Publications
Department of Medicine faculty members published more than 3,600 peer-reviewed articles in 2024.
2015
PURPOSE
Progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) trials has been inconsistently defined and poorly associated with overall survival (OS). A reproducible quantitative definition of radiographic PFS (rPFS) was tested for association with a coprimary end point of OS in a randomized trial of abiraterone in patients with mCRPC.
PATIENTS AND METHODS
rPFS was defined as ≥ two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ≥ two new confirmed lesions on any scan ≥ 12 weeks after random assignment, and/or progression in nodes or viscera on cross-sectional imaging, or death. rPFS was assessed by independent review at 15% of deaths and by investigator review at 15% and 40% of deaths. rPFS and OS association was evaluated by Spearman's correlation.
RESULTS
A total of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone. At first interim analysis, the hazard ratio (HR) by independent review was 0.43 (95% CI, 0.35 to 0.52; P < .001; abiraterone plus prednisone: median rPFS, not estimable; prednisone: median rPFS, 8.3 months). Similar HRs were obtained by investigator review at the first two interim analyses (HR, 0.49; 95% CI, 0.41 to 0.60; P < .001 and HR, 0.53; 95% CI, 0.45 to 0.62; P < .001, respectively), validating the imaging data assay used. Spearman's correlation coefficient between rPFS and OS was 0.72.
CONCLUSION
rPFS was highly consistent and highly associated with OS, providing initial prospective evidence on further developing rPFS as an intermediate end point in mCRPC trials.
View on PubMed2015
2015
2015
PURPOSE
Recent anatomic studies have suggested that the dominant arterial supply of the patella enters through the inferior pole. Based upon these findings, we hypothesized that bone-patellar tendon-bone graft harvest can significantly diminish patellar vascularity.
METHODS
Nine matched pair cadaveric knee specimens (mean age 47.4 years) were dissected and cannulated. A single knee was selected to undergo routine graft harvest, and the contralateral knee was left intact to serve as a control. Gadolinium was injected, and magnetic resonance imaging (MRI) signal enhancement was quantified to determine differences in uptake. Each matched pair was subsequently injected with a urethane polymer compound and dissected to correlate vessel disruption with MRI findings.
RESULTS
We identified two predominating patterns of vessel entry. In one pattern, the vessel entered the inferomedial aspect (five o'clock/right, seven o'clock/left) of the patella and was disrupted by graft harvest in 2/9 (22.2 %) pairs. In the second pattern, the vessel entered further medial (four o'clock/right, eight o'clock/left) and was not disrupted (7/9, 78.8 %). The mean decrease in gadolinium uptake following disruption of the predominant vessel measured 56.2 % (range 42.6-69.5 %) compared to an average decrease of 18.3 % (range 7.1-29.1 %) when the dominant arterial supply to the inferior pole remained intact (p < 0.04).
CONCLUSION
Medial entry of the predominant vessel precluded vessel disruption. Disruption of the dominant arterial supply can result in a significant decrease in patellar vascularity. Modification of graft harvest techniques and areas of surgical dissection should be explored to minimize vascular insult. Further correlation with clinical studies/outcomes is necessary to determine a potential association between vascular insult and anterior knee pain.
View on PubMed2015
2015
2015
2015
BACKGROUND
Studies of the quality of tuberculosis (TB) diagnostic evaluation of patients in high burden countries have generally shown poor adherence to international or national guidelines. Health worker perspectives on barriers to improving TB diagnostic evaluation are critical for developing clinic-level interventions to improve guideline implementation.
METHODS
We conducted structured, in-depth interviews with staff at six district-level health centers in Uganda to elicit their perceptions regarding barriers to TB evaluation. Interviews were transcribed, coded with a standardized framework, and analyzed to identify emergent themes. We used thematic analysis to develop a logic model depicting health system and contextual barriers to recommended TB evaluation practices. To identify possible clinic-level interventions to improve TB evaluation, we categorized findings into predisposing, enabling, and reinforcing factors as described by the PRECEDE model, focusing on potentially modifiable behaviors at the clinic-level.
RESULTS
We interviewed 22 health center staff between February 2010 and November 2011. Participants identified key health system barriers hindering TB evaluation, including: stock-outs of drugs/supplies, inadequate space and infrastructure, lack of training, high workload, low staff motivation, and poor coordination of health center services. Contextual barrier challenges to TB evaluation were also reported, including the time and costs borne by patients to seek and complete TB evaluation, poor health literacy, and stigma against patients with TB. These contextual barriers interacted with health system barriers to contribute to sub-standard TB evaluation. Examples of intervention strategies that could address these barriers and are related to PRECEDE model components include: assigned mentors/peer coaching for new staff (targets predisposing factor of low motivation and need for support to conduct job duties); facilitated workshops to implement same day microscopy (targets enabling factor of patient barriers to completing TB evaluation), and recognition/incentives for good TB screening practices (targets low motivation and self-efficacy).
CONCLUSIONS
Our findings suggest that health system and contextual barriers work together to impede TB diagnosis at health centers and, if not addressed, could hinder TB case detection efforts. Qualitative research that improves understanding of the barriers facing TB providers is critical to developing targeted interventions to improve TB care.
View on PubMed2015
OBJECTIVE
To better understand why immunosuppressed individuals with systemic lupus erythematosus (SLE) fail to receive influenza and pneumococcal vaccines.
METHODS
These cross-sectional data were derived from the 2009 cycle of the Lupus Outcomes Study (LOS), an annual longitudinal telephone survey of individuals with confirmed SLE. Respondents were included in the analysis if they had taken immunosuppressive medications in the past year. We assessed any prior receipt of pneumococcal vaccine and influenza vaccine in the past year, and then elicited reasons for not receiving vaccination. We used bivariate statistics and multivariate logistic regression to assess frequency and predictors of reported reasons for not obtaining influenza or pneumococcal vaccines.
RESULTS
Among 508 respondents who received immunosuppressants, 485 reported whether they had received vaccines. Among the 175 respondents who did not receive an influenza vaccine, the most common reason was lack of doctor recommendation (55%), followed by efficacy or safety concerns (21%), and lack of time (19%). Reasons for not receiving pneumococcal vaccine (N = 159) were similar: lack of recommendation (87%), lack of time (7%), and efficacy or safety concerns (4%). Younger, less-educated, non-white patients with shorter disease duration, as well as those immunosuppressed with steroids alone, were at the greatest risk for not receiving indicated vaccine recommendations.
CONCLUSIONS
The most common reason why individuals with SLE did not receive pneumococcal and influenza vaccines was that physicians failed to recommend them. Data suggest that increasing vaccination rates in SLE will require improved process quality at the provider level, as well as addressing patient concerns and barriers.
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