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1.  Frailty, pre-frailty and employment outcomes in the Health and Employment after Fifty (HEAF) study 
Objectives
Demographic changes are requiring people to work longer. No previous studies, however, have focussed on whether the ‘frailty’ phenotype (which predicts adverse events in the elderly) is associated with employment difficulties. To provide information, we assessed associations in the HEAF study, a population-based cohort of 50-65 year-olds.
Methods
Subjects, who were recruited from 24 English general practices, completed a baseline questionnaire on ‘pre-frailty’ and ‘frailty’ (adapted Fried criteria) and several work outcomes, including health-related job loss (HRJL), prolonged sickness absence (>20 days vs. less, past 12 months), having to cut down substantially at work and difficulty coping with work’s demands. Associations were assessed using logistic regression and population attributable fractions (PAFs) were calculated.
Results
In all, 3.9% of 8,095 respondents were classed as ‘frail’ and 31.6% as ‘pre-frail’. Three-quarters of the former were not in work, while 60% had left their last job on health grounds (odds ratio (OR) for HRJL, vs. non-frail subjects, 30.0 (95% Confidence Interval 23.0-39.2). Among those in work, ORs for prolonged sickness absence, cutting down substantially at work and struggling with work’s physical demands ranged from 10.7 to 17.2. The PAF for HRJL when any frailty marker was present was 51.8% and that for prolonged sickness absence was 32.5%. Associations were strongest with slow reported walking speed. Several associations were stronger in manual workers than in managers.
Conclusions
Fried frailty symptoms are not uncommon in mid-life and are strongly linked with economically important adverse employment outcomes. Frailty could represent an important target for prevention.
doi:10.1136/oemed-2016-104103
PMCID: PMC5474319  PMID: 28062832
work; frail; job loss; sickness absence; work limitations
2.  Modifiable risk factors of maternal postpartum weight retention: an analysis of their combined impact and potential opportunities for prevention 
Background/Objectives
Pregnancy triggers a physiological change in weight status. Postpartum weight retention in the childbearing years can substantially alter a woman’s weight gain trajectory, with several potential contributing factors identified. Most research has relied on women’s recall of pre-pregnancy weight during pregnancy or later, and not considered risk factors in combination. Using measured pre-pregnancy weight, this study aimed to examine the associations of maternal postpartum weight retention with parity, pre-pregnancy BMI, excessive gestational weight gain (GWG), maternal serum vitamin D concentration and dietary Glycaemic Index in early and late pregnancy and breastfeeding duration, including analysis of the combined impact of potentially modifiable risk factors.
Subjects/Methods
Prospective cohort study of 12,583 non-pregnant women aged 20-34 years in Southampton (UK) who were assessed prior to pregnancy, with those who subsequently became pregnant followed up in early and late gestation, and after delivery (n=2,559 in the final sample). Linear regression models examined potential predictors of weight retention in adjusted individual and multivariate analyses, and as a risk factor score.
Results
Compared with pre-pregnancy weight, 73% of women retained some weight at six months postpartum [mean (SD): 3.5 (6.2) kg]. In the adjusted multivariate model, women who were primiparous, had a lower pre-pregnancy BMI, excessive GWG, a lower early pregnancy vitamin D concentration and breastfed for <6 months had greater weight retention six months postpartum (p<0.05 for all variables). For each additional modifiable risk factor (excessive GWG, low vitamin D concentration in early pregnancy and short breastfeeding duration; scale 0-3), women retained an additional 2.49 kg (95%CI: 2.16, 2.82; p<0.001).
Conclusions
Having a greater number of modifiable risk factors was associated with greater weight retention six months postpartum. Initiatives supporting women to target these risk factors in the years prior to, during and after pregnancy could impact on their weight gain trajectory and later risk of adverse weight related outcomes.
doi:10.1038/ijo.2017.78
PMCID: PMC5500180  PMID: 28337028
gestational weight gain; pre-gravid BMI; breastfeeding; vitamin D; overweight; obesity; pregnancy
3.  Patients’ preferences for anti-osteoporosis drug treatment: a cross-European discrete-choice experiment 
Rheumatology (Oxford, England)  2017;56(7):1167-1176.
Objectives
To estimate the preferences of osteoporotic patients for medication attributes, and analyse data from seven European countries.
Methods
A discrete choice experiment was conducted in Belgium, France, Ireland, the Netherlands, Spain, Switzerland and United Kingdom. Patients were asked to choose repeatedly between two hypothetical unlabelled drug treatments (and an opt-out option) that varied with respect to four attributes: efficacy in reducing the risk of fracture, type of potential common side-effects, mode and frequency of administration. In those countries in which patients contribute to the cost of their treatment directly, a fifth attribute was added: out-of-pocket cost. A mixed logit panel model was used to estimate patients’ preferences.
Results
In total 1,124 patients completed the experiment, with sample of between 98 and 257 patients per country. In all countries, patients preferred treatment with higher effectiveness and 6-monthly subcutaneous injection was always preferred over weekly oral tablets. In five countries, patients also preferred monthly oral tablet and yearly intravenous injections over weekly oral tablets. In the three countries where the out-of-pocket cost was included as an attribute, lower costs significantly contribute to the treatment preference. Between countries there were statistically significant differences for 13 out of 42 attribute/levels interactions.
Conclusions
We find statistically significant differences in patients’ preferences for anti-osteoporosis medications between countries, especially for the mode of administration. Our findings emphasize that international treatment recommendations should allow for local adaptation and that understanding individual preferences is important if we want to improve the quality clinical care for patients with osteoporosis.
doi:10.1093/rheumatology/kex071
PMCID: PMC5563450  PMID: 28398547
Cross-Country Comparison; Discrete choice experiment; Drug treatment; Osteoporosis; Patients; Preferences
5.  Cognitive abilities in later life and the onset of physical frailty: the Lothian Birth Cohort 1936 
Structured Abstract
Objectives
To investigate whether poorer cognitive ability is a risk factor for the development of physical frailty, and whether this risk varies by cognitive domain.
Design
Prospective longitudinal study with six-year follow-up.
Setting
Edinburgh, Scotland.
Participants
594 members of the Lothian Birth Cohort 1936.
Measurements
Frailty was assessed at ages 70 and 76 using the Fried criteria. Cognitive functions were assessed at ages 70, 73, and 76. Factor score estimates were derived for baseline level of and change in four cognitive domains: visuospatial ability, memory, processing speed, and crystallized cognitive ability.
Results
Higher baseline levels of processing speed, memory, visuospatial ability and crystallized ability derived from ages 70, 73 and 76, and less decline in speed, memory and crystallized ability were associated with a reduced risk of becoming physically frail by age 76. When all cognitive domains were modelled together, processing speed was only domain associated with frailty risk: for a standard deviation increment in initial level of processing speed, the relative risk for frailty (RR) (95% confidence interval (CI)) was 0.53 (0.33, 0.85), after adjustment for age, sex, baseline frailty status, social class, depressive symptoms, number of chronic physical diseases, levels of inflammatory biomarkers, and other cognitive factor score estimates; for a SD increment in processing speed change (i.e. less decline) the RR (95% CI) was 0.26 (0.16, 0.42). When we conducted additional analyses using a single test of processing speed that did not require fast motor responses—Inspection Time—results were similar.
Conclusions
The speed with which older people process information and the rate at which this declines over time may be an important indicator of the risk of physical frailty.
doi:10.1111/jgs.14787
PMCID: PMC5482391  PMID: 28248416
Fried frailty phenotype; processing speed; memory; visuospatial ability; crystallized ability
6.  Perinatal DNA methylation at CDKN2A is associated with offspring bone mass: Findings from the Southampton Women’s Survey 
Poor intrauterine and childhood growth has been linked with the risk of osteoporosis in later life, a relationship which may in part be mediated through altered epigenetic regulation of genes. We previously identified a region within the promoter of the long non-coding RNA ANRIL encoded by the CDKN2A locus, at which differential DNA methylation at birth showed correlations with offspring adiposity. Given the common lineage of adipocytes and osteoblasts, we investigated the relationship between perinatal CDKN2A methylation and bone mass at ages 4 and 6 years. Using sodium bisulfite pyrosequencing we measured the methylation status of the 9 CpGs within this region in umbilical cord samples from discovery (n=332) and replication (n=337) cohorts of children from the Southampton Women’s Survey, whose bone mass was assessed by DXA (Hologic Discovery). Inverse associations were found between perinatal CDKN2A methylation and whole body minus head bone area (BA), bone mineral content (BMC) and areal bone-mineral density (BMD). This was confirmed in replication and combined data sets (all p<0.01), with each 10% increase in methylation being associated with a decrease in BMC of 4-9 g at age 4 years (p≤0.001). Relationships were similar with 6 year bone mass. Functional investigation of the differentially methylated region in the SaOS-2 osteosarcoma cell line showed that transcription factors bound to the identified CpGs in a methylation specific manner, and that CpG mutagenesis modulated ANRIL expression. In conclusion, perinatal methylation at CDKN2A is associated with childhood bone development, and has significance for cell function.
doi:10.1002/jbmr.3153
PMCID: PMC5528139  PMID: 28419547
Osteoporosis; Epidemiology; Epigenetics; DXA; CDKN2A; Development
7.  Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis patients 
Introduction
Rheumatoid arthritis is a systemic inflammatory disease, and classical disease-modifying antirheumatic drugs (cDMARDs) have proven efficacy. It is unknown what impact cDMARDs might have on dementia as an outcome.
Methods
Incident diagnoses of rheumatoid arthritis in persons over 18 years from 1995 to 2011 were identified from the UK Clinical Practice Research Datalink. There were 3876 cDMARD users and were propensity score matched to 1938 nonusers, on a wide range of confounders. Impact on dementia was assessed using survival models.
Results
cDMARD users were at reduced risk of dementia (hazard ratio: 0.60; 95% confidence interval: 0.42–0.85). The effect was strongest in methotrexate users (hazard ratio: 0.52; 95% confidence interval; 0.34–0.82).
Discussion
The strong effect of cDMARD use on halving of dementia risk requires replication in a trial and may provide an important therapeutic pharmacological treatment.
doi:10.1016/j.trci.2017.10.002
PMCID: PMC5700830
Dementia; Rheumatoid arthritis; Epidemiology; Disease-modifying antirheumatic drugs (DMARDs); Methotrexate; Propensity score matching; Fine and gray models; Clinical Practice Research Datalink; Alzheimer's disease
8.  Perinatal DNA Methylation at CDKN2A Is Associated With Offspring Bone Mass: Findings From the Southampton Women's Survey 
Journal of Bone and Mineral Research  2017;32(10):2030-2040.
ABSTRACT
Poor intrauterine and childhood growth has been linked with the risk of osteoporosis in later life, a relationship that may in part be mediated through altered epigenetic regulation of genes. We previously identified a region within the promoter of the long non‐coding RNA ANRIL encoded by the CDKN2A locus, at which differential DNA methylation at birth showed correlations with offspring adiposity. Given the common lineage of adipocytes and osteoblasts, we investigated the relationship between perinatal CDKN2A methylation and bone mass at ages 4 and 6 years. Using sodium bisulfite pyrosequencing, we measured the methylation status of the 9 CpGs within this region in umbilical cord samples from discovery (n = 332) and replication (n = 337) cohorts of children from the Southampton Women's Survey, whose bone mass was assessed by dual‐energy X‐ray absorptiomietry (DXA; Hologic Discovery). Inverse associations were found between perinatal CDKN2A methylation and whole‐body minus head bone area (BA), bone mineral content (BMC), and areal bone mineral density (BMD). This was confirmed in replication and combined data sets (all p < 0.01), with each 10% increase in methylation being associated with a decrease in BMC of 4 to 9 g at age 4 years (p ≤ 0.001). Relationships were similar with 6‐year bone mass. Functional investigation of the differentially methylated region in the SaOS‐2 osteosarcoma cell line showed that transcription factors bound to the identified CpGs in a methylation‐specific manner and that CpG mutagenesis modulated ANRIL expression. In conclusion, perinatal methylation at CDKN2A is associated with childhood bone development and has significance for cell function. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
doi:10.1002/jbmr.3153
PMCID: PMC5528139  PMID: 28419547
OSTEOPOROSIS; EPIDEMIOLOGY; EPIGENETICS; DXA; CDKN2A; DEVELOPMENT
9.  Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures 
Introduction
This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly fall into 4 distinct themes: Case-finding and management of individuals at high risk of fracturePublic awareness of osteoporosis and fragility fracturesReimbursement and health system policyEpidemiology of fracture in the developing world
Methods
Findings from cohort studies, randomised controlled trials, systematic reviews and meta-analyses, in addition to current clinical guidelines, position papers and national and international audits are summarised, with the intention of providing a prioritised approach to delivery of optimal bone health for all.
Results
Systematic approaches to case-finding individuals who are at high risk of sustaining fragility fractures are described. These include strategies and models of care intended to improve case-finding for individuals who have sustained fragility fractures, those undergoing treatment with medicines which have an adverse effect on bone health, and people who have diseases whereby bone loss and, consequently, fragility fractures are a common comorbidity. Approaches to deliver primary fracture prevention in a clinically effective and cost-effective manner are also explored.
Public awareness of osteoporosis is low worldwide. If older people are to be more pro-active in the management of their bone health, that needs to change. Effective disease awareness campaigns have been implemented in some countries, but need to be undertaken in many more. A major need exists to improve awareness of the risk that osteoporosis poses to individuals who have initiated treatment, with the intention of improving adherence in the long-term. A multisector effort is also required to support patients and their clinicians to have meaningful discussions concerning the risk-benefit ratio of osteoporosis treatment.
With regard to prioritisation of fragility fracture prevention in national policy, there is much to be done. In the developing world, robust epidemiological estimates of fracture incidence are required to inform policy development.
Conclusion
As the aging of the Baby Boomer generation is upon us, this review provides a comprehensive analysis of how bone health can be improved worldwide for all.
doi:10.1007/s00198-016-3894-y
PMCID: PMC5392413  PMID: 28175979
Fragility fracture; osteoporosis; case-finding; disease awareness; policy; prioritization; secondary prevention; primary prevention
10.  Relationship between Low Bone Mineral Density and Fractures with Incident Cardiovascular Disease: A Systematic Review and Meta-analysis† 
An increasing evidence base suggests that low bone mineral density (BMD) and fractures are associated with cardiovascular disease (CVD). We conducted a systematic review and meta-analysis summarizing the evidence of low BMD and fractures as risk factors for future CVD. Two independent authors searched major databases from inception to 1st August 2016 for longitudinal studies reporting data on CVD incidence (overall and specific CVD) and BMD status and fractures. The association between low BMD, fractures and CVD across longitudinal studies was explored by calculating pooled adjusted hazard ratios (HRs)±95% confidence intervals (CIs) with a random-effects meta-analysis. Twenty-eight studies (18 regarding BMD and 10 fractures) followed-up a total of 1,107,885 participants for a median of 5 years. Taking those with higher BMD as the reference, people with low BMD were at increased risk of developing CVD during follow-up (11 studies; HR=1.33; 95%CI: 1.27-1.38; I2=53%), after adjusting for a median of 8 confounders. This finding was confirmed using a decrease in one standard deviation of baseline BMD (9 studies; HR=1.16; 95%CI: 1.09-1.24; I2=69%). The presence of fractures at baseline was associated with an increased risk of developing CVD (HR=1.20; 95%CI: 1.06-1.37; I2=91%). Regarding specific CVD, low BMD was associated with an increased risk of developing coronary artery disease, cerebrovascular conditions, and CVD associated death. Fractures at baseline was associated with an increased risk of cerebrovascular conditions and death due to CVD. In conclusion, low BMD and fractures are associated with a small, but significant increased risk of CVD risk and possibly death.
doi:10.1002/jbmr.3089
PMCID: PMC5417361  PMID: 28138982
osteoporosis; bone mineral density; cardiovascular disease; meta-analysis
11.  Analysis of the MAVIDOS trial - Author's reply 
doi:10.1016/S2213-8587(17)30113-4
PMCID: PMC5432024  PMID: 28434488
12.  Associations of lifetime walking and weight bearing exercise with accelerometer-measured high impact physical activity in later life 
Preventive Medicine Reports  2017;8:183-189.
High impact physical activity (PA) is thought to benefit bone. We examined associations of lifetime walking and weight bearing exercise with accelerometer-measured high impact and overall PA in later life. Data were from 848 participants (66.2% female, mean age = 72.4 years) from the Cohort for Skeletal Health in Bristol and Avon, Hertfordshire Cohort Study and MRC National Survey of Health and Development. Acceleration peaks from seven-day hip-worn accelerometer recordings were used to derive counts of high impact and overall PA. Walking and weight bearing exercise up to age 18, between 18–29, 30–49 and since age 50 were recalled using questionnaires. Responses in each age category were dichotomised and cumulative scores derived. Linear regression was used for analysis. Greater lifetime walking was related to higher overall, but not high impact PA, whereas greater lifetime weight bearing exercise was related to higher overall and high impact PA. For example, fully-adjusted differences in log-overall and log-high impact PA respectively for highest versus lowest lifetime scores were: walking [0.224 (0.087, 0.362) and 0.239 (− 0.058, 0.536)], and weight bearing exercise [0.754 (0.432, 1.076) and 0.587 (0.270, 0.904)]. For both walking and weight bearing exercise, associations were strongest in the ‘since age 50’ category. Those reporting the most walking and weight bearing exercise since age 50 had highest overall and high impact PA, e.g. fully-adjusted difference in log-high impact PA versus least walking and weight bearing exercise = 0.588 (0.226, 0.951). Promoting walking and weight bearing exercise from midlife may help increase potentially osteogenic PA levels in later life.
Highlights
•Exposure to higher impact PA in old age is thought to improve skeletal health.•It is unclear how walking and exercise history relate to high impact PA in old age.•More frequent weight bearing exercise was more strongly related to high impact PA.•Associations were strongest for highest levels of walking and weight bearing exercise.•Performing both activity types from midlife might promote osteogenic PA at old age.
doi:10.1016/j.pmedr.2017.10.011
PMCID: PMC5671612
Accelerometer; Exercise; Life course; Physical activity
13.  Nausea and vomiting in early pregnancy: Effects on food intake and diet quality 
Maternal & Child Nutrition  2016;13(4):e12389.
Abstract
Experiences of nausea and/or vomiting in pregnancy (NVP) vary greatly, but the paucity of studies with pre‐pregnancy dietary data mean that little is known about the effects of NVP on diet. Using an administered food frequency questionnaire, diet was assessed before pregnancy and at 11 and 34 weeks' gestation in 2270 participants in a UK birth cohort study (Southampton Women's Survey). Experience of NVP in early pregnancy was graded as none, mild, moderate, or severe. Participants reported their level of food consumption as more, the same, or less than before pregnancy. “Prudent” diet scores (derived using principal component analysis) were used to describe participants' diet quality before, in early and late pregnancy.
In early pregnancy, 89% of women were nauseous, although most commonly, the NVP experienced was mild (48%) or moderate (30%); 11% had severe NVP. A total of 39% of women reported an increase in their level of food intake in early pregnancy; 34% reported a reduction. Increasing severity of nausea was associated with changes in intake of a range of foods, most notably reduced consumption of vegetables, tea/coffee, rice/pasta, breakfast cereals, beans/pulses and citrus fruits/fruit juices and increased consumption of white bread, and soft drinks. Increasing severity of nausea was also associated with decreasing prudent diet score from before to early pregnancy, such that women with severe nausea had prudent diet scores 0.29 SDs lower than those with no nausea (P < 0.001). However, this was transient as NVP was not related to change in diet quality from before to late pregnancy.
doi:10.1111/mcn.12389
PMCID: PMC5400073  PMID: 27896913
cohort study; diet; food frequency questionnaire; nausea; pregnancy; vomiting
14.  Diurnal cortisol and mental well-being in middle and older age: evidence from four cohort studies 
BMJ Open  2017;7(10):e016085.
Objectives
We conducted an individual participant meta-analysis to test the hypothesis that cortisol patterns indicative of dysregulated hypothalamic–pituitary–adrenal axis functioning would be prospectively associated with poorer well-being at follow-up.
Setting
Four large UK-based cohort studies.
Participants
Those providing valid salivary or serum cortisol samples (n=7515 for morning cortisol; n=1612 for cortisol awakening response) at baseline (age 44–82) and well-being data on the Warwick Edinburgh Mental Wellbeing Scale at follow-up (0–8 years) were included.
Results
Well-being was not associated with morning cortisol, diurnal slope or awakening response though a borderline association with evening cortisol was found. Adjusting for sex and follow-up time, each 1 SD increase in evening cortisol was associated with a −0.47 (95% CI −1.00 to 0.05) point lower well-being. This was attenuated by adjustment for body mass index, smoking and socioeconomic position. Between-study heterogeneity was low.
Conclusions
This study does not support the hypothesis that diurnal cortisol is prospectively associated with well-being up to 8 years later. However, replication in prospective studies with cortisol samples over multiple days is required.
doi:10.1136/bmjopen-2017-016085
PMCID: PMC5652457  PMID: 29025828
meta-analysis; individual participant data; positive psychology
15.  Prenatal exposure to vitamin D from fortified margarine and risk of fractures in late childhood. Period and cohort results from 222 000 subjects in the D-tect observational study 
The British journal of nutrition  2017;117(6):872-881.
Prenatal low vitamin D may have consequences for bone health. By means of a nationwide mandatory vitamin D fortification program, we examined the risk of fractures among 10-18 year old children from proximate birth cohorts born around the date of the termination of the program. For all subjects born in Denmark during 1983-1988, civil registration numbers were linked to the Danish National Patient Registry for incident and recurrent fractures occurring at ages 10-18 years. Multiplicative Poisson models were used to examine the association between birth cohort and fracture rates. The variation in fracture rates across birth cohorts was analyzed by fitting an age-cohort model to the data. We addressed the potential modification of the effect of vitamin D availability by season of birth. The risk of fractures was increased among both girls and boys who were born before the vitamin D fortification terminated in 1985 (rate ratio (RR) exposed vs. non-exposed girls: 1.15 (95% confidence interval (CI): 1.11, 1.20; RR exposed vs. non-exposed boys: 1.11 (95% CI: 1.07, 1.14). However, these associations no longer persisted after including the period effects. There was no interaction between season of birth and vitamin D availability in relation to fracture risk.The study did not provide evidence that prenatal exposure to extra vitamin D from a mandatory fortification program of 1.25 µg vitamin D/100 g margarine was sufficient to influence the risk of fractures in late childhood, regardless of season of birth. Replication studies are needed.
doi:10.1017/S000711451700071X
PMCID: PMC5426325  PMID: 28393739
epidemiology; vitamin D; fracture risk; fortification; children
16.  Degenerative Inter-Vertebral Disc Disease (Osteochondrosis Intervertebralis) in Europe: Prevalence, Geographic Variation, and Radiological Correlates in Men and Women Aged 50 and Over 
Rheumatology (Oxford, England)  2017;56(7):1189-1199.
Objectives
To assess the prevalence across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal bone mineral density (aBMD) and change in aBMD with time.
Methods
In the population-based European Prospective Osteoporosis Study 27 age-stratified samples of men and women from across the continent aged 50+ had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature.
Results
Images from 10,132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD.
Discussion
KL Grades 3 and 4 are often used clinically to categorise radiological DDD. Highly variable European prevalences of radiologically-defined DDD Grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes.
doi:10.1093/rheumatology/kex040
PMCID: PMC5582627  PMID: 28398504
17.  International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates 
Background
Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients.
Methods
The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis.
Results
Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and three months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%.
Conclusions
If a significant decrease is observed the treatment can continue but if no decrease occurs the clinician should reassess to identify problems with the treatment, mainly low adherence
doi:10.1007/s00198-017-3906-6
PMCID: PMC5302161  PMID: 28093634
Adherence; Bisphosphonates; Osteoporosis treatment; Screening; Position paper
18.  Sleep disturbance and the older worker: findings from the Health and Employment After Fifty study 
Objectives
To characterise the descriptive epidemiology of insomnia in mid-life and explore the relative importance of different occupational risk factors for insomnia in older workers.
Methods
A questionnaire was mailed to all adults aged 50-64 years registered with 24 English general practices. Insomnia was defined as having at least one of four problems with sleep severely in the past 3 months. Subjects were also asked about employment conditions, feelings concerning work, and their health. Associations were assessed by logistic regression and population attributable fractions (PAF) calculated.
Results
Analysis was based on 8067 respondents (5470 in paid work). Insomnia was reported by 18.8% of subjects, being commoner in women, smokers, obese individuals, those living alone, and those in financial hardship, and less prevalent in the educated, those in South-East England, and those with friendships and leisure-time pursuits. Occupational risk factors included unemployment, shift working, lack of control and support at work, job insecurity, job dissatisfaction and several of its determinants (lacking a sense of achievement, feeling unappreciated, having difficult work colleagues, feeling unfairly criticised). Population burden of insomnia was associated more strongly with difficulties in coping with work demands, job insecurity, difficult colleagues, and lack of friendships at work (PAF 15-33%) than shift work and lack of autonomy or support (PAF 5-7%). It was strongly associated with seven measures of poorer self-assessed health.
Conclusions
Employment policies aimed at tackling insomnia in older workers may benefit from focussing particularly on job-person fit, job security and relationships in the workplace.
doi:10.5271/sjweh.3618
PMCID: PMC5367516  PMID: 28052164
19.  Influences on diet quality in older age: the importance of social factors 
Age and ageing  2017;46(2):277-283.
Background
Poor diet quality is common among older people, but little is known about influences on food choice, including the role of psychosocial factors at this age.
Objective
To identify psychosocial correlates of diet quality in a community-dwelling population of men and women aged 59-73 years; to describe relationships with change in diet quality over 10 years.
Design
Longitudinal cohort, Hertfordshire Cohort Study (HCS).
Subjects
HCS participants assessed at baseline (1998-2001: 1048 men, 862 women); 183 men and 189 women re-assessed in 2011.
Methods
Diet was assessed by administered food frequency questionnaire; diet scores were calculated to describe diet quality at baseline and follow-up. A range of psychosocial factors (social support, social network, participation in leisure activities, depression and anxiety, sense of control) were assessed by questionnaire.
Results
At baseline, better diet quality was related to a range of social factors, including increased confiding/emotional social support (men and women), practical support (men), and a larger social network (women) (all p<0.05). For both men and women, greater participation in social and cognitive leisure activities was related to better diet quality (p<0.005). There were few associations between measured psychosocial factors at baseline and change in diet score over 10 years, in the follow-up sub-group. However, greater participation in leisure activities, especially cognitive activities, at baseline was associated with smaller declines in diet quality over the 10-year follow-up period for both men (p=0.017) and women (p=0.014).
Conclusions
In community-dwelling older adults, a range of social factors, that includes greater participation in leisure activities, were associated with diets of better quality.
doi:10.1093/ageing/afw180
PMCID: PMC5390861  PMID: 27744301
ageing; diet; older people; social relationships; UK
20.  English translation and validation of the SarQoL®, a quality of life questionnaire specific for sarcopenia 
Age and ageing  2017;46(2):271-276.
Background
the first quality of life questionnaire specific to sarcopenia, the SarQoL®, has recently been developed and validated in French. To extend the availability and utilisation of this questionnaire, its translation and validation in other languages is necessary.
Objective
the purpose of this study was therefore to translate the SarQoL® into English and validate the psychometric properties of this new version.
Design
cross-sectional.
Setting
Hertfordshire, UK.
Subjects
in total, 404 participants of the Hertfordshire Cohort Study, UK.
Methods
the translation part was articulated in five stages: (i) two initial translations from French to English; (ii) synthesis of the two translations; (iii) backward translations; (iv) expert committee to compare the backward translations with the original questionnaire and (v) pre-test. To validate the English SarQoL®, we assessed its validity (discriminative power, construct validity), reliability (internal consistency, test–retest reliability) and floor/ceiling effects.
Results
the SarQoL® questionnaire was translated without any major difficulties. Results indicated a good discriminative power (lower score of quality of life for sarcopenic subjects, P = 0.01), high internal consistency (Cronbach’s alpha of 0.88), consistent construct validity (high correlations found with domains related to mobility, usual activities, vitality, physical function and low correlations with domains related to anxiety, self-care, mental health and social problems) and excellent test– retest reliability (intraclass coefficient correlation of 0.95, 95%CI 0.92–0.97). Moreover, no floor/ceiling has been found.
Conclusions
a valid SarQoL® English questionnaire is now available and can be used with confidence to better assess the disease burden associated with sarcopenia. It could also be used as a treatment outcome indicator in research.
doi:10.1093/ageing/afw192
PMCID: PMC5396804  PMID: 27789428
older people; sarcopenia; quality of life; translation; validation
21.  The relationship between dietary quality and the local food environment differs according to level of educational attainment: A cross-sectional study 
PLoS ONE  2017;12(8):e0183700.
There is evidence that food outlet access differs according to level of neighbourhood deprivation but little is known about how individual circumstances affect associations between food outlet access and diet. This study explored the relationship between dietary quality and a measure of overall food environment, representing the balance between healthy and unhealthy food outlet access in individualised activity spaces. Furthermore, this study is the first to assess effect modification of level of educational attainment on this relationship. A total of 839 mothers with young children from Hampshire, United Kingdom (UK) completed a cross-sectional survey including a 20-item food frequency questionnaire to measure diet and questions about demographic characteristics and frequently visited locations including home, children’s centre, general practitioner, work, main food shop and physical activity location. Dietary information was used to calculate a standardised dietary quality score for each mother. Individualised activity spaces were produced by creating a 1000m buffer around frequently visited locations using ArcGIS. Cross-sectional observational food outlet data were overlaid onto activity spaces to derive an overall food environment score for each mother. These scores represented the balance between healthy and unhealthy food outlets using weightings to characterise the proportion of healthy or unhealthy foods sold in each outlet type. Food outlet access was dominated by the presence of unhealthy food outlets; only 1% of mothers were exposed to a healthy overall food environment in their daily activities. Level of educational attainment moderated the relationship between overall food environment and diet (mid vs low, p = 0.06; high vs low, p = 0.04). Adjusted stratified linear regression analyses showed poorer food environments were associated with better dietary quality among mothers with degrees (β = -0.02; 95%CI: -0.03, -0.001) and a tendency toward poorer dietary quality among mothers with low educational attainment, however this relationship was not statistically significant (β = 0.01; 95%CI: -0.01, 0.02). This study showed that unhealthy food outlets, like takeaways and convenience stores, dominated mothers’ food outlet access, and provides some empirical evidence to support the concept that individual characteristics, particularly educational attainment, are protective against exposure to unhealthy food environments. Improvements to the imbalance of healthy and unhealthy food outlets through planning restrictions could be important to reduce dietary inequalities.
doi:10.1371/journal.pone.0183700
PMCID: PMC5571951  PMID: 28841678
22.  How clinical practitioners assess frailty in their daily practice: an international survey 
Introduction
Various operational definitions have been proposed to assess the frailty condition among older individuals. Our objective was to assess how practitioners measure the geriatric syndrome of frailty in their daily routine.
Methods
An online survey was sent to national geriatric societies affiliated to the European Union Geriatric Medicine Society (EUGMS) and to members of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).
Results
A total of 388 clinicians from 44 countries answered to the survey. Most of them were medical doctors (93%), and their primary field of practice was geriatrics (83%). Two hundred and five clinicians (52.8%) always assessed frailty in their daily practice, 38.1% reported to “sometimes” measure it, and 9.1% never assess it. A substantial proportion of clinicians (64.9%) diagnose frailty using more than one instrument. The most widely used tool was the gait speed test, adopted by 43.8% of the clinicians, followed by clinical frailty scale (34.3%), the SPPB test (30.2%), the frailty phenotype (26.8%) and the frailty index (16.8%).
Conclusion
A variety of tools is used to assess frailty of older patients in clinical practice highlighting the need for standardisation and guidelines.
doi:10.1007/s40520-017-0806-8
PMCID: PMC5589778  PMID: 28770478
Frailty; Survey; Clinical practice; Standardisation
23.  How Hand Osteoarthritis, Comorbidity and Pain Interact to Determine Functional Limitation in Older People: Observations from the EPOSA Study 
Objective
To examine the role of comorbidity and pain in the associations of hand osteoarthritis (OA) with self-reported and performance-based physical function in a general population of elderly persons.
Methods
We studied data from 2,942 participants ages 65-85 years in the European Project on OSteoArthritis, a collaborative observational study of 6 European cohorts (from Germany, Italy, The Netherlands, Spain, Sweden and the UK). Outcomes measures included self-reported physical function of the hands measured by the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) for hand OA physical function subscale and performance-based grip strength measured using a strain gauge dynamometer.
Results
Comorbidity was not a confounder in the association of hand OA with self-reported and performance-based functional limitations, while the role of pain as a mediator was confirmed. Anxiety, depression, stroke and osteoporosis were associated with AUSCAN scores reflecting more impairment. Depression and osteoporosis were associated with less grip strength.
Conclusions
Although comorbidity was decidedly and independently associated with hand functional limitation, it had no effect on the relationship of hand OA with physical function. Hand OA was found to be associated with both self-reported and performance-based physical function impairment; the association was found to be partially mediated by pain, which reduces its impact.
doi:10.1002/art.39757
PMCID: PMC5521250  PMID: 27214708
osteoarthritis; comorbidity; functional limitations; AUSCAN; pain
24.  Cognitive Ability in Late Life and Onset of Physical Frailty: The Lothian Birth Cohort 1936 
Objectives
To investigate whether poorer cognitive ability is a risk factor for development of physical frailty and whether this risk varies according to cognitive domain.
Design
Prospective longitudinal study with 6‐year follow‐up.
Setting
Edinburgh, Scotland.
Participants
Members of the Lothian Birth Cohort 1936 (N = 594).
Measurements
Frailty was assessed at ages 70 and 76 using the Fried criteria. Cognitive function was assessed at age 70, 73, and 76. Factor score estimates were derived for baseline level of and change in four cognitive domains: visuospatial ability, memory, processing speed, and crystallized cognitive ability.
Results
Higher baseline levels of processing speed, memory, visuospatial ability and crystallized ability at age 70, and less decline in speed, memory, and crystallized ability were associated with less risk of becoming physically frail by age 76. When all cognitive domains were modelled together, processing speed was the only domain associated with frailty risk, for a standard deviation (SD) increment in initial level of processing speed, the risk of frailty was 47% less (0.53 95% confidence interval (CI) = 0.33–0.85) after adjustment for age, sex, baseline frailty status, social class, depressive symptoms, number of chronic physical diseases, levels of inflammatory biomarkers, and other cognitive factor score estimates; for a SD increment in processing speed change (less decline) risk of frailty was 74% less (RRR = 0.26, 95% CI = 0.16–0.42). When additional analyses were conducted using a single test of processing speed that did not require fast motor responses (inspection time), results were similar.
Conclusions
The speed with which older adults process information and the rate at which this declines over time may be an important indicator of the risk of physical frailty.
doi:10.1111/jgs.14787
PMCID: PMC5482391  PMID: 28248416
fried frailty phenotype; processing speed; memory; visuospatial ability; crystallized ability
25.  Associations Between Perceived Neighbourhood Problems and Quality of Life in Older Adults With and Without Osteoarthritis: Results from the Hertfordshire Cohort Study 
Health & place  2017;43:144-150.
This study examined whether the association of quality of life (QoL) with perceived neighbourhood problems is stronger in older adults with osteoarthritis (OA) than in those without OA. Of all 294 participants, 23.8% had OA. More perceived neighbourhood problems were associated with a stronger decrease in QoL over time in participants with OA (B=-0.018; p=0.02) than in those without OA (B=-0.004; p=0.39). Physical activity did not mediate this relationship. Older adults with OA may be less able to deal with more challenging environments.
doi:10.1016/j.healthplace.2016.11.013
PMCID: PMC5289497  PMID: 28061391
Neighbourhood problems; Older population; Osteoarthritis; Physical activity; Quality of life

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