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INTRODUCTION: The association between chronic pain and frailty might indicate that pain is an independent driver of frailty but might alternatively be explained by inclusion within frailty identification tools of morbidities that commonly lead to chronic pain. This research examines the extent to which the association of pain with frailty might be attributed to morbidities. METHODS: A cross-sectional analysis of older people in a UK cohort with or at risk of musculoskeletal problems or frailty (Investigating Musculoskeletal Health and Wellbeing study), used multivariable logistic regression and Z-tests to assess the degrees of associations of pain (McGill Pain Rating Index), and painful and non-painful morbidity counts with frailty (modified FRAIL questionnaire). RESULTS: Data were from 2,185 participants, 56% female, median age 73 (range 60 to 96) years. 430 (20%) participants were classified as frail. In a fully adjusted standardised model, pain (aOR 2.07 (95%CI 1.83 to 2.33) and 'any' morbidity aOR (1.74 (95%CI 1.54 to 1.97) were both significantly associated with frailty. When morbidity was subclassified as painful or non-painful, painful (aOR 1.48 (95%CI 1.30 to 1.68) and non-painful (aOR1.39 (95%CI 1.24 to 1.56)) morbidities each were associated with frailty, as also was pain (aOR 2.07 (95%CI 1.83 to 2.34, p < 0.001). CONCLUSIONS: Pain is associated with frailty, over and above any effect of painful and non-painful morbidities. This forms the justification for future research which focuses on pain management in the identification, prevention, and treatment of frailty.
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Dor Crônica , Fragilidade , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Vida Independente , Estudos Transversais , Idoso Fragilizado , Dor Crônica/diagnóstico , Dor Crônica/epidemiologia , Dor Crônica/terapia , Morbidade , Avaliação GeriátricaRESUMO
OBJECTIVE: In order to facilitate data pooling between studies, we explored harmonisation of patient-reported outcome measures (PROMs) in people with knee pain due to osteoarthritis or knee trauma, using the Patient Acceptable Symptom State scores (PASS) as a criterion. METHODS: We undertook a systematic literature review (SLR) of PASS scores, and performed individual participant data (IPD) analysis of score distributions from concurrently completed PROM pairs. Numerical rating scales (NRS), visual analogue scales, KOOS and WOMAC pain questionnaires were standardised to 0 to 100 (worst) scales. Meta-regression explored associations of PASS. Bland Altman plots compared PROM scores within individuals using IPD from WebEx, KICK, MenTOR and NEKO studies. RESULTS: SLR identified 18 studies reporting PASS in people with knee pain. Pooled standardised PASS was 27 (95% CI: 21 to 35; n = 6,339). PASS was statistically similar for each standardised PROM. Lower PASS was associated with lower baseline pain (ß = 0.49, P = 0.01) and longer time from treatment initiation (Q = 6.35, P = 0.04). PASS scores were lowest in ligament rupture (12, 95% CI: 11 to 13), but similar between knee osteoarthritis (31, 95% CI: 26 to 36) and meniscal tear (27, 95% CI: 20 to 35). In IPD, standardised PROMs each revealed similar group mean scores, but scores within individuals diverged between PROMs (LoA between -7 to -38 and +25 to 52). CONCLUSION: Different standardised PROMs give similar PASS thresholds in group data. PASS thresholds may be affected more by patient and treatment characteristics than between PROMs. However, different PROMs give divergent scores within individuals, possibly reflecting different experiences of pain.
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Traumatismos do Joelho , Osteoartrite do Joelho , Humanos , Medidas de Resultados Relatados pelo Paciente , Articulação do Joelho , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/terapia , DorRESUMO
BACKGROUND: There is an increasing focus on the development of research capacity and culture in Nursing, Midwifery and Allied Health Professions (NMAHP). However, better understanding of the existing research success and skills, motivators, barriers, and development needs of NMAHP professionals is required to inform this development. This study sought to identify such factors within a university and an acute healthcare organisation. METHODS: An online survey, incorporating the Research Capacity and Culture tool, was administered to NMAHP professionals and students at a university and an acute healthcare organisation in the United Kingdom. Ratings of success/skill levels of teams and individuals were compared between professional groups using Mann-Whitney U tests. Motivators, barriers, and development needs were reported using descriptive statistics. Descriptive thematic analysis was used for open-ended text responses. RESULTS: A total of 416 responses were received (N&M n = 223, AHP n = 133, Other n = 60). N&M respondents were more positive than their AHP counterparts about the success/skill levels of their teams. There were no significant differences between N&M and AHP in their ratings of individual successes/skills. Finding and critically reviewing relevant literature were identified as specific individual strengths; with weaknesses in securing research funding, submitting ethics applications, writing for publication, and advising less experienced researchers. The main motivators for research were to develop skills, increased job satisfaction, and career advancement; whilst barriers included lack of time for research and other work roles taking priority. Key support needs identified included mentorship (for teams and individuals) and in-service training. Open-ended questions generated main themes of 'Employment & staffing', 'Professional services support', 'Clinical & academic management', 'Training & development', 'Partnerships' and 'Operating principles'. Two cross-cutting themes described issues common to multiple main themes: 'Adequate working time for research' and 'Participating in research as an individual learning journey'. CONCLUSIONS: Rich information was generated to inform the development of strategies to enhance research capacity and culture in NMAHP. Much of this can be generic but some nuances may be required to address some specific differences between professional groups, particularly related to perceived team success/skills and priorities identified for support and development.
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Tocologia , Gravidez , Humanos , Feminino , Universidades , Pessoal Técnico de Saúde , Inquéritos e Questionários , Atenção à SaúdeRESUMO
OBJECTIVES: Bone marrow lesions (BMLs) are associated with pain in osteoarthritis (OA), but histological scores for OA focus on cartilage pathology. We developed a new scoring system, the Osteoarthritis Bone Score (OABS), to characterise OA-related BMLs. METHODS: BML/non-BML tissues identified by Magnetic Resonance Imaging (MRI) in 10 knee OA subjects were harvested at total knee replacement (TKR). Osteochondral tissue from a further 140 TKR and 23 post-mortem (PM) cases was assessed. Histological features distinguishing MRI-defined BML/non-BML tissues on qualitative analysis were classified as present (0) or absent (1), summated for the OABS, validated by Rasch analysis and sensitivity to distinguish between sample groups. Immunohistochemistry for PGP9.5 assessed innervation. RESULTS: Subchondral characteristics associated with BML tissues were cysts, fibrosis, hypervascularity, cartilage islands, trabecular thickening, loss of tidemark integrity and inflammatory cell infiltration. PGP9.5 immunoreactive perivascular nerves were associated with BMLs. OABS performed well as a measurement tool, displayed good reliability (Cronbach alpha = 0.68), had a 2-factor structure (trabecular/non-trabecular), with moderate correlation between the two factors (r = 0.56, 95% CI 0.46, 0.65). OABS scores were higher in TKR than PM cases with chondropathy, median difference 1.5 (95% CI -2, 0). OABS and Mankin scores similarly distinguished TKR from non-OA controls, but only OABS was higher in BML than non-BML tissues, median difference -4 (95% CI -5 to -2). CONCLUSIONS: OABS identifies and validly quantifies histopathological changes associated with OA BMLs. Histopathology underlying BMLs may represent 2 inter-related pathological processes affecting trabecular/non-trabecular structures. Increased vascularity/perivascular innervation in BMLs might contribute to pain.
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Doenças Ósseas , Doenças das Cartilagens , Osteoartrite do Joelho , Doenças Ósseas/patologia , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Osso e Ossos/patologia , Doenças das Cartilagens/patologia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Dor/patologia , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: Pain is the prevailing symptom of knee osteoarthritis. Central sensitisation creates discordance between pain and joint pathology. We previously reported a Central Pain Mechanisms trait derived from eight discrete characteristics: Neuropathic-like pain, Fatigue, Cognitive-impact, Catastrophising, Anxiety, Sleep disturbance, Depression, and Pain distribution. We here validate and show that an 8-item questionnaire, Central Aspects of Pain in the Knee (CAP-Knee) is associated both with sensory- and affective- components of knee pain severity. METHODS: Participants with knee pain were recruited from the Investigating Musculoskeletal Health and Wellbeing study in the East Midlands, UK. CAP-Knee items were refined following cognitive interviews. Psychometric properties were assessed in 250 participants using Rasch-, and factor-analysis, and Cronbach's alpha. Intra-class correlation coefficients tested repeatability. Associations between CAP-Knee and McGill Pain questionnaire pain severity scores were assessed using linear regression. RESULTS: CAP-Knee targeted the knee pain sample well. Cognitive interviews indicated that participants interpreted CAP-Knee items in diverse ways, which aligned to their intended meanings. Fit to the Rasch model was optimised by rescoring each item, producing a summated score from 0 to 16. Internal consistency was acceptable (Cronbach's alpha = 0.74) and test-retest reliability was excellent (ICC2,1 = 0.91). Each CAP-Knee item contributed uniquely to one discrete 'Central Mechanisms trait' factor. High CAP-Knee scores associated with worse overall knee pain intensity, and with each of sensory- and affective- McGill Pain Questionnaire scores. CONCLUSION: CAP-Knee is a simple and valid self-report questionnaire, which measures a single 'Central Mechanisms' trait, and may help identify and target centrally-acting treatments aiming to reduce the burden of knee pain.
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Artralgia/diagnóstico , Sensibilização do Sistema Nervoso Central , Autoavaliação Diagnóstica , Articulação do Joelho , Autorrelato , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Subchondral bone may contribute to knee osteoarthritis (OA) pain. Nerve growth factor (NGF) can stimulate nerve growth through TrkA. We aimed to identify how sensory nerve growth at the osteochondral junction in human and rat knees associates with OA pain. METHODS: Eleven symptomatic chondropathy cases were selected from people undergoing total knee replacement for OA. Twelve asymptomatic chondropathy cases who had not presented with knee pain were selected post-mortem. OA was induced in rat knees by meniscal transection (MNX) and sham-operated rats were used as controls. Twice-daily oral doses (30 mg/kg) of TrkA inhibitor (AR786) or vehicle were administered from before and up to 28 days after OA induction. Joints were analysed for macroscopic appearances of articular surfaces, OA histopathology and calcitonin gene-related peptide-immunoreactive (CGRP-IR) sensory nerves in medial tibial plateaux, and rats were assessed for pain behaviors. RESULTS: The percentage of osteochondral channels containing CGRP-IR nerves in symptomatic chondropathy was higher than in asymptomatic chondropathy (difference: 2.5% [95% CI: 1.1-3.7]), and in MNX-than in sham-operated rat knees (difference: 7.8% [95%CI: 1.7-15.0]). Osteochondral CGRP-IR innervation was significantly associated with pain behavior in rats. Treatment with AR786 prevented the increase in CGRP-IR nerves in osteochondral channels and reduced pain behavior in MNX-operated rats. Structural OA was not significantly affected by AR786 treatment. CONCLUSIONS: CGRP-IR sensory nerves within osteochondral channels are associated with pain in human and rat knee OA. Reduced pathological innervation of the osteochondral junction might contribute to analgesic effects of reduced NGF activity achieved by blocking TrkA.
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Artralgia/fisiopatologia , Cartilagem Articular/patologia , Articulação do Joelho/inervação , Osteoartrite do Joelho/fisiopatologia , Nervos Periféricos/fisiopatologia , Tíbia/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Doenças Assintomáticas , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Meniscos Tibiais/cirurgia , Pessoa de Meia-Idade , Fator de Crescimento Neural/metabolismo , Nervos Periféricos/metabolismo , Nervos Periféricos/patologia , Inibidores de Proteínas Quinases/farmacologia , Ratos , Receptor trkA/antagonistas & inibidores , Receptor trkA/metabolismoRESUMO
OBJECTIVES: We investigated whether baseline scores for a self-report trait linked to central mechanisms predict 1 year pain outcomes in the Knee Pain in the Community cohort. METHOD: 1471 participants reported knee pain at baseline and responded to a 1-year follow-up questionnaire, of whom 204 underwent pressure pain detection thresholds (PPTs) and radiographic assessment at baseline. Logistic and linear regression models estimated the relative risks (RRs) and associations (ß) between self-report traits, PPTs and pain outcomes. Discriminative performance for each predictor was compared using receiver-operator characteristics (ROC) curves. RESULTS: Baseline Central Mechanisms trait scores predicted pain persistence (Relative Risk, RR = 2.10, P = 0.001) and persistent pain severity (ß = 0.47, P < 0.001), even after adjustment for age, sex, BMI, radiographic scores and symptom duration. Baseline joint-line PPTs also associated with pain persistence (RR range = 0.65 to 0.68, P < 0.02), but only in univariate models. Lower baseline medial joint-line PPT was associated with persistent pain severity (ß = -0.29, P = 0.013) in a fully adjusted model. The Central Mechanisms trait model showed good discrimination of pain persistence cases from resolved pain cases (Area Under the Curve, AUC = 0.70). The discrimination power of other predictors (PPTs (AUC range = 0.51 to 0.59), radiographic OA (AUC = 0.62), age, sex and BMI (AUC range = 0.51 to 0.64), improved significantly (P < 0.05) when the central mechanisms trait was included in each logistic regression model (AUC range = 0.69 to 0.74). CONCLUSION: A simple summary self-report Central Mechanisms trait score may indicate a contribution of central mechanisms to poor knee pain prognosis.
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Artralgia/fisiopatologia , Sensibilização do Sistema Nervoso Central , Osteoartrite do Joelho/fisiopatologia , Autorrelato , Idoso , Ansiedade/psicologia , Artralgia/psicologia , Catastrofização/psicologia , Cognição , Depressão/psicologia , Fadiga/fisiopatologia , Feminino , Seguimentos , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/psicologia , Limiar da Dor , Pressão , Transtornos do Sono-Vigília/fisiopatologiaRESUMO
BACKGROUND: The study objective was to obtain consensus on physical therapy (PT) in the rehabilitation of critical illness survivors after hospital discharge. Research questions were: what are PT goals, what are recommended measurement tools, and what constitutes an optimal PT intervention for survivors of critical illness? METHODS: A Delphi consensus study was conducted. Panelists were included based on relevant fields of expertise, years of clinical experience, and publication record. A literature review determined five themes, forming the basis for Delphi round one, which was aimed at generating ideas. Statements were drafted and ranked on a 5-point Likert scale in two additional rounds with the objective to reach consensus. Results were expressed as median and semi-interquartile range, with the consensus threshold set at ≤0.5. RESULTS: Ten internationally established researchers and clinicians participated in this Delphi panel, with a response rate of 80 %, 100 %, and 100 % across three rounds. Consensus was reached on 88.5 % of the statements, resulting in a framework for PT after hospital discharge. Essential handover information should include information on 15 parameters. A core set of outcomes should test exercise capacity, skeletal muscle strength, function in activities of daily living, mobility, quality of life, and pain. PT interventions should include functional exercises, circuit and endurance training, strengthening exercises for limb and respiratory muscles, education on recovery, and a nutritional component. Screening tools to identify impairments in other health domains and referral to specialists are proposed. CONCLUSIONS: A consensus-based framework for optimal PT after hospital discharge is proposed. Future research should focus on feasibility testing of this framework, developing risk stratification tools and validating core outcome measures for ICU survivors.
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Consenso , Estado Terminal/reabilitação , Modalidades de Fisioterapia/normas , Reabilitação/métodos , Atividades Cotidianas , Técnica Delphi , Humanos , Alta do Paciente/tendências , Reabilitação/normas , SobreviventesRESUMO
OBJECTIVES: Blockade of transient receptor potential vanilloid 1 (TRPV1) with systemic antagonists attenuates osteoarthritis (OA) pain behaviour in rat models, but on-target-mediated hyperthermia has halted clinical trials. The present study investigated the potential for targeting TRPV1 receptors within the OA joint in order to produce analgesia. METHODS: The presence of TRPV1 receptors in human synovium was detected using western blotting and immunohistochemistry. In a rat model of OA, joint levels of an endogenous ligand for TRPV1, 12-hydroxy-eicosatetraenoic acid (12-HETE), were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Effects of peripheral administration of the TRPV1 receptor antagonist JNJ-17203212 on afferent fibre activity, pain behaviour and core body temperature were investigated. Effects of a spinal administration of JNJ-17203212 on dorsal horn neuronal responses were studied. RESULTS: We demonstrate increased TRPV1 immunoreactivity in human OA synovium, confirming the diseased joint as a potential therapeutic target for TRPV1-mediated analgesia. In a model of OA pain, we report increased joint levels of 12-HETE, and the sensitisation of joint afferent neurones to mechanical stimulation of the knee. Local administration of JNJ-17203212 reversed this sensitisation of joint afferents and inhibited pain behaviour (weight-bearing asymmetry), to a comparable extent as systemic JNJ-17203212, in this model of OA pain, but did not alter core body temperature. There was no evidence for increased TRPV1 function in the spinal cord in this model of OA pain. CONCLUSIONS: Our data provide a clinical and mechanistic rationale for the future investigation of the therapeutic benefits of intra-articular administration of TRPV1 antagonists for the treatment of OA pain.
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Artralgia/metabolismo , Dor Nociceptiva/metabolismo , Osteoartrite/metabolismo , Membrana Sinovial/metabolismo , Canais de Cátion TRPV/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Idoso , Aminopiridinas/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Cromatografia Líquida , Modelos Animais de Doenças , Humanos , Injeções Intra-Articulares , Pessoa de Meia-Idade , Piperazinas/farmacologia , Ratos Sprague-Dawley , Canais de Cátion TRPV/antagonistas & inibidores , Espectrometria de Massas em TandemRESUMO
OBJECTIVES: The distribution and function of lymphatic vessels in normal and diseased human knees are understood incompletely. This study aimed to investigate whether lymphatic density is associated with clinical, histological or radiographic parameters in osteoarthritis (OA). METHODS: Sections of synovium from 60 knees from patients with OA were compared with 60 post mortem control knees (from 37 individuals). Lymphatic vessels were identified using immunohistochemistry for podoplanin, and quantified as lymphatic vessel density (LVD) and lymphatic endothelial cell (LEC) fractional area. Effusion status was determined by clinical examination, radiographs were scored for OA changes, and inflammation grading used haematoxylin and eosin stained sections of synovium. RESULTS: Lymphatic vessels were present in synovia from both disease groups, but were not identified in subchondral bone. Synovial lymphatic densities were independent of radiological severity and age. Synovia from patients with OA displayed lower LVD (z=-3.4, P=0.001) and lower LEC fractional areas (z=-4.5, P<0.0005) than non-arthritic controls. In patients with OA, low LVD was associated with clinically detectable effusion (z=-2.2, P=0.027), but not with histological evidence of synovitis. The negative associations between lymphatics and OA/effusion appeared to be independent of other measured confounders. CONCLUSION: Lymphatic vessels are present in lower densities in OA synovia. Abnormalities of synovial fluid drainage may confound the value of effusion as a clinical sign of synovitis in OA.
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Articulação do Joelho/patologia , Vasos Linfáticos/patologia , Osteoartrite do Joelho/patologia , Idoso , Artroplastia do Joelho , Estudos de Casos e Controles , Edema/etiologia , Edema/patologia , Endotélio Linfático/patologia , Feminino , Humanos , Artropatias/patologia , Articulação do Joelho/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Radiografia , Membrana Sinovial/irrigação sanguínea , Membrana Sinovial/patologiaRESUMO
OBJECTIVE: To systematically review the use of quantitative sensory testing (QST) in pain characterisation (phenotyping) in osteoarthritis (OA). METHODS: Six bibliographic databases (Medline, Embase, Amed, Cinahl, PubMed, Web of Science) were searched to identify studies published before May 2011. Data were extracted based on the primary site of OA, QST modalities, outcome measures and test sites. Standardised mean difference (SMD) and 95% confidence intervals (CIs) were calculated if possible. Publication bias was determined using funnel plot and Egger's test. Heterogeneity was examined using Cochran Q test and I2 statistic. Random effects model was used to pool the results. RESULTS: Of 41 studies (2281 participants) included, 23 were case control studies, 15 case only studies, two randomised controlled trials, and one uncontrolled trial. The majority of studies examined pressure pain with smaller numbers using electrical and/or thermal stimuli. QST was more often applied to the affected joint than distal and remote sites. Of 20 studies comparing people with OA and healthy controls, seven provided sufficient information for meta-analysis. Compared with controls, people with OA had lower pressure pain thresholds (PPTs) both at the affected joint (SMD = -1.24, 95% CI -1.54, -0.93) and at remote sites (SMD = -0.88, 95% CI -1.11, -0.65). CONCLUSION: QST of PPTs demonstrated good ability to differentiate between people with OA and healthy controls. Lower PPTs in people with OA in affected sites may suggest peripheral, and in remote sites central, sensitisation. PPT measurement merits further evaluation as a tool for phenotyping OA pain.
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Osteoartrite/fisiopatologia , Medição da Dor/métodos , Limiar da Dor/fisiologia , Dor/fisiopatologia , Feminino , Humanos , Articulações/patologia , Articulações/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite/complicações , Osteoartrite/diagnóstico , Dor/complicações , Dor/diagnóstico , Estimulação Física , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: Although knee injury has been implicated as a risk factor for the development of knee osteoarthritis (OA), there is great disparity in the magnitude of quantifiable risk. Our aim was to systematically review the relationship between history of knee injuries and knee OA. METHODS: Six electronic databases were searched between August and October 2010. Relative risk estimates or odds ratio (OR) and 95% confidence intervals (95% CI) were extracted or calculated from observational studies meeting the inclusion criteria. Publication bias was determined using funnel plot and the Egger's test. Heterogeneity was examined using Cochran Q test and I(2) statistic. Random effects model was used to pool the heterogeneous results and OR was used to present the results. Subgroup analyses were performed to examine potential causes of heterogeneity. RESULTS: Twenty-four observational studies (20,997 subjects) were included in the meta-analysis of which there were seven cohort, five cross-sectional and 12 case-control studies. The overall pooled OR was 4.20 (95% CI 3.11-5.66, I(2) = 81.0%). Association between history of knee injuries and knee OA was significantly different for specified injuries such as ligament or tendon injuries; meniscus damage or meniscectomy; and fracture of femur, knee or lower part of the leg (OR = 5.95, 95% 4.57-7.75), compared to unspecified injuries (OR = 3.12, 95% 2.17-4.50). CONCLUSION: History of knee injury is a major risk factor for the development of knee OA irrespective of study design and definition of knee injury. As one of the few modifiable/preventable risk factors, knee injury should be part of the future prevention programme in reducing the risk of knee OA.
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Traumatismos do Joelho/complicações , Osteoartrite do Joelho/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Fêmur/complicações , Humanos , Traumatismos da Perna/complicações , Ligamentos Articulares/lesões , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Traumatismos dos Tendões/complicações , Lesões do Menisco Tibial , Adulto JovemRESUMO
INTRODUCTION: Systematic reviews agree that knee osteoarthritis (OA) is related to occupational activities, but have not quantified the overall risks. METHODS: Systematic review of observational studies of knee OA and occupation. Job titles, elite sport, heavy work, kneeling, and other activities were included. Relative risk estimate and 95% confidence interval (CI) compared to sedentary work were retrieved or calculated for meta-analysis. Publication bias was examined with Egger tests and heterogeneity was determined with I(2) values and Q tests. Subgroup analysis was performed to examine causes of heterogeneity. A random effects model was performed to combine the data. RESULTS: Studies of knee OA (n=51), persistent knee pain (n=12) and knee OA progression (n=3) were retrieved. Occupational risks for knee OA were examined in a total of 526,343 subjects in 8 cohort/prospective/longitudinal studies, 25 cross-sectional studies and 18 case control studies. The overall odds ratio (OR) was 1.61 (95% CI 1.45-1.78) with significant heterogeneity (I(2)=83.6%). Study designs showed a positive association between knee OA and occupational activities; cohort (OR 1.38, 95% CI 1.10-1.74), cross-sectional (OR 1.57, 95% CI 1.37-1.81) and case control (OR 1.80, 95% CI 1.48-2.19). Overall there was evidence of publication bias (P<0.0001) which was apparent in the cross-sectional and case control studies (P<0.0001 and P=0.0247 respectively). CONCLUSIONS: Some occupational activities increase the risk of knee OA, although the influences of publication bias and heterogeneity are important limitations of this study. Prospective studies would greatly improve the evidence base.
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Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Osteoartrite do Joelho/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de RiscoRESUMO
OBJECTIVE: To examine the risk of large joint osteoarthritis (OA) in those becoming overweight during early adult life, and to assess the risks associated with high body mass index (BMI) and other anthropometric measures of obesity. METHODS: BMI, waist and hip circumference were measured in the GOAL case-control study comprising hip OA cases (n=1007), knee OA cases (n=1042) and asymptomatic controls (n=1121). Retrospective estimates of lifetime weight, body shape and other risk factors were collected using an interview-lead questionnaire. Odds ratios (ORs), adjusted OR (aOR), 95% confidence intervals (CIs) and P values were calculated using logistic regression analysis. RESULTS: BMI was associated with knee OA (aOR 2.68, 95% CI 2.33-3.09, P-trend<0.001) and hip OA (aOR 1.65, 95% CI 1.46-1.87, P-trend<0.001). Those who became overweight earlier in adulthood showed higher risks of lower limb OA (P-trend<0.001 for knee OA and hip OA). Self-reported body shape was also associated with knee OA and hip OA, following a similar pattern to current and life-course BMI measures. Waist:hip ratio (WHR) at time of examination did not associate with OA independently of BMI, except in women-only analysis. Waist circumference was associated with lower limb OA risk. CONCLUSIONS: Becoming overweight earlier in adult life increased the risks of knee OA and hip OA. Different distribution patterns of adiposity may be related to OA risk in women.
Assuntos
Índice de Massa Corporal , Obesidade/epidemiologia , Osteoartrite do Quadril/epidemiologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Osteoartrite do Quadril/etiologia , Osteoartrite do Joelho , Sobrepeso/epidemiologia , Fatores de Risco , Fatores Sexuais , Relação Cintura-QuadrilRESUMO
OBJECTIVES: To determine the community incidence of knee pain and associated risk factors over a 12-year period in people over the age of 40 years. METHOD: A cohort study of knee pain was undertaken in 2156 people from four general practices in North Nottinghamshire, UK. Knee pain was defined as 'pain around the knee for most days of at least a month'. Cumulative incidence over 12 years and person-year incidence rate of knee pain were estimated. Survival analysis was undertaken for time to the onset of knee pain. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for relative risk between exposure and non-exposure. Cox regression model was used to adjust for confounding factors. RESULTS: The 12-year cumulative incidence of knee pain was 34.4% (32% for men and 35% for women), corresponding to an average incidence rate of 32 (31 for men and 34 for women)/1000 person-years. Incident knee pain was associated with female gender (HR 1.27, 95% CI 1.08, 1.49), obesity (1.80; 95% CI 1.37, 2.38), varus (1.68, 95% CI 1.15, 2.47) and valgus (1.83, 95% CI 1.05, 3.20) mal-alignment, and knee injury (2.37, 95% CI 2.98, 2.85). CONCLUSIONS: For people over age 40, one in three will develop knee pain within 12 years. On average, the risk of knee pain was 32/1000 person-years. This risk is associated with a variety of constitutional and environmental biomechanical insults to the knee. Some of these could be modified to possibly reduce the incidence of the condition.
Assuntos
Articulação do Joelho/fisiopatologia , Doenças Musculoesqueléticas/complicações , Dor/epidemiologia , Adulto , Idoso , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Fatores de Risco , Análise de SobrevidaRESUMO
OBJECTIVE: Normal cartilage is resistant to vascular invasion and anti-angiogenic protease inhibitors may contribute to its avascular status. We hypothesized that dysregulated expression of four key anti-angiogenic protease inhibitors may contribute to increased osteochondral vascularity in osteoarthritis (OA). DESIGN: Medial tibial plateaux from OA patients (n=40) were compared with those from non-arthritic controls collected post-mortem (PM, n=10). Immunohistochemistry was performed for protease inhibitors TIMP-1, TIMP-3, PAI-1 and SLPI and the pro-angiogenic factor vascular endothelial growth factor (VEGF). Immunoreactivity in articular chondrocytes was scored. Chondropathy was measured as a modified Mankin score, and osteochondral vascular density as number of channels crossing each mm of tidemark. Non-parametric analyses were used for all data. RESULTS: All protease inhibitors and VEGF were localised to chondrocytes near the articular surface, less often in the middle zone, and rarely to deep chondrocytes. Scores for VEGF, TIMP-1, TIMP-3, SLPI and PAI-1 were all increased in OA compared with PM, and higher scores were associated with greater chondropathy. Chondrocyte expression of VEGF was associated with higher osteochondral vascular density (r=0.32, P<0.05), whereas protease inhibitors were not. CONCLUSIONS: The resistance of normal articular cartilage to vascular invasion may be more due to its matrix environment than ongoing protease inhibitor expression. Upregulation of protease inhibitors by superficial chondrocytes in OA may moderate the angiogenic effects of growth factors such as VEGF. However, failure of deep chondrocytes to express anti-angiogenic protease inhibitors may permit vascular invasion into the articular cartilage.
Assuntos
Condrócitos/metabolismo , Neovascularização Fisiológica/fisiologia , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/fisiopatologia , Inibidores de Proteases/metabolismo , Tíbia/metabolismo , Humanos , Imuno-Histoquímica , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Tíbia/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: Severity of structural change in knee osteoarthritis (OA) can be measured radiologically, macroscopically or microscopically. Existing methods have limitations for use in laboratory studies. We have developed a Photographic Chondropathy Score (PCS) for use with pathological samples. We have compared the ability of the different severity measures to distinguish between samples obtained at total knee replacement surgery or postmortem (PM), and to detect associations between structural severity and synovitis. METHOD: Tibial plateaux and femoral condyles were collected from 84 patients undergoing surgery or PM. Each sample was photographed and scored. Limits of agreement and repeatability coefficients were calculated for PCS. Scores for radiological joint space narrowing (JSN) and osteophytes, histological cartilage changes (Mankin), and synovitis were assigned. Data were analysed using Mann-Whitney U tests, Spearman's correlation coefficient or logistic regression. RESULTS: A total of 116 knees were analysed from 84 patients. Both medial tibial plateaux and total joint PCS showed good repeatability, internal consistency and reliability between observers. PCS, radiographic and Mankin's scores were all modestly positively correlated (r values 0.28-0.55). PCS and Mankin scores were greater in surgical than PM samples. Synovial inflammation was associated with higher PCS and radiological JSN scores (r values 0.43-0.48), irrespective of diagnosis. CONCLUSION: Macroscopic, microscopic and radiographical severity scores are complementary measures of structural severity in knee OA. Synovial inflammation was associated with increased OA structural severity, suggesting a possible role of chronic synovitis in cartilage damage.
Assuntos
Articulação do Joelho/patologia , Osteoartrite do Joelho/patologia , Fotografação , Idoso , Artroplastia do Joelho , Cadáver , Progressão da Doença , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Radiografia , Índice de Gravidade de Doença , Sinovite/complicações , Sinovite/patologiaRESUMO
Background: Among ESRD patients, obesity may improve dialysis-survival but decreases likelihood of transplantation, and as such, obesity prevalence may directly affect growth of the dialysis population. Objective: The objective of this study was to assess BMI trends in the ESRD population as compared to the general population. Materials and Methods: Incident adult ESRD patients were identified from the United States Renal Data System from 01/01/1995-12/31/2010 (n=1,458,350). Data from the Behavioral Risk Factor Surveillance System (n=4,303,471) represented the US population. Trends in BMI, obesity classes I (BMI of 30-34.9), II (BMI of 35-39.9), and III (BMI ≥ 40), were examined by year of dialysis initiation. Trends in BMI slope were compared between the ESRD and US populations using linear regression. Results: Mean BMI of ESRD patients in 1995 was 25.2 as compared to 29.4 in 2010, a 16.7% increase, while the US population's mean BMI increased from 25.3 to 27.2, a 7.5% increase. BMI increase among the ESRD population was significantly more rapid than among the US population (ß: 0.16, 95% CI: 0.14-0.18, p<0.001). Conclusions and Recommendations: Mean BMI among the ESRD population is increasing more rapidly than the US population. Given decreased access to kidney transplantation among ESRD patients with obesity, future research should be directed at controlling healthcare expenditures by identifying strategies to address the obesity epidemic among the US ESRD population.
RESUMO
BACKGROUND: Twenty-five percent of the British population over the age of 50 years experiences knee pain. Knee pain can limit physical ability and cause distress and bears significant socioeconomic costs. The objectives of this study were to develop and validate the first risk prediction model for incident knee pain in the Nottingham community and validate this internally within the Nottingham cohort and externally within the Osteoarthritis Initiative (OAI) cohort. METHODS: A total of 1822 participants from the Nottingham community who were at risk for knee pain were followed for 12 years. Of this cohort, two-thirds (n = 1203) were used to develop the risk prediction model, and one-third (n = 619) were used to validate the model. Incident knee pain was defined as pain on most days for at least 1 month in the past 12 months. Predictors were age, sex, body mass index, pain elsewhere, prior knee injury and knee alignment. A Bayesian logistic regression model was used to determine the probability of an OR >1. The Hosmer-Lemeshow χ2 statistic (HLS) was used for calibration, and ROC curve analysis was used for discrimination. The OAI cohort from the United States was also used to examine the performance of the model. RESULTS: A risk prediction model for knee pain incidence was developed using a Bayesian approach. The model had good calibration, with an HLS of 7.17 (p = 0.52) and moderate discriminative ability (ROC 0.70) in the community. Individual scenarios are given using the model. However, the model had poor calibration (HLS 5866.28, p < 0.01) and poor discriminative ability (ROC 0.54) in the OAI cohort. CONCLUSIONS: To our knowledge, this is the first risk prediction model for knee pain, regardless of underlying structural changes of knee osteoarthritis, in the community using a Bayesian modelling approach. The model appears to work well in a community-based population but not in individuals with a higher risk for knee osteoarthritis, and it may provide a convenient tool for use in primary care to predict the risk of knee pain in the general population.
Assuntos
Artralgia/epidemiologia , Teorema de Bayes , Articulação do Joelho/patologia , Modelos Logísticos , Idoso , Algoritmos , Estudos de Coortes , Feminino , Humanos , Incidência , Traumatismos do Joelho/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/epidemiologia , Dor/epidemiologia , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
PURPOSE: Patients recovering from critical illness may be left with significant muscle mass loss. This study aimed to evaluate whether a 6-week program of enhanced physiotherapy and structured exercise (PEPSE) and an essential amino acid supplement drink (glutamine and essential amino acid mixture [GEAA]) improves physical and psychological recovery. MATERIALS AND METHODS: Intensive care patients aged 45 years or older, with a combined intensive care unit stay/pre-intensive care unit stay of 5 days or more were recruited to a randomized controlled trial examining the effect of PEPSE and GEAA on recovery. The 2 factors were tested in a 2 × 2 factorial design: (1) GEAA drink twice daily for 3 months and (2) 6-week PEPSE in first 3 months. Primary efficacy outcome was an improvement in the 6-minute walking test at 3 months. RESULTS: A total of 93 patients were randomized to the study. Patients receiving the PEPSE and GEA had the biggest gains in distance walked in 6-minute walking test (P < .0001). There were also significant reductions in rates of anxiety in study groups control supplement/PEPSE (P = .047) and GEAA supplement/PEPSE (P = .036) and for GEAA supplement/PEPSE in depression (P = .0009). CONCLUSION: Enhanced rehabilitation combined with GEAA supplement may enhance physical recovery and reduce anxiety and depression.