The Experts below are selected from a list of 38430 Experts worldwide ranked by ideXlab platform
Gregory A. Poland - One of the best experts on this subject based on the ideXlab platform.
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evaluation of sex race body mass index and pre vaccination serum progesterone levels and post vaccination serum anti anthrax protective immunoglobulin g on injection site adverse events following anthrax vaccine adsorbed ava in the cdc ava Human clin
Vaccine, 2014Co-Authors: Tracy Pondo, Scott Parker, Gregory A. Poland, Robert M. Jacobson, Charles E. Rose, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Michael M. McneilAbstract:Abstract Background Anthrax vaccine adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. Methods We analyzed data from the CDC AVA Human Clinical Trial. This double blind, randomized, placebo controlled Trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the Trial's vaccinated cohort (n = 1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n = 227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Results Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Conclusions Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants.
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assessing agreement of repeated binary measurements with an application to the cdc s anthrax vaccine Clinical Trial
The International Journal of Biostatistics, 2013Co-Authors: Charles E. Rose, Gregory A. Poland, Robert M. Jacobson, Brock Stewart, Harry L. Keyserling, Michael Haber, Josep L Carrasco, Michael M. McneilAbstract:Cohen’s kappa coefficient, which was introduced in 1960, serves as the most widely employed coefficient to assess inter-observer agreement for categorical outcomes. However, the original kappa can only be applied to cross-sectional binary measurements and, therefore, cannot be applied in the practical situation when the observers evaluate the same subjects at repeated time intervals. This study summarizes six methods of assessing agreement of repeated binary outcomes under different assumptions and discusses under which condition we should use the most appropriate method in practice. These approaches are illustrated using data from the CDC anthrax vaccine adsorbed (AVA) Human Clinical Trial comparing the agreement for two solicited adverse events after AVA between the 1–3 day in-clinic medical record and the patient’s diary on the same day. We hope this article can inspire researchers to choose the most appropriate method to assess agreement for their own study with longitudinal binary data.
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Health-related quality of life in the CDC Anthrax Vaccine Adsorbed Human Clinical Trial.
Vaccine, 2012Co-Authors: Brock Stewart, Scott D. Parker, Robert M. Jacobson, Charles E. Rose, Jerome I. Tokars, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Gregory A. PolandAbstract:Abstract Background After the Department of Defense implemented a mandatory anthrax vaccination program in 1998 concerns were raised about potential long-term safety effects of the current anthrax vaccine. The CDC multicenter, randomized, double-blind, placebo-controlled Anthrax Vaccine Adsorbed (AVA) Human Clinical Trial to evaluate route change and dose reduction collected data on participants’ quality of life. Our objective is to assess the association between receipt of AVA and changes in health-related quality of life, as measured by the SF-36 health survey (Medical Outcomes Trust, Boston, MA), over 42 months after vaccination. Methods 1562 Trial participants completed SF-36v2 health surveys at 0, 12, 18, 30 and 42 months. Physical and mental summary scores were obtained from the survey results. We used Generalized Estimating Equations (GEE) analyses to assess the association between physical and mental score difference from baseline and seven study groups receiving either AVA at each dose, saline placebo at each dose, or a reduced AVA schedule substituting saline placebo for some doses. Results Overall, mean physical and mental scores tended to decrease after baseline. However, we found no evidence that the score difference from baseline changed significantly differently between the seven study groups. Conclusions These results do not favor an association between receipt of AVA and an altered health-related quality of life over a 42-month period.
Brendan Lee - One of the best experts on this subject based on the ideXlab platform.
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long term correction of ornithine transcarbamylase deficiency by wpre mediated overexpression using a helper dependent adenovirus
Molecular Therapy, 2004Co-Authors: Asad Mian, Arthur L Beaudet, Michael W Mccormack, Viraj Mane, Soledad Kleppe, Milton J Finegold, William E Obrien, John R Rodgers, Brendan LeeAbstract:The urea cycle disorders (UCDs) are important models for developing gene replacement therapy for liver diseases. Long-term correction of the most common UCD, ornithine transcarbamylase (OTC) deficiency, has yet to be achieved in Clinical or preClinical settings. The single Human Clinical Trial using early-generation adenovirus (Ad) failed to show any biochemical correction. In adult OTC-deficient mice, an E1/E2-deleted Ad vector expressing the mouse OTC gene, but not the Human, was only transiently therapeutic. By using post-transcriptional overexpression in the context of the less immunogenic helper-dependent adenoviral vector, we achieved metabolic correction of adult OTC-deficient mice for >6 months. Demonstrating this result were normalized orotic aciduria, normal hepatic enzyme activity, and elevated OTC RNA and protein levels in the absence of chronic hepatotoxicity. Overexpressing the Human protein may have overcome two potential mechanisms accounting for poor cross-species complementation: a kinetic block at the level of mitochondrial import or a dominant negative effect by the mutant polypeptide. These data represent an important approach for treating Human inborn errors of hepatocyte metabolism like the UCDs that require high-level transduction and gene expression for Clinical correction.
Martin Mates - One of the best experts on this subject based on the ideXlab platform.
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surgical ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction first in Human Clinical Trial
European Journal of Heart Failure, 2021Co-Authors: Filip Malek, Piotr Gajewski, Robert Zymlinski, Dariusz Janczak, Mariusz Chabowski, Marat Fudim, Tomas Martinca, Petr Neužil, Jan Biegus, Martin MatesAbstract:Aims Inappropriate control of blood volume redistribution may be a mechanism responsible for exercise intolerance in heart failure with preserved ejection fraction (HFpEF). We propose to address this underlying pathophysiology with selective blockade of sympathetic signalling to the splanchnic circulation by surgical ablation of the right greater splanchnic nerve (GSN). Methods and results In a single-arm, prospective, two-centre Trial, 10 patients with HFpEF (50% male, mean age 70 ± 3 years) all with New York Heart Association (NYHA) class III, left ventricular ejection fraction >40%, pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg with supine cycle ergometry, underwent ablation of the right GSN via thoracoscopic surgery. Patients were evaluated at baseline, 1, 3, 6 and 12 months after the procedure. The primary endpoint was a reduction in exercise PCWP at 3 months. There were no adverse events related to the blockade of the nerve during 12-month follow-up but three patients had significant peri-procedural adverse events related to the surgical procedure itself. At 3 months post-GSN ablation, patients demonstrated a reduction in 20 W exercise PCWP when compared to baseline [-4.5 mmHg (95% confidence interval, CI -14 to -2); P = 0.0059], which carried over to peak exercise [-5 mmHg (95% CI -11 to 0; P = 0.016). At 12 months, improvements were seen in NYHA class [3 (3) vs. 2 (1, 2); P = 0.0039] and quality of life assessed with the Minnesota Living with Heart Failure Questionnaire [60 (51, 71) vs. 22 (16, 27); P = 0.0039]. Conclusion In this first-in-Human study, GSN ablation in HFpEF proved to be feasible, with a suggestion of reduced cardiac filling pressure during exercise, improved quality of life and exercise capacity.
Tamaz Shaburishvili - One of the best experts on this subject based on the ideXlab platform.
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endovascular ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction first in Human Clinical Trial
Journal of Cardiac Failure, 2020Co-Authors: Sanjiv J Shah, Teona Zirakashvili, Nikoloz Shaburishvili, Giorgi Shaishmelashvili, Horst Sievert, Kolja Sievert, Anisha Bapna, Zoar J Engelman, Daniel Burkhoff, Tamaz ShaburishviliAbstract:Background In HFpEF, increased sympathetic outflow to the splanchnic venous system causes chronic redistribution of blood volume into the central circulation, which leads to exercise limitations, hemodynamic deterioration, and worsening outcomes. We have previously shown that surgical right greater splanchnic nerve (GSN) ablation in HFpEF leads to a reduction of PCWP, improved quality of life and exercise capacity. Objective Demonstrate feasibility of a novel transvenous approach to right-sided GSN ablation for the treatment of HFpEF. Methods In a non-randomized, open-label Trial, 11 HFpEF patients (3 male, 8 female, 70±8 years) with NYHA class II/III, LVEF ≥ 50% and high baseline PCWP at rest or with exercise, underwent right GSN ablation with the Axon Transvenous GSN Ablation System. Follow-up assessments (1 and 3 months) include the 6MWT, KCCQ, blood labs, and echocardiography. Change from baseline ablation to each follow-up were compared using paired Wilcoxon rank-sum tests. Data shown as mean ± standard deviation, unless otherwise noted. Results Two procedure related events were reported in 2 patients prior to the 1-month timepoint: bradycardia due to anesthesia and acute decrease in eGFR of >20 ml/min/1.73 m2, both of which returned to baseline without sequelae. Expected AEs related to the catheterization procedure were observed and resolved without sequalae, including access site hematoma (1), access site pain (1), right intercostal pain (1). There were no device related adverse cardiac events and no unanticipated adverse device effects. Efficacy results (Table) demonstrate marked improvements and/or favorable trends in quality of life (NYHA and KCCQ), exercise capacity (6MWT), diastolic function (E/e’ ratio) and HF severity (NTproBNP). Although the study was underpowered to show a statistically significant improvement in 6MWT from baseline, there was a Clinically relevant improvement in distance compared to baseline of at least 30 m in all patients at 1 and 3 months, and at least a 45 m in 5/11 patients at 1 month and 8/11 patients at 3 months. Conclusion These results demonstrate, for the first time ever, the feasibility of treating HFpEF with endovascular right-sided GSN ablation. The encouraging safety and efficacy results provide rationale for a phase 2 randomized controlled Trial.
Sharan Raghow - One of the best experts on this subject based on the ideXlab platform.
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Antiestrogens and selective estrogen receptor modulators reduce prostate cancer risk
World Journal of Urology, 2003Co-Authors: Mitchell S. Steiner, Sharan RaghowAbstract:The development of chemoprevention strategies against prostate cancer would have the greatest overall impact both medically and economically against prostate cancer. Estrogens are required for prostate carcinogenesis. Estrogenic stimulation through estrogen receptor α in a milieu of decreasing androgens contributes significantly to the genesis of benign prostatic hyperplasia, prostate dysplasia, and prostate cancer. The ability of antiestrogens and selective estrogen receptor modulators (SERMs) to delay and to suppress prostate carcinogenesis is supported by preClinical, Clinical, and epidemiological studies. SERMs have many features that make them attractive candidates for prostate cancer chemoprevention including their favorable safety profile and efficacy in preClinical prostate cancer models. The true Clinical benefits of SERMs for chemoprevention to prevent prostate cancer, however, should continue to be investigated through Human Clinical Trials. A phase IIb/III Human Clinical Trial is currently evaluating safety and efficacy of toremifene, a SERM, in men who have high-grade prostatic intraepithelial neoplasia.