Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Feasibility of a clinical trial to assess the effect of dietary calcium v. supplemental calcium on vascular and bone markers in healthy postmenopausal women.

Whether supplemental Ca has similar effects to dietary Ca on vascular and bone markers is unknown. The present trial investigated the feasibility of applying dietary and supplemental interventions in a randomised-controlled trial (RCT) aiming to estimate the effect of supplemental Ca as compared with dietary Ca on vascular and bone markers in postmenopausal women. In total, thirteen participants were randomised to a Ca supplement group (CaSuppl) (750 mg Ca from CaCO3+450 mg Ca from food+20 µg vitamin D supplement) or a Ca diet group (CaDiet) (1200 mg Ca from food+10 µg vitamin D supplement). Participants were instructed on Ca consumption targets at baseline. Monthly telephone follow-ups were conducted to assess adherence to interventions (±20 % of target total Ca) using the multiple-pass 24-h recall method and reported pill count. Measurements of arterial stiffness, peripheral blood pressure and body composition were performed at baseline and after 6 and 12 months in all participants who completed the trial (n 9). Blood and serum biomarkers were measured at baseline and at 12 months. Both groups were compliant to trial interventions (±20 % of target total Ca intake; pill count ≥80 %). CaSuppl participants maintained a significantly lower average dietary Ca intake compared with CaDiet participants throughout the trial (453 (sd 187) mg/d v. 1241 (sd 319) mg/d; P<0·001). There were no significant differences in selected vascular outcomes between intervention groups over time. Our pilot trial demonstrated the feasibility of conducting a large-scale RCT to estimate the differential effects of supplemental and dietary Ca on vascular and bone health markers in healthy postmenopausal women.

Cell Signaling in Tenocytes: Response to Load and Ligands in Health and Disease.

Signaling in tenocytes during development, homeostasis and injury involves multiple and redundant pathways. Given that tendons transmit mechanical forces from muscle to bone to effect movement, a key function for tenocytes is the detection of and response to mechanical stimulation. Mechanotransduction involves matrix-integrin-cytoskeleton to nucleus signaling, gap junction intercellular communication, changes in intracellular calcium (Ca(2+)), activation of receptors and their pathways, and responses to biochemical factors such as hormones, growth factors, adenosine triphosphate (ATP) and its derivatives, and neuromodulators. The primary cilium also plays a key role in the detection of mechanical signals. During development, transforming growth factor-ß (TGF-ß), bone morphogenetic protein (BMP), and hedgehog (Hh) signaling modulate tendon differentiation and formation. The response to injury is complex and varied involving not only inflammatory mediators such as interleukin-1ß but also mechanosensing. This chapter reviews the signaling pathways tenocytes use during mechanotransduction, development and in response to injury.

Fracture risk assessment in long-term care: a survey of long-term care physicians.

BACKGROUND: The majority of frail elderly who live in long-term care (LTC) are not treated for osteoporosis despite their high risk for fragility fractures. Clinical Practice Guidelines for the diagnosis and management of osteoporosis provide guidance for the management of individuals 50 years and older at risk for fractures, however, they cannot benefit LTC residents if physicians perceive barriers to their application. Our objectives are to explore current practices to fracture risk assessment by LTC physicians and describe barriers to applying the recently published Osteoporosis Canada practice guidelines for fracture assessment and prevention in LTC. METHODS: A cross-sectional survey was conducted with the Ontario Long-Term Care Physicians Association using an online questionnaire. The survey included questions that addressed members' attitudes, knowledge, and behaviour with respect to fracture risk assessment in LTC. Closed-ended responses were analyzed using descriptive statistics and thematic framework analysis for open-ended responses. RESULTS: We contacted 347 LTC physicians; 25% submitted completed surveys (81% men, mean age 60 (Standard Deviation [SD] 11) years, average 32 [SD 11] years in practice). Of the surveyed physicians, 87% considered prevention of fragility fractures to be important, but a minority (34%) reported using validated fracture risk assessment tools, while 33% did not use any. Clinical risk factors recommended by the OC guidelines for assessing fracture risk considered applicable included; glucocorticoid use (99%), fall history (93%), age (92%), and fracture history (91%). Recommended clinical measurements considered applicable included: weight (84%), thyroid-stimulating hormone (78%) and creatinine (73%) measurements, height (61%), and Get-Up-and-Go test (60%). Perceived barriers to assessing fracture risk included difficulty acquiring necessary information, lack of access to tests (bone mineral density, x-rays) or obtaining medical history; resource constraints, and a sentiment that assessing fracture risk is futile in this population because of short life expectancy and polypharmacy. CONCLUSION: Perceived barriers to fracture risk assessment and osteoporosis management in LTC have not changed recently, contributing in part to the ongoing care gap in osteoporosis management. Our findings highlight the importance to adapt guidelines to be applicable to the LTC environment, and to develop partnerships with stakeholders to facilitate their use in clinical practice.

Personalized Telehealth: Redesigning Complex Care Delivery for the 65+ During the COVID Pandemic: a Survey of Patients, Caregivers, and Health-care Providers.

Background: In the context of the ongoing COVID-19 pandemic, rapid transitions have been made towards telehealth. Optimal use of telehealth in elderly patients remains poorly understood and adaptation challenges persist. Our study aimed at identifying perceptions, barriers, and possible facilitators to telehealth use amongst elderly patients with comorbidities, their caregivers, and health-care providers (HCPs). Methods: Health-care providers, patients 65 years and older with multiple comorbidities, and caregivers were recruited from outpatient clinics and invited to complete an electronic self-administered or telephone-administered survey on their perceptions of telehealth and of barriers to its implementation. Results: A total of 39 health-care providers, 40 patients, and 22 caregivers responded to the survey. Most patients (90%), caregivers (82%), and HCPs (97%) had experienced telephone visits, but few were conducted via videoconference platforms. Patients and caregivers showed interest in pursuing some future telehealth visits (68%, 86%, respectively), but felt they lacked access to technology and skills (n=8, 20%), and some felt that telehealth visits may be inferior to in-person visits (n=9, 23%). HCPs showed interest in incorporating telehealth visits into practice (n=32, 82%), but identified challenges in lack of administrative support (n=37), lack of HCP (n=28) and patient (n=37) technological skills, and limited infrastructure (n=37)/internet access (n=33). Conclusions: Older patients, caregivers, and HCPs show interest in pursuing future telehealth visits but elucidate similar barriers. Facilitating access to technology, as well as to administrative and technology support guides, could promote high quality and equal access to virtual care for the older adult.

Development of an analytical microbial consortia method for enhancing performance monitoring at aerobic wastewater treatment plants.

An analytical method to produce profiles of bacterial biomass fatty acid methyl esters (FAME) was developed employing rapid agitation followed by static incubation (RASI) using selective media of wastewater microbial communities. The results were compiled to produce a unique library for comparison and performance analysis at a Wastewater Treatment Plant (WWTP). A total of 146 samples from the aerated WWTP, comprising 73 samples of each secondary and tertiary effluent, were included analyzed. For comparison purposes, all samples were evaluated via a similarity index (SI) with secondary effluents producing an SI of 0.88 with 2.7% variation and tertiary samples producing an SI 0.86 with 5.0% variation. The results also highlighted significant differences between the fatty acid profiles of the tertiary and secondary effluents indicating considerable shifts in the bacterial community profile between these treatment phases. The WWTP performance results using this method were highly replicable and reproducible indicating that the protocol has potential as a performance-monitoring tool for aerated WWTPs. The results quickly and accurately reflect shifts in dominant bacterial communities that result when processes operations and performance change.

Mobile App Prototype in Older Adults for Postfracture Acute Pain Management: User-Centered Design Approach.

BACKGROUND: Postfracture acute pain is often inadequately managed in older adults. Mobile health (mHealth) technologies can offer opportunities for self-management of pain; however, insufficient apps exist for acute pain management after a fracture, and none are designed for an older adult population. OBJECTIVE: This study aims to design, develop, and evaluate an mHealth app prototype using a human-centered design approach to support older adults in the self-management of postfracture acute pain. METHODS: This study used a multidisciplinary and user-centered design approach. Overall, 7 stakeholders (ie, 1 clinician-researcher specialized in internal medicine, 2 user experience designers, 1 computer science researcher, 1 clinical research assistant researcher, and 2 pharmacists) from the project team, together with 355 external stakeholders, were involved throughout our user-centered development process that included surveys, requirement elicitation, participatory design workshops, mobile app design and development, mobile app content development, and usability testing. We completed this study in 3 phases. We analyzed data from prior surveys administered to 305 members of the Canadian Osteoporosis Patient Network and 34 health care professionals to identify requirements for designing a low-fidelity prototype. Next, we facilitated 4 participatory design workshops with 6 participants for feedback on content, presentation, and interaction with our proposed low-fidelity prototype. After analyzing the collected data using thematic analysis, we designed a medium-fidelity prototype. Finally, to evaluate our medium-fidelity prototype, we conducted usability tests with 10 participants. The results informed the design of our high-fidelity prototype. Throughout all the phases of this development study, we incorporated inputs from health professionals to ensure the accuracy and validity of the medical content in our prototypes. RESULTS: We identified 3 categories of functionalities necessary to include in the design of our initial low-fidelity prototype: the need for support resources, diary entries, and access to educational materials. We then conducted a thematic analysis of the data collected in the design workshops, which revealed 4 themes: feedback on the user interface design and usability, requests for additional functionalities, feedback on medical guides and educational materials, and suggestions for additional medical content. On the basis of these results, we designed a medium-fidelity prototype. All the participants in the usability evaluation tests found the medium-fidelity prototype useful and easy to use. On the basis of the feedback and difficulties experienced by participants, we adjusted our design in preparation for the high-fidelity prototype. CONCLUSIONS: We designed, developed, and evaluated an mHealth app to support older adults in the self-management of pain after a fracture. The participants found our proposed prototype useful for managing acute pain and easy to interact with and navigate. Assessment of the clinical outcomes and long-term effects of our proposed mHealth app will be evaluated in the future.

Modulation of collagen gel compaction by extracellular ATP is MAPK and NF-kappaB pathways dependent.

Understanding the mechanisms that regulate mechanosensitivity in osteoblasts is important for controlling bone homeostasis and the development of new drugs to combat bone loss. It is believed that prestress or force generation (the tensile stress within the cell body) plays an important role in regulating cellular mechanosensitivity. In the present study, a three-dimensional (3D) collagen culture was used to monitor the change in prestress of the osteoblast-like cells. Collagen hydrogel compaction has been used as an indicator of the change in the degree of cell prestress. Previous results in this model demonstrated that extracellular ATP reduced the mechanosensitivity of osteoblasts by reducing cellular prestress. To elucidate the potential mechanisms involved in this process, the signaling pathways downstream of P2 purinoceptors involved in regulating the compaction of type I collagen gels were investigated. By using specific inhibitors to these signaling pathways, we found that ATP-induced reduction in collagen gel compaction rate is dependent on mitogen-activated protein kinase (MAKP) and NF-kappaB pathways. However, blocking protein kinase C with GF109203X did not change the compaction kinetics in the presence of ATPgammaS. Moreover, blocking cyclic AMP (cAMP), phosphatidylinositol-3 kinase (PI3K), calmodulin (CaM) or L-type voltage sensitive calcium channels did not affect ATP's ability to reduce collagen gel compaction. The results from the present and previous studies indicate that extracellular ATP may act as a negative feedback modulator in the mechanotransduction system since mechanical stimuli increase ATP release from stimulated cells.

The effects of music therapy for older people with dementia.

UNLABELLED: The aim of this literature review is to explore how music therapy influences the behaviour of older people with dementia. BACKGROUND: Music therapy is often informally used in residential care units to enhance communication, emotional, cognitive and behavioural skills in elderly patients diagnosed with dementia both nationally and internationally. However, in Ireland the benefits of music therapy have not been fully recognized. Many studies have been carried out to establish the effectiveness of music therapy on the behaviour of older people with dementia with positive findings. Music therapy should be welcomed into care of the elderly settings in Ireland and elsewhere; however, more research is required to validate the effects of this therapy as a holistic tool to build altruistic connections between carers and clients. METHOD: A comprehensive review of nursing literature using the online databases CINAHL, PsycINFO and MEDLINE were carried out. The search was limited to articles in the English language and peer-reviewed journals dating 2003-2009. RESULTS: Thirteen studies were reviewed and the majority of these studies reported that music therapy influenced the behaviour of older people with dementia in a positive way by reducing levels of agitation. The research further identified a positive increase in participants' mood and socialization skills, with carers having a significant role to play in the use of music therapy in care of the elderly nursing. However, methodological limitations were apparent throughout each of the studies reviewed. RECOMMENDATIONS: With reference to clinical practice, the authors recommend the undertaking of further research to explore the effects of music therapy on the behaviour and wellbeing of older people with dementia.

Comprehensive geriatric assessment predicts azacitidine treatment duration and survival in older patients with myelodysplastic syndromes.

BACKGROUND: Treatment of older patients with myelodysplastic syndrome (MDS) is based on disease biology and performance status. Performance status, however, does not reflect increasing co-morbidities, functional dependence or psychosocial issues in older patients. PATIENTS AND METHODS: This prospective study evaluated the burden of geriatric related health issues, assessed feasibility of "tailored" Comprehensive Geriatric Assessment (CGA), and compared treatment duration and survival in older patients with MDS and oligoblastic acute myeloid leukemia with and without deficits in CGA domains (n = 98). RESULTS: Although only 27 (28%) patients had an Eastern Cooperative Oncology Group score ≥2, 78% (n = 77) patients had deficits in at least one CGA domain. Deficits were spread across all CGA domains, including dependence for instrumental activity of daily living (iADL; n = 33, 34%). Importantly, patients who were dependent for iADL (3.7 ±â€¯2.6 vs 12.1 ±â€¯7.9; p = .009), had cognitive impairment (3.5 ±â€¯2.1 vs. 10.9 ±â€¯7.9; p = .034) or impaired mobility (3.8 ±â€¯2.5 vs. 13.2 ±â€¯7.6; p = .001) completed significantly less azacitidine cycles as compared to those without these deficits. Cox-proportional regression showed that iADL dependency (hazard ratio 3.37; p = .008) and higher comorbidities (hazard ratio 4.7; p < .001) were associated with poor prognosis independent of disease related factors. Poor survival of iADL dependent patients was seen in both azacitidine (6 vs 19 months; p < .001) and supportive care cohorts (26 vs 48 months; p = .01). CONCLUSION: CGA detected geriatric related health issues, predicted poor survival and identified patients less likely to continue and benefit from azacitidine. Hence, CGA should be included in the treatment decision algorithm of older patients with MDS.

Key developments that impacted the field of mechanobiology and mechanotransduction.

Advances in mechanobiology have evolved through insights from multiple disciplines including structural engineering, biomechanics, vascular biology, and orthopaedics. In this paper, we reviewed the impact of key reports related to the study of applied loads on tissues and cells and the resulting signal transduction pathways. We addressed how technology has helped advance the burgeoning field of mechanobiology (over 33,600 publications from 1970 to 2016). We analyzed the impact of critical ideas and then determined how these concepts influenced the mechanobiology field by looking at the citation frequency of these reports as well as tracking how the overall number of citations within the field changed over time. These data allowed us to understand how a key publication, idea, or technology guided or enabled the field. Initial observations of how forces acted on bone and soft tissues stimulated the development of computational solutions defining how forces affect tissue modeling and remodeling. Enabling technologies, such as cell and tissue stretching, compression, and shear stress devices, allowed more researchers to explore how deformation and fluid flow affect cells. Observation of the cell as a tensegrity structure and advanced methods to study genetic regulation in cells further advanced knowledge of specific mechanisms of mechanotransduction. The future of the field will involve developing gene and drug therapies to simulate or augment beneficial load regimens in patients and in mechanically conditioning organs for implantation. Here, we addressed a history of the field, but we limited our discussions to advances in musculoskeletal mechanobiology, primarily in bone, tendon, and ligament tissues. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:605-619, 2018.

Effects of serial passaging on the adipogenic and osteogenic differentiation potential of adipose-derived human mesenchymal stem cells.

Adipose-derived human mesenchymal stem cells (hMSCs) will be more valuable for tissue engineering applications if they can be extensively subcultured without loss of phenotype and multilineage differentiation ability. This study examined the effects of serial passaging on growth rate, gene expression, and differentiation potential of adipose-derived hMSCs. Differentiation was assessed by analyzing changes in messenger RNA (mRNA) expression of osteogenic and adipogenic marker genes and by determining production of calcium deposits and lipid vacuoles. Cells cultured in osteogenic medium for 2 weeks upregulated expression of alkaline phosphatase mRNA relative to cells in growth medium, and deposited calcium. Calcium deposition decreased in cells from passages 4 to 6 but returned to levels near or above those of primary cells by passage 10. Cells cultured in adipogenic medium upregulated expression of lipoprotein lipase and peroxisome proliferator activated receptor-gamma mRNA relative to cells in growth medium, and formed lipid vacuoles at all passages. By passage 8, however, cells in adipogenic medium also deposited calcium. Growth rate was stable through passage 5, then decreased. The results of this study indicate that adipose-derived hMSCs are capable of both adipogenic and osteogenic differentiation through 10 passages (34 population doublings) but that osteogenic differentiation may start to dominate at later passages.

Comparison of cellular strain with applied substrate strain in vitro.

Strain magnitudes within tenocytes undergoing substrate tensile strain are not well defined. It was hypothesized that strain magnitudes at the cellular level would reflect those of the applied substrate (equibiaxial or uniaxial) strain. A vacuum-operated device was used to apply equibiaxial or uniaxial tension to a flexible substrate upon which tenocytes were cultured in monolayer. Images of tenocytes labeled with Fura-2, to detect free intracellular calcium ions, and MitoFluor Green, to detect mitochondria, were taken prior to strain and for 20 min during application of static strain. A custom-written, texture correlation program computed strain magnitudes in the cell based on the change in pixel pattern displacements between images of non-strained and strained cells. On average, cellular strain was approximately 37+/-8% and 63+/-11% of the applied equibiaxial and uniaxial substrate strain, respectively. The largest cell strains were detected in cells oriented parallel to the direction of applied uniaxial tensile strain. However, strain magnitudes within a cell were heterogeneous. The variance in strain magnitude within and among tenocytes is dependent on cell orientation, cell stiffness, cytoskeleton organization, subcellular organelles, or placement and type of cell-substrate contacts. Results of the present study indicate that cultured tenocytes experience a moderate fraction of the applied substrate strain.

Complementary and alternative therapies: survey of knowledge and attitudes of health professionals at a tertiary pediatric/women's care facility.

Nurses, physicians, and allied health professionals at the IWK Health Centre, Halifax, NS, Canada, a tertiary care, regional center for a population of 2.5 million were surveyed. We examined personal attitudes and professional practice in addressing the use of complementary and alternative medicine (CAM) use by patients. We also examined the availability of CAM-related information to health professionals. The findings suggest that health professionals: (1) are supportive of the use of selected CAM therapies by patients; (2) have almost no personal experience of CAM; (3) have limited knowledge about CAM and acquire that information mainly from the Internet, friends or family rather than professional journals; (4) are uncomfortable discussing CAM with patients and; (5) rarely or never ask patients about CAM use. We have identified barriers for health professionals to effective communication about CAM use by their patients and families. Improved access to existing policies and scientific publications, and specific continuing professional development opportunities focused on speaking openly and non-judgmentally with patients are likely to enhance accurate guidance of patients in the highly prevalent use of CAM.

Developing and implementing a career ladder program.

A career ladder program is a formal management tool used not only by managers looking to recognize and retain employees, but also by employees seeking growth opportunities. A career ladder program involves careful development, frequent and effective communication during implementation, and activities focused on measuring program effectiveness. Career ladders are a way to increase productivity and staff versatility; improve morale, clinical quality, and staff satisfaction; reduce turnover; promote professional growth and job enrichment; and improve patient care.

A 51-item calcium-focused food frequency questionnaire is a reliable tool to assess dietary calcium intake in postmenopausal women.

Given the lack in a valid biomarker to assess dietary calcium intake (dCai), reproducible estimation of usual dCai is crucial for better understanding of its interaction with health outcomes in specific populations. This study tested the hypothesis that a calcium-focused food frequency questionnaire (FFQ) may be used to estimate dCai of women ≥50 years residing in a multicultural environment (Montreal, Canada). One hundred and eight women (age, 63.1±7.7 years; 98% postmenopausal) completed the FFQ twice and 4 nonconsecutive 24-hour recalls (24HRs) over 1 month. Medians of dCai were compared by Wilcoxon signed rank test. Reproducibility and relative validity of the FFQ were assessed by Spearman correlation (rs) and Cohen's weighted kappa (κw). Agreement was further assessed by cross-classification by quartiles, Bland-Altman plot, and sensitivity and specificity analyses. The median (interquartile range) dCai estimated by the FFQ and 24HRs were 723 (524-1033) mg/d and 854 (666-1068) mg/d, respectively (P<.001). The FFQs had a strong correlation (rs=0.72, P<.001) and moderate agreement (κw=0.55). The FFQ and 24HRs were moderately correlated (rs=0.65, P<.001). Cross-classification showed moderate agreement (κw=0.42), with 85% of the participants classified into identical or contiguous quartiles and 2.8% into extreme opposite quartiles. According to the Bland-Altman plot, the FFQ underestimated dCai with a bias of 99 mg/d (95% limits of agreement, -677 to +480 mg/d). Sensitivity and specificity of identifying intakes <1000 mg/d were 90% and 57%, respectively. This FFQ is a useful tool to discriminate dCai <600 and ≥1000 mg/d in postmenopausal women and to rank dCai in epidemiological studies.

HIV-associated female sexual dysfunction - clinical experience and literature review.

Women form an increasing proportion of HIV-infected individuals in the developed world. Early data suggest that women with HIV are at particular risk of developing sexual problems. The aim of this study was to describe our anecdotal experience of HIV-infected women and to ascertain their sexual dysfunction, and also to conduct a national survey to evaluate what sexual dysfunction services are provided for women in other UK HIV centres. Retrospective analysis of clinic notes of women attending our HIV clinic and letter surveys of HIV centres in the UK were carried out. About half our cohort reported that they had sexual problems or were not satisfied with sex over the preceding 12 months. Contextual issues seemed to be the commonest cause of these problems. Sixty percent of HIV physicians in the UK rarely/never ask their female HIV patients about sexual functioning. Sexual dysfunction is probably common in HIV-infected women. Most physicians seeing women with HIV in the UK do not ask about sexual functioning. 'Physician coaching' could help to redress this situation, so that at the least the sexual problems could be brought up in discussion.

Assessment of femur geometrical parameters using EOS™ imaging technology in patients with atypical femur fractures; preliminary results.

Atypical femur fractures (AFF) arise in the subtrochanteric and diaphyseal regions. Because of this unique distribution, we hypothesized that patients with AFF demonstrate specific geometrical variations of their lower limb whereby baseline tensile forces applied to the lateral cortex are higher and might favor the appearance of these rare stress fractures, when exposed to bisphosphonates. Using the low irradiation 2D-3D X-ray scanner EOS™ imaging technology we aimed to characterize and compare femur geometric parameters between women who sustained bisphosphonate-associated AFF and those who had experienced similar duration of exposure to bisphosphonates but did not sustain fractures. Conditional logistic regression models were constructed to estimate the association between selected geometric parameters and the occurrence of AFF. We identified 16 Caucasian women with AFF and recruited 16 ethnicity-, sex-, age-, height- and cumulative bisphosphonate exposure-matched controls from local osteoporosis clinics. Compared to controls, those with AFF had more lateral femur bowing (-3.2° SD [3.4] versus -0.8° SD [1.9] p=0.02). In regression analysis, lateral femur bowing was associated with the risk of AFF (aOR 1.54; 95% CI 1.04-2.28, p=0.03). Women who sustained a subtrochanteric AFF demonstrated a lesser femoral neck shaft angle (varus geometry) than those with a fracture at a diaphyseal site (121.9 [3.6]° versus 127.6 [7.2]°, p=0.07), whereas femur bowing was more prominent in those with a diaphyseal fracture compared to those with a subtrochanteric fracture (-4.3 [3.2]° versus -0.9 [2.7]°, p=0.07). Our analyses support that subjects with AFF exhibit femoral geometry parameters that result in higher tensile mechanical load on the lateral femur. This may play a critical role in the pathogenesis of AFF and requires further evaluation in a larger size population.

Ligament cells stretch-adapted on a microgrooved substrate increase intercellular communication in response to a mechanical stimulus.

An in vitro model was used to investigate the effect of mechanical stimuli on adaptation to load and calcium signaling in aligned medial collateral ligament cells (MCL). This model used a patterned silicone membrane to align the cells parallel with the direction of the microgrooves. Alignment created an architecture that simulated a degree of cell orientation in native ligament tissue. It was hypothesized that aligned ligament cells would be more efficient at calcium wave propagation than cells that were randomly oriented. It was further hypothesized that calcium wave propagation would be greater among cells that were both aligned and subjected to mechanical stretch compared to cells that were aligned but not stretched. Rat MCL cells were loaded with Fura-2AM, a calcium-binding dye, and mechanically indented using a micropipette tip. A ratio-imaging fluorescence technique was used to quantitate the calcium (Ca2+) response. It was concluded that stretching ligament cells prior to stimulation increased their sensitivity to load and their ability to propagate a calcium wave. However, the ability of aligned cells to propagate this wave was not significantly different when compared to nonaligned cells. Treatment of cultures with inhibitors such as apyrase and suramin significantly reduced the number of cells recruited in the calcium response. Hence, it was concluded that ATP released from mechanically stimulated cells was a principal mediator responsible for the rise in intracellular calcium in ligament cells. Further, purinoceptor activation may amplify the signal to alert and recruit more cells in a response to mechanical stimulation.

Evaluation of extended-release diltiazem once daily for cats with hypertrophic cardiomyopathy.

Serum diltiazem concentrations were evaluated following either 30 mg or 60 mg of an extended-release diltiazem administered orally once daily to 13 cats. Sequential blood samples were obtained over 24 hours. Both dosages usually resulted in elevated serum concentrations of >200 ng/mL at 6, 12, 18, and 24 hours. The 30-mg dosage was sometimes associated with low serum concentrations of <50 ng/mL at 18 and 24 hours. The 60-mg dosage (9.3 to 14.8 mg/kg) was associated with lethargy, gastrointestinal disturbances, and weight loss in nine (36%) of 25 client-owned cats. Gastrointestinal disturbances were recognized within 1 week, and weight loss was detected after 2 to 6 months of treatment.