Allostatic load and pain severity in older adults:Results from the English Longitudinal Study of Ageing

Pain is common in older adults, is frequently experienced as stressful, and is associated with increased morbidity and mortality. Stress regulatory systems are adaptive to challenge and change, allostasis, until demands exceed the adaptive capacity contributing to dysregulation, resulting in a high allostatic load. A high allostatic load is associated with increased risk of morbidity and mortality. Pain severity, based on the average intensity of frequent pain, was hypothesized to be positively associated with AL. Four formulations of AL were investigated. Cross-sectional data from Wave 4 (2008-2009) of the English Longitudinal Study of Aging (ELSA) were analyzed. Covariates in the model included age, sex, education, smoking status, alcohol consumption, activity level, depression and common comorbid health conditions. A total of 5341 individuals were included; mean age 65.3(±9.2) years, 55% female, 62.4% infrequent or no pain, 12.6% mild pain, 19.1% moderate pain, and 5.9% severe pain. Severe pain was associated with greater AL defined by all four formulations. The amount of variance explained by pain severity and the covariates was highest when allostatic load was defined by the high risk quartile (12.9%) and by the clinical value (11.7%). Findings indicate a positive relationship between pain severity and AL. Further investigation is needed to determine if there is a specific AL signature for pain that differs from other health conditions

Population-based estimates of healthy working life expectancy in England at age 50 years: analysis of data from the English Longitudinal Study of Ageing.

BACKGROUND: Retirement ages are rising in many countries to offset the challenges of population ageing, but people's capacity to work for more years in their later working life (>50 years) is unclear. We aimed to estimate healthy working life expectancy in England. METHODS: This analysis included adults aged 50 years and older from six waves (2002-13) of the English Longitudinal Study of Ageing (ELSA), with linked mortality data. Healthy working life expectancy was defined as the average number of years expected to be spent healthy (no limiting long-standing illness) and in paid work (employment or self-employment) from age 50 years. Healthy working life expectancy was estimated for England overall and stratified by sex, educational attainment, deprivation level, occupation type, and region by use of interpolated Markov chain multi-state modelling. FINDINGS: There were 15?284 respondents (7025 men and 8259 women) with survey and mortality data for the study period. Healthy working life expectancy at age 50 years was on average 9·42 years (10·94 years [95% CI 10·65-11·23] for men and 8·25 years [7·92-8·58] for women) and life expectancy was 31·76 years (30·05 years for men and 33·49 years for women). The number of years expected to be spent unhealthy and in work from age 50 years was 1·84 years (95% CI 1·74-1·94) in England overall. Population subgroups with the longest healthy working life expectancy were the self-employed (11·76 years [95% CI 10·76-12·76]) or those with non-manual occupations (10·32 years [9·95-10·69]), those with a tertiary education (11·27 years [10·74-11·80]), those living in southern England (10·73 years [10·16-11·30] in the South East and 10·51 years [9·80-11·22] in the South West), and those living in the least deprived areas (10·53 years [10·06-10·99]). INTERPRETATION: Healthy working life expectancy at age 50 years in England is below the remaining years to State Pension age. Older workers of lower socioeconomic status and in particular regions in England might benefit from proactive approaches to improve health, workplace environments, and job opportunities to improve their healthy working life expectancy. Continued monitoring of healthy working life expectancy would provide further examination of the success of such approaches and that of policies to extend working lives. FUNDING: Economic and Social Research Council

Onset and persistence of person-perceived participation restriction in older adults: a 3-year follow-up study in the general population

<p>Abstract</p> <p>Background</p> <p>Participation restriction is defined as "problems an individual may experience in involvement in life situations" and refers to the personal and societal consequences of health conditions. There is a growing interest in participation restriction because (i) problems with work or looking after others may be more concerning to individuals than the signs and symptoms of health conditions and (ii) even when poor health persists, participation may still be maintained. The natural history of participation restriction in the general population is unknown and the aim of this report is to describe change in status of person-perceived participation restriction over three years in community-dwelling adults aged 50 years and over.</p> <p>Method</p> <p>Prospective cohort study (baseline and 3-year follow-up) using postal questionnaires mailed to a population-based sample of older adults. Responders were included in this study if they completed all items of the Keele Assessment of Participation at baseline (n = 6965). Estimates of onset and persistence of person-perceived participation restriction at 3-year follow-up were calculated for any and for each aspect of life in the sample as a whole, and then by age and gender using attrition re-weighted logistic regression to take account of sample attrition.</p> <p>Results</p> <p>In the whole sample of 6965 persons, overall participation status at three years was unchanged in 69%, and changed in 31%. Of 3431 persons with no restriction at baseline, it is estimated that 29.8% (95% confidence interval: 27.6%, 32.0%) would report restriction in at least one aspect of life at 3-year follow-up. Of 3534 persons who had baseline restriction, it is estimated that 68.8% (66.2%, 71.3%) would report continuing restriction in at least one aspect of life after 3 years. Onset and persistence both increased with age, and were most frequently recorded for restricted mobility outside the home.</p> <p>Conclusion</p> <p>Although most older persons do not change their overall participation status during a three-year period, change does occur which implies that population approaches to improving participation can be sought. Both onset and persistence of person-perceived participation restriction are more common the older the age-group.</p

Kinematic measures provide useful information after intracranial aneurysm treatment

Introduction; Current methods of assessing the outcomes of intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage are relatively insensitive, and thus unlikely to detect subtle deficits. Failures to identify cognitive and motor outcomes of intracranial aneurysm treatment might prevent delivery of optimal post-operative care. There are also concerns over risks associated with using intracranial aneurysm treatment as a preventative measure. Methods; We explored whether our kinematic tool would yield useful information regarding motor/cognitive function in patients who underwent intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage or unruptured aneurysm. Computerised kinematic motor and learning tasks were administered alongside standardised clinical outcome measures of cognition and functional ability, in 10 patients, as a pilot trial. Tests at post-intracranial aneurysm treatment discharge and six-week follow-up were compared to see which measures detected changes. Results; Kinematic tests captured significant improvements from discharge to six-week follow-up, indexed by reduced motor errors and improved learning. Increased Addenbrooke’s Cognitive Examination-Revised scores reflected some recovery of memory function for most individuals, but other standardised cognitive measures, functional outcome scores and a psychological questionnaire showed no changes. Conclusions; Kinematic measures can identify variation in performance in individuals with only slightly improved abilities post-intracranial aneurysm treatment. These measures may provide a sensitive way to explore post-operative outcomes following intracranial aneurysm treatment, or other similar surgical procedures

The impact of socioeconomic status on the link between osteoarthritis and the onset of common comorbidities

Objectives The temporal relationship between osteoarthritis and comorbidity is unclear and may vary with socioeconomic status. The aims of this study were to identify if osteoarthritis was associated with onset of common comorbidities, and if the association was moderated by deprivation. Methods Prospective cohort study combining questionnaire and medical record data (n=3910). Associations between osteoarthritis and onset of comorbidity at three year follow-up were examined using regression models. Interaction terms and stratified analysis were used to examine moderation. Results Osteoarthritis was associated with onset of all comorbidities (p<0.05). After adjusting for confounders, osteoarthritis was associated with onset of widespread pain (adjusted odds ratio 2.49; 95% confidence interval 1.96-3.17) and insomnia (1.58;1.14-1.19). Interactions between osteoarthritis and change in income and onset cognitive impairment (p=0.047; onset was higher when income became inadequate), and between osteoarthritis and education and onset widespread pain (p=0.012; onset was higher in those with high levels of education) were significant. Conclusion Consulters for osteoarthritis were more likely to develop physical and psychological comorbidities than those without osteoarthritis. The moderation analyses indicate that mechanisms to comorbidity differ by socio-economic strata and a need for different approaches to prevent comorbidity for consulters with OA from different levels of deprivation

A Proteomic Approach to Analyze the Aspirin-mediated Lysine Acetylome

This work is supported by Cancer Research UK Grant C434/A13067 (M.H.T & R.T.H) and Wellcome Trust Grant 098391/Z/12/7 (R.T.H.).Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d3, in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies endogenous acetylation signals at the majority of detectable endogenous sites, cells tolerate aspirin mediated acetylation very well unless cellular deacetylases are inhibited. Although most endogenous acetylations are amplified by orders of magnitude, lysine acetylation site occupancies remain very low even after high doses of aspirin. This work shows that while aspirin has enormous potential to alter protein function, in the majority of cases aspirin-mediated acetylations do not accumulate to levels likely to elicit biological effects. These findings are consistent with an emerging model for cellular acetylation whereby stoichiometry correlates with biological relevance, and deacetylases act to minimize the biological consequences non-specific chemical acetylations.Publisher PDFPeer reviewe

Extending Working Lives: A Systematic Review of Healthy Working Life Expectancy at Age 50

Retirement ages for receipt of state/social pensions are rising in many countries in response to population ageing and increasing life expectancy. However, sickness absence and early retirement for health reasons (especially among adults aged?=?50) present challenges to this. Estimates of the average number of years people are both healthy and in work from age 50 are needed to inform policy making and assess the feasibility of policy changes. A systematic review was carried out to identify existing population indicators, and estimates, of life expectancy in health and work. Nine databases were systematically searched on the 30th January 2019. Eligible papers were identified using inclusion/exclusion criteria. Evidence synthesis was undertaken to explore indicators and estimates. Four studies were included for review from 1485 identified by the search. A narrative review was carried out; quantitative pooling of the results was not feasible due to high heterogeneity between studies. All estimates of the average number of years spent in both health and work from age 50 were below 10 years with the exception of a population subgroup of Finnish male executives (11.91 years). The review indicated that population indicators of health and work that could estimate the average number of years people are healthy and in work are rarely used, and that there are no current and reliable estimates. One indicator, Healthy Working Life Expectancy (measuring life expectancy in health and work from age 50), offers the potential to be a suitable measure for monitoring life expectancy in health and work

Where does it hurt? Small area estimates and inequality in the prevalence of chronic pain

Background: Chronic pain affects up to half of UK adults, impacting quality of life and demand on local health services. Whilst local health planning is currently based on subnational prevalence estimates, associations between pain and sociodemographic characteristics suggest that inequalities in the prevalence of chronic and high‐impact chronic pain between neighbourhoods within local authorities are likely. We aimed to derive lower super output area (LSOA) estimates of the prevalence of chronic and high‐impact chronic pain. Methods: Presence of self‐reported chronic and high‐impact chronic pain were measured in adults aged 35+ in North Staffordshire and modelled using multilevel regression as a function of demographic and geographic predictors. Multilevel model predictions were post‐stratified using the North Staffordshire age‐sex population structure and LSOA demographic characteristics to estimate the prevalence of chronic and high‐impact chronic pain in 298 LSOAs, corrected for ethnic diversity underrepresented in the data. Confidence intervals were generated for high‐impact chronic pain using bootstrapping. Results: Data were analysed from 4162 survey respondents (2358 women, 1804 men). The estimated prevalence of chronic and high‐impact chronic pain in North Staffordshire LSOAs ranged from 18.6% to 50.1% and 6.18 [1.71, 16.0]% to 33.09 [13.3, 44.7]%, respectively. Conclusions: Prevalence of chronic and high‐impact chronic pain in adults aged 35+ varies substantially between neighbourhoods within local authorities. Further insight into small‐area level variation will help target resources to improve the management and prevention of chronic and high‐impact chronic pain to reduce the impact on individuals, communities, workplaces, services and the economy. Significance: Post‐stratified multilevel model predictions can produce small‐area estimates of pain prevalence and impact. The evidence of substantial variation indicates a need to collect local‐level data on pain and its impact to understand health needs and to guide interventions

Reasons why osteoarthritis predicts mortality:Path analysis within a Cox proportional hazards model

Objectives To identify potentially modifiable factors that mediate the association between symptomatic osteoarthritis (OA) and premature mortality. Methods A population-based prospective cohort study; primary care medical record data were linked to self-report information collected by questionnaire in adults aged 50 years and over (n=10 415). OA was defined by primary care consultation and moderate-to-severe pain interference in daily life. A Cox proportional hazards analysis determined the total effect (TE) of OA on mortality after adjustment for potential confounders. Within the Cox model, path analysis was used to decompose the TE to assess the indirect and direct effects for selected potential mediators (anxiety, depression, unrefreshed sleep and walking frequency). Results are expressed as HRs with 95% CIs derived from bootstrap resampling. Results OA was significantly associated with mortality (TE-adjusted HR 1.14; 95% CI 1.00 to 1.29). The indirect effects for walking frequency were 1.05 (95% CI 1.04 to 1.06), depression 1.02 (95% CI 1.02 to 1.03), anxiety 1.01 (95% CI 1.00 to 1.02) and unrefreshed sleep 1.01 (95% CI 1.00 to 1.01). Conclusions The analysis indicates that encouraging people to walk and get out and about' in addition to targeting OA could be protective against excessive mortality. The findings also suggest that depression, anxiety and unrefreshed sleep have a role in premature mortality for people with OA; however, this has low clinical significance

Chronic pain-mental health comorbidity and excess prevalence of health risk behaviours: a cross-sectional study

Background: Chronic musculoskeletal pain and anxiety/depression are significant public health problems. We hypothesised that adults with both conditions constitute a group at especially high risk of future cardiovascular health outcomes. Aim: To determine whether having comorbid chronic musculoskeletal pain and anxiety/depression is associated with the excess prevalence of selected known cardiovascular health risk behaviours. Method: A cross-sectional survey of adults aged 35+ years randomly sampled from 26 GP practice registers in West Midlands, England. Respondents were classified into four groups based on self-reported presence/absence of chronic musculoskeletal pain (pain present on most days for six months) and anxiety or depression (Hospital Anxiety and Depression Score 11+). Standardised binomial models were used to estimate standardised prevalence ratios and prevalence differences between the four groups in self-reported obesity, tobacco smoking, physical inactivity, and unhealthy alcohol consumption after controlling for age, sex, ethnicity, deprivation, employment status and educational attainment. The excess prevalence of each risk factor in the group with chronic musculoskeletal pain–anxiety/depression comorbidity was estimated. Findings: Totally, 14 519 respondents were included, of whom 1329 (9%) reported comorbid chronic musculoskeletal pain–anxiety/depression, 3612 (25%) chronic musculoskeletal pain only, 964 (7%) anxiety or depression only, and 8614 (59%) neither. Those with comorbid chronic musculoskeletal pain–anxiety/depression had the highest crude prevalence of obesity (41%), smoking (16%) and physical inactivity (83%) but the lowest for unhealthy alcohol consumption (18%). After controlling for covariates, the standardised prevalence ratios and differences for the comorbid group compared with those with neither chronic musculoskeletal pain nor anxiety/depression were as follows: current smoking [1.86 (95% CI 1.58, 2.18); 6.8%], obesity [1.93 (1.76, 2.10); 18.9%], physical inactivity [1.21 (1.17, 1.24); 14.3%] and unhealthy alcohol consumption [0.81 (0.71, 0.92); –5.0%]. The standardised prevalences of smoking and obesity in the comorbid group exceeded those expected from simple additive interaction