Why patients stop using their home telehealth technologies over time: Predictors of discontinuation in Veterans with heart failure.

BACKGROUND: Daily use of home telehealth (HT) technologies decreases over time. Barriers to continued use are unclear. PURPOSE: To examine predictors of drop-out from HT in Veterans with heart failure. METHODS: Data for Veterans with heart failure enrolled in the Veterans Affairs HT Program were analyzed using a mixed effects Cox regression model to determine risk of dropping-out over a 1-year period. FINDINGS: Older (hazard ratio [HR] 1.01), sicker (prior hospital readmission [HR 1.39]), higher probability of hospital admission/death [HR 1.23], functional impairments [1.14]) and white Veterans (compared to black; HR 1.41) had higher risk of drop-out in HT Programs. Users of VA's online patient portal (HR 0.90) had lower risk of drop-out. DISCUSSION: Older and sicker patients are at most risk of stopping HT use, yet use of a patient portal shows promise in improving continued use. Interventions targeting patients at high risk for HT discontinuation are needed to promote ongoing engagement.

Adherence to the Use of Home Telehealth Technologies and Emergency Room Visits in Veterans with Heart Failure.

Background: Prior studies have posited poor patient adherence to remote patient monitoring as the reason for observed lack of benefits. Introduction: The purpose of this study was to examine the relationship between average adherence to the daily use of home telehealth (HT) and emergency room (ER) visits in Veterans with heart failure. Materials and Methods: This was a retrospective study using administrative data of Veterans with heart failure enrolled in Veterans Affairs (VA) HT Program in the first half of 2014. Zero-inflated negative binomial regression was used to determine which predictors affect the probability of having an ER visit and the number of ER visits. Results: The final sample size was 3,449 with most being white and male. There were fewer ER visits after HT enrollment (mean ± standard deviation of 1.85 ± 2.8) compared with the year before (2.2 ± 3.4). Patient adherence was not significantly associated with ER visits. Age and being from a racial minority group (not white or black) and belonging to a large HT program were associated with having an ER visit. Being in poorer health was associated with higher expected count of ER visits. Discussion: Subgroups of patients (e.g., with depression, sicker, or from a racial minority group) may benefit from added interventions to decrease ER use. Conclusions: This study found that adherence was not associated with ER visits. Reasons other than adherence should be considered when looking at ER use in patients with heart failure enrolled in remote patient monitoring programs.

Home Telehealth Technologies for Heart Failure: An Examination of Adherence Among Veterans.

The current retrospective cohort study uses Department of Veterans Affairs (VA) clinical and facility data of Veterans with heart failure enrolled in the VA Home Tele-health (HT) Program. General estimating equations with facility as a covariate were used to model percent average adherence at 1, 3, 6, and 12 months post-enrollment. Most HT patients were White, male, and of older age (mean = 71 years). Average adherence increased the longer patients remained in the HT program. Number of weekly reports of HT use, not having depression, and being of older age were all associated with higher adherence. Compared to White Veterans, Black and other non-White Veterans had lower adherence. These findings identify subgroups of patients (e.g., those with depression, of younger age, non-White) that may benefit from additional efforts to improve adherence to HT technologies. [Journal of Gerontological Nursing, 46(7), 26-34.].

Assessment of Lipid and Metabolite Changes in Obese Calf Muscle Using Multi-Echo Echo-planar Correlated Spectroscopic Imaging.

Obesity-related conditions including heart disease, stroke, and type 2 diabetes are leading causes of preventable death. Recent evidence suggests that altered myocellular lipid metabolism in obesity may lead to increased insulin resistance (IR) that predisposes to these disorders. To test the hypothesis that muscles rich in type I vs. type II muscle fibers would exhibit similar changes in intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) content in obesity, we utilized a new four-dimensional multi echo echo-planar correlated spectroscopic imaging technique that allows separate determination of IMCL and EMCL content in individual calf muscles in obese vs. normal healthy human subjects. Calf muscles were scanned in 32 obese and 11 healthy subjects using a 3T MRI/MRS scanner, and IR in the obese subjects was documented by glucose tolerance testing. In obese subjects, elevation of both IMCL and EMCL content was observed in the gastrocnemius and tibialis anterior muscles (with mixed type I and II fiber content), while a significant increase in only IMCL content (+48%, p < 0.001) was observed in the soleus muscle (predominantly type I fibers). These observations indicate unexpected differences in changes in myolipid metabolism in type I vs. type II rich muscle regions in obesity, perhaps related to IR, and warrant further investigation.

A pilot validation of multi-echo based echo-planar correlated spectroscopic imaging in human calf muscles.

A current limitation of MR spectroscopic imaging of multiple skeletal muscles is prolonged scan duration. A significant reduction in the total scan duration using the echo-planar correlated spectroscopic imaging (EP-COSI) sequence was accomplished using two bipolar readout trains with different phase-encoded echoes for one of two spatial dimensions within a single repetition time (TR). The second bipolar readout was used for spatially encoding the outer k-space, whereas the first readout was used for the central k-space only. The performance of this novel sequence, called multi-echo based echo-planar correlated spectroscopic imaging (ME-EPCOSI), was demonstrated by localizing specific key features in calf muscles and bone marrow of 11 healthy volunteers and five subjects with type 2 diabetes (T2D). A 3 T MRI-MRS scanner equipped with a transmit-receive extremity coil was used. Localization of the ME-EPCOSI sequence was in good agreement with the earlier single-readout based EP-COSI sequence and the required scan time was reduced by a factor of two. In agreement with an earlier report using single-voxel based 2D MRS, significantly increased unsaturated pools of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) and decreased IMCL and EMCL unsaturation indices (UIs) were observed in the soleus and tibialis anterior muscle regions of subjects with T2D compared with healthy controls. In addition, significantly decreased choline content was observed in the soleus of T2D subjects compared with healthy controls. Multi-voxel characterization of IMCL and EMCL ratios and UI in the calf muscle may be useful for the non-invasive assessment of altered lipid metabolism in the pathophysiology of T2D.

Older age at rheumatoid arthritis onset and comorbidities correlate with less Health Assessment Questionnaire-Disability Index and Clinical Disease Activity Index response to etanercept in the RADIUS 2 registry.

BACKGROUND: Controversy exists in understanding the effects of age at onset and comorbidities in predicting rheumatoid arthritis (RA) response to biologic therapy. OBJECTIVE: The objective of this study was to investigate the influence of age at onset and number of comorbidities on Health Assessment Questionnaire-Disability Index (HAQ-DI) and Clinical Disease Activity Index (CDAI) responses in active RA patients after 6 months of treatment with etanercept. METHODS: One thousand eight hundred ninety-nine RA patients were assessed after 6 months of etanercept therapy. Patients met the following inclusion criteria: initiated etanercept, continued therapy for at least 6 months, and were not in CDAI low disease activity (LDA) at baseline (CDAI ≤10.0). Changes in HAQ-DI and CDAI scores over 6 months were analyzed across age of onset quintiles. Multivariate regression models evaluated the independent association between both age at onset and number of comorbidities with change in HAQ-DI/CDAI scores or achieving LDA, while accounting for other covariates. RESULTS: Significant improvements in HAQ-DI and CDAI scores were observed in all age-onset groups, although HAQ-DI improvements were less in older-onset patients. Results of multiple linear regression demonstrated that younger age at onset, higher baseline HAQ-DI/CDAI score, rheumatoid factor positivity, shorter disease duration, and fewer comorbidities at baseline were independently associated with improvement in both HAQ-DI and CDAI scores. Similarly, achieving CDAI LDA after 6 or more months of etanercept was associated with younger age at onset, higher baseline CDAI, shorter disease duration, and fewer comorbidities. CONCLUSIONS: These patients with older-onset RA and more comorbidities clinically improved with etanercept, but had lower odds of achieving CDAI LDA. Age of onset and number of comorbidities may be important in determining RA tumor necrosis factor inhibitor response.

Comorbidities are associated with poorer outcomes in community patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the impact of comorbidities on achieving remission by examining changes in the clinical disease activity index (CDAI) in RA patients in the community-based Consortium of Rheumatology Researchers of North America (CORRONA) registry. METHODS: A subcohort of 1548 RA subjects with varying disease duration met the following inclusion criteria: started a DMARD/biologic agent, continued therapy ≥ 3 months, CDAI ≥ 2.8 at study entry and followed longitudinally from baseline to follow-up (mean time 7.46 months). Patients reported comorbidities according to a standardized list of 33 conditions. Entry characteristics were compared across age categories using one-way analysis of variance. Linear and logistic regression models were constructed to assess characteristics [e.g. age, disease duration, number of previous DMARDs/biologics, baseline modified health assessment questionnaire (MHAQ), baseline CDAI and number of comorbidities] associated with primary outcomes: change in CDAI (baseline to follow-up) and CDAI remission (yes/no). RESULTS: Although disease activity measures at entry were similar across age categories, older patients had more comorbidities, less improvement in CDAI/MHAQ and were less likely to attain remission at follow-up. However, after adjusting covariates an increasing number of patient-reported comorbidities and higher baseline CDAI (but not age) were consistently and independently associated with a lower likelihood of clinical improvement or remission (P < 0.001). CONCLUSION: In this observational cohort of community RA patients an increasing number of patients reported comorbidities, independently correlated with less CDAI improvement over time. These results reaffirm that comorbidities may be an important factor in consideration of treat-to-target recommendations and aid in understanding achievable RA therapeutic goals.

Predictors and outcomes of early adherence to the use of a home telehealth device by older veterans with heart failure.

OBJECTIVES: The present study examined home telehealth (HT) adherence, and its potential predictors and outcomes, in older Veterans with heart failure (HF) using the Health Buddy (Bosch Healthcare, Palo Alto, CA) device. SUBJECTS AND METHODS: This was a retrospective study using secondary data from the Department of Veterans Affairs (VA) databases, describing adherence rates and patterns in the first 90 days after enrollment in 248 older Veterans with HF enrolled in the VA HT Programs using the Health Buddy at five medical centers in Southern California and Nevada, between June 1, 2006 and June 1, 2008. Adherence to the use of Health Buddy was defined as the number of days the patient completed an HT session over different time frames during the study period. RESULTS: Significant differences occurred between average adherence across all three 30-day time frame increments, with adherence decreasing over time. Despite the use of standardized VA HT protocols and equipment, the department in which the HT program was embedded was a consistent significant predictor of patient adherence in all time frames, with odds ratios of 2.2-4.0 for the department with the consistent best adherence versus that with the worse adherence (confidence intervals varying with the time frame, p<0.03). Increased co-morbidity burden was associated with decreased adherence only in the first 30 days after enrollment. In this short-term study, no relationship was found between adherence to the use of the Health Buddy and outcomes. CONCLUSIONS: Program and patient characteristics warrant further study as potential predictors of HT device adherence. Additional research is also needed to further examine the relationships between HT device adherence and various outcomes.

The use of Internet technology for psychoeducation and support with dementia caregivers.

A large randomized trial evaluated the benefits of online education, support, and self-care promotion for caregivers of persons with dementia. Anecdotal reports from participants indicated enjoyment of the materials, convenient access from home, and support from professionals and other caregivers. A substantial number of screened caregivers experienced obstacles of access, cost, and time regarding use of technology. Telephone options are being explored, and future caregiving generations are expected to have increased exposure and willingness to use computer technology, such as the program described here.

Characterization of Intra-myocellular Lipids using 2D Localized Correlated Spectroscopy and Abdominal Fat using MRI in Type 2 Diabetes.

A major goal of this pilot study was to quantify intramyocellular lipids (IMCL), extramyocellular lipids (EMCL), unsaturation index (UI) and metabolites such as creatine (Cr), choline (Ch) and carnosine (Car), in the soleus muscle using two-dimensional (2D) localized correlated spectroscopy (L-COSY). Ten subjects with type 2 diabetes (T2D), controlled by lifestyle management alone, and 9 healthy control subjects, were studied. In T2D patients only, the following measurements were obtained: body mass index (BMI); waist circumference (WC); abdominal visceral and subcutaneous fat quantified using breath-held magnetic resonance imaging (MRI); a fasting blood draw for assessment of glucose, insulin, and estimation of homeostasis model assessment of insulin resistance (HOMA-IR), HbA1c, and high-sensitivity c-reactive protein (hs-CRP). Analysis of the soleus muscle 2D L-COSY spectral data showed significantly elevated IMCL ratios with respect to Cr and decreased IMCL UI in T2D when compared to healthy subjects (P < 0.05). In T2D subjects, Pearson correlation analysis showed a positive correlation of IMCL/Cr with EMCL/Cr (0.679, P < 0.05) and HOMA-IR (0.633, P < 0.05), and a non-significant correlation of visceral and subcutaneous fat with magnetic resonance spectroscopy (MRS) and other metrics. Characterization of muscle IMCL and EMCL ratios, UI, and abdominal fat, may be useful for the noninvasive assessment of the role of altered lipid metabolism in the pathophysiology of T2D, and for assessment of the effects of future therapeutic interventions designed to alter metabolic dysfunction in T2D.

Do SSRIs play a role in decreasing bone mineral density?

Osteoporosis is expected to increase as our population pyramid shifts toward old age. It is associated with increased risk of fractures, leading to complications of limitation of ambulation, loss of independence, and chronic pain. Depression is also a common occurrence in the elderly population. Currently, up to 35% of residents in long term care may experience either major depression or clinically significant depressive symptoms. Selective serotonin receptor inhibitors constitute 62% of all antidepressant drug prescribing. Recently, serotonin transporters have been described in bone, raising the question of whether medications that block serotonin reuptake could affect bone metabolism and ultimately affect osteoporosis-related fractures. Current evidence suggests that depression, particularly in the setting of selective serotonin receptor inhibitors use, should be considered as an addition to the list of risk factors prompting clinicians to evaluate bone health status.

Novel oxysterols have pro-osteogenic and anti-adipogenic effects in vitro and induce spinal fusion in vivo.

Stimulation of bone formation by osteoinductive materials is of great clinical importance in spinal fusion surgery, repair of bone fractures, and in the treatment of osteoporosis. We previously reported that specific naturally occurring oxysterols including 20(S)-hydroxycholesterol (20S) induce the osteogenic differentiation of pluripotent mesenchymal cells, while inhibiting their adipogenic differentiation. Here we report the characterization of two structural analogues of 20S, Oxy34 and Oxy49, which induce the osteogenic and inhibit the adipogenic differentiation of bone marrow stromal cells (MSC) through activation of Hedgehog (Hh) signaling. Treatment of M2-10B4 MSC with Oxy34 or Oxy49 induced the expression of osteogenic differentiation markers Runx2, Osterix (Osx), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN), as well as ALP enzymatic activity and robust mineralization. Treatment with oxysterols together with PPARγ activator, troglitazone (Tro), inhibited mRNA expression for adipogenic genes PPARγ, LPL, and aP2, and inhibited the formation of adipocytes. Efficacy of Oxy34 and Oxy49 in stimulating bone formation in vivo was assessed using the posterolateral intertransverse process rat spinal fusion model. Rats receiving collagen implants with Oxy 34 or Oxy49 showed comparable osteogenic efficacy to BMP2/collagen implants as measured by radiography, MicroCT, and manual inspection. Histological analysis showed trabecular and cortical bone formation by oxysterols and rhBMP2 within the fusion mass, with robust adipogenesis in BMP2-induced bone and significantly less adipocytes in oxysterol-induced bone. These data suggest that Oxy34 and Oxy49 are effective novel osteoinductive molecules and may be suitable candidates for further development and use in orthopedic indications requiring local bone formation.

Parathyroid surgery in the elderly.

INTRODUCTION: The prevalence of primary hyperparathyroidism (PHPT) is expected to increase in developed nations as the aged population grows. This review discusses issues related to PHPT in the elderly population with a focus on differences in disease presentation, medical and surgical management, and outcomes. METHODS: Literature review of English-language studies of PHPT or parathyroidectomy (PTx) in the elderly was performed. Surgical literature reviewed included original clinical studies published after 1990. Priority was given to studies with >30 patients where institutional practice and outcomes have not changed significantly over time. RESULTS: Elderly patients primarily present with nonclassic symptoms of PHPT that can sometimes be missed in favor of other diagnoses. They have equivalent surgical outcomes, including morbidity, mortality, and cure rates, compared with younger patients, although their length of hospital stay is significantly longer. Several recent studies demonstrate the safety and efficacy of outpatient, minimally invasive parathyroidectomy in an elderly population. Patients are referred for PTx less frequently with each advancing decade, although surgical referral patterns have increased over time in centers that offer minimally invasive parathyroidectomy. Elderly patients experience increased fracture-free survival after PTx. The majority of elderly patients report symptomatic relief postoperatively. CONCLUSION: PTx can offer elderly patients with PHPT improved quality of life. PTx is safe and effective in elderly patients, and advanced age alone should not deter surgical referral.

Feasibility study of home telerehabilitation for physically inactive veterans.

The aim of this study was to develop a system for and determine the feasibility of monitoring home exercise for physically inactive older adults using a Health Buddy (HB) text messaging device (Robert Bosch Healthcare; Palo Alto, California). Questions and messages related to exercise adherence are displayed on the HB screen and participants choose a response by pressing the corresponding button on the device. Responses are transmitted through a landline connection and high-risk responses are highlighted by the system for follow-up. We developed the questions and messages based on input from patient and clinician focus groups. We evaluated feasibility by administering the intervention to inpatient and outpatient adults aged 60 or older. We gave participants a choice of exercise monitoring by HB (n = 20) or telephone (n = 18). The results showed that home exercise monitoring by HB and telephone is safe, as evidenced by low adverse event rates. We saw a decline in exercise adherence rates to both the HB and telephone after 8 weeks, although adherence was better for HB than telephone. Taken together, the results demonstrate the feasibility of using text messaging to monitor home exercise adherence in physically inactive older adults.

Hedgehog signaling and osteogenic differentiation in multipotent bone marrow stromal cells are inhibited by oxidative stress.

Oxidative stress may play a major role in age-related osteoporosis in part by inhibiting osteoblast generation from osteoprogenitors cells. In the present study, we hypothesized that oxidative stress may inhibit the osteogenic differentiation of bone marrow stromal cells (MSC) in part by inhibiting the Hedgehog (Hh) signaling pathway, which is essential for bone development and maintenance and induces osteogenic differentiation of osteoprogenitor cells. To test this hypothesis, we examined the effects of oxidative stress on Sonic Hh (Shh)-induced osteogenic differentiation and signaling in M2-10B4 (M2) MSC, C3H10T1/2 embryonic fibroblasts, and mouse primary MSC. Treatment of cells with H(2)O(2) inhibited Shh-induced osteogenic differentiation determined by the inhibition of Shh-induced expression of osteogenic differentiation markers alkaline phosphatase (ALP), osterix (OSX), and bone sialoprotein (BSP). Similar effects were found when oxidative stress was induced by xanthine/xanthine oxidase (XXO) or minimally oxidized LDL (MM-LDL). H(2)O(2) , XXO, and MM-LDL treatment inhibited Shh-induced expression of the Hh target genes Gli1 and Patched1 as well as Gli-dependent transcriptional activity in M2 cells. H(2)O(2) treatment also inhibited Hh signaling induced by the direct activation of Smoothened by purmorphamine (PM), but not by Gli1 overexpression. This suggests that oxidative stress may inhibit Hh signaling upstream of Gli activation and Gli-induced gene expression. These findings demonstrate for the first time that oxidative stress inhibits Hh signaling associated with osteogenic differentiation. Inhibition of Hh signaling-mediated osteogenic differentiation of osteoprogenitor cells may in part explain the inhibitory effects of oxidative stress on osteoblast development, differentiation, and maintenance in aging.

Underutilization of parathyroidectomy in elderly patients with primary hyperparathyroidism.

CONTEXT: Primary hyperparathyroidism (PHPT) disproportionately affects older patients, who may face higher thresholds for surgical intervention compared to young patients. OBJECTIVE: The aim was to examine for differences in the utilization of parathyroidectomy attributable to age. DESIGN: We conducted a retrospective cohort study. PARTICIPANTS: Patients with biochemically diagnosed PHPT during the years 1995-2008 were identified within an integrated health care delivery system in Southern California encompassing approximately 3 million individuals. MAIN OUTCOME MEASURES: The outcome measures were parathyroidectomy (PTx) and time interval to surgery. RESULTS: We found 3388 patients with PHPT, 964 (28%) of whom underwent PTx. Patients aged 60+ yr comprised 60% of the study cohort. The likelihood of PTx decreased linearly among patients aged 60+ when compared to patients aged 50-59, an effect that persisted in multivariate analysis: odds ratio 0.68 for ages 60-69 (P < 0.05); 0.41 for ages 70-79 (P < 0.0001), and 0.11 for age 80+ (P < 0.0001). The PTx rate for patients aged 70+ was 14%. Among patients meeting 2002 consensus criteria for surgical treatment, 45% of those aged 60-69 and 24% of those aged 70+ underwent PTx. A Cox proportional hazards model showed that patients aged 60+ experienced significantly longer delays from diagnosis to surgery compared to young patients (P < 0.0001). CONCLUSIONS: PHPT is undertreated in the elderly. We observed a progressive age-related decline in PTx rate that renders patients aged 70+ unlikely to have definitive treatment, irrespective of comorbidity and eligibility for surgery.

Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells.

We previously reported that specific oxysterols stimulate osteogenic differentiation of pluripotent bone marrow stromal cells (MSCs) through activation of hedgehog (Hh) signaling and may serve as potential future therapies for intervention in osteopenia and osteoporosis. In this study we report that the osteogenic oxysterol 20(S)-hydroxycholesterol (20S) induces the expression of genes associated with Notch signaling. Using M2-10B4 (M2) MSCs, we found that 20S significantly induced HES-1, HEY-1, and HEY-2 mRNA expression compared with untreated cells, with maximal induction after 48 hours, whereas the nonosteogenic oxysterols did not. Similar observations were made when M2 cells were treated with sonic hedgehog (Shh), and the specific Hh pathway inhibitor cyclopamine blocked 20S-induced Notch target gene expression. 20S did not induce Notch target genes in Smo(-/-) mouse embryonic fibroblasts, further confirming the role of Hh signaling in 20S-induced expression of Notch target genes. Despite the inability of liver X-receptor (LXR) synthetic ligand TO901317 to induce Notch target genes in M2 cells, LXR knockdown studies using siRNA showed inhibition of 20S-induced HEY-1 but not HES-1 expression, suggesting the partial role of LXR signaling in MSC responses to 20S. Moreover, 20S-induced Notch target gene expression was independent of canonical Notch signaling because neither 20S nor Shh induced CBF1 luciferase reporter activity or NICD protein accumulation in the nucleus, which are hallmarks of canonical Notch signaling activation. Finally, HES-1 and HEY-1 siRNA transfection significantly inhibited 20S-induced osteogenic genes, suggesting that the pro-osteogenic effects of 20S are regulated in part by HES-1 and HEY-1.

20(S)-hydroxycholesterol inhibits PPARgamma expression and adipogenic differentiation of bone marrow stromal cells through a hedgehog-dependent mechanism.

UNLABELLED: Specific oxysterols have been shown to be pro-osteogenic and anti-adipogenic. However, the molecular mechanism(s) by which oxysterols inhibit adipogenic differentiation is unknown. We show that the anti-adipogenic effects of osteogenic oxysterol, 20(S)-hydroxycholesterol, are mediated through a hedgehog-dependent mechanism(s) and are associated with inhibition of PPARgamma expression. INTRODUCTION: Multipotent bone marrow stromal cells (MSCs) are common progenitors of osteoblasts and adipocytes. A reciprocal relationship between osteogenic and adipogenic differentiation may explain the increased adipocyte and decreased osteoblast formation in aging and osteoporosis. We have previously reported that specific oxysterols stimulate osteogenic differentiation of MSCs while inhibiting their adipogenic differentiation. MATERIALS AND METHODS: The M2-10B4 (M2) murine pluripotent bone MSC line was used to assess the inhibitory effects of 20(S)-hydroxycholesterol (20S) and sonic hedgehog (Shh) on peroxisome proliferator-activated receptor gamma (PPARgamma) and adipogenic differentiation. All results were analyzed for statistical significance using ANOVA. RESULTS AND CONCLUSIONS: Treatment of M2 cells with the osteogenic oxysterol 20S completely inhibited adipocyte formation induced by troglitazone after 10 days. PPARgamma mRNA expression assessed by RT-qPCR was significantly induced by Tro after 48 (5-fold) and 96 h (130-fold), and this induction was completely inhibited by 20S. In contrast, 20S did not inhibit PPARgamma transcriptional activity in M2 cells overexpressing PPARgamma and retinoid X receptor (RXR). To elucidate the molecular mechanism(s) by which 20S inhibits PPARgamma expression and adipogenic differentiation, we focused on the hedgehog signaling pathway, which we previously showed to be the mediator of osteogenic responses to oxysterols. The hedgehog signaling inhibitor, cyclopamine, reversed the inhibitory effects of 20S and Shh on troglitazone-induced adipocyte formation in 10-day cultures of M2 cells by 70% and 100%, respectively, and the inhibitory effect of 20S and Shh on troglitazone-induced PPARgamma expression was fully reversed at 48 h by cyclopamine. Furthermore, 20S and Shh greatly inhibited PPARgamma2 promoter activity induced by CCAAT/enhancer-binding protein alpha overexpression. These studies show that, similar to the induction of osteogenesis, the inhibition of adipogenesis in murine MSCs by the osteogenic oxysterol, 20S, is mediated through a hedgehog-dependent mechanism(s).

Memory impairment among primary care veterans.

Memory impairment is the most frequent cognitive dysfunction for older patients. Though studies have shown that dementia is often overlooked in primary care settings, there has been minimal focus specifically on memory impairment, on patients' concerns about memory, or their desire to address these concerns. The objectives of this study were to (1) investigate the prevalence of memory impairment among patients without dementia diagnoses, (2) determine the degree of patients' concern about memory impairment and (3) identify other patient characteristics associated with memory impairment among older primary care patients. Using telephone versions of a four-item memory test and proxy-reported cognitive decline for patients unable to complete interviews, we performed memory assessment of randomly selected patients, 75 years and older, without dementia diagnoses who see primary care physicians at least twice every six months. Among 260 patients and 20 proxies, 19.8% had memory impairment at a level indicative of probable dementia. Adjusting for age, ethnicity, and education, subjects who were more concerned about memory impairment were more likely to be impaired. (Adjusted odds ratio [AOR]: 1.4 (for each additional level of concern); 95% confidence interval [CI]: (1.0-2.0)). Similarly, subjects wanting their physician to discuss with them their memory concerns were more likely to be impaired (AOR: 1.4; 95% CI: 1.0-1.9). Memory impairment is common among older primary care patients without diagnosed dementia. Knowing patients' concerns about memory impairment and their desire to discuss these concerns may facilitate cognitive screening in this setting.

Barriers in the management of glucocorticoid-induced osteoporosis.

OBJECTIVE: To determine present practice for the management of glucocorticoid-induced osteoporosis (GIOP) in veterans; to characterize provider knowledge, beliefs, and practice behaviors regarding management of GIOP; and to identify potential barriers and interventions in the management of GIOP. METHODS: To characterize current management of GIOP in an academic veterans administration medical center, we conducted a retrospective chart review of 100 patients who were prescribed a 90-day supply of prednisone. To assess clinicians' knowledge of GIOP clinical guidelines and perceptions of GIOP management, primary care clinicians and subspecialists completed a questionnaire and participated in focus groups. RESULTS: Chart review revealed that only 32 of 100 patients receiving long-term glucocorticoid treatment underwent bone mineral density testing, and only 32 patients were prescribed the recommended calcium supplements. Of the 23 providers who completed the questionnaire and participated in the focus groups, 4 correctly identified both the dose and duration of glucocorticoid use at which GIOP prevention measures should be instituted. Common GIOP management barriers cited by participants were lack of knowledge, having limited time during the clinic visit to address all problems, patient nonadherence, and system problems. The most commonly mentioned potential interventions were the use of computerized clinical reminders and patient education. CONCLUSION: Clinicians frequently do not follow recommended guidelines for the management of GIOP. Improving the management of GIOP will likely require a fundamental redesigning of care processes for this disorder in order to overcome provider, patient-related, and system barriers.