The American Orthopaedic Association's Own the Bone® database: a national quality improvement project for the treatment of bone health in fragility fracture patients.

The American Orthopaedic Association initiated the Own the Bone (OTB) quality improvement program in 2009. Herein we show that the data collected through this program is similar to that collected in other large studies. Thus, the OTB registry functions as an externally valid cohort for studying fragility fracture patients. INTRODUCTION: The American Orthopedic Association initiated the Own the Bone (OTB) quality improvement program in 2009 to improve secondary prevention of fragility fractures. In this study, we present a summary of the data collected by the OTB program and compare it to data from other large fragility fracture registries with an aim to externally validate the OTB registry. METHODS: The OTB registry contained 35,038 unique cases of fragility fracture as of September, 2016. We report the demographics, presenting fracture characteristics, past fracture history, and bone mineral density (BMD) data and compare these to data from large fragility fracture studies across the world. RESULTS: Seventy-three percent of the patients in the OTB registry were female, Caucasian, and post-menopausal. In 54.4% of cases, patients had a hip fracture; spine fractures were the second most common fracture type occurring in 11.1% of patients. Thirty-four percent of the patients had a past history of fragility fracture, and the most common sites were the spine and hip. The average femoral neck T-score was - 2.06. When compared to other studies, the OTB database showed similar findings with regard to patient age, gender, race, BMI, BMD profile, prior fracture history, and family history of fragility fractures. CONCLUSION: OTB is the first and largest multi-center voluntary fragility fracture registry in the USA. The data collected through the OTB program is comparable to that collected in international studies. Thus, the OTB registry functions as an externally valid cohort for further studies assessing the clinical characteristics, interventions, and outcomes achieved in patients who present with a fragility fracture in the USA.

Elevated incidence of fractures in women with invasive breast cancer.

UNLABELLED: This study evaluates the incidence of bone fractures in women with BC.We found that women with invasive breast cancer are at an increased risk for bone fractures, with fractures most commonly occurring at lower extremity and vertebral sites. The risk is further increased in women undergoing cancer therapy. INTRODUCTION: Bone loss and fractures in breast cancer have generally been attributed to aromatase inhibitor use. This study assessed the incidence of fractures after invasive breast cancer diagnosis and evaluated bone density and FRAX risk calculation at time of fracture occurrence. METHODS: Retrospective cohort study of women with invasive breast cancer [June 2003-December 2011] who participated in an academic hospital based genetic biobank. Demographic and clinical characteristics were abstracted from the electronic medical record (EMR). RESULTS: A total of 422 women with invasive breast cancer were assessed; 79 (28 %) sustained fractures during the observation period; fractures occurred at multiple skeletal sites in 27 cases (116 fractures). The incidence of fractures was 40 per 1000 person-years. Women who sustained fractures were mostly white and had a family history of osteoporosis (36.9 %, p = 0.03) or history of a prior fracture (6/79, p = 0.004). Fractures occurred 4.0 years (range 0-12 years) after cancer diagnosis. Fracture cases had femoral neck bone mineral density (BMD) of 0.72 + 0.12 g/cm(2), T-score of -1.2, that is, within the low bone mass range. Fractures most commonly occurred in lower extremities, vertebral, and wrist sites. Hip fractures accounted for 11 % of fractures, occurring at a median age of 61 years. CONCLUSIONS: Fractures occur shortly after commencing cancer therapy. Rapid bone loss associated with cancer therapy may precipitate fractures. Fractures occur at relatively higher BMD in BC. Occurrence of fractures in invasive breast cancer raises the possibility of cancer-induced impairment in bone quality.

Development of an electronic medical record based intervention to improve medical care of osteoporosis.

UNLABELLED: Osteoporosis is infrequently addressed during hospitalization for osteoporotic fractures. An EMR-based intervention (osteoporosis order set) was developed with physician and patient input. There was a trend toward greater calcium supplementation from July 2008 to April 2009 (s = 0.058); however, use of antiresorptives (13%) or discharge instructions for BMD testing and osteoporosis treatment (10%) remained low. INTRODUCTION: Osteoporosis is infrequently addressed during hospitalization for osteoporotic fractures. The study population consisted of patients over 50 years of age. METHODS: Northwestern Memorial Hospital is a tertiary care academic hospital in Chicago. This study was conducted from September 1, 2007 through June 30, 2009. RESULTS: Physicians reported that barriers to care comprised nonacute nature of osteoporosis, belief that osteoporosis should be addressed by the PCP, low awareness of recurrent fractures, and radiographs with terms such as "compression deformity", "wedge deformity", or "vertebral height loss" which in their opinion were not clearly indicative of vertebral fractures. An EMR-based intervention was developed with physician and patient input. Over the evaluation period, 295 fracture cases in individuals over the age of 50 years in the medicine floors were analyzed. Mean age was 72 ± 11 years; 74% were female. Sites of fracture included hip n = 78 (27%), vertebral n = 87 (30%), lower extremity n = 61 (21%), upper extremity n = 43 (15%) and pelvis n = 26 (9%). There was no increase in documentation of osteoporosis in the medical record from pre- to post-EMR implementation (p = 0.89). There was a trend toward greater calcium supplementation from July 2008 to April 2009 (p = 0.058); however, use of antiresorptives (13%) or discharge instructions for BMD testing and osteoporosis treatment (10%) remained low. CONCLUSION: An electronic medical record intervention without electronic reminders created with physician input achieves an increase in calcium supplementation but fails to increase diagnosis or treatment for osteoporosis at the time of hospitalization for a fragility fracture.

High-fidelity scaling relationships for determining dissipative particle dynamics parameters from atomistic molecular dynamics simulations of polymeric liquids.

An optimized Dissipative Particle Dynamics (DPD) model with simple scaling rules was developed for simulating entangled linear polyethylene melts. The scaling method, which can be used for mapping dimensionless (reduced units) DPD simulation data to physical units, was based on scaling factors for three fundamental physical units; namely, length, time, and viscosity. The scaling factors were obtained as ratios of equilibrium Molecular Dynamics (MD) simulation data in physical units and equivalent DPD simulation data for relevant quantities. Specifically, the time scaling factor was determined as the ratio of longest relaxation times, the length scaling factor was obtained as the ratio of the equilibrium end-to-end distances, and the viscosity scaling factor was calculated as the ratio of zero-shear viscosities, each as obtained from the MD (in physical units) and DPD (reduced units) simulations. The scaling method was verified for three MD/DPD model liquid pairs under several different nonequilibrium conditions, including transient and steady-state simple shear and planar elongational flows. Comparison of the MD simulation results with those of the scaled DPD simulations revealed that the optimized DPD model, expressed in terms of the proposed scaling method, successfully reproduced the computationally expensive MD results using relatively cheaper DPD simulations.

Greater osteoporosis educational outreach is desirable among Chinese immigrants in Chinatown, Chicago.

UNLABELLED: Osteoporosis beliefs were assessed in immigrant Chinese women in Chinatown, Chicago. Results from a survey utilizing the Osteoporosis Health Belief Scale showed that women expressed concern about osteoporosis but lacked both knowledge of preventive care and health motivation. INTRODUCTION: The objective of this study was to assess osteoporosis beliefs in immigrant Chinese women in Chinatown, Chicago. METHODS: In a community-based health fair, osteoporosis knowledge and self-efficacy among postmenopausal Chinese immigrants were assessed using the translated Osteoporosis Health Belief Scale. Bone mineral density (BMD) was assessed with calcaneal ultrasound. RESULTS: The study population included 94 women with mean age of 51 +/- 9 years, mean length of residence in the United States of 9 +/- 7 years, and 73% (n = 76) of whom were recent immigrants. Women expressed concern about the seriousness of osteoporosis and their relative susceptibility to osteoporosis. In particular, women with a prior fracture reported higher seriousness to osteoporosis. Nonetheless, women exhibited low health motivation and low awareness of the benefits of calcium and exercise. Bone densitometry results corresponded to a T score of -1.2 +/- 1.5. Multiple regression analysis revealed that a younger age and longer length of residence in the USA were associated with higher BMD. CONCLUSION: Chinese immigrant women in Chicago exhibit concern regarding osteoporosis, but are unaware of the benefits of calcium and exercise, and exhibit low health motivation. Chinese women in Chinatown lack necessary knowledge about osteoporosis to develop adequate self-efficacy. Public health initiatives should be undertaken among recent immigrant Chinese women.

Visualization of conformational changes of linear short-chain polyethylenes under shear and elongational flows.

We have performed nonequilibrium molecular dynamic simulations of the linear short-chain polyethylene liquids C(24)H(50), C(50)H(102), C(78)H(158), and C(128)H(258) under homogenous shear and elongational flows. We present visualizations of the molecular structure of each of the four liquids under shear and elongation, and compare them with their equilibrium static structures. These graphics provide a structural understanding of the various statistical measures that have been used in the literature to characterize the change in chain conformation as a function of strain rate and chain length. Moreover, these graphics allow a visualization of the inherent chain dynamics and orientation induced by shear and elongational flows. We discuss the molecular-level mechanisms apparent in the graphics.

Age-related changes in amylin secretion.

Amylin (islet amyloid polypeptide) is a recently identified pancreatic peptide. It has been shown to affect glucose metabolism both in vitro and in vivo. A cross sectional analysis of the effects of age on amylin secretion following a 75 g glucose tolerance test in a young (20-40 years), middle aged (41-60 years) and older (61-90 years) group was performed. Thirty lean (BMI less than 25) non-diabetic individuals were studied. Amylin secretion exhibited a U-shaped curve with greater secretion in young and old subjects than in middle aged persons. Baseline levels were 7.2 +/- 1, 4.7 +/- 1, and 5.3 +/- 0.75 pM respectively, at 60 min 9.5 +/- 0.9 (y), 5.5 +/- 1 (m), 8.6 +/- 1 (o) pM; and at 120 min 10.3 +/- 2 (y), 4.4 +/- 0.5 (m), 10.9 +/- 1.5 (o) pM. Amylin production (area under the curve) was 1102 +/- 131, 619.5 +/- 79 and 1043 +/- 120 pM per min respectively (P < 0.05). Amylin secretion was similar in both sexes. Variability in the insulin to amylin ratio for each of the age groups at different time points following a glucose load was found, suggesting that insulin and amylin are not co-secreted in a fixed ratio. A significant association was found between both maximum amylin and rise in amylin (delta) and a glucose greater than 120 mg/dl at 2 h. (P < 0.001, P < 0.001). This correlation of glucose and amylin may be interpreted as suggestive of a counterregulatory role for amylin. However, aging is also associated with changes in glucose metabolism and amylin may merely be acting as a marker of impaired glucose metabolism.

Relationship of age and calcitonin gene-related peptide to postprandial hypotension.

Falls following a meal occur commonly in older persons. These falls have been related to a decrease in postprandial blood pressure due to carbohydrates in the meal. The mechanism by which this occurs is not known. In this study, we examined the possible role of a vasodilatory peptide, calcitonin gene-related peptide (CGRP), which is released following carbohydrate loading in the pathophysiology of postprandial hypotension. Levels were assessed in 29 community-dwelling individuals aged 20-83 years during an oral glucose tolerance test, and heart rate and blood pressure were measured. Five subjects exhibited a postprandial reduction in systolic blood pressure (SBP) greater than 15 mmHg (mean reduction -30 +/- 4 mmHg). Four were aged over 60 (40% of the individuals in that group) and one was middle aged (11%). One individual in the older group was temporarily symptomatic, complaining of light-headedness. Linear regression analysis showed a significant association between the changes in CGRP and in blood pressure: SBP (r = 0.39, P = 0.037), and mean blood pressure (MBP) (r = 0.356, P = 0.06) in the oldest group. Individuals in this group with a greater than 15 mmHg drop in blood pressure, exhibited significantly greater changes in CGRP (SBP: P = 0.001, diastolic blood pressure (DBP): P = 0.05, MBP: P = 0.006). This association of log CGRP delta and BP change was not present in young or middle aged individuals. Thus, increases in CGRP levels were associated with blood pressure reduction, with older individuals more susceptible to these changes than younger individuals. CGRP may play a role in the pathogenesis of postprandial hypotension.

Effects of prostaglandin E1 in twelve-hour lung preservation.

The effects of hypothermic lung preservation were evaluated in 12 mongrel dogs receiving double lung allografts. Animals underwent transplant procedures after 12 hours of static preservation at 4 degrees C following pulmonary artery flush with 60 to 80 ml/kg cold modified Collins solution. Donors were pretreated with allopurinol and recipients with methylprednisolone and perireperfusion deferoxamine. Six donor animals received a PGE1 infusion (20 to 500 ng/kg/min) for 20 minutes before harvest at doses causing a significant reduction in pulmonary vascular resistance. After implantation, recipients were maintained at ventilator settings identical to those used in donors. A fixed FIO2 (0.4) was maintained, except for 15-minute periods of FIO2 1.0 that were used to measure left-to-right intrapulmonary shunt fraction (Qs/Qt) and alveolar-arterial oxygen gradients (PAO2-PaO2). Cardiopulmonary function was studied for 20 hours. Pretreatment with PGE1 resulted in reduced survival (p less than 0.05) and increased PAO2-PaO2 (p less than 0.05) and Qs/Qt (p less than 0.05) 30 minutes after reperfusion. After 60 minutes of reperfusion, mean arterial pO2 (FIO2 0.4) was 148 mm Hg in controls and 80.5 mm Hg in the PGE1 group (p less than 0.02). There was no significant difference in pulmonary vascular resistance, cardiac output, mixed venous oxygen saturation, airway resistance, compliance and physiologic dead space between groups at any time after implantation. After 20 hours of reperfusion, pO2 (FIO2 0.4) in the control group was well maintained at 140 (+/- 52) mm Hg. The method of lung preservation in control animals resulted in good survival and adequate gas exchange after 12 hours of ischemia and 20 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylin.

Amylin is a 37 amino-acid peptide which is secreted from the pancreatic islets of Langerhans. It has major sequence homology with calcitonin gene related peptide. Amylin can precipitate out in these cells to form amyloid. Amylin is secreted by similar stimuli to those that secrete insulin. Amylin has a number of effects that may counteract the effect of secreted insulin, i.e., decreased second phase insulin secretion, increased hepatic glucose output, and inhibition of insulin effects on skeletal muscle. It must, however, be recognized that in many cases the doses necessary to produce these effects appear to be supraphysiological. The putative role of amylin in the hyperglycemia of aging and Type II diabetes mellitus therefore remains controversial. Amylin has a number of other effects including inhibition of osteoclastic activity, vasodilatation, anorectic effects and enhanced memory retention. This review postulates a role for amylin in the pathogenesis of a number of age-related changes.

Age-related osteoporosis.

Osteoporosis is an important public health problem. Over the next few years the health-care demands of osteoporosis and hip fractures are expected to increase ten-fold. In this article, the pathogenesis and classification of age-related osteoporosis are analyzed. Treatment options are examined and a rational management plan for this entity is discussed.

Assistive technology for postsecondary students with learning disabilities.

An increasing number of students with learning disabilities are attending postsecondary institutions. To meet the educational demands of these students, support service providers will likely rely on assistive technology. This article lists types of assistive technology appropriate for use with persons with learning disabilities at the postsecondary level and discusses ways in which assistive technology enhances learning. Additionally, an overview of legislation that has had an impact on assistive technology at the postsecondary level is presented. Issues involving assistive technology programs at the postsecondary level are discussed. Postsecondary assistive technology program components, device selection, and training guidelines also are outlined.

Advancing pharmacovigilance through academic-legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis-a Research on Adverse Drug Events and Reports (RADAR) report.

OBJECTIVE: To compare and contrast three databases, that is, The International Centre for Nephrogenic Systemic Fibrosis Registry (ICNSFR), the Food and Drug Administration Adverse Event Reporting System (FAERS) and a legal data set, through pharmacovigilance and to evaluate international nephrogenic systemic fibrosis (NSF) safety efforts. METHODS: The Research on Adverse Drug events And Reports methodology was used for assessment-the FAERS (through June 2009), ICNSFR and the legal data set (January 2002 to December 2010). Safety information was obtained from the European Medicines Agency, the Danish Medicine Agency and the Food and Drug Administration. RESULTS: The FAERS encompassed the largest number (n = 1395) of NSF reports. The ICNSFR contained the most complete (n = 335, 100%) histopathological data. A total of 382 individual biopsy-proven, product-specific NSF cases were analysed from the legal data set. 76.2% (291/382) identified exposure to gadodiamide, of which 67.7% (197/291) were unconfounded. Additionally, 40.1% (153/382) of cases involved gadopentetate dimeglumine, of which 48.4% (74/153) were unconfounded, while gadoversetamide was identified in 7.3% (28/382) of which 28.6% (8/28) were unconfounded. Some cases involved gadobenate dimeglumine or gadoteridol, 5.8% (22/382), all of which were confounded. The mean number of exposures to gadolinium-based contrast agents (GBCAs) was gadodiamide (3), gadopentetate dimeglumine (5) and gadoversetamide (2). Of the 279 unconfounded cases, all involved a linear-structured GBCA. 205 (73.5%) were a non-ionic GBCA while 74 (26.5%) were an ionic GBCA. CONCLUSION: Clinical and legal databases exhibit unique characteristics that prove complementary in safety evaluations. Use of the legal data set allowed the identification of the most commonly implicated GBCA. ADVANCES IN KNOWLEDGE: This article is the first to demonstrate explicitly the utility of a legal data set to pharmacovigilance research.

Reporting of serious adverse events during cancer clinical trials to the institutional review board: an evaluation by the research on adverse drug events and reports (RADAR) project.

Global introspection is considered an unreliable method for attribution of causality of serious adverse events (SAEs), yet remains widely used for cancer drug clinical trials. Here, we compare structured case abstraction (SCA) to the routine method for detecting, evaluating, and reporting ADEs during cancer drug clinical trials to an Institutional Review Board (IRB). We obtained all SAE reports (2001-2008) received by one IRB for six clinical trials involving bevacizumab or oxaliplatin for treatment of gastrointestinal cancers. We compared the routine IRB SAE method to SCA for adverse event detection and causality attribution. Of 205 adverse events, 182 events (75%) were not reported; of these, 6 (20%) of 30 SAEs requiring an IRB report were unreported. For the 10 item Naranjo score, the amount of information useful for causality attribution was higher with SCA than the routine method (6.0 vs. 2.4 items, P < .0001). One-fifth of SAEs requiring an IRB report were unreported to the IRB via the routine method. SCA provided more useful information as to whether an SAE was caused by a cancer drug exposure. Our results suggest that SCA may improve SAE detection and the accuracy of attribution of causality during cancer drug clinical trials.

Elevated incidence of fractures in solid-organ transplant recipients on glucocorticoid-sparing immunosuppressive regimens.

This study was conducted to assess the occurrence of fractures in solid-organ transplant recipients. Methods. Medical record review and surveys were performed. Patients received less than 6 months of glucocorticoids. Results. Of 351 transplant patients, 175 patients provided fracture information, with 48 (27.4%) having fractured since transplant (2-6 years). Transplants included 19 kidney/liver (50% male), 47 kidney/pancreas (53% male), 92 liver (65% male), and 17 pancreas transplants (41% male). Age at transplant was 50.8 ± 10.3 years. Fractures were equally seen across both genders and transplant types. Calcium supplementation (n = 94) and bisphosphonate therapy (n = 52) were observed, and an association with a lower risk of fractures was noted for bisphosphonate users (OR = 0.45 95% C.I. 0.24, 0.85). Fracture location included 8 (16.7%) foot, 12 (25.0%) vertebral, 3 (6.3%) hand, 2 (4.2%) humerus, 5 (10.4%) wrist, 10 (20.8%) fractures at other sites, and 7 (14.6%) multiple fractures. The estimated relative risk of fracture was nearly seventeen-times higher in male liver transplant recipients ages 45-64 years compared with the general male population, and comparable to fracture rates on conventional immunosuppressant regimens. Conclusion. We identify a high frequency of fractures in transplant recipients despite limited glucocorticoid use.