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Search Results: 1 - 10 of 10925 matches for " Joseph Mrus "
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Patterns of Use and Outcomes in Patients Treated with Etravirine in the HIV Research Network
Kelly Gebo,Cindy Voss,Joseph Mrus
AIDS Research and Treatment , 2013, DOI: 10.1155/2013/492831
Do medical house officers value the health of veterans differently from the health of non-veterans?
Michael S Yi, Sara Luckhaupt, Joseph M Mrus, Joel Tsevat
Health and Quality of Life Outcomes , 2004, DOI: 10.1186/1477-7525-2-19
Abstract: All medicine residents in a teaching hospital were asked to watch a digital video of an actor depicting a 72-year-old patient with mild-moderate congestive heart failure. Residents were randomized to 2 groups: in one group, the patient was described as a veteran of the Korean War, and in the other, he was referred to only as a male. The respondents assessed the patient's health state using 4 measures: rating scale (RS), time tradeoff (TTO), standard gamble (SG), and willingness to pay (WTP). We also ascertained residents' demographics, risk attitudes, residency program type, post-graduate year level, current rotation, experience in a Veterans Affairs hospital, and how many days it had been since they were last on call. We performed univariate and multivariable analyses using the RS, TTO, SG and WTP as dependent variables.Eighty-one residents (89.0% of eligible) participated, with 36 (44.4%) viewing the video of the veteran and 45 (55.6%) viewing the video of the non-veteran. Their mean (SD) age was 28.7 (3.1) years; 51.3% were female; and 67.5% were white. There were no differences in residents' characteristics or in RS, TTO, SG and WTP scores between the veteran and non-veteran groups. The mean RS score was 0.60 (0.14); the mean TTO score was 0.80 (0.20); the mean SG score was 0.91 (0.10); and the median (25th, 75th percentile) WTP was $10,000 ($7600, $20,000) per year. In multivariable analyses, being a resident in the categorical program was associated with assigning higher RS scores, but no residency-associated variables were associated with the TTO, SG or WTP scores.Physicians in training appear not to be biased either in favor of or against military veterans when judging the value of a patient's health.Health-related quality of life (HRQOL) may be assessed by two fundamentally different approaches: (1) health status measurement and (2) health values or utility assessment [1]. Health status measures evaluate functioning in one or multiple specific domains such
Patterns of Use and Outcomes in Patients Treated with Etravirine in the HIV Research Network
Kelly Gebo,Cindy Voss,Joseph Mrus,HIV Research Network
AIDS Research and Treatment , 2013, DOI: 10.1155/2013/492831
Abstract: This observational analysis examined the clinical outcomes of patients receiving etravirine-(ETR-) based therapy, particularly with protease inhibitors (PIs) other than darunavir (DRV) and with raltegravir (RAL). Data included treatment-experienced adults in the HIV Research Network who began ETR-containing antiretroviral regimens in 2008–2010. The primary objective was to assess 6-month outcomes (durability, i.e., still on an ETR-containing regimen; change in CD4+ cell count and HIV-1 RNA <400?copies/mL). The cohort included 587 patients receiving ETR; 42% of ETR use was in patients not on DRV/ritonavir (r). Patients receiving ETR plus DRV/r had longer durability versus those on ETR plus a PI other than DRV/r at months 6 (91.2% versus 85.5%) and 12 (77.4% versus 65.2%), respectively. Patients on regimens with a PI other than DRV/r were the least likely to be receiving ETR at month 6 (85.5%) versus patients on other ETR-based regimens. Patients on regimens without a PI and without RAL had lower virologic suppression (month 6, 54.2%; month 12, 63.2%) versus patients on other ETR-based regimens. In a clinical care, nontrial setting, ETR was used in regimens without DRV/r. In this population, the 6-month response rates were similar and durable across all regimens, except when ETR was used without RAL and without a PI. 1. Introduction Aside from registrational trial data, there is limited information on the utilization and clinical outcomes of patients treated with etravirine-(ETR-) based therapy. To date, ETR has demonstrated high efficacy rates, as well as good tolerability and safety profiles [1, 2]. However, in most studies of ETR, including the Phase III trials, all patients also received darunavir/ritonavir (DRV/r). In the DUET 1 and DUET 2 trials, for example, 61% of patients receiving ETR 200?mg twice daily (bid) plus a background regimen that included DRV/r 600/100?mg bid achieved HIV-1 RNA <50 copies/mL at 48 weeks, compared with 40% of patients receiving placebo plus a background regimen that included DRV/r 600/100?mg bid [2]. Interestingly, in the GRACE (Gender, Race, And Clinical Experience) trial, which investigated the efficacy and safety of DRV/r plus an optimized background regimen that could include ETR in treatment-experienced patients, ETR use was associated with higher virologic response rates [3]. Despite encouraging data on the use of ETR plus DRV/r, limited data exist on the use of ETR with protease inhibitors (PIs) other than DRV/r, and with novel agents like raltegravir (RAL) [1, 4–6]. The few data that do exist are promising. The
Impact of HIV/AIDS on care and outcomes of severe sepsis
Joseph M Mrus, LeeAnn Braun, Michael S Yi, Walter T Linde-Zwirble, Joseph A Johnston
Critical Care , 2005, DOI: 10.1186/cc3811
Abstract: We assessed data from all 1999 discharge abstracts from all non-federal hospitals in six US states. Patient demographic characteristics, discharge diagnoses, resource use, and outcomes were extracted. Analyses were performed using chi-square, Wilcoxon rank sum, or regression techniques, as appropriate.We identified 74,020 patients with severe sepsis (7,638 (10.3%) had HIV/AIDS) using ICD-9-CM codes. Patients with severe sepsis and HIV/AIDS had a similar mean length of stay (16.9 days versus 17.7 days; p = 0.0669), had lower mean hospitalization cost ($24,382 versus $30,537; p < 0.0001), were less likely to be admitted to the intensive care unit (37% versus 56%; p < 0.0001), and had a greater mortality (29% versus 20%; p < 0.0001) than those without HIV/AIDS. After adjustment for cohort differences, patients with severe sepsis and HIV/AIDS had increased likelihood of death (OR (95% CI) = 2.41 (2.23–2.61)) and were substantially less likely to be admitted to the intensive care unit (OR (95% CI) = 0.54 (0.51–0.59)). When compared with those with severe sepsis and HIV/AIDS, patients with severe sepsis without HIV/AIDS were universally more likely to be admitted to the intensive care unit, even when they had comorbid illnesses with equal or worse expected in-hospital mortality (e.g., metastatic cancer).For patients with severe sepsis, there are differences in care and outcomes for those with HIV/AIDS. Further research is needed to examine the delivery of care for patients with severe sepsis and HIV/AIDS.With the advent of highly active antiretroviral therapy (HAART) in the late 1990s, opportunistic infection and mortality rates for patients with HIV/AIDS have dramatically decreased, thus transforming HIV/AIDS from a uniformly fatal condition to a more manageable chronic illness [1-5]. Improvement in care and survival have also extended to HIV/AIDS patients with severe infections and those who receive care in the intensive care unit (ICU) [6-9]. While studies have shown d
Health-Related Quality of Life in the Gender, Race, And Clinical Experience Trial
Judith Feinberg,Michael Saag,Kathleen Squires,Judith Currier,Robert Ryan,Bruce Coate,Joseph Mrus
AIDS Research and Treatment , 2011, DOI: 10.1155/2011/349165
Abstract: Background. We report health-related QoL (HRQoL) from GRACE (Gender, Race, And Clinical Experience) study by sex and race over 48 weeks. Methods. 429 treatment-experienced adults (HIV-1 ?copies/mL) received darunavir/ritonavir 600/100?mg twice daily plus an appropriate background regimen. QoL was measured by the Functional Assessment of HIV Infection (FAHI) questionnaire. Results. 67% women and 77% men, including 67.4% black, 76.0% Hispanic, and 73.8% white patients, completed the trial. Baseline total FAHI scores were similar between sexes and races. Total FAHI of the entire population improved by Week 4 ( ); near-maximum changes obtained by Week 12 were maintained through Week 48. Women and black patients demonstrated larger improvements in total FAHI versus men, and Hispanic and white patients, respectively. Conclusion. HRQoL improved in all sex and racial/ethnic groups. Sex-based and race-based differences in improvements in FAHI subscales may provide insight into subtle differences of HIV-1 and treatment on HRQoL in different populations. 1. Introduction Improvements in antiretroviral (ARV) therapy have increased the life expectancy of patients with HIV-1 infection, and HIV is now considered a manageable chronic disease [1]. The maintenance of a high quality of life (QoL), as well as optimization of physical, emotional, and social health, is an important aspect of disease management for HIV-1–infected patients. Health-related quality of life (HRQoL) measures are used to quantify the physical and mental aspects of HIV-1 infection that can impact a patient’s overall well-being. Additionally, several studies have demonstrated a correlation between HRQoL and survival of HIV-1–infected patients [2–4], highlighting the need for monitoring and optimizing HRQoL. The GRACE (Gender, Race, And Clinical Experience) study was designed to investigate sex-based and race-based differences in outcomes with darunavir/ritonavir-(DRV/r-) based therapy in treatment-experienced patients. The primary outcomes of the GRACE study have been reported [5]. Here, we report the HRQoL results from GRACE by sex and race over 48 weeks. 2. Methods 2.1. Study Design and Patients GRACE was a 48-week, open-label, Phase IIIb study conducted at 65 study sites across the United States, Canada, and Puerto Rico. Treatment-experienced adults (HIV-1 RNA ≥ 1000 copies/mL) received DRV/r 600/100?mg twice daily plus an appropriate ARV background regimen, chosen on the basis of resistance testing [5]. Details of the study design and the primary outcomes of the GRACE study have been reported
Improvements in Immune Function and Activation with 48-Week Darunavir/Ritonavir-Based Therapy: GRACE Substudy
Christos Tsoukas,Louise Gilbert,Trevor Lewis,George Hatzakis,Ron Falcon,Joseph Mrus
ISRN AIDS , 2013, DOI: 10.1155/2013/358294
Abstract: Objective. During the course of HIV infection, progressive immune deficiency occurs. The aim of this prospective substudy was to evaluate the recovery of functional immunity in a subset of patients from the GRACE (Gender, Race, And Clinical Experience) study treated with a DRV/r-based regimen. Methods. The recovery of functional immunity with a darunavir/ritonavir-based regimen was assessed in a subset of treatment-experienced, HIV-1 infected patients from the GRACE study. Results. 19/32 patients (59%) enrolled in the substudy were virologically suppressed (<50 copies/mL). In these patients, median (range) CD4+ cell count increased from 222 (2, 398) cells/mm3 at baseline to 398 (119, 812) cells/mm3 at Week 48. CD8+% decreased significantly from baseline to Week 48 ( ). Proliferation of CD4+ lymphocytes in response to CD3+/CD28+, phytohemagglutinin, and pokeweed was significantly increased ( ) by Week 12. Proliferation in response to Candida and tetanus was significantly increased by Week 48 ( and , resp.). Staphylococcal enterotoxin B-stimulated tumor necrosis factor-alpha and interleukin-2 in CD4+ cells was significantly increased by Week 12 ( ) and Week 48 ( ), respectively. Conclusions. Darunavir/ritonavir-based therapy demonstrated improvements in CD4+ cell recovery and association with progressive functional immune recovery over 48 weeks. This trial is registered with NCT00381303. 1. Introduction During the course of HIV-1 infection, multifactorial T-lymphocyte (T-cell)-mediated mechanisms contribute to the progressive loss of host immune function [1–5]. In infected individuals, immune dysregulation occurs early and is characterized by a decrease in CD4+ cell count, a concurrent rise in CD8+ cells, a progressive decline in the CD4+/CD8+ ratio, and defective thymocyte proliferation [6]. During late-stage disease, loss of T-cell homeostasis also occurs [7, 8]. T cells are chronically activated throughout the course of HIV infection, as indicated by an increase in the expression of the antigens Ki67, CD38, and human leukocyte antigen (HLA)-DR, with CD38 recognized as the most reliable marker of immune activation [1–3, 5, 9]. Immune activation provides the virus with a steady pool of target cells and has been linked with increased polyclonal T-cell proliferation and turnover, as well as increases in the apoptotic marker CD95 [10–13] and activation-induced cell death [12, 14–16]. Concomitant with the decline of CD4 cells in the peripheral blood, the frequency of the CD4+ CD28 null subset increases with disease progression and eventual progression to
Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial
Thomas Kakuda,Vanitha Sekar,Peter Vis,Bruce Coate,Robert Ryan,David Anderson,Guy De La Rosa,Joseph Mrus
AIDS Research and Treatment , 2012, DOI: 10.1155/2012/186987
Abstract: Objectives. Evaluation of pharmacokinetics and pharmacodynamics of darunavir and etravirine among HIV-1–infected, treatment-experienced adults from GRACE, by sex and race. Methods. Patients received darunavir/ritonavir 600/100mg twice daily plus other antiretrovirals, which could include etravirine 200mg twice daily. Population pharmacokinetics for darunavir and etravirine were determined over 48 weeks and relationships assessed with virologic response and safety. Rich sampling for darunavir, etravirine, and ritonavir was collected in a substudy at weeks 4, 24, and 48. Results. Pharmacokinetics were estimated in 376 patients for darunavir and 190 patients for etravirine. Median darunavir and were 60,642ng·h/mL and 3624ng/mL, respectively; and for etravirine were 4183ng?·?h/mL and 280ng/mL, respectively. There were no differences in darunavir or etravirine or by sex or race. Age, body weight, or use of etravirine did not affect darunavir exposure. No relationships were seen between darunavir pharmacokinetics and efficacy or safety. Patients with etravirine exposure in the lowest quartile generally had lower response rates. Rich sampling showed no time-dependent relationship for darunavir, etravirine, or ritonavir exposure over 48 weeks. Conclusions. Population pharmacokinetics showed no relevant differences in darunavir or etravirine exposure by assessed covariates. Lower etravirine exposures were associated with lower response rates. 1. Introduction Differences in antiretroviral pharmacokinetic parameters between women and men, caused by variables such as body weight, plasma volume, and cytochrome P450 activity, could lead to different drug concentrations and toxicity profiles between sexes [1–3]. Previous pharmacokinetic data from the antiretroviral therapy with TMC114 examined in na?ve subjects (ARTEMIS) and TMC114/r in treatment-experienced patients na?ve to lopinavir (TITAN) trials, which studied 343 treatment-na?ve and 298 treatment-experienced patients receiving darunavir/ritonavir, respectively, have demonstrated small, nonclinically relevant differences in darunavir pharmacokinetic parameters between women and men and across races [4, 5]. The once-daily darunavir in treatment-experienced patients (ODIN) trial, which studied 294 patients receiving once-daily darunavir versus 296 patients receiving twice-daily darunavir, found that women had higher exposures than men, and Asian patients had lower exposure than white patients; however, these differences were not considered clinically significant [6]. Data from the pooled TMC125 to demonstrate
Gender differences in health-related quality of life of adolescents with cystic fibrosis
Renata Arrington-Sanders, Michael S Yi, Joel Tsevat, Robert W Wilmott, Joseph M Mrus, Maria T Britto
Health and Quality of Life Outcomes , 2006, DOI: 10.1186/1477-7525-4-5
Abstract: We used the 87-item child self-report form of the Child Health Questionnaire to measure 12 health domains. Data was also collected on age and forced expiratory volume in 1 second (FEV1). We analyzed data from 98 subjects and performed univariate analyses and linear regression or ordinal logistic regression for multivariable analyses.The mean (SD) age was 14.6 (2.5) years; 50 (51.0%) were female; and mean FEV1 was 71.6% (25.6%) of predicted. There were no statistically significant gender differences in age or FEV1. In univariate analyses, females reported significantly poorer HRQOL in 5 of the 12 domains. In multivariable analyses controlling for FEV1 and age, we found that female gender was associated with significantly lower global health (p < 0.05), mental health (p < 0.01), and general health perceptions (p < 0.05) scores.Further research will need to focus on the causes of these differences in HRQOL and on potential interventions to improve HRQOL of adolescent patients with CF.Cystic fibrosis (CF) is a genetic disorder that affects multiple organ systems. Treatments have improved overall survival so that those born today have a median life expectancy of approximately 40 years [1]. Much of the morbidity and mortality associated with cystic fibrosis is due to pulmonary disease, and investigations have shown that early, aggressive, and center-based care improves prognosis [2]. Objective clinical parameters, such as aerobic fitness, pulmonary function, nutritional status, and aggressive treatment with antibiotics, are associated with improved health outcomes [2]. In the past, clinical morbidity and mortality rates in children and adolescents were monitored as primary outcomes [3], but more recently, to provide the scientific basis for practice guidelines and to measure treatment effectiveness from patients' perspectives, there has been increasing focus on the examination of health-related quality of life (HRQOL) [4,5], Thus, the Cystic Fibrosis Foundation and the Na
Self-rated health of primary care house officers and its relationship to psychological and spiritual well-being
Michael S Yi, Joseph M Mrus, Caroline V Mueller, Sara E Luckhaupt, Amy H Peterman, Christina M Puchalski, Joel Tsevat
BMC Medical Education , 2007, DOI: 10.1186/1472-6920-7-9
Abstract: A questionnaire was administered to house officers in 4 residency programs at a large Midwestern medical center. Self-rated health was determined by using a health rating scale (ranging from 0 = death to 100 = perfect health) and a Likert scale (ranging from "poor" health to "excellent" health). Independent variables included demographics, residency program type, post-graduate year level, current rotation, depressive symptoms, religious affiliation, religiosity, religious coping, and spirituality.We collected data from 227 subjects (92% response rate). The overall mean (SD) health rating score was 87 (10; range, 40–100), with only 4 (2%) subjects reporting a score of 100; on the Likert scale, only 88 (39%) reported excellent health. Lower health rating scores were significantly associated (P < 0.05) with internal medicine residency program, post-graduate year level, depressive symptoms, and poorer spiritual well-being. In multivariable analyses, lower health rating scores were associated with internal medicine residency program, depressive symptoms, and poorer spiritual well-being.Residents' self-rated health was poorer than might be expected in a cohort of relatively young physicians and was related to program type, depressive symptoms, and spiritual well-being. Future studies should examine whether treating depressive symptoms and attending to spiritual needs can improve the overall health and well-being of primary care house officers.Although physicians generally undergo residency training when they are in their physical prime, residency is physically and emotionally demanding. [1-17] A number of cross-sectional and longitudinal studies over the past decades have examined the negative impact of residency training on fatigue level, [1,14,16,17] stress, [1-13,15] and even physiologic measures (e.g., blood pressure and heart rate) [2] in resident physicians. In a recent review, levels of burnout among house officers were found to be high, [18] with the potential to
Stationary Super-Gravitational States  [PDF]
Joseph Towe
Journal of Modern Physics (JMP) , 2011, DOI: 10.4236/jmp.2011.21007
Abstract: The string background AdS7XS4 is adopted and the early universe is modeled in the eleven dimensional SUGRA theory that is dual to this background. Specifically the ground state of the vacuum is associated with an arbitrary distribution of closed, spin-2 strings, and excited states are modeled as geometric combinations of individual strings. Combinations or combining iterations are, by hypothesis, admissible or geometric if each iteration intrinsically incorporates the metrical scale that is assigned to the individual spin-2 string. It is demonstrated that a generalization of this process, if appropriately calibrated, establishes theoretical fermionic masses that correspond approximately to observed values. The proposed model also predicts a new quark of mass .
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