705 research outputs found
Mega-gifts in American Philanthropy: General & Jewish Giving Patterns Between 1995-2000
The researchers collected data on gifts of $10 million or above in order to compile this report. From this set, they identified gifts from Jewish philanthropists and offer some conclusions about the nature of high-end giving. Among other findings, the authors note that the largest number of gifts, by far, went to private educational institutions, and among Jewish donors, arts and culture was the second most popular recipient group. A listing of the donations is included in the appendices. With bibliographic references
Comparative effectiveness of abatacept versus tocilizumab in rheumatoid arthritis patients with prior TNFi exposure in the US Corrona registry
BACKGROUND:
We compared the effectiveness of abatacept (ABA) vs tocilizumab (TCA) in tumor necrosis factor inhibitor (TNFi) experienced patients. METHODS:
We identified rheumatoid arthritis (RA) patients from a large observational US cohort (1 January 2010-31 May 2014) who had discontinued at least one TNFi and initiated ABA or TCZ in moderate or high disease activity based on the Clinical Disease Activity Index (CDAI) and had no prior exposure to the comparator drug. Using propensity score matching (1:1) stratified by prior TNF use (1 TNFi vs ≥2 TNFis), effectiveness at 6 months after initiation was evaluated. Mean change in CDAI over 6 months following initiation was the primary outcome, with secondary outcomes of achievement of low disease activity/remission (CDAI ≤ 10) and mean change in modified Health Assessment Questionnaire (mHAQ) score. RESULTS:
The 264 pairs of propensity score-matched ABA and TCZ initiators were well matched with no substantial differences in the baseline characteristics, defined as standardized differences \u3e0.1 in the stratification. Both treatment groups had similar mean change in CDAI at 6 months (-11.3 in ABA vs -9.9 in TCZ; mean difference -1.27, 95% CI -3.65, 1.11). Similar proportions of both treatment groups achieved low disease activity/remission (adjusted odds ratio for ABA vs TCZ 0.99, 95% CI 0.69, 1.43). Mean change in mHAQ was -0.12 in ABA initiators vs -0.11 in TCZ initiations (mean difference -0.01, 95% CI -0.09, 0.06). CONCLUSIONS:
Patients receiving either ABA or TCZ had substantial improvement in clinical disease activity. In this propensity score-matched sample, similar outcomes were observed for both treatment cohorts
The comparative effectiveness of abatacept versus anti-tumour necrosis factor switching for rheumatoid arthritis patients previously treated with an anti-tumour necrosis factor
OBJECTIVE: We compared the effectiveness of abatacept (ABA) versus a subsequent anti-tumour necrosis factor inhibitor (anti-TNF) in rheumatoid arthritis (RA) patients with prior anti-TNF use.
METHODS: We identified RA patients from a large observational US cohort (2/1/2000-8/7/2011) who had discontinued at least one anti-TNF and initiated either ABA or a subsequent anti-TNF. Using propensity score (PS) matching (n:1 match), effectiveness was measured at 6 and 12 months after initiation based on mean change in Clinical Disease Activity Index (CDAI), modified American College of Rheumatology (mACR) 20, 50 and 70 responses, modified Health Assessment Questionnaire (mHAQ) and CDAI remission in adjusted regression models.
RESULTS: The PS-matched groups included 431 ABA and 746 anti-TNF users at 6 months and 311 ABA and 493 anti-TNF users at 12 months. In adjusted analyses comparing response following treatment with ABA and anti-TNF, the difference in weighted mean change in CDAI (range 6-8) at 6 months (0.46, 95% CI -0.82 to 1.73) and 12 months was similar (-1.64, 95% CI -3.47 to 0.19). The mACR20 responses were similar at 6 (28-32%, p=0.73) and 12 months (35-37%, p=0.48) as were the mACR50 and mACR70 (12 months: 20-22%, p=0.25 and 10-12%, p=0.49, respectively). Meaningful change in mHAQ was similar at 6 and 12 months (30-33%, p=0.41 and 29-30%, p=0.39, respectively) as was CDAI remission rates (9-10%, p=0.42 and 12-13%, p=0.91, respectively).
CONCLUSIONS: RA patients with prior anti-TNF exposures had similar outcomes if they switched to a new anti-TNF as compared with initiation of ABA
Immunosuppressive treatment and the risk of diabetes in rheumatoid arthritis
OBJECTIVE: Inflammation and anti-inflammatory treatments might influence the risk of diabetes. The objective of this study was to assess factors associated with incident diabetes in rheumatoid arthritis (RA).
METHODS: The study population consisted of RA patients from a multi-center cohort study, Corrona. To assess risk associated with disease modifying antirheumatic drug (DMARD) exposure, we assessed five mutually exclusive DMARD groups. Additionally, we assessed the risk associated with body mass index (BMI, \u3c 25, 25-30, \u3e 30 kg/m2) and glucocorticoid usage. Incident cases of diabetes were confirmed through adjudication, and Cox regression models were fit to estimate the risk of incident diabetes.
RESULTS: We identified 21,775 DMARD treatment regimens, the mean (SD) age at the index visit was 58 (13) years, disease duration 10 (10) years, and 30% used oral glucocorticoids at the time. Eighty-four incident cases of diabetes were confirmed within the treatment exposure periods. The hazard ratio (HR, 95% confidence interval) for diabetes was significantly reduced in patients receiving TNF inhibitors, HR 0.35 (0.13, 0.91), compared to patients treated with non-biologic DMARDs other than hydroxychloroquine and methotrexate. Hydroxychloroquine, methotrexate and use of other biologic DMARDs had a numerically reduced risk compared to the same group. Patients prescribed \u3e /=7.5 mg of glucocorticoids had a HR of 2.33 (1.68, 3.22) of incident diabetes compared with patients not prescribed oral glucocorticoids. RA patients with a BMI \u3e 30 had a HR of 6.27 (2.97, 13.25) compared to patients with BMI \u3c /=25.
CONCLUSION: DMARDs, glucocorticoids and obesity influenced the risk of incident diabetes in a large cohort of RA patients. Monitoring for the occurrence of diabetes should be part of routine RA management with a focus on specific subgroups
Identifying factors associated with concordance with the American College of Rheumatology rheumatoid arthritis treatment recommendations
BACKGROUND: Factors associated with care concordant with the American College of Rheumatology (ACR) recommendations for the use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) are unknown.
METHODS: We identified a national cohort of biologic-naive patients with RA with visits between December 2008 and February 2013. Treatment acceleration (initiation or dose escalation of biologic and nonbiologic DMARDs) in response to moderate to high disease activity (using the Clinical Disease Activity Index) was assessed. The population was divided into two subcohorts: (1) methotrexate (MTX)-only users and (2) multiple nonbiologic DMARD users. In both subcohorts, we compared the characteristics of patients who received care consistent with the ACR recommendations (e.g., prescriptions for treatment acceleration) and their providers with the characteristics of those who did not at the conclusion of one visit and over two visits, using logistic regression and adjusting for clustering of patients by rheumatologist.
RESULTS: Our study included 741 MTX monotherapy and 995 multiple nonbiologic DMARD users cared for by 139 providers. Only 36.2 % of MTX monotherapy users and 39.6 % of multiple nonbiologic DMARD users received care consistent with the recommendations after one visit, which increased over two visits to 78.3 % and 76.2 %, respectively (25-30 % achieved low disease activity by the second visit without DMARD acceleration). Increasing time since the ACR publication on RA treatment recommendations was not associated with improved adherence.
CONCLUSIONS: Allowing two encounters for treatment acceleration was associated with an increase in care concordant with the recommendations; however, time since publication was not
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Insights into the subsurface structure of the Caloris basin, Mercury, from assessments of mechanical layering and changes in long-wavelength topography
The volcanic plains that fill the Caloris basin, the largest recognized impact basin on Mercury, are deformed by many graben and wrinkle ridges, among which the multitude of radial graben of Pantheon Fossae allow us to resolve variations in the depth extent of associated faulting. Displacement profiles and displacement-to-length scaling both indicate that faults near the basin center are confined to a ~ 4-km-thick mechanical layer, whereas faults far from the center penetrate more deeply. The fault scaling also indicates that the graben formed in mechanically strong material, which we identify with dry basalt-like plains. These plains were also affected by changes in long-wavelength topography, including undulations with wavelengths of up to 1300 km and amplitudes of 2.5 to 3 km. Geographic correlation of the depth extent of faulting with topographic variations allows a first-order interpretation of the subsurface structure and mechanical stratigraphy in the basin. Further, crosscutting and superposition relationships among plains, faults, craters, and topography indicate that development of long-wavelength topographic variations followed plains emplacement, faulting, and much of the cratering within the Caloris basin. As several examples of these topographic undulations are also found outside the basin, our results on the scale, structural style, and relative timing of the topographic changes have regional applicability and may be the surface expression of global-scale interior processes on Mercury
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Insights into the subsurface structure of the Caloris basin, Mercury, from assessments of mechanical layering and changes in long-wavelength topography
The volcanic plains that fill the Caloris basin, the largest recognized impact basin on Mercury, are deformed by many graben and wrinkle ridges, among which the multitude of radial graben of Pantheon Fossae allow us to resolve variations in the depth extent of associated faulting. Displacement profiles and displacement-to-length scaling both indicate that faults near the basin center are confined to a ~ 4-km-thick mechanical layer, whereas faults far from the center penetrate more deeply. The fault scaling also indicates that the graben formed in mechanically strong material, which we identify with dry basalt-like plains. These plains were also affected by changes in long-wavelength topography, including undulations with wavelengths of up to 1300 km and amplitudes of 2.5 to 3 km. Geographic correlation of the depth extent of faulting with topographic variations allows a first-order interpretation of the subsurface structure and mechanical stratigraphy in the basin. Further, crosscutting and superposition relationships among plains, faults, craters, and topography indicate that development of long-wavelength topographic variations followed plains emplacement, faulting, and much of the cratering within the Caloris basin. As several examples of these topographic undulations are also found outside the basin, our results on the scale, structural style, and relative timing of the topographic changes have regional applicability and may be the surface expression of global-scale interior processes on Mercury
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Human Immunodeficiency Virus (HIV)-Infected CCR6+ Rectal CD4+ T Cells and HIV Persistence On Antiretroviral Therapy.
BackgroundIdentifying where human immunodeficiency virus (HIV) persists in people living with HIV and receiving antiretroviral therapy is critical to develop cure strategies. We assessed the relationship of HIV persistence to expression of chemokine receptors and their chemokines in blood (n = 48) and in rectal (n = 20) and lymph node (LN; n = 8) tissue collected from people living with HIV who were receiving suppressive antiretroviral therapy.MethodsCell-associated integrated HIV DNA, unspliced HIV RNA, and chemokine messenger RNA were quantified by quantitative polymerase chain reaction. Chemokine receptor expression on CD4+ T cells was determined using flow cytometry.ResultsIntegrated HIV DNA levels in CD4+ T cells, CCR6+CXCR3+ memory CD4+ T-cell frequency, and CCL20 expression (ligand for CCR6) were highest in rectal tissue, where HIV-infected CCR6+ T cells accounted for nearly all infected cells (median, 89.7%). Conversely in LN tissue, CCR6+ T cells were infrequent, and there was a statistically significant association of cell-associated HIV DNA and RNA with CCL19, CCL21, and CXCL13 chemokines.ConclusionsHIV-infected CCR6+ CD4+ T cells accounted for the majority of infected cells in rectal tissue. The different relationships between HIV persistence and T-cell subsets and chemokines in rectal and LN tissue suggest that different tissue-specific strategies may be required to eliminate HIV persistence and that assessment of biomarkers for HIV persistence may not be generalizable between blood and other tissues
FEV1 over time in patients with connective tissue disease-related bronchiolitis
SummaryBackgroundFibrosis or inflammation of the bronchioles is a well-known manifestation of connective tissue disease (CTD). However, the natural history of CTD-related bronchiolitis is largely unknown.MethodsWe analyzed consecutive patients evaluated at National Jewish Health (Denver, CO) from 1998 to 2008 with CTD and surgical lung biopsy-confirmed bronchiolitis. Linear mixed effects models were used to estimate the longitudinal postbronchodilator FEV1 %predicted (%pred) course and differences between subjects with or without constrictive bronchiolitis (CB).ResultsOf 28 subjects with a mean age of 53 ± 9 years, fourteen (50%) had CB. The most common CTD diagnosis was rheumatoid arthritis (n = 14; 50%). There were no significant differences in demographics, smoking status, underlying CTD diagnoses, 6-min walk distance, dyspnea score or drug therapy between subjects with CB and those with cellular bronchiolitis. Three subjects with CB (11%) and four with cellular bronchiolitis (14%) died. Compared with subjects with CB, those with cellular bronchiolitis had higher mean FEV1 %pred at all times. There were no significant differences in FEV1 %pred slope within- or between-groups (CB vs. cellular bronchiolitis) preceding surgical lung biopsy or afterward.ConclusionSubjects with CTD-related CB had lower FEV1 %pred values than those with CTD-related cellular bronchiolitis at all time points, but FEV1 %pred remained stable over time in both groups regardless of therapy received
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