Biobehavioral Intervention Targeting Physical Activity Behavior Change for Older Veterans after Nontraumatic Amputation: A Randomized Controlled Trial.

BACKGROUND: Lower-limb amputation (LLA) due to non-traumatic vascular etiology is linked to extremely low physical activity and high disability. OBJECTIVE: To test the feasibility of a biobehavioral intervention designed to promote physical activity. DESIGN: A randomized, single-blind feasibility trial with a crossover design. SETTING: Veterans Administration Medical Center. PARTICIPANTS: Military veterans (age: 65.7 [7.8] years; mean [standard deviation]) with nontraumatic lower-limb amputation (LLA), randomized to two groups: GROUP1 (n = 16) and GROUP2 (n = 15). Both groups had similar baseline amputation characteristics (level of amputation and time since amputation). INTERVENTIONS: Twelve weekly, 30-minute telehealth sessions of physical activity behavior-change intervention, with GROUP1 participating in weeks 1-12 and GROUP2 in weeks 13-24. GROUP1 noncontact phase in weeks 13-24 and GROUP2 attention control telehealth phase in weeks 1-12. MAIN OUTCOME MEASURES: Feasibility (participant retention, dose goal attainment, intervention acceptability [Intrinsic Motivation Inventory [IMI] Interest and Enjoyment scale], safety) and signal of efficacy (free-living physical activity [accelerometer-based average daily step count], Late Life Function and Disability Index - Disability Scale [LLFDI-DS]). RESULTS: Participant retention rate was high (90%), with three participants lost to follow-up during the intervention period. Dose goal attainment was low, with only 10% of participants achieving an a priori walking dose goal. Intervention was rated as acceptable, with mean IMI Interest and Enjoyment score (5.8) statistically higher than the null value of 5.0 (P = .002). There were no between-group differences in adverse event rates (falls: P = .19, lower extremity wounds: P = .60). There was no signal of efficacy for change in average daily step count (d = -0.15) or LLFDI-DS (d = -0.22 and 0.17 for frequency and limitations scales, respectively). CONCLUSIONS: Telehealth delivered biobehavioral intervention resulted in acceptable participant retention, low dose goal attainment, high participant acceptability, and low safety risk, while having no signal of efficacy (physical activity, disability) for people with nontraumatic LLA.

Vascular dysfunction across the stages of the menopausal transition is associated with menopausal symptoms and quality of life.

OBJECTIVE: The menopausal transition is associated with somatic symptoms and increased rates of depression, which can impair quality of life (QOL) and increase cardiovascular disease (CVD) risk. This period is also associated with accelerated vascular aging (arterial stiffening and endothelial dysfunction), an antecedent to CVD. This secondary analysis sought to explore associations between depression, menopausal symptoms and QOL, and vascular aging across menopause stages. METHODS: Arterial stiffness (carotid artery compliance), endothelial function (brachial artery flow-mediated dilation [FMD]), menopausal symptoms (Menopausal Symptom List [MSL]), depression (Center for Epidemiologic Studies Depression Scale [CES-D]), and QOL (Utian QOL Scale [UQOL]) were measured in 138 women (19-70 years) classified as premenopausal (n = 41, 34 ±â€Š8 years; mean ±â€ŠSD), early (n = 25, 49 ±â€Š3 years), or late perimenopausal (n = 26, 50 ±â€Š4 years), or early (n = 22, 55 ±â€Š4 years) or late postmenopausal (n = 24, 61 ±â€Š5 years). Differences across menopause stages were determined using one-way analysis of variance; associations between vascular measures and MSL, CES-D, and UQOL were tested using Pearson's correlation analyses. RESULTS: Menopausal symptoms, depression, and QOL worsened across menopause stages, particularly in late perimenopausal women. Vasosomatic symptom frequency, and general somatic symptom frequency and severity were inversely correlated with carotid artery compliance and FMD (r = -0.27 to -0.18, all P < 0.05). Only correlations with general somatic symptoms were significant after adjusting for multiple comparisons. Total QOL was positively correlated with carotid artery compliance (r = 0.23, P = 0.01). CES-D scores were not correlated with carotid artery compliance or FMD (r = -0.08, -0.03, P = 0.35). CONCLUSIONS: Vascular dysfunction across the stages of menopause was associated with greater frequency and severity of menopausal symptoms, and lower QOL, but not depression. Mechanisms underlying these associations (eg, inflammation, oxidative stress) should be explored.

Epidemiology of Infectious Disease-Related Death After Release from Prison, Washington State, United States, and Queensland, Australia: A Cohort Study.

OBJECTIVES: People in prison may be at high risk for infectious diseases and have an elevated risk of death immediately after release compared with later; their risk of death is elevated for at least a decade after release. We compared rates, characteristics, and prison-related risk factors for infectious disease-related mortality among people released from prisons in Queensland, Australia, and Washington State, United States, regions with analogous available data. METHODS: We analyzed data from retrospective cohort studies of people released from prison in Queensland (1997-2007, n=37,180) and Washington State (1999-2009, n=76,208) and linked identifiers from each cohort to its respective national death index. We estimated infectious disease-related mortality rates (deaths per person-years in community) and examined associations using Cox proportional hazard models. RESULTS: The most frequent infectious disease-related underlying cause of death after release from prison was pneumonia (43%, 23/54 deaths) in the Australian cohort and viral hepatitis (40%, 69/171 deaths) in the U.S. cohort. The infectious disease-related mortality rate was significantly higher in the U.S. cohort than in the Australian cohort (51.2 vs. 26.5 deaths per 100,000 person-years; incidence rate ratio = 1.93, 95% confidence interval 1.42, 2.62). In both cohorts, increasing age was strongly associated with mortality from infectious diseases. CONCLUSION: Differences in the epidemiology of infectious disease-related mortality among people released from prison may reflect differences in patterns of community health service delivery in each region. These findings highlight the importance of preventing and treating hepatitis C and other infectious diseases during the transition from prison to the community.

A NOTCH1 gene copy number gain is a prognostic indicator of worse survival and a predictive biomarker to a Notch1 targeting antibody in colorectal cancer.

Dysregulation of the Notch1 receptor has been shown to facilitate the development and progression of colorectal cancer (CRC) and has been identified as an independent predictor of disease progression and worse survival. Although mutations in the NOTCH1 receptor have not been described in CRC, we have previously discovered a NOTCH1 gene copy number gain in a portion of CRC tumor samples. Here, we demonstrated that a NOTCH1 gene copy number gain is significantly associated with worse survival and a high percentage of gene duplication in a cohort of patients with advanced CRC. In our CRC patient-derived tumor xenograft (PDTX) model, tumors harboring a NOTCH1 gain exhibited significant elevation of the Notch1 receptor, JAG1 ligand and cleaved Notch1 activity. In addition, a significant association was identified between a gain in NOTCH1 gene copy number and sensitivity to a Notch1-targeting antibody. These findings suggest that patients with metastatic CRC that harbor a gain in NOTCH1 gene copy number have worse survival and that targeting this patient population with a Notch1 antibody may yield improved outcomes.