Real-Time Visualization and Quantitation of Vascular Permeability In Vivo: Implications for Drug Delivery

The leaky, heterogeneous vasculature of human tumors prevents the even distribution of systemic drugs within cancer tissues. However, techniques for studying vascular delivery systems in vivo often require complex mammalian models and time-consuming, surgical protocols. The developing chicken embryo is a well-established model for human cancer that is easily accessible for tumor imaging. To assess this model for the in vivo analysis of tumor permeability, human tumors were grown on the chorioallantoic membrane (CAM), a thin vascular membrane which overlays the growing chick embryo. The real-time movement of small fluorescent dextrans through the tumor vasculature and surrounding tissues were used to measure vascular leak within tumor xenografts. Dextran extravasation within tumor sites was selectively enhanced an interleukin-2 (IL-2) peptide fragment or vascular endothelial growth factor (VEGF). VEGF treatment increased vascular leak in the tumor core relative to surrounding normal tissue and increased doxorubicin uptake in human tumor xenografts. This new system easily visualizes vascular permeability changes in vivo and suggests that vascular permeability may be manipulated to improve chemotherapeutic targeting to tumors

Turnaround Time Modeling for Conceptual Rocket Engines

Recent years have brought about a paradigm shift within NASA and the Space Launch Community regarding the performance of conceptual design. Reliability, maintainability, supportability, and operability are no longer effects of design; they have moved to the forefront and are affecting design. A primary focus of this shift has been a planned decrease in vehicle turnaround time. Potentials for instituting this decrease include attacking the issues of removing, refurbishing, and replacing the engines after each flight. less, it is important to understand the operational affects of an engine on turnaround time, ground support personnel and equipment. One tool for visualizing this relationship involves the creation of a Discrete Event Simulation (DES). A DES model can be used to run a series of trade studies to determine if the engine is meeting its requirements, and, if not, what can be altered to bring it into compliance. Using DES, it is possible to look at the ways in which labor requirements, parallel maintenance versus serial maintenance, and maintenance scheduling affect the overall turnaround time. A detailed DES model of the Space Shuttle Main Engines (SSME) has been developed. Trades may be performed using the SSME Processing Model to see where maintenance bottlenecks occur, what the benefits (if any) are of increasing the numbers of personnel, or the number and location of facilities, in addition to trades previously mentioned, all with the goal of optimizing the operational turnaround time and minimizing operational cost. The SSME Processing Model was developed in such a way that it can easily be used as a foundation for developing DES models of other operational or developmental reusable engines. Performing a DES on a developmental engine during the conceptual phase makes it easier to affect the design and make changes to bring about a decrease in turnaround time and costs

Racial Differences in Opioid Use for Chronic Nonmalignant Pain

BACKGROUND: Chronic pain is a frequent cause of suffering and disability that negatively affects patients' quality of life. There is growing evidence that disparities in the treatment of pain occur because of differences in race. OBJECTIVE: To determine whether race plays a role in treatment decisions involving patients with chronic nonmalignant pain in a primary care population. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional survey was administered to patients with chronic nonmalignant pain and their treating physicians at 12 academic medical centers. We enrolled 463 patients with nonmalignant pain persisting for more than 3 consecutive months and the primary care physicians participating in their care. RESULTS: Analysis of the 397 black and white patients showed that blacks had significantly higher pain scores (6.7 on a scale of 0 to 10, 95% confidence interval (CI) 6.4 to 7.0) compared with whites (5.6, 95% CI 5.3 to 5.9); however, white patients were more likely to be taking opioid analgesics compared with blacks (45.7% vs 32.2%, P<.006). Even after controlling for potentially confounding variables, white patients were significantly more likely (odds ratio (OR) 2.67, 95% CI 1.71 to 4.15) to be taking opioid analgesics than black patients. There were no differences by race in the use of other treatment modalities such as physical therapy and nonsteroidal anti-inflammatories or in the use of specialty referral. CONCLUSION: Equal treatment by race occurs in nonopioid-related therapies, but white patients are more likely than black patients to be treated with opioids. Further studies are needed to better explain this racial difference and define its effect on patient outcomes

Complementary and alternative medicine use by primary care patients with chronic pain

To describe the characteristics and attitudes toward complementary and alternative medicine (CAM) use among primary care patients with chronic pain disorders and to determine if CAM use is associated with better pain control. Cross-sectional survey. Four hundred sixty-three patients suffering from chronic, nonmalignant pain receiving primary care at 12 U.S. academic medical centers. Self-reported current CAM usage by patients with chronic pain disorders. The survey had an 81% response rate. Fifty-two percent reported current use of CAM for relief of chronic pain. Of the patients that used CAM, 54% agreed that nontraditional remedies helped their pain and 14% indicated that their individual alternative remedy entirely relieved their pain. Vitamin and mineral supplements were the most frequently used CAM modalities. There was no association between reported use of CAM and pain severity, functional status, or perceived self-efficacy. Patients who reported having at least a high school education (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.02-1.19, P = 0.016) and high levels of satisfaction with their health care (OR 1.47, 95% CI 1.13-1.91, P = 0.004) were significantly more likely to report using CAM. Complementary and alternative therapies were popular among patients with chronic pain disorders surveyed in academic primary care settings. When asked to choose between traditional therapies or CAM, most patients still preferred traditional therapies for pain relief. We found no association between reported CAM usage and pain severity, functional status, or self-efficacy

When race matters: disagreement in pain perception between patients and their physicians in primary care.

Patients and physicians often disagree in their assessment of pain intensity. This study explores the impact of patient factors on underestimation of pain intensity in chronic noncancer pain. We surveyed patients and their physicians in 12 primary care centers. To measure pain intensity, patients completed an 11-point numeric rating scale for which pain scores range from 0 (no pain) to 10 (unbearable pain). Physicians rated patients' pain on the same scale. We defined disagreement of pain intensity as underestimation or overestimation by 22 points. Of 601 patients approached, 463 (77%) completed the survey. The majority of participants were black (39%) or white (47%), 67% were female, and the mean age was 53 years. Physicians underestimated pain intensity relative to their patients 39% of the time. Forty-six percent agreed with their patients' pain perception, and 15% of physicians overestimated their patients' pain levels by > or =2 points. In both the bivariate and multivariable models, black race was a significant variable associated with underestimation of pain by physicians (p < 0.05; OR = 1.92; 95% CI: 1.31-2.81). This study finds that physicians are twice as likely to underestimate pain in blacks patients compared to all other ethnicities combined. A qualitative study exploring why physicians rate blacks patients' pain low is warranted

The Influence of Discordance in Pain Assessment on the Functional Status of Patients with Chronic Nonmalignant Pain

Chronic pain is a frequent cause of suffering and disability that seriously affects patients’ quality of life and imposes a staggering socioeconomic toll on society. Little is known about the impact of patient-physician disagreement (discordance) regarding the assessment of chronic pain on patients’ quality of life in primary care settings. This study evaluates the role of discordance and other potentially modifiable factors that affect the quality of life and functional status of chronic pain patients. We evaluated 436 patient-physician encounters at 12 academic medical centers in the United States. We surveyed chronic nonmalignant pain patients to understand their pain perceptions. We concurrently surveyed their physicians about their perceptions of their patient’s pain in primary care settings. More than 50% of physicians disagreed with their patient’s pain. Thirty-nine percent of primary care physicians underestimated their patient’s pain. In the multivariate analysis, this discordance was associated with poor physical functioning and worse bodily pain (P < 0.018 and P < 0.001 respectively). Patients with chronic, nonmalignant pain have reductions in physical function and bodily pain domains of the SF-36 compared to age-matched populations. Depression and obesity represented other associations. Patients with chronic nonmalignant pain have poor physical functioning and worse bodily pain. Discordance, obesity, and depression are other modifiable factors. Prospective studies are needed to design interventions. However, a multifaceted approach appears to represent the best opportunity to reduce the pain and suffering of this challenging population