Quantitative Trait Loci for Bone Lengths on Chromosome 5 Using Dual Energy X-Ray Absorptiometry Imaging in the Twins UK Cohort

Human height is a highly heritable and complex trait but finding important genes has proven more difficult than expected. One reason might be the composite measure of height which may add heterogeneity and noise. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) for lengths of spine, femur, tibia, humerus and radius. These were investigated as alternative measures for height in a large, population–based twin sample with the potential to find genes underlying bone size and bone diseases. 3,782 normal Caucasian females, 18–80 years old, with whole body dual energy X-ray absorptiometry (DXA) images were used. A novel and reproducible method, linear pixel count (LPC) was used to measure skeletal sizes on DXA images. Intraclass correlations and heritability estimates were calculated for lengths of spine, femur, tibia, humerus and radius on monozygotic (MZ; n = 1,157) and dizygotic (DZ; n = 2,594) twins. A genome-wide linkage scan was performed on 2000 DZ twin subjects. All skeletal sites excluding spine were highly correlated. Intraclass correlations showed results for MZ twins to be significantly higher than DZ twins for all traits. Heritability results were as follows: spine, 66%; femur, 73%; tibia, 65%; humerus, 57%; radius, 68%. Results showed reliable evidence of highly suggestive linkage on chromosome 5 for spine (LOD score  =  3.0) and suggestive linkage for femur (LOD score  =  2.19) in the regions of 105cM and 155cM respectively. We have shown strong heritability of all skeletal sizes measured in this study and provide preliminary evidence that spine length is linked to the chromosomal region 5q15-5q23.1. Bone size phenotype appears to be more useful than traditional height measures to uncover novel genes. Replication and further fine mapping of this region is ongoing to determine potential genes influencing bone size and diseases affecting bone

Measuring care of the elderly: psychometric testing and modification of the Time in Care instrument for measurement of care needs in nursing homes

<p>Abstract</p> <p>Background</p> <p>Aging entails not only a decrease in the ability to be active, but also a trend toward increased dependence to sustain basic life functions. An important aspect for appropriately elucidating the individual's care needs is the ability to measure them both simply and reliably. Since 2006 a new version of the Time in Care needs (TIC-n) instrument (19-item version) has been explored and used in one additional municipality with the same structure as the one described in an earlier study.</p> <p>Methods</p> <p>The TIC-n assessment was conducted on a total of 1282 care recipients. Factor analysis (principal component) was applied to explore the construct validity of the TIC-n. Cronbach's alpha was calculated to test reliability and for each of the items remaining in the instrument after factor analysis, an inter-rater comparison was carried out on all recipients in both municipalities. Independently of each other, a weighted Kappa (K_w) was calculated. Results. The mean of each weighted Kappa (K_w) for the dimensions in the two municipalities was 0.75 and 0.76, respectively. Factor analysis showed that all 19 items had a factor loading of ≥ 0.40. Three factors (General Care, Medical Care and Cognitive Care) were created.</p> <p>Conclusion</p> <p>The TIC-n instrument has now been tested for validity and reliability in two municipalities with satisfactory results. However, TIC-n can not yet be used as a golden standard, but it can be recommended for use of measurement of individual care needs in municipal elderly care.</p

Unmet need and psychological distress predict emergency department visits in community-dwelling elderly women: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Unmet need to perform activities of daily living (ADL) is associated with increased use of urgent health services by the elderly. However, the reported associations may be confounded by psychological distress. We examine the independent effects of unmet need and psychological distress upon emergency department (ED) visits.</p> <p>Methods</p> <p>We conducted a prospective study of randomly selected community-dwelling adults aged ≥ 75. We report here the results for women only (n = 530). In-person interviews collected data on self-reported unmet need and the 14-item <it>l'Indice de détresse psychologique de Santé Québec </it>psychological distress scale. ED visits were identified from an administrative database. Multivariable logistic regression was used to identify predictors of any ED visit in the 6 months following the baseline interview.</p> <p>Results</p> <p>In multivariable analysis, unmet need in instrumental ADL was associated with subsequent ED visits (odds ratio = 1.57, 95% confidence interval = 1.02-2.41), as was psychological distress (odds rate = 1.30, 95% confidence interval = 1.02-1.67). The magnitude of the association between unmet need and ED visits was overestimated in statistical models that did not adjust for psychological distress.</p> <p>Conclusions</p> <p>Both unmet need and psychological distress were independent predictors of ED visits. Future investigations of unmet need and health services utilization should include psychological distress to control for confounding and improve the internal validity of statistical models.</p

Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover

Osteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels. INTRODUCTION: Bone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels. METHODS: Post-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo. RESULTS: In the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290). CONCLUSION: The vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states

Should the provision of home help services be contained?: Validation of the new preventive care policy in Japan

<p>Abstract</p> <p>Background</p> <p>To maintain the sustainability of public long-term care insurance (LTCI) in Japan, a preventive care policy was introduced in 2006 that seeks to promote active improvement in functional status of elderly people who need only light care. This policy promotes the use of day care services to facilitate functional improvement, and contains the use of home help services that provide instrumental activity of daily living (IADL) support. However, the validity of this approach remains to be demonstrated.</p> <p>Methods</p> <p>Subjects comprised 241 people aged 65 years and over who had recently been certified as being eligible for the lightest eligibility level and had began using either home help or day care services between April 2007 and October 2008 in a suburban city of Tokyo. A retrospective cohort study was conducted ending October 2009 to assess changes in the LTCI eligibility level of these subjects. Cox's proportional hazards model was used to calculate the relative risk of declining in function to eligibility Level 4 among users of the respective services.</p> <p>Results</p> <p>Multivariate analysis adjusted for factors related to service use demonstrated that the risk of decline in functional status was lower for users of home help services than for users of day care services (HR = 0.55, 95% CI: 0.31-0.98). The same result was obtained when stratified by whether the subject lived with family or not. Furthermore, those who used two or more hours of home help services did not show an increase in risk of decline when compared with those who used less than two hours.</p> <p>Conclusions</p> <p>No evidence was obtained to support the effectiveness of the policy of promoting day care services and containing home help services for those requiring light care.</p

A protective personal factor against disability and dependence in the elderly: an ordinal regression analysis with nine geographically-defined samples from Spain

Background Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. Methods A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). Results High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29–0.87) and dependence (OR = 0.33; 95% CI = 0.19–0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22–0.70 and OR = 0.39; 95%CI = 0.21–0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. Conclusions Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain.This project was partially funded by a research contract in support of the project “Epidemiological Study of Dementia in Spain” signed by the Pfizer Foundation and Carlos III Institute of HealthS