Musculoskeletal pain and ageing

Musculoskeletal pain is a complex phenomenon involving biomechanics, inflammation and central pain processing pathways. The ageing process and ageing-related conditions can affect the course of musculoskeletal pain; conversely, the presence of pain can affect the ageing process, contributing to increased risks of adverse health outcomes. Despite the importance of managing pain in older adults, questions remain in terms of the best approach as the use of analgesics in this population is associated with increased risks of adverse events. This thesis contributes to the current knowledge of how age-related conditions such as multimorbidity and frailty interact with musculoskeletal pain and its management. The specific aims are: a) to determine whether frailty status is a risk factor for development of chronic or intrusive musculoskeletal pain; b) to determine whether pain increases the risk of developing the frailty phenotype; c) to describe the current management of vertebral compression fractures, a common and painful musculoskeletal condition typically seen in older adults; and d) to review and appraise the literature on the efficacy and safety of opioid analgesics for older adults with musculoskeletal pain.«br /» To address the first and the second aims, longitudinal data from the Concord Health and Ageing in Men Project (CHAMP), a prospective population based cohort study, were used.«strong» «/strong»A total of 1705 men aged 70 years or older, living in an urban area of New South Wales, Australia, were included in the CHAMP baseline study. Data on the presence of chronic pain (daily pain for at least 3 months), intrusive pain (pain causing moderate to severe interference with activities) and the criteria for the Cardiovascular Health Study frailty phenotype were collected in three waves, from January 2005 to October 2013. After adjusting for potential confounders, no association between frailty and future chronic or intrusive pain was observed. However, non-frail (robust and pre-frail) men who reported chronic pain were 1.60 (95% confidence interval (CI): 1.02 to 2.51, p=0.039) times more likely to develop frailty at follow-up, compared to those with no pain. For those reporting intrusive pain, the odds of developing future frailty were 1.64 (95%CI: 0.97-2.78, p=0.063). In summary, the presence of chronic pain increased the risk of developing the physical frailty phenotype in community-dwelling older men.«br /» To address the third aim, data from the Bettering the Evaluation And Care of Health (BEACH) program collected between April 2005 and March 2015 were used. Each year, a random national sample of approximately 1,000 GPs each recorded information on 100 consecutive patient encounters. All encounters at which vertebral compression fracture was managed were selected. Vertebral compression fractures were managed in 211 (0.022%; 95% CI: 0.018–0.025) of the 977,300 BEACH encounters recorded April 2005– March 2015. At encounters with patients aged 50 years or over, prescription of opioids analgesics (47.1 per 100 vertebral fractures; 95% CI: 38.4–55.7) was the most common management action. Prescriptions of paracetamol (8.2 per 100 vertebral fractures; 95% CI: 4-12.4) or non-steroidal anti-inflammatory drugs (4.1 per 100 vertebral fractures; 95% CI: 1.1-7.1) were less frequent. Non-pharmacological treatment was provided at a rate of 22.4 per 100 vertebral fractures (95% CI: 14.6-30.1). In summary, prescription of oral opioid analgesics remains the commonest general practice approach for vertebral compression fractures management, despite the lack of evidence to support this approach.«br /» The fourth aim concerns the efficacy and safety of using opioid analgesics in older adults with musculoskeletal pain. A systematic review with meta-analysis was performed including 23 randomized controlled trials with mean population age of 60 years or older that compared the efficacy and safety of opioid analgesics with placebo for musculoskeletal pain conditions. Opioid analgesics had a small effect on decreasing pain intensity (Standardised mean difference (SMD): -0.27; 95% CI: -0.33 to -0.20) and improving function (SMD: -0.27, 95%CI: -0.36 to -0.18), which was not associated with daily dose or treatment duration. The risk of adverse events was three times higher (OR: 2.94; 95% CI: 2.33 to 3.72) and treatment discontinuation four times higher (OR: 4.04; 95% CI: 3.10 to 5.25) in opioid treated patients. The systematic review concluded that, in older adults suffering from musculoskeletal pain, using opioid analgesics had only a small effect on pain and function at the cost of a higher risk of adverse events and treatment discontinuation. Therefore, for this specific population, the opioid-related risks may outweigh the benefits.«br /» From the results presented in the chapters of this thesis, important conclusions can be drawn: a) chronic musculoskeletal pain increases the risk of developing frailty in older adults and therefore, pain management should be part of a potential strategy to prevent frailty; b) despite being commonly prescribed for musculoskeletal pain in older adults, opioid analgesics alone are not likely to result in significant relief of chronic pain in these patients; c) instead of recommending opioid analgesics for persistent pain in older patients, guidelines should recommend comprehensive pain assessment, multimodal strategies and multidisciplinary approaches

Polimorfismo da apolipoproteína E e sua associação com incapacidade funcional em idosos: Projeto Bambuí

Submitted by Nuzia Santos ([email protected]) on 2015-04-08T16:23:52Z No. of bitstreams: 1 Dissertacao_RodrigoZunzarrenMegale.pdf: 246231 bytes, checksum: f703785837f5a2ce30980bbb75fb6e1c (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-04-08T16:24:01Z (GMT) No. of bitstreams: 1 Dissertacao_RodrigoZunzarrenMegale.pdf: 246231 bytes, checksum: f703785837f5a2ce30980bbb75fb6e1c (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-04-08T16:24:22Z (GMT) No. of bitstreams: 1 Dissertacao_RodrigoZunzarrenMegale.pdf: 246231 bytes, checksum: f703785837f5a2ce30980bbb75fb6e1c (MD5)Made available in DSpace on 2015-04-08T16:24:22Z (GMT). No. of bitstreams: 1 Dissertacao_RodrigoZunzarrenMegale.pdf: 246231 bytes, checksum: f703785837f5a2ce30980bbb75fb6e1c (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Vários estudos tem demonstrado o papel da genética no envelhecimento mas ainda não se sabe como os genes influenciam esse processo, sendo possível o envolvimento de vários genes, cada um deles com apenas um modesto efeito. Entre os genes potencialmente relacionados ao. envelhecimento mais estudados, destaca-se o gene da apolipoproteína E. Além de participar do transporte de lipídeos, essa apolipoproteína tem papel importante na aterosclerose, no reparo e manutenção de células do sistema nervoso central e na inflamação. Inúmeros estudos tem associado o alelo ε4 da apoE a doenças comuns em idosos como a doença arterial coronariana, o acidente vascular encefálico e a doença de Alzheimer. Mais recentemente, o gene da apolipoproteína E também tem sido considerado um gene da vulnerabilidade já que portadores de ε4 apresentam um pior prognóstico em várias outras condições clínicas como traumatismo craniano, doença arterial periférica e diabetes. Idosos mais vulneráveis tendem a acumular mais incapacidades com o. envelhecimento e, se o gene da apolipoproteína E for realmente um gene ligado a vulnerabilidade, é possível imaginar que existam variações genótipo-dependentes no desempenho funcional dos idosos.. Para avaliar a associação do genótipo da apolipoproteína E com incapacidade funcional e com um fenótipo de “envelhecimento bem sucedido” 1408 idosos incluídos na linha de base do Projeto Bambuí foram submetidos a genotipagem da apolipoproteína E e constituíram a amostra desse estudo. Os participantes responderam a um questionário para avaliação da funcionalidade e foram classificados de acordo com a presença ou ausência de incapacidades em atividades relacionadas à. AVDs, AIVDs e mobilidade. Um subgrupo de idosos que não apresentavam nenhuma dificuldade nas tarefas avaliadas foram considerados idosos com “envelhecimento bem sucedido”. A associação do genótipo da apolipoproteína E e os fenótipos descritos foi avaliada pela regressão logística múltipla, considerando as possíveis variáveis de confusão.. Não houve diferenças significativas em relação a presença de incapacidades em AVDs e AIVDs e o genótipo da apoE mas a presença do alelo ε4 foi associado a uma menor frequência de comprometimento na mobilidade, tanto quando comparado ao grupo ε3ε3 (OR=0,71; IC95%=0,50-. 1,00), quando comparado aos idosos sem a presença do alelo ε4 (OR=0,69; IC95%=0,49-0,97). A presença do alelo ε4 também foi associada ao envelhecimento bem sucedido, aumentando a chance. de um envelhecimento livre de incapacidades em cerca de 40% (OR=1,41; IC95%=1,02-1,94).. Em Bambuí a presença do alelo ε4 esteve relacionada a um melhor desempenho funcional em idosos em relação às tarefas de mobilidade, ressaltando a importância de estudos sobre a associação desse genótipo com a funcionalidade de idosos em diferentes populações..The genetic influence in the aging process has been shown in several studies but it is still not known which genes play an important role in this process and how they work. The genetic architecture of this process is quite complex and involves a lot of genes, each one with just a small effect. There are several genetic polymorphisms potentially related to the aging process but the apolipoprotein E polymorphism deserves special attention. This apolipoprotein has a key function in lipid transport but also plays an important role in atherosclerosis, maintenance and repair of neurons, and inflammation. There is a strong association between the apoE ε4 allele and aging-related diseases like coronary heart disease, stroke, and Alzheimer's disease. Recently, the apoE gene has been viewed as a “frailty” gene. Frailty elders tend to have more accumulated deficits and disabilities in aging. If the apolipoprotein E gene is really linked to frailty, it would be easy to imagine the presence of genotype-dependent variations on elderly´s functional performance. To analyze the apoE genotypes associations with functional disability considering ADL, IADL and mobility and with a “successful aging” phenotype the participants of the Bambui Health and Aging Study, 1408 elders were genotyped for apoE polymorphisms and were included in this study. They answered several questions about disabilities and were finally classified as dependent or independent in ADL, IADL and mobility. A subgroup of participants that didn´t show any problems in assessed tasks was considered “successful aging” elders. The associations with apoE genotypes and the aforementioned phenotypes were assessed using logistic regression models. No differences in genotypes distribution were found for ADL and IADL but the presence of ε4 allele decreased the odds ratio (OR=0,69; IC95%=0,49-0,97) of mobility impairment on the adjusted analysis. We unexpectedly found that the allele ε4 is associated with the “successful aging” phenotype. Individuals with ε3/ε4 or ε4/ε4 genotype have 40% more chances to reach a disability-free aging (OR=1,41; IC95%=1,02-1,94). In Bambui Health and Aging Study, the presence of ε4 allele was associated with a better functional performance in mobility among the elderly. The importance of studies comparing apoE polymorphisms and functional performance in different populations was reinforced

Apolipoprotein E polymorphism and functional disability in Brazilian elders: the Bambuí Health and Aging Study

Abstract Numerous studies have associated the apolipoprotein E (apoE) ε4 allele with worse health status, but few have assessed the existence of genotype-dependent variations in functional performance. Among participants in the Bambuí Health and Aging Study, Minas Gerais State, Brazil, 1,408 elderly underwent apoE genotyping. Functionality was assessed with a questionnaire, and individuals were classified as dependent in basic activities of daily living (BADLs), instrumental activities of daily living (IADLs), and mobility. The association between apoE genotype and functional status was assessed by logistic regression, taking confounding factors into account. Presence of ε4 allele was associated with lower odds of mobility deficit (OR = 0.65; 95%CI: 0.47-0.92) in the adjusted analysis. There were no significant differences in relation to presence of dependency in BADLs and IADLs. The reasons are not entirely understood, but they may involve the role of ε4 allele as a “thrifty gene” in a sample exposed to high risk of infectious and nutritional diseases in the past