Citations

Purrpose: To evaluate myocardial microvascular disease in patients with type 2 diabetes mellitus (DM) using myocardial contrast echocardiography (MCE) and to report on its diagnostic accuracy using single photon emission tomography (SPECT) as reference test. Methods: We prospectively enrolled 79 patients (25 DM; 66±11 years) who underwent simultaneous SPECT and MCE with contrast agent during adenosine stress. MCE and SPECT were visually analyzed using 17 segments. Quantitative MCE parameters were derived from replenishment curves. Microbubble velocity (β min −1 ), absolute myocardial blood flow (MBF ml/min/g), and reserve values were calculated. Diagnostic accuracy and area under curve (AUC) was reported. Results: Patients with DM had higher BMI vs non DM (33±7 vs 28±5kg/m 2 P=0 .007), with more prior myocardial infarction (40 vs 15% P=.01). Visual MCE was abnormal in 40 (51%) patients (60% in DM vs 46% in non DM P=0.04). SPECT was abnormal in 38 (48%) patients [60% in DM vs 42% non DM, P=0.01]. Reserve parameters were lower in DM vs. non DM patients: (β 1.77±1.12 vs 2.20±1.4, P<0.001 and MBF 2.86± 2.62 vs. 3.67±2.84, P<0.001). DM patients without CAD on SPECT had significantly lower β, and MBF reserve compared to non DM patients without CAD. Compared to SPECT, β reserve cutoff 1.6 had AUC 0.817, sensitivity 81%, and specificity 66% while MBF reserve cutoff 1.9 had AUC 0.760, sensitivity 79%, and specificity 63% in DM patients. Conclusion: Diabetes is associated with myocardial microvascular abnormalities as evidenced by abnormal myocardial perfusion on visual and quantitative MCE.

A greater understanding of participant views regarding reimbursement will help investigators plan studies that have better potential for reaching target enrollment, maximize efficient recruitment, maintain scientific integrity, and enhance retention over time. As part of a clinical trial in the area of sexual health, healthy women's perceptions of reimbursement for research participation were investigated. Semi-structured, audio-recorded, qualitative interviews were conducted immediately upon women's completion of the clinical trial to enable a participant-driven understanding of perceptions about monetary reimbursement. Audio-recordings were transcribed and analyzed using framework analysis. Women (N = 30) had a mean age of 29.5 ± 5.7 years (range 22–45 years). Sixty-three percent of participants (n = 19) were non-Hispanic (white n = 13, black n = 4, and Asian n = 2), while the remaining were Hispanic (n = 11). Seventy-three percent (n = 22) reported previous participation in research. In general, women viewed reimbursement as a benefit to research participation, the amount of which should reflect time, the inconvenience to the research subject, and the potential for unknown risks in the short- and long-term. They believed reimbursement should take into account the degree of risk of the study, with investigations of experimental products offering greater reimbursement. Women believed that monetary reimbursement is unlikely to coerce an individual to volunteer for a study involving procedures or requirements that they found unacceptable. The results of this study can be used to provide guidance to those planning and evaluating reimbursement for research participation.

AbstractAlthough proinflammatory and chemotactic cytokines can profoundly affect the tumor microenvironment, and many of them have been shown to have therapeutic efficacy in preclinical models, the role of these molecules in Waldenström macroglobulinemia (WM) remains poorly understood. In this study, simultaneous analysis of WM patient sera and bone marrow biopsies identified a set of dysregulated cytokines including CCL5, G-CSF, and soluble IL-2 receptor, that were significantly elevated in WM patients whereas IL-8 and EGF levels were significantly lower in these patients compared with healthy controls. Interestingly, CCL5 levels positively correlated with features of disease aggressiveness such as elevated IgM levels and bone marrow involvement. Functional analysis of tumor microenvironment revealed a functional correlation between CCL5 levels and IL-6 levels, a proinflammatory cytokine with an important role in normal and malignant B-cell biology. Furthermore, CCL5 stimulated IL-6 secretion in WM stromal cells resulting in increased IgM secretion by WM malignant cells via the JAK/STAT signaling pathway. Thus, together these results define a novel signaling network in the WM tumor microenvironment controlling IgM secretion and suggest CCL5 as a potential target for the treatment of this disease.

Background Intermediate outcome variables can often be used as auxiliary variables for the true outcome of interest in randomized clinical trials. For many cancers, time to recurrence is an informative marker in predicting a patient's overall survival outcome and could provide auxiliary information for the analysis of survival times. Purpose To investigate whether models linking recurrence and death combined with a multiple imputation procedure for censored observations can result in efficiency gains in the estimation of treatment effects and be used to shorten trial lengths. Methods Recurrence and death times are modeled using data from 12 trials in colorectal cancer. Multiple imputation is used as a strategy for handling missing values arising from censoring. The imputation procedure uses a cure model for time to recurrence and a time-dependent Weibull proportional hazards model for time to death. Recurrence times are imputed, and then death times are imputed conditionally on recurrence times. To illustrate these methods, trials are artificially censored 2 years after the last accrual, the imputation procedure implemented, and a log-rank test and Cox model used to analyze and compare these new data with the original data. Results The results show modest, but consistent gains in efficiency in the analysis using the auxiliary information in recurrence times. Comparison of analyses show the treatment effect estimates and log-rank test results from the 2-year censored imputed data to be in between the estimates from the original data and the artificially censored data, indicating that the procedure was able to recover some of the lost information due to censoring. Limitations The models used are all fully parametric, requiring distributional assumptions of the data. Conclusions The proposed models may be useful in improving the efficiency in estimation of treatment effects in cancer trials and shortening trial length.