Publications

Readmissions to the hospital are common and costly, often resulting from poor care coordination. Despite increased attention given to improving the quality and safety of care transitions, little is known about patient and provider perspectives of the transitional care needs of rehospitalized Veterans. As part of a larger quality improvement initiative to reduce hospital readmissions, the authors conducted semi-structured interviews with 25 patients and 14 of their interdisciplinary health care providers to better understand their perspectives of the transitional care needs and challenges faced by rehospitalized Veterans. Patients identified 3 common themes that led to rehospitalization: (1) knowledge gaps and deferred power; (2) difficulties navigating the health care system; and (3) complex psychiatric and social needs. Providers identified different themes that led to rehospitalization: (1) substance abuse and mental illness; (2) lack of social or financial support and homelessness; (3) premature discharge and poor communication; and (4) nonadherence with follow-up. Results underscore that rehospitalized Veterans have a complex overlapping profile of real and perceived physical, mental, and social needs. A paradigm of disempowerment and deferred responsibility appears to exist between patients and providers that contributes to ineffective care transitions, resulting in readmissions. These results highlight the cultural constraints on systems of care and suggest that process improvements should focus on increasing the sense of partnership between patients and providers, while simultaneously creating a culture of empowerment, ownership, and engagement, to achieve success in reducing hospital readmissions.

Pulmonary fibrosis is a vexing clinical problem with no proven therapeutic options. In the normal lung there is continuous collagen synthesis and collagen degradation, and these two processes are precisely balanced to maintain normal tissue architecture. With lung injury there is an increase in the rate of both collagen production and collagen degradation. The increase in collagen degradation is critical in preventing the formation of permanent scar tissue each time the lung is exposed to injury. In pulmonary fibrosis, collagen degradation does not keep pace with collagen production, resulting in extracellular accumulation of fibrillar collagen. Collagen degradation occurs through both extracellular and intracellular pathways. The extracellular pathway involves cleavage of collagen fibrils by proteolytic enzyme including the metalloproteinases. The less-well-described intracellular pathway involves binding and uptake of collagen fragments by fibroblasts and macrophages for lysosomal degradation. The relationship between these two pathways and their relevance to the development of fibrosis is complex. Fibrosis in the lung, liver, and skin has been associated with an impaired degradative environment. Much of the current scientific effort in fibrosis is focused on understanding the pathways that regulate increased collagen production. However, recent reports suggest an important role for collagen turnover and degradation in regulating the severity of tissue fibrosis. The objective of this review is to evaluate the roles of the extracellular and intracellular collagen degradation pathways in the development of fibrosis and to examine whether pulmonary fibrosis can be viewed as a disease of impaired matrix degradation rather than a disease of increased matrix production.

AIMS

Genetic and pharmacological studies have shown that impairment of the nitric oxide (NO) synthase (NOS) pathway is associated with hypertension and insulin-resistance (IR). In addition, inhibition of NOS by the endogenous inhibitor, asymmetric dimethylarginine (ADMA), may also result in hypertension and IR. On the other hand, overexpression of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes ADMA, in mice is associated with lower ADMA, increased NO and enhanced insulin sensitivity. Since DDAH carries a farnesoid X receptor (FXR)-responsive element, we aimed to upregulate its expression by an FXR-agonist, INT-747, and evaluate its effect on blood pressure and insulin sensitivity.

METHODS AND RESULTS

In this study, we evaluated the in vivo effect of INT-747 on tissue DDAH expression and insulin sensitivity in the Dahl rat model of salt-sensitive hypertension and IR (Dahl-SS). Our data indicates that high salt (HS) diet significantly increased systemic blood pressure. In addition, HS diet downregulated tissue DDAH expression while INT-747 protected the loss in DDAH expression and enhanced insulin sensitivity compared to vehicle controls.

CONCLUSION

Our study may provide the basis for a new therapeutic approach for IR by modulating DDAH expression and/or activity using small molecules.

Hispanic women in the USA have lower breast cancer incidence than non-Hispanic white (NHW) women. Genetic factors may contribute to this difference. Breast cancer genome-wide association studies (GWAS) conducted in women of European or Asian descent have identified multiple risk variants. We tested the association between 10 previously reported single nucleotide polymorphisms (SNPs) and risk of breast cancer in a sample of 4697 Hispanic and 3077 NHW women recruited as part of three population-based case-control studies of breast cancer. We used stratified logistic regression analyses to compare the associations with different genetic variants in NHWs and Hispanics classified by their proportion of Indigenous American (IA) ancestry. Five of 10 SNPs were statistically significantly associated with breast cancer risk. Three of the five significant variants (rs17157903-RELN, rs7696175-TLR1 and rs13387042-2q35) were associated with risk among Hispanics but not in NHWs. The odds ratio (OR) for the heterozygous at 2q35 was 0.75 [95% confidence interval (CI) = 0.50-1.15] for low IA ancestry and 1.38 (95% CI = 1.04-1.82) for high IA ancestry (P interaction 0.02). The ORs for association at RELN were 0.87 (95% CI = 0.59-1.29) and 1.69 (95% CI = 1.04-2.73), respectively (P interaction 0.03). At the TLR1 locus, the ORs for women homozygous for the rare allele were 0.74 (95% CI = 0.42-1.31) and 1.73 (95% CI = 1.19-2.52) (P interaction 0.03). Our results suggest that the proportion of IA ancestry modifies the magnitude and direction of the association of 3 of the 10 previously reported variants. Genetic ancestry should be considered when assessing risk in women of mixed descent and in studies designed to discover causal mutations.