Validity of the Falls Risk for Older People in the Community (FROP‑Com) tool to predict falls and fall injuries for older people presenting to the emergency department after falling

The aims of this study were to (1) externally validate the accuracy of the Falls Risk for Older People in the Community (FROP-Com) falls risk assessment tool in predicting falls and (2) undertake initial validation of the accuracy of the FROPCom to predict injurious falls (requiring medical attention) in people aged ≥ 60 years presenting to emergency departments (EDs) after falling. Two hundred and thirteen participants (mean age = 72.4 years; 59.2% women) were recruited (control group of a randomised controlled trial). A FROP-Com assessment was completed at a home visit within 2 weeks of ED discharge. Data on falls and injurious falls requiring medical attention were collected via monthly falls calendars for the next 12 months. Predictive accuracy was evaluated using sensitivity and specificity of a high-risk FROP-Com classification (score ≥ 19) in predicting a fall and injurious falls requiring medical attention. Fifty per cent of participants fell, with 60.4% of falls requiring medical attention. Thirty-two per cent were classified as high, 49% as moderate and 19% low falls risk. Low sensitivity was achieved for the FROP-Com high-risk classification for predicting falls (43.4%) and injurious falls (34.4%), although specificity was high (79.4% and 78.6%, respectively). Despite the FROP-Com’s low predictive accuracy, the high fall rate and high falls risk of the sample suggest that older people who fall, present to ED and are discharged home are at high risk of future falls. In high-falls-risk populations such as in this study, the FROP-Com is not a valid tool for classifying risk of falls or injurious falls. Its potential value may instead be in identifying risk factors for falling to direct tailoring of falls prevention interventions to reduce future falls

Tai Chi for osteopenic women: design and rationale of a pragmatic randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Post-menopausal osteopenic women are at increased risk for skeletal fractures. Current osteopenia treatment guidelines include exercise, however, optimal exercise regimens for attenuating bone mineral density (BMD) loss, or for addressing other fracture-related risk factors (e.g. poor balance, decreased muscle strength) are not well-defined. Tai Chi is an increasingly popular weight bearing mind-body exercise that has been reported to positively impact BMD dynamics and improve postural control, however, current evidence is inconclusive. This study will determine the effectiveness of Tai Chi in reducing rates of bone turnover in post-menopausal osteopenic women, compared with standard care, and will preliminarily explore biomechanical processes that might inform how Tai Chi impacts BMD and associated fracture risks.</p> <p>Methods/Design</p> <p>A total of 86 post-menopausal women, aged 45-70y, T-score of the hip and/or spine -1.0 and -2.5, have been recruited from primary care clinics of a large healthcare system based in Boston. They have been randomized to a group-based 9-month Tai Chi program plus standard care or to standard care only. A unique aspect of this trial is its pragmatic design, which allows participants randomized to Tai Chi to choose from a pre-screened list of community-based Tai Chi programs. Interviewers masked to participants' treatment group assess outcomes at baseline and 3 and 9 months after randomization. Primary outcomes are serum markers of bone resorption (C-terminal cross linking telopeptide of type I collagen), bone formation (osteocalcin), and BMD of the lumbar spine and proximal femur (dual-energy X-ray absorptiometry). Secondary outcomes include health-related quality-of-life, exercise behavior, and psychological well-being. In addition, kinetic and kinematic characterization of gait, standing, and rising from a chair are assessed in subset of participants (n = 16) to explore the feasibility of modeling skeletal mechanical loads and postural control as mediators of fracture risk.</p> <p>Discussion</p> <p>Results of this study will provide preliminary evidence regarding the value of Tai Chi as an intervention for decreasing fracture risk in osteopenic women. They will also inform the feasibility, value and potential limitations related to the use of pragmatic designs for the study of Tai Chi and related mind-body exercise. If the results are positive, this will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study.</p> <p>Trial registration</p> <p>This trial is registered in Clinical Trials.gov, with the ID number of NCT01039012.</p

Community-based fall assessment compared with hospital-based assessment in community-dwelling older people over 65 at high risk of falling: a randomized study

This study showed the increased risk of falling according to community-based fall assessment program with respect to a traditional hospital-based one in community-dwelling older adults at high risk of falling

A Prospective Comparison of 18F-FDG PET/CT and CT as Diagnostic Tools to Identify the Primary Tumor Site in Patients with Extracervical Carcinoma of Unknown Primary Site

BACKGROUND. The aim of the present study was to evaluate prospectively the diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and conventional CT regarding the ability to detect the primary tumor site in patients with extracervical metastases from carcinoma of unknown primary (CUP) site. PATIENTS AND METHODS. From January 2006 to December 2010, 136 newly diagnosed CUP patients with extracervical metastases underwent (18)F-FDG PET/CT. A standard of reference (SR) was established by a multidisciplinary team to ensure that the same set of criteria were used for classification of patients, that is, either as CUP patients or patients with a suggested primary tumor site. The independently obtained suggestions of primary tumor sites using PET/CT and CT were correlated with the SR to reach a consensus regarding true-positive (TP), true-negative, false-negative, and false-positive results. RESULTS. SR identified a primary tumor site in 66 CUP patients (48.9%). PET/CT identified 38 TP primary tumor sites and CT identified 43 TP primary tumor sites. No statistically significant differences were observed between (18)F-FDG PET/CT and CT alone in regard to sensitivity, specificity, and accuracy. CONCLUSION. In the general CUP population with multiple extracervical metastases (18)F-FDG PET/CT does not represent a clear diagnostic advantage over CT alone regarding the ability to detect the primary tumor site

Controlling intramolecular interactions in the design of selective, high-affinity, ligands for the CREBBP Bromodomain

CREBBP (CBP/KAT3A) and its paralogue EP300 (KAT3B) are lysine acetyltransferases (KATs) that are essential for human development. They each comprise ten domains through which they interact with >400 proteins, making them important transcriptional coactivators, and key nodes in the human protein-protein interactome. The bromodomains of CREBBP and EP300 enable binding of acetylated lysine residues from histones, and a number of other important proteins, including p53, p73, E2F and GATA1. Here we report work to develop a high affinity, small molecule, ligand for the CREBBP and EP300 bromodomains [(−)-OXFBD05] that shows >100-fold selectivity over a representative member of the BET bromodomains, BRD4(1). Cellular studies using this ligand demonstrate that inhibition of the CREBBP/EP300 bromodomain in HCT116 colon cancer cells results in lowered levels of c-Myc, and a reduction in H3K18 and H3K27 acetylation. In hypoxia (<0.1% O2), inhibition of the CREBBP/EP300 bromodomain results in enhanced stabilization of HIF-1α