Prevention of falls and fractures in old people by administration of calcium and vitamin d. randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>There are many studies that associate vitamin D serum levels in older persons with muscle strength, physical performance and risk of fractures and falls. However, current evidence is insufficient to make a general recommendation for administrating calcium and vitamin D to older persons. The objective of this study is to determine the effectiveness of calcium and vitamin D supplementation in improving musculoskeletal function and decreasing the number of falls in person aged over 65 years.</p> <p>Methods/Design</p> <p>Phase III, randomized, double blind, placebo-controlled trial to evaluate the efficacy of already marketed drugs in a new indication. It will be performed at Primary Care doctor visits at several Healthcare Centers in different Spanish Health Areas. A total of 704 non-institutionalized subjects aged 65 years or older will be studied (sample size calculated for a statistical power of 80%, alpha error 0.05, annual incidence of falls 30% and expected reduction of 30% to 20% and expected loss to follow up of 20%). The test drug containing 800 IU of vitamin D and 1000 mg of calcium will be administered daily. The control group will receive a placebo. The subjects will be followed up over two years. The primary variable will be the incidence of spontaneous falls. The secondary variables will include: consequences of the falls (fractures, need for hospitalization), change in calcidiol plasma levels and other analytical determinations (transaminases, PTH, calcium/phosphorous, albumin, creatinine, etc.), change in bone mass by densitometry, change in muscle strength in the dominant hand and change in musculoskeletal strength, risk factors for falls, treatment compliance, adverse effects and socio-demographic data.</p> <p>Discussion</p> <p>The following principles have been considered in the development of this Project: the product data are sufficient to ensure that the risks assumed by the study participants are acceptable, the study objectives will probably provide further knowledge on the problem studied and the available information justifies the performance of the study and its possible risk for the participants.</p> <p>If calcium and vitamin D supplementation is effective in the prevention of falls and fractures in the elderly population, a recommendation may be issued with the aim of preventing some of the consequences of falls that affect quality of life and the ensuing personal, health and social costs.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01452243">NCT01452243</a></p> <p>Clinical trial authorized by the Spanish Medicines Agency: EudraCT number 2006-001643-63.</p

The feasibility of whole body vibration in institutionalised elderly persons and its influence on muscle performance, balance and mobility: a randomised controlled trial [ISRCTN62535013]

BACKGROUND: Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents. Low-volume exercise interventions with similar training effects might be an alternative. The aim of this randomised controlled trial was to investigate the feasibility of Whole Body Vibration (WBV) in institutionalised elderly, and its impact on functional capacity and muscle performance. METHODS: Twenty-four nursing home residents (15 female, 9 male; mean age 77.5 ± 11.0 years) were randomised (stratification for age, gender and ADL-category) to 6 weeks static WBV exercise (WBV+, N = 13) or control (only static exercise; N = 11). Outcome measures were exercise compliance, timed up-and-go, Tinetti-test, back scratch, chair sit-and-reach, handgrip strength and linear isokinetic leg extension. RESULTS: At baseline, WBV+ and control groups were similar for all outcome variables. Twenty-one participants completed the program and attended respectively 96% and 86% of the exercise sessions for the WBV+ and control groups. Training-induced changes in timed up-and-go and Tinetti-test were better for WBV+ compared to control (p = 0.029 for timed up-and-go, p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively). In an alternative analysis (Worst Rank Score & Last Observation Carried Forward) the differences in change remained significant on the Tinetti body balance and total score. No other significant differences in change between both groups were observed. CONCLUSION: In nursing home residents with limited functional dependency, six weeks static WBV exercise is feasible, and is beneficial for balance and mobility. The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further

The TIP30 Protein Complex, Arachidonic Acid and Coenzyme A Are Required for Vesicle Membrane Fusion

Efficient membrane fusion has been successfully mimicked in vitro using artificial membranes and a number of cellular proteins that are currently known to participate in membrane fusion. However, these proteins are not sufficient to promote efficient fusion between biological membranes, indicating that critical fusogenic factors remain unidentified. We have recently identified a TIP30 protein complex containing TIP30, acyl-CoA synthetase long-chain family member 4 (ACSL4) and Endophilin B1 (Endo B1) that promotes the fusion of endocytic vesicles with Rab5a vesicles, which transport endosomal acidification enzymes vacuolar (H+)-ATPases (V-ATPases) to the early endosomes in vivo. Here, we demonstrate that the TIP30 protein complex facilitates the fusion of endocytic vesicles with Rab5a vesicles in vitro. Fusion of the two vesicles also depends on arachidonic acid, coenzyme A and the synthesis of arachidonyl-CoA by ACSL4. Moreover, the TIP30 complex is able to transfer arachidonyl groups onto phosphatidic acid (PA), producing a new lipid species that is capable of inducing close contact between membranes. Together, our data suggest that the TIP30 complex facilitates biological membrane fusion through modification of PA on membranes

Geographical gradient of the <em>eIF4E</em> alleles conferring resistance to potyviruses in pea (<em>Pisum</em>) germplasm

<div><p>Background</p><p>The eukaryotic translation initiation factor 4E was shown to be involved in resistance against several potyviruses in plants, including pea. We combined our knowledge of pea germplasm diversity with that of the <i>eIF4E</i> gene to identify novel genetic diversity.</p><p>Methodology/Principal findings</p><p>Germplasm of 2803 pea accessions was screened for <i>eIF4E</i> intron 3 length polymorphism, resulting in the detection of four <i>eIF4E^A-B-C-S</i> variants, whose distribution was geographically structured. The <i>eIF4E^A</i> variant conferring resistance to the P1 PSbMV pathotype was found in 53 accessions (1.9%), of which 15 were landraces from India, Afghanistan, Nepal, and 7 were from Ethiopia. A newly discovered variant, <i>eIF4E^B</i>, was present in 328 accessions (11.7%) from Ethiopia (29%), Afghanistan (23%), India (20%), Israel (25%) and China (39%). The <i>eIF4E^C</i> variant was detected in 91 accessions (3.2% of total) from India (20%), Afghanistan (33%), the Iberian Peninsula (22%) and the Balkans (9.3%). The <i>eIF4E^S</i> variant for susceptibility predominated as the wild type. Sequencing of 73 samples, identified 34 alleles at the whole gene, 26 at cDNA and 19 protein variants, respectively. Fifteen alleles were virologically tested and 9 alleles (<i>eIF4E^{A-1-2-3-4-5-6-7}</i>, <i>eIF4E^B-1</i>, <i>eIF4E^C-2</i>) conferred resistance to the P1 PSbMV pathotype.</p><p>Conclusions/Significance</p><p>This work identified novel <i>eIF4E</i> alleles within geographically structured pea germplasm and indicated their independent evolution from the susceptible <i>eIF4E^S1</i> allele. Despite high variation present in wild <i>Pisum</i> accessions, none of them possessed resistance alleles, supporting a hypothesis of distinct mode of evolution of resistance in wild as opposed to crop species. The Highlands of Central Asia, the northern regions of the Indian subcontinent, Eastern Africa and China were identified as important centers of pea diversity that correspond with the diversity of the pathogen. The series of alleles identified in this study provides the basis to study the co-evolution of potyviruses and the pea host.</p></div

Effects of risk-based multifactorial fall prevention on health-related quality of life among the community-dwelling aged: a randomized controlled trial

BACKGROUND: This study aimed to assess the effects of a risk-based, multifactorial fall prevention programme on health-related quality of life among the community-dwelling aged who had fallen at least once during the previous 12 months. METHODS: The study is a part of a single-centre, risk-based, multifactorial randomised controlled trial. The intervention lasted for 12 months and consisted of a geriatric assessment, guidance and treatment, individual instruction in fall prevention, group exercise, lectures on themes related to falling, psychosocial group activities and home exercise. Of the total study population (n = 591, 97% of eligible subjects), 513(251 in the intervention group and 262 in the control group) participated in this study. The effect of the intervention on quality of life was measured using the 15D health-related quality of life instrument consisting of 15 dimensions. The data were analysed using the chi-square test or Fisher's exact test, the Mann-Whitney U-test and logistic regression. RESULTS: In men, the results showed significant differences in the changes between the intervention and control groups in depression (p = 0.017) and distress (p = 0.029) and marginally significant differences in usual activities (p = 0.058) and sexual activity (p = 0.051). In women, significant differences in the changes between the groups were found in usual activities (p = 0.005) and discomfort/symptoms (p = 0.047). For the subjects aged 65 to 74 years, significant differences in the changes between the groups were seen in distress (p = 0.037) among men and in usual activities (p = 0.011) among women. All improvements were in favour of the intervention group. CONCLUSION: Fall prevention produced positive effects on some dimensions of health-related quality of life in the community-dwelling aged. Men benefited more than women

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Minimising disability and falls in older people through a post-hospital exercise program: a protocol for a randomised controlled trial and economic evaluation

Background: Disability and falls are particularly common among older people who have recently been hospitalised. There is evidence that disability severity and fall rates can be reduced by well-designed exercise interventions. However, the potential for exercise to have these benefits in older people who have spent time in hospital has not been established. This randomised controlled trial will investigate the effects of a home-based exercise program on disability and falls among people who have had recent hospital stays. The cost-effectiveness of the exercise program from the health and community service provider's perspective will be established. In addition, predictors for adherence with the exercise program will be determined. Methods and design: Three hundred and fifty older people who have recently had hospital stays will participate in the study. Participants will have no medical contraindications to exercise and will be cognitively and physically able to complete the assessments and exercise program. The primary outcome measures will be mobility-related disability (measured with 12 monthly questionnaires and the Short Physical Performance Battery) and falls (measured with 12 monthly calendars). Secondary measures will be tests of risk of falling, additional measures of mobility, strength and flexibility, quality of life, fall-related self efficacy, health-system and community-service contact, assistance from others, difficulty with daily tasks, physical activity levels and adverse events. After discharge from hospital and completion of all hospital-related treatments, participants will be randomly allocated to an intervention group or usual-care control group. For the intervention group, an individualised home exercise program will be established and progressed during ten home visits from a physiotherapist. Participants will be asked to exercise at home up to 6 times per week for the 12-month study period. Discussion: The study will determine the impact of this exercise intervention on mobility-related disability and falls in older people who have been in hospital as well as cost-effectiveness and predictors of adherence to the program. Thus, the results will have direct implications for the design and implementation of interventions for this high-risk group of older people.7 page(s

Identification of elderly fallers by muscle strength measures

For efficient prevention of falls among older adults, individuals at a high risk of falling need to be identified. In this study, we searched for muscle strength measures that best identified those individuals who would fall after a gait perturbation and those who recovered their balance. Seventeen healthy older adults performed a range of muscle strength tests. We measured maximum and rate of development of ankle plantar flexion moment, knee extension moment and whole leg push-off force, as well as maximum jump height and hand grip strength. Subsequently, their capacity to regain balance after tripping over an obstacle was determined experimentally. Seven of the participants were classified as fallers based on the tripping outcome. Maximum isometric push-off force in a leg press apparatus was the best measure to identify the fallers, as cross-validation of a discriminant model with this variable resulted in the best classification (86% sensitivity and 90% specificity). Jump height and hand grip strength were strongly correlated to leg press force (r = 0.82 and 0.59, respectively) and can also be used to identify fallers, although with slightly lower specificity. These results indicate that whole leg extension strength is associated with the ability to prevent a fall after a gait perturbation and might be used to identify the elderly at risk of falling