medicine ,Humans ,030212 general & internal medicine ,Ebola Vaccines ,Seroconversion ,Ebolavirus ,Ebola virus ,Ebola vaccine ,biology ,business.industry ,Immunogenicity ,General Medicine ,Hemorrhagic Fever, Ebola ,Middle Aged ,medicine.disease ,biology.organism_classification ,Virology ,Recombinant Proteins ,030104 developmental biology ,Vesicular stomatitis virus ,Female ,business - Abstract
The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD.We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed.The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months.This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSV∆G-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408 .).
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- 2017
6. The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts
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Kathleen Proudfoot, Shmuel Shoham, Angela Ademposi, Rachel J. Hagey, Charles Fiorentino, Susan Reed, Tyler Bristol, Rani Athota, Jeffery K. Taubenberger, Matthew J. Memoli, Lindsay Czajkowski, and Jocelyn Voell
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Adult ,Male ,Serum ,Microbiology (medical) ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Population ,Immunocompromised Host ,Young Adult ,Pharmacotherapy ,Intensive care ,Influenza, Human ,Pandemic ,Humans ,Medicine ,Prospective Studies ,education ,Articles and Commentaries ,Aged ,education.field_of_study ,business.industry ,Mortality rate ,Middle Aged ,medicine.disease ,Virus Shedding ,Patient Outcome Assessment ,Vaccination ,Nasal Mucosa ,Pneumonia ,Infectious Diseases ,Immunology ,Coinfection ,Cytokines ,Female ,business - Abstract
During the past half-century, medical advances have led to an increase in the world's population of immunosuppressed individuals. This includes those receiving immunosuppressive therapies, those with acquired immunosuppressive diseases such as the 34 million worldwide with human immunodeficiency virus (HIV) and AIDS [1], and individuals living longer with any of the over 150 known primary immunodeficiencies [2]. The most severely immunocompromised are those who have been diagnosed with a hematologic malignancy, solid organ tumor, or who receive other immunosuppressive therapies such as chemotherapy and/or solid organ or stem cell transplants. Over 100 000 individuals annually receive solid organ transplants (SOT) worldwide [3] and more than 50 000 with hematologic malignancies and other diseases are treated with hematopoietic stem cell transplants (HSCT) annually [4], leaving most of these individuals immunosuppressed for long periods. Even larger numbers of individuals are receiving immunosuppressive chemotherapies making immunocompromised individuals a larger part of the population than during any of the influenza pandemics of the twentieth century. Epidemiologic studies have shown that severe immunosuppression is a major comorbidity that places individuals at the highest risk of severe morbidity and mortality due to influenza infection. Patients with AIDS have increased duration of disease due to influenza and higher incidence of pneumonia leading to increased mortality [5–7]. A study of hospitalized patients with leukemia and influenza reported 80% with pneumonia and 33% mortality [8]. More recently during the 2009 pandemic, studies reported similarly high levels of lower respiratory tract disease and need for hospitalization in those with hematologic malignancies and solid tumors undergoing chemotherapy [9]. Similarly, in a large retrospective study of HSCT recipients, 1.3% of all patients developed influenza infection and 29% developed pneumonia [10]. A more recent study of HSCT patients demonstrated that up to 75% developed pneumonia after influenza infection with mortality as high as 43% [11]. In SOT, nosocomial outbreaks [12] and severe complications of influenza such as myocarditis [13] and severe pneumonitis [14] have been reported, even in those previously vaccinated. Multicenter studies of A(H1N1)pdm09 infection in SOT recipients have reported that 30%–40% of individuals infected developed pneumonia, 16%–17.5% required intensive care, with mortality as high as 7% [15]. Influenza following SOT leads to higher morbidity and mortality rates [16], with increased rates of influenza pneumonia following lung transplantation, and a >20% mortality rate observed in SOT recipients infected with influenza [17, 18]. In addition to increased morbidity and mortality following infection, severely immunocompromised patients have been reported to show prolonged influenza shedding [19–25]. This has been associated with intrahost viral evolution, including antigenic drift within a single immunosuppressed host [24], the development of antiviral resistance after therapy [19, 21–23, 25, 26], and simultaneous coinfection with 2 influenza subtypes [27]. Rigorous vaccination programs and improved pharmacotherapy have decreased the impact of influenza on the general population; however, influenza still remains a serious threat to severely immunocompromised individuals. The 2009 pandemic was a reminder that it is still unclear how well current vaccination strategies and current pharmacotherapy can perform in preventing and mitigating illness in immunocompromised individuals. The primary goal of this study was to compare the natural history of influenza infection in those who were severely immunocompromised to individuals who were not immunocompromised. Careful examination of symptoms and signs of infection, virological measurements, immunological studies, and clinical parameters were performed to investigate the natural pathogenesis of influenza in this group of severely immunocompromised hosts.
- Published
- 2013
7. Safety and Immunogenicity of Multiple and Higher Doses of an Inactivated Influenza A/H5N1 Vaccine
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John H. Beigel, Jocelyn Voell, H. Clifford Lane, Peter D. Burbelo, and Chiung Yu Huang
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Adult ,Male ,Time Factors ,Adolescent ,animal diseases ,Orthomyxoviridae ,Dose-Response Relationship, Immunologic ,Antibodies, Viral ,medicine.disease_cause ,Article ,Virus ,Young Adult ,Neutralization Tests ,Influenza, Human ,Pandemic ,medicine ,Influenza A virus ,Humans ,Immunology and Allergy ,Influenza A Virus, H5N1 Subtype ,biology ,Immunogenicity ,virus diseases ,Hemagglutination Tests ,Middle Aged ,biology.organism_classification ,Virology ,Influenza A virus subtype H5N1 ,Vaccination ,Infectious Diseases ,Influenza Vaccines ,Immunology ,Female ,Viral disease - Abstract
H5N1 avian influenza represents an episodic zoonotic disease with the potential to cause a pandemic, and antiviral resistance is of considerable concern. We sought to generate high-titer H5N1 antibodies in healthy volunteers for the purpose of developing hyperimmune intravenous immunoglobulin.We conducted a dose-escalating, unblinded clinical trial involving 75 subjects aged 18-59 years. Three cohorts of twenty-five subjects were enrolled sequentially and received 90, 120, or 180 microg of H5N1 A/Vietnam/1203/04 vaccine in 4 doses administered approximately 28 days apart.No statistically significant dose-related increases in the geometric mean titers (GMTs) of serum hemagglutination inhibition antibody were observed when the 90-microg, 120-microg, and 180-microg cohorts were compared. When the cohorts were analyzed together to determine the effect of additional vaccinations, the GMTs of hemagglutination inhibition antibody after the first, second, third, and fourth vaccinations were 1:15.7, 1:22.2, 1:36.0, and 1:32.0, respectively (first vaccination vs. baseline, P.001; second vs. first vaccination, P=.02; and third vs. second vaccination, P.001). The microneutralization GMTs after the first, second, third, and fourth vaccinations were 1:17.5, 1:33.1, 1:55.7, and 1:68.4, respectively (P.001 for all comparisons).The results of our study suggest that a third and fourth dose of the H5N1 A/Vietnam/1203/04 vaccine may result in higher hemagglutination inhibition and microneutralization GMTs, compared with the GMTs resulting from fewer doses. There was no benefit to increasing the dose of the vaccine.Clinical Trials.gov identifier: NCT00383071.
- Published
- 2009
8. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects
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Raul M. Alfaro, Richard T. Davey, Jocelyn Voell, Scott R. Penzak, Sarah M. Robertson, and Elizabeth Formentini
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Adult ,Male ,Midazolam ,Pyrimidinones ,Pharmacology ,Lopinavir ,Cytochrome P-450 Enzyme System ,Pharmacokinetics ,immune system diseases ,medicine ,Cytochrome P-450 CYP3A ,Humans ,Drug Interactions ,Protease Inhibitors ,Protease inhibitor (pharmacology) ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Ritonavir ,Fexofenadine ,CYP3A4 ,biology ,Plant Extracts ,Ginkgo biloba ,business.industry ,virus diseases ,HIV Protease Inhibitors ,General Medicine ,biology.organism_classification ,Female ,Terfenadine ,business ,Phytotherapy ,medicine.drug - Abstract
Animal and in vitro data suggest that Ginkgo biloba extract (GBE) may modulate CYP3A4 activity. As such, GBE may alter the exposure of HIV protease inhibitors metabolized by CYP3A4. It is also possible that GBE could alter protease inhibitor pharmacokinetics (PK) secondary to modulation of P-glycoprotein (P-gp). The primary objective of the study was to evaluate the effect of GBE on the exposure of lopinavir in healthy volunteers administered lopinavir/ritonavir. Secondary objectives were to compare ritonavir exposure pre- and post-GBE, and assess the effect of GBE on single doses of probe drugs midazolam and fexofenadine.This open-label study evaluated the effect of 2 weeks of standardized GBE administration on the steady-state exposure of lopinavir and ritonavir in 14 healthy volunteers administered lopinavir/ritonavir to steady-state. In addition, single oral doses of probe drugs midazolam and fexofenadine were administered prior to and after 4 weeks of GBE (following washout of lopinavir/ritonavir) to assess the influence of GBE on CYP3A and P-gp activity, respectively.Lopinavir, ritonavir and fexofenadine exposures were not significantly affected by GBE administration. However, GBE decreased midazolam AUC(0-infinity) and C(max) by 34% (p = 0.03) and 31% (p = 0.03), respectively, relative to baseline. In general, lopinavir/ritonavir and GBE were well tolerated. Abnormal laboratory results included mild elevations in hepatic enzymes, cholesterol and triglycerides, and mild-to-moderate increases in total bilirubin.Our results suggest that GBE induces CYP3A metabolism, as assessed by a decrease in midazolam concentrations. However, there was no change in the exposure of lopinavir, likely due to ritonavir's potent inhibition of CYP3A4. Thus, GBE appears unlikely to reduce the exposure of ritonavir-boosted protease inhibitors, while concentrations of unboosted protease inhibitors may be affected. Limitations to our study include the single sequence design and the evaluation of a ritonavir-boosted protease inhibitor exclusively.
- Published
- 2008
9. INSIGHT FLU005: An Anti-Influenza Virus Hyperimmune Intravenous Immunoglobulin Pilot Study
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Mamta K. Jain, Tauseef Rehman, P. Coburn, Alain G. DuChene, K. Quan, Paul F. Riska, Jennifer A. Whitaker, Adriana Sanchez, L. H. Makohon, Fred M. Gordin, Norman Markowitz, Julia A. Metcalf, Edward M. Gardner, C. Solorzano, John H. Beigel, Elizabeth Finley, A. Shoen, D. Bigley, J. Moghe, T. Petersen, Marie L. Hoover, Jocelyn Voell, H. Clifford Lane, Venn Natarajan, B. Omotosho, Nicole Engen, J. Scott, John Tierney, Robin Dewar, Timothy M. Uyeki, Barbara Standridge, James D. Neaton, Stacey A. Rizza, Eileen Denning, Richard T. Davey, L. Harlow, Abdel Babiker, Deborah Wentworth, H Preston Holley, Gordon E. Thompson, John D. Baxter, L. L. Faber, Raquel Nahra, M. Harrison, R. Mcconnell, Zelalem Temesgen, and Hari Polenakovik
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0301 basic medicine ,Adult ,Male ,Adolescent ,Orthomyxoviridae ,Pilot Projects ,medicine.disease_cause ,Antibodies, Viral ,Virus ,Placebos ,03 medical and health sciences ,Young Adult ,Major Articles and Brief Reports ,0302 clinical medicine ,Influenza A Virus, H1N1 Subtype ,Double-Blind Method ,Pandemic ,Influenza, Human ,Influenza A virus ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Aged ,Aged, 80 and over ,biology ,business.industry ,Influenzavirus B ,Influenza A Virus, H3N2 Subtype ,Antibody titer ,Immunization, Passive ,virus diseases ,Immunoglobulins, Intravenous ,Hemagglutination Inhibition Tests ,Middle Aged ,biology.organism_classification ,Virology ,Influenza B virus ,030104 developmental biology ,Infectious Diseases ,Treatment Outcome ,Immunization ,Immunology ,biology.protein ,Female ,Antibody ,business - Abstract
Hemagglutination inhibition (HAI) antibody responses to anti–influenza virus hyperimmune intravenous immunoglobulin (hIVIG) were characterized. Thirty-one patients with influenza during the 2013–2014 season were randomly assigned to receive 0.25 g/kg of hIVIG (n = 16) or placebo (n = 15). For hIVIG recipients, the ratio of geometric mean titers (1 hour after infusion/before infusion) was 4.00 (95% confidence interval [CI], 2.61–6.13) for 2009 pandemic influenza A(H1N1) and 1.76 (95% CI, 1.33–2.32) for influenza A(H3N2) and influenza B. Among patients with 2009 pandemic influenza A(H1N1), ratios for hIVIG (n = 9) versus placebo (n = 8) were higher 1 hour after infusion (3.9 [95% CI, 2.3–6.7]) and sustained through day 3 (2.0 [95% CI, 1.0–4.0]). hIVIG administration significantly increases HAI titer levels among patients with influenza, supporting the need to perform a clinical outcomes study. Clinical trials registration: NCT02008578.
- Published
- 2015
10. Lopinavir-ritonavir: effects on endothelial cell function in healthy subjects
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Jessica R. Grubb, Henry Masur, Mark T. Gladwin, Joseph A. Kovacs, Jocelyn Voell, William C. Blackwelder, Andre Dejam, Richard O. Cannon, and Peter A. Sklar
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Adult ,Male ,medicine.medical_specialty ,Endothelium ,Lopinavir/ritonavir ,Vasodilation ,Pyrimidinones ,Lopinavir ,Forearm ,immune system diseases ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Enzyme Inhibitors ,Ritonavir ,omega-N-Methylarginine ,business.industry ,virus diseases ,Endothelial Cells ,HIV Protease Inhibitors ,medicine.disease ,Acetylcholine ,Endothelial stem cell ,Infectious Diseases ,Endocrinology ,medicine.anatomical_structure ,Regional Blood Flow ,Female ,Endothelium, Vascular ,business ,Dyslipidemia ,medicine.drug - Abstract
To differentiate between the effects that antiretroviral drugs have on the endothelium and the secondary effects that they have on immune function, viral load, and dyslipidemia, 6 non-human immunodeficiency virus-infected human subjects were treated with lopinavir-ritonavir for 1 month and, on the basis of forearm blood flow, the treatment's effects on endothelial cell function were measured. Surprisingly, after exposure to lopinavir-ritonavir, absolute forearm blood-flow responses to the endothelium-dependent vasodilator, acetylcholine, increased significantly (P = .03), and forearm blood flow decreased to a greater extent during specific inhibition of NO synthase by N G -monomethyl-L-arginme. Thus, in this small cohort of subjects, short-term treatment with lopinavir-ritonavir does not appear to directly promote endothelial cell dysfunction.
- Published
- 2005
11. Pravastatin does not have a consistent antiviral effect in chronically HIV-infected individuals on antiretroviral therapy
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Jessica R. Grubb, Eric O. Freed, Henry Masur, James Witek, Jocelyn Voell, Frank Maldarelli, Peter Sklar, and Akira Ono
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Adult ,Male ,Anti-HIV Agents ,medicine.medical_treatment ,Immunology ,HIV Infections ,Acquired immunodeficiency syndrome (AIDS) ,Immunopathology ,Hiv infected ,medicine ,Immunology and Allergy ,Humans ,Viremia ,Sida ,Pravastatin ,Chemotherapy ,biology ,business.industry ,Anticholesteremic Agents ,Viral Load ,medicine.disease ,biology.organism_classification ,Antiretroviral therapy ,Virology ,Infectious Diseases ,Cholesterol ,Female ,Viral disease ,business ,medicine.drug - Published
- 2005
12. Nurses' job satisfaction and organizational climate in a dynamic work environment
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Jocelyn Voell, Elaine Larson, Eileen Byrne, and Karen Keuter
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Adult ,Male ,Job description ,Organizational commitment ,Nursing Staff, Hospital ,Job Satisfaction ,Nursing ,Surveys and Questionnaires ,Personnel Downsizing ,Medicine ,Humans ,Personnel psychology ,Workplace ,General Nursing ,business.industry ,Job design ,Reproducibility of Results ,Job attitude ,Middle Aged ,Organisation climate ,Organizational Culture ,Organizational Innovation ,Nursing Administration Research ,Job Description ,Job performance ,Hospital Restructuring ,Regression Analysis ,Job satisfaction ,Female ,sense organs ,business - Abstract
The infrastructure and organization of hospitals are changing rapidly as a result of major transitions in health care. Downsizing in hospitals has caused employees to have to take on new tasks and, often, multiple tasks with a decrease in available resources and an increase in job complexity. Naturally, such organizational changes have a profound effect on the nature and duration of patient hospitalization and on the job responsibilities and roles of inpatient staff. In many hospitals, there is a perception of chaos, sometimes resulting in frustration among the nursing personnel. The purpose of this study was to describe the relationship between nurses' job satisfaction and organizational climate.
- Published
- 2000
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