Lifestyle Intervention Strategy to Treat Diabetes in Older Adults: A Randomized Controlled Trial.

OBJECTIVE: Lifestyle intervention is recommended as first-line treatment of diabetes at all ages; however, little is known about the efficacy of lifestyle intervention in older adults with diabetes. We aimed to determine whether lifestyle intervention would improve glycemic control and age-relevant outcomes in older adults with diabetes and comorbidities. RESEARCH DESIGN AND METHODS: A total of 100 older adults with diabetes were randomly assigned to 1-year intensive lifestyle intervention (ILI) (diet and exercise at a facility transitioned into community-fitness centers and homes) or healthy lifestyle (HL) group. The primary outcome was change in HbA1c. Secondary outcomes included glucoregulation, body composition, physical function, and quality of life. Changes between groups were analyzed with mixed-model repeated-measures ANCOVA following the intention-to-treat principle. RESULTS: HbA1c improved more in the ILI than the HL group (mean ± SE -0.8 ± 0.1 vs. 0.1 ± 0.1%), associated with improved insulin sensitivity (1.2 ± 0.2 vs. -0.4 ± 0.2) and disposition (26.0 ± 8.9 vs. -13.0 ± 8.4 109 min-1) indices (between-group P < 0.001 to 0.04). Body weight and visceral fat decreased more in the ILI than HL group (-8.4 ± 0.6 vs. -0.3 ± 0.6 kg, P < 0.001, and -261 ± 29 vs. -30 ± 27 cm3, P < 0.001, respectively). Physical Performance Test score increased more in the ILI than HL group (2.9 ± 0.6 vs. -0.1 ± 0.4, P < 0.001) as did VO2peak (2.2 ± 0.3 vs. -1.2 ± 0.2 mL/kg/min, P < 0.001). Strength, gait, and 36-Item Short Form Survey (SF-36) Physical Component Summary score also improved more in the ILI group (all P < 0.001). Total insulin dose decreased in the ILI group by 19.8 ± 4.4 units/day. Adverse events included increased episodes of mild hypoglycemia in the ILI group. CONCLUSIONS: A lifestyle intervention strategy is highly successful in improving metabolic and functional health of older adults with diabetes.

Hypogonadal men with type 2 diabetes mellitus have smaller bone size and lower bone turnover.

INTRODUCTION: Both hypogonadism and type 2 diabetes mellitus (T2D) are associated with increased fracture risk. Emerging data support the negative effect of low testosterone on glucose metabolism, however, there is little information on the bone health of hypogonadal men with diabetes. We evaluated the bone mineral density (BMD), bone geometry and bone turnover of hypogonadal men with T2D compared to hypogonadal men without diabetes. MATERIALS AND METHODS: Cross-sectional study, men 40-74years old, with average morning testosterone (done twice) of<300ng/dl. Areal BMD (aBMD) was measured by DXA; volumetric BMD (vBMD) and bone geometry by peripheral-quantitative-computed-tomography; serum C-telopeptide (CTX), osteocalcin, sclerostin and sex hormone-binding globulin (SHBG) by ELISA, testosterone and 25-hydroxyvitamin D (25OHD) by automated immunoassay and estradiol by liquid-chromatography/mass-spectrometry. Groups were compared by ANOVA adjusted for covariates. RESULTS: One-hundred five men, 49 with and 56 without diabetes were enrolled. Adjusted vBMD at 38% tibia was higher in diabetic than non-diabetic men (857.3±69.0mg/cm3 vs. 828.7±96.7mg/cm3, p=0.02). Endosteal (43.9±5.8mm vs. 47.1±7.8mm, p=0.04) and periosteal (78.4±5.0mm vs. 81.3±6.5mm, p=0.02) circumferences and total area (491.0±61.0mm2 vs. 527.7±87.2mm2, p=0.02) at 38% tibia, were lower in diabetic men even after adjustments for covariates. CTX (0.25±0.14ng/ml vs. 0.40±0.19ng/ml, p<0.001) and osteocalcin (4.8±2.8ng/ml vs. 6.8±3.5ng/ml, p=0.006) were lower in diabetic men; there were no differences in sclerostin and 25OHD. Circulating gonadal hormones were comparable between the groups. CONCLUSION: Among hypogonadal men, those with T2D have higher BMD, poorer bone geometry and relatively suppressed bone turnover. Studies with larger sample size are needed to verify our findings and possible even greater risk for fractures among hypogonadal diabetic men.

Aerodigestive fistula formation as a rare side effect of antiangiogenic tyrosine kinase inhibitor therapy for thyroid cancer.

BACKGROUND: In the past decade, targeted therapy with antiangiogenic drugs has become standard of care for most types of metastatic, progressive thyroid cancer. While these drugs were thought initially to be less toxic than traditional chemotherapy, they can have rare but serious and fatal toxicities. Once such toxicity that has been reported in other tumor types is upper airway fistula formation, which can be life-threatening. SUMMARY: Here, we describe three patients treated with antiangiogenic tyrosine kinase inhibitors at two academic institutions who developed aerodigestive fistula. All three patients had risk factors for fistula formation, which included external beam radiation and/or large tumor with invasion of the tracheal wall. CONCLUSIONS: Fistula formation is a known but rare side effect of antiangiogenic tyrosine kinase inhibitors. Knowledge of the risk factors that may predispose thyroid cancer patients to this serious adverse event is vital prior to prescribing antiangiogenics. Particular caution should be observed when using these drugs in patients undergoing radiation therapy or surgery, or in patients whose tumor is invading vital structures of the neck, as they may be at higher risk of developing this rare complication. In these patients, antiangiogenic tyrosine kinase inhibitors should be used cautiously, patients should be aware of the risk, and physicians should monitor patients for symptoms of fistula.

Stigma associated with PTSD: perceptions of treatment seeking combat veterans.

OBJECTIVE: Although stigma associated with serious mental illness, substance abuse disorders, and depression has been studied very little is known about stigma associated with Posttraumatic Stress Disorder (PTSD). This study explored stigma related to PTSD among treatment-seeking Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) combat veterans. METHOD: Sixteen treatment-seeking OEF/OIF veterans with combat-related PTSD participated in focus groups. We used qualitative methods to explore PTSD-related stigma. RESULTS: Common perceived stereotypes of treatment-seeking veterans with PTSD included labels such as "dangerous/violent," or "crazy," and a belief that combat veterans are responsible for having PTSD. Most participants reported avoiding treatment early on to circumvent a label of mental illness. Participants initially reported experiencing some degree of self-stigma; however, following engagement in treatment they predominantly resisted these stereotypes. Although most participants considered combat-related PTSD as less stigmatizing than other mental illnesses, they reported difficulties with reintegration. Such challenges likely stem from both PTSD symptoms and veterans' perceptions of how the public views them. Most reported that fellow combat veterans best understood them. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Awareness of public stereotypes impacts help seeking at least early in the course of illness. Peer-based outreach and therapy groups may help veterans engage in treatment early and resist stigma.

Partnering with communities to address the mental health needs of rural veterans.

PURPOSE: Many veterans who face mental illness and live in rural areas never obtain the mental health care they need. To address these needs, it is important to reach out to community stakeholders who are likely to have frequent interactions with veterans, particularly those returning from Operations Enduring and Iraqi Freedom (OEF/OIF). METHODS: Three community stakeholder groups-clergy, postsecondary educators, and criminal justice personnel-are of particular importance for OEF/OIF veterans living in rural areas and may be more likely to come into contact with rural veterans struggling with mental illness or substance abuse than the formal health care system. This article briefly describes the conceptualization, development, initial implementation, and early evaluation of a Veterans Affairs (VA) medical center-based program designed to improve engagement in, and access to, mental health care for veterans returning to rural areas. FINDINGS: One year since initial funding, 90 stakeholders have attended formal training workshops (criminal justice personnel = 36; educators = 31; clergy = 23). Two training formats (a 2-hour workshop and an intensive 2.5-day workshop) have been developed and provided to clergy in 1 rural county with another county scheduled for training. A veteran outreach initiative, which has received 32 referrals for various student services, has been established on 4 rural college campuses. A Veterans Treatment Court also has been established with 16 referrals for eligibility assessments. CONCLUSIONS: While this pilot program is in the early stages of evaluation, its success to date has encouraged program and VA clinical leadership to expand beyond the original sites.

Predicting implementation from organizational readiness for change: a study protocol.

BACKGROUND: There is widespread interest in measuring organizational readiness to implement evidence-based practices in clinical care. However, there are a number of challenges to validating organizational measures, including inferential bias arising from the halo effect and method bias - two threats to validity that, while well-documented by organizational scholars, are often ignored in health services research. We describe a protocol to comprehensively assess the psychometric properties of a previously developed survey, the Organizational Readiness to Change Assessment. OBJECTIVES: Our objective is to conduct a comprehensive assessment of the psychometric properties of the Organizational Readiness to Change Assessment incorporating methods specifically to address threats from halo effect and method bias. METHODS AND DESIGN: We will conduct three sets of analyses using longitudinal, secondary data from four partner projects, each testing interventions to improve the implementation of an evidence-based clinical practice. Partner projects field the Organizational Readiness to Change Assessment at baseline (n = 208 respondents; 53 facilities), and prospectively assesses the degree to which the evidence-based practice is implemented. We will conduct predictive and concurrent validities using hierarchical linear modeling and multivariate regression, respectively. For predictive validity, the outcome is the change from baseline to follow-up in the use of the evidence-based practice. We will use intra-class correlations derived from hierarchical linear models to assess inter-rater reliability. Two partner projects will also field measures of job satisfaction for convergent and discriminant validity analyses, and will field Organizational Readiness to Change Assessment measures at follow-up for concurrent validity (n = 158 respondents; 33 facilities). Convergent and discriminant validities will test associations between organizational readiness and different aspects of job satisfaction: satisfaction with leadership, which should be highly correlated with readiness, versus satisfaction with salary, which should be less correlated with readiness. Content validity will be assessed using an expert panel and modified Delphi technique. DISCUSSION: We propose a comprehensive protocol for validating a survey instrument for assessing organizational readiness to change that specifically addresses key threats of bias related to halo effect, method bias and questions of construct validity that often go unexplored in research using measures of organizational constructs.

p90RSK2 is essential for FLT3-ITD- but dispensable for BCR-ABL-induced myeloid leukemia.

p90 ribosomal S6 kinase 2 (p90RSK2) is important in diverse cellular processes including gene expression, cell proliferation, and survival. We found that p90RSK2 is commonly activated in diverse leukemia cell lines expressing different leukemogenic tyrosine kinases, including BCR-ABL and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD). Interestingly, in a murine BM transplantation (BMT) model, genetic deficiency of RSK2 did not affect the pathogenesis or disease progression of BCR-ABL-induced myeloproliferative neoplasm (PN). In contrast, FLT3-ITD induced a T-cell acute lymphoblastic leukemia in BMT mice receiving RSK2 knockout (KO) BM cells, phenotypically distinct from the myeloproliferative neoplasm induced by FLT3-ITD using wild-type BM cells. In consonance with these results, inhibition of RSK2 by an RSK inhibitor, fmk, did not effectively induce apoptosis in BCR-ABL-expressing murine Ba/F3 cells, human K562 cells or primary tissue samples from CML patients, whereas fmk treatment induced significant apoptotic cell death not only in FLT3-ITD-positive Ba/F3 cells, human Molm14 and Mv(4;11) leukemia cells, but also in primary tissue samples from AML patients. These results suggest that RSK2 is dispensable for BCR-ABL-induced myeloid leukemia, but may be required for pathogenesis and lineage determination in FLT3-ITD-induced hematopoietic transformation. RSK2 may thus represent an alternative therapeutic target in the treatment of FLT3-ITD-positive leukemia.

Collaborative research between clinicians and researchers: a multiple case study of implementation.

BACKGROUND: Bottom-up, clinician-conceived and directed clinical intervention research, coupled with collaboration from researcher experts, is conceptually endorsed by the participatory research movement. This report presents the findings of an evaluation of a program in the Veterans Health Administration meant to encourage clinician-driven research by providing resources believed to be critical. The evaluation focused on the extent to which funded projects: maintained integrity to their original proposals; were methodologically rigorous; were characterized by collaboration between partners; and resulted in sustained clinical impact. METHODS: Researchers used quantitative (survey and archival) and qualitative (focus group) data to evaluate the implementation, evaluation, and sustainability of four clinical demonstration projects at four sites. Fourteen research center mentors and seventeen clinician researchers evaluated the level of collaboration using a six-dimensional model of participatory research. RESULTS: Results yielded mixed findings. Qualitative and quantitative data suggested that although the process was collaborative, clinicians' prior research experience was critical to the quality of the projects. Several challenges were common across sites, including subject recruitment, administrative support and logistics, and subsequent dissemination. Only one intervention achieved lasting clinical effect beyond the active project period. Qualitative analyses identified barriers and facilitators and suggested areas to improve sustainability. CONCLUSIONS: Evaluation results suggest that this participatory research venture was successful in achieving clinician-directed collaboration, but did not produce sustainable interventions due to such implementation problems as lack of resources and administrative support.

Employing external facilitation to implement cognitive behavioral therapy in VA clinics: a pilot study.

BACKGROUND: Although for more than a decade healthcare systems have attempted to provide evidence-based mental health treatments, the availability and use of psychotherapies remains low. A significant need exists to identify simple but effective implementation strategies to adopt complex practices within complex systems of care. Emerging evidence suggests that facilitation may be an effective integrative implementation strategy for adoption of complex practices. The current pilot examined the use of external facilitation for adoption of cognitive behavioral therapy (CBT) in 20 Department of Veteran Affairs (VA) clinics. METHODS: The 20 clinics were paired on facility characteristics, and 23 clinicians from these were trained in CBT. A clinic in each pair was randomly selected to receive external facilitation. Quantitative methods were used to examine the extent of CBT implementation in 10 clinics that received external facilitation compared with 10 clinics that did not, and to better understand the relationship between individual providers' characteristics and attitudes and their CBT use. Costs of external facilitation were assessed by tracking the time spent by the facilitator and therapists in activities related to implementing CBT. Qualitative methods were used to explore contextual and other factors thought to influence implementation. RESULTS: Examination of change scores showed that facilitated therapists averaged an increase of 19% [95% CI: (2, 36)] in self-reported CBT use from baseline, while control therapists averaged a 4% [95% CI: (-14, 21)] increase. Therapists in the facilitated condition who were not providing CBT at baseline showed the greatest increase (35%) compared to a control therapist who was not providing CBT at baseline (10%) or to therapists in either condition who were providing CBT at baseline (average 3%). Increased CBT use was unrelated to prior CBT training. Barriers to CBT implementation were therapists' lack of control over their clinic schedule and poor communication with clinical leaders. CONCLUSIONS: These findings suggest that facilitation may help clinicians make complex practice changes such as implementing an evidence-based psychotherapy. Furthermore, the substantial increase in CBT usage among the facilitation group was achieved at a modest cost.

Evaluating a community-based participatory research project for elderly mental healthcare in rural America.

The purpose of this evaluation was to explore the collaborative nature of partners in a rural mental health program for the elderly, and to test an adapted method of assessing the collaborative process. Sixteen collaborative partners were interviewed to explore ratings of collaboration across 6 domains identified as critical to participatory research. Results indicate that the context of rural Missouri and uniqueness of the program necessitated an approach to collaboration that began with a top-down approach, but greater community responsibility developed over time. Partners recognized the efforts of the program's directors to seek input. Most were satisfied with their roles and the degree of success achieved by the program, although several wanted to have more input in the future in some domains, but not in others. Interviews revealed numerous barriers to achieving sustainability. Methods to improve the assessment of collaboration are discussed and areas for improvement are offered.

Translating clinical training into practice in complex mental health systems: toward opening the 'black box' of implementation.

BACKGROUND: Implementing clinical training in a complex health care system is challenging. This report describes two successive training programs in one Veterans Affairs healthcare network and the lessons we drew from their success and failures. The first training experience led us to appreciate the value of careful implementation planning while the second suggested that use of an external facilitator might be an especially effective implementation component. We also describe a third training intervention in which we expect to more rigorously test our hypothesis regarding the value of external facilitation. RESULTS: Our experiences appear to be consonant with the implementation model proposed by Fixsen. In this paper we offer a modified version of the Fixsen model with separate components related to training and implementation. CONCLUSION: This report further reinforces what others have noted, namely that educational interventions intended to change clinical practice should employ a multilevel approach if patients are to truly benefit from new skills gained by clinicians. We utilize an implementation research model to illustrate how the aims of the second intervention were realized and sustained over the 12-month follow-up period, and to suggest directions for future implementation research. The present report attests to the validity of, and contributes to, the emerging literature on implementation research.

Blockade of invasion and metastasis of breast cancer cells via targeting CXCR4 with an artificial microRNA.

miRNAs have been shown to function as regulatory molecules and to play an important role in cancer progression. Very little is currently known about the increasing invasion and metastasis of breast cancer due to the loss of expressive levels of certain miRNAs in breast tumor cells. In order to determine whether the CXCR4/SDF-1 pathway is regulated by expression of miRNAs, we designed and synthesized pre-miRNA against CXCR4. This double-stranded miRNA gene was ligated with a miR-155-based Block-iT Pol II miR RNAi Expression Vector (Invitrogen). Expression levels of CXCR4 in CXCR4-miRNA-transfected breast tumor cells had significantly declined. These cells exhibited reduced migration and invasion in vitro. Furthermore, they formed fewer lung metastases in vivo compared to ctrl-miRNA-transfected cells. These data support the conclusion that miRNA against CXCR4 can serve as an alterative means of therapy to lower CXCR4 expression and to block the invasion and metastasis of breast cancer cells.

Comparison of two enhanced consent procedures for patients with mild Alzheimer disease or mild cognitive impairment.

OBJECTIVE: The objective of this study was to evaluate the feasibility, acceptability, and preliminary efficacy of two enhanced consent procedures provided to patients with Alzheimer disease or mild cognitive impairment that used either a PowerPoint presentation or an enhanced printed consent form. METHODS: Patients randomly assigned to an enhanced written consent procedure or slideshow presentation were assessed with the MacArthur Competence Assessment Tool for Clinical Research. RESULTS: Verbal reexplanation was associated with improved understanding in both conditions. Level of understanding did not significantly differ between the two consent groups, but administration time for slideshow presentation was less than that for an enhanced written consent procedure. CONCLUSION: Enhanced consent procedures are feasible and useful for consent to research among patients with mild cognitive impairment or mild Alzheimer disease.

Characteristics of persons approving of physician-assisted death.

The present study describes the characteristics and attitudes of non-terminally ill persons who support physician-assisted death (PAD) along with their expectations and preferences for care in the future. Participants (N = 101) completed a survey assessing current affect and attitudes and those expected if terminally ill. Participants' responses indicated they were a well-adjusted group with little evidence of depressive symptoms or past suicidal ideation. Current attitudes were differentially related to future care preferences. Findings suggest a need for longitudinal research on the stability of current attitudes and how they relate to PAD among non-terminally ill supporters of assisted death.

End-of-life care in nursing homes: the interface of policy, research, and practice.

Much attention has begun to focus on the quality of care for persons near the end of life. Palliative care, especially through hospice, has generated much discussion as possibly the most holistic care available. Consideration of how chronically ill older adults receive such care as a result of public policy can benefit from adopting a multidimensional perspective. This paper adopts Bronfenbrenner's ecological model to understand current end-of-life care for nursing home residents, followed by consideration of how each of these dimensions or levels of influence can be used to foster both research agendas and policy reforms to improve end-of-life care of nursing home residents. Specifically, the benefits of considering the influence of such policy initiatives as the Medicare hospice benefit and the Patient Self-Determination Act (PSDA) on end-of-life care in nursing homes and the means through which policy can be informed by clinical research is emphasized.