Intervertebral disc degeneration (IDD) is a common and debilitating disorder that results in reduced flexibility of the spine, pain, and reduced mobility. Risk factors for IDD include age, genetic predisposition, injury, and other environmental factors such as smoking. Loss of proteoglycans (PGs) contributes to IDD with advancing age. Currently there is a lack of a model for rapid investigation of disc aging and evaluation of therapeutic interventions. Here we examined progression of disc aging in a murine model of a human progeroid syndrome caused by deficiency of the DNA repair endonuclease, ERCC1–XPF (Ercc1−/Δ mice). The ERCC1-deficient mice showed loss of disc height and degenerative structural changes in their vertebral bodies similar to those reported for old rodents. Compared to their wild-type littermates, Ercc1−/Δ mice also exhibit other age-related IDD characteristics, including premature loss of disc PG, reduced matrix PG synthesis, and enhanced apoptosis and cell senescence. Finally, the onset of age-associated disc pathologies was further accelerated in Ercc1−/Δ mice following chronic treatment with the chemotherapeutic agent mechlorethamine. These results demonstrate that Ercc1−/Δ mice represent an accurate and rapid model of disc aging and provide novel evidence that DNA damage negatively impacts PG synthesis.

Next steps include working with VHA leaders to develop and test implementation approaches to help ensure that the next generation of PMs motivate truly patient-centered care and are clinically meaningful.

Background Accurately estimating cardiovascular risk is fundamental to good decision-making in cardiovascular disease (CVD) prevention, but risk scores developed in one population often perform poorly in dissimilar populations. We sought to examine whether a large integrated health system can use their electronic health data to better predict individual patients’ risk of developing cardiovascular disease (CVD). Methods We created a cohort using all patients ages 45–80 who used Department of Veterans Affairs (VA) ambulatory care services in 2006 with no history of CVD, heart failure, or loop diuretics. Our outcome variable was new-onset CVD in 2007–11. We then developed a series of recalibrated scores, including a fully re-fit “VA Risk Score – CVD (VARS-CVD).” We tested the different scores using standard measures of prediction quality. Results For the 1,512,092 patients in the study, the ASCVD risk score had similar discrimination as the VARS-CVD (C-statistic of 0.66 in men and 0.73 in women), but the ASCVD model had poor calibration, predicting 63% more events than observed. Calibration was excellent in the fully recalibrated VARS-CVD tool, but simpler techniques tested proved less reliable. Conclusions We found that local electronic health record data can be used to estimate CVD better than an established risk score based on research populations. Recalibration improved estimates dramatically, and the type of recalibration was important. Such tools can also easily be integrated into health system’s electronic health record and can be more readily updated.

Abstract-Obesity is a significant health problem among Veterans who receive care from the Department of Veterans Affairs, as it is for so many other Americans. Veterans from Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) experience a myriad of chronic conditions, which can make it difficult to maintain a physically active lifestyle. This pilot study tested the feasibility and user satisfaction with three low-cost, home-based diet and exercise programs, as well as point-of-decision prompts among these Veterans. The three programs target mechanisms that have been shown to improve healthy behavior change, including (1) online mediated social support, (2) objective monitoring of physical activity, and (3) structured high-intensity workouts. This was a randomized crossover trial; each participant used two of the three programs, and all used the point-of-decision prompts. Our qualitative results identified five overall themes related to social support, objective monitoring, structured activity, awareness and understanding, and the point-of-decision prompts. In general, participants were satisfied with and lost weight with each of the interventions. This study demonstrated that these lowcost interventions could be successful with the OIF/OEF Veteran population. A larger and longer study is planned to further investigate the effectiveness of these interventions.