Epidemiology of osteoarthritis and associated comorbidities in the United Kingdom

Background Osteoarthritis (OA) is very common and is the main cause of chronic joint pain and disability in older people. According to this systematic review nearly 67% of people with OA had comorbidity. There is little information available on how the incidence and prevalence of OA has changed over the past 20 years in the UK, and what is the likelihood of having other chronic conditions, their progression, and associated outcomes. Objectives This research aimed to answer five questions: 1) how common is osteoarthritis in the UK and what are the trends over the past twenty years; 2) are people with osteoarthritis more likely to have other chronic conditions and multimorbidity (two or more conditions in an individual)than people without osteoarthritis; 3) in people with OA how do these long-term conditions coexist; 4) how does the group of long-term conditions progress with time; and 5) does the presence of long-term conditions in osteoarthritis add to the burden both to patients and to health services. Methods A large nationally representative UK primary care database known as the Clinical Practice Research Datalink(CPRD)GOLD was used for the study. Six different studies were performed in this thesis in people aged 20 years or more with OA and age, sex, and practice matched controls. These are:1) epidemiology of osteoarthritis in the UK (chapter 3); 2) risk of comorbidities occurring before and after the diagnosis of osteoarthritis using both case-control and cohort design(chapter 4); 3) clusters of multimorbidity in people with OA and controls using latent class analysis (chapter 5); 4) illness pathways (transition and trajectories) of multimorbidity clusters in people with OA and controls using latent transition analysis and latent class growth analysis, respectively (chapter 6 and 7); 5) outcomes such as all-cause mortality, outpatient visits, inpatient admission and disability adjusted life years (DALYs) associated with OA and their comorbidities (chapter 8). Results The prevalence of OA in the UK primary care in 2017 was 10.7% and the incidence was 6.8 per 1000 person-years in people aged 20 and over. OA was more common in women compared to men and increased with age, especially after age 40 years. The prevalence has increased at a rate of 1.4% per year since 1998, whereas the incidence is declining at a rate of -1.6% per year. The burden of joint pain defined as OA is quite high, constituting nearly one third of primary care adult patients. People with OA are more likely to have multimorbidity prior to (aOR1.71, 95%CI1.69-1.74) and after the diagnosis of OA (aHR1.29, 95%CI1.28-1.30) than people without OA. Musculoskeletal (MSK), gastrointestinal (GI), cardiovascular (CV) and psychological conditions were associated with OA before and after the diagnosis of OA, whereas dementia and systemic lupus erythematous (SLE)were only associated with OA after its diagnosis. Other conditions that showed significant associations with OA both before and after diagnosis, were anaemia, inflammatory bowel disease (IBD), benign prostatic hypertrophy (BPH), gall stones, liver diseases, cancer, and hearing impairment. Five multimorbidity clusters were identified in OA. These clusters were led by both pain and hypertension, hypertension only, depression, back pain only, and relative healthy group (lowest number of any conditions). Over time, comorbidity clusters changed after the diagnosis of OA. About 30% of people changed from the cluster driven by either back pain or hypertension to the cluster driven by both back pain and hypertension. The accumulation of multimorbidity in people with OA happens in five different ways, and 17.5% of people develop multimorbidity quicker compared to relative healthy group. Obesity, smoking and alcohol use during the diagnosis of OA are strongly associated with the faster development of multimorbidity. People with OA were 1.2 times more likely to consult with general practitioners (GP),1.1 times more likely to be hospitalised, 3.25 times likely to get higher DALYs and 1.9 times more likely to die. Within OA, people with multimorbidity had higher mortality, burden, and health utilisations. Conclusions OA affects one in ten people aged 20 years or more in the UK. The burden of both GP diagnosed OA and joint pain in primary care is consistently high and increasing further. People with OA are more likely to develop other chronic conditions. Five different comorbidity clusters have been identified. While younger people are likely to have pain and depression, the elderly are likely to have CV-MSK comorbidities. The growth of multimorbidity in people with OA differs with 17.5% developing it faster than others. People with OA and CV-MSK and CV comorbidity have worse health outcomes. This information from this study can be used to develop personalised care in primary care. Further research is needed to understand the causality between OA and comorbidity

Epidemiology of osteoarthritis and associated comorbidities in the United Kingdom

Background Osteoarthritis (OA) is very common and is the main cause of chronic joint pain and disability in older people. According to this systematic review nearly 67% of people with OA had comorbidity. There is little information available on how the incidence and prevalence of OA has changed over the past 20 years in the UK, and what is the likelihood of having other chronic conditions, their progression, and associated outcomes. Objectives This research aimed to answer five questions: 1) how common is osteoarthritis in the UK and what are the trends over the past twenty years; 2) are people with osteoarthritis more likely to have other chronic conditions and multimorbidity (two or more conditions in an individual)than people without osteoarthritis; 3) in people with OA how do these long-term conditions coexist; 4) how does the group of long-term conditions progress with time; and 5) does the presence of long-term conditions in osteoarthritis add to the burden both to patients and to health services. Methods A large nationally representative UK primary care database known as the Clinical Practice Research Datalink(CPRD)GOLD was used for the study. Six different studies were performed in this thesis in people aged 20 years or more with OA and age, sex, and practice matched controls. These are:1) epidemiology of osteoarthritis in the UK (chapter 3); 2) risk of comorbidities occurring before and after the diagnosis of osteoarthritis using both case-control and cohort design(chapter 4); 3) clusters of multimorbidity in people with OA and controls using latent class analysis (chapter 5); 4) illness pathways (transition and trajectories) of multimorbidity clusters in people with OA and controls using latent transition analysis and latent class growth analysis, respectively (chapter 6 and 7); 5) outcomes such as all-cause mortality, outpatient visits, inpatient admission and disability adjusted life years (DALYs) associated with OA and their comorbidities (chapter 8). Results The prevalence of OA in the UK primary care in 2017 was 10.7% and the incidence was 6.8 per 1000 person-years in people aged 20 and over. OA was more common in women compared to men and increased with age, especially after age 40 years. The prevalence has increased at a rate of 1.4% per year since 1998, whereas the incidence is declining at a rate of -1.6% per year. The burden of joint pain defined as OA is quite high, constituting nearly one third of primary care adult patients. People with OA are more likely to have multimorbidity prior to (aOR1.71, 95%CI1.69-1.74) and after the diagnosis of OA (aHR1.29, 95%CI1.28-1.30) than people without OA. Musculoskeletal (MSK), gastrointestinal (GI), cardiovascular (CV) and psychological conditions were associated with OA before and after the diagnosis of OA, whereas dementia and systemic lupus erythematous (SLE)were only associated with OA after its diagnosis. Other conditions that showed significant associations with OA both before and after diagnosis, were anaemia, inflammatory bowel disease (IBD), benign prostatic hypertrophy (BPH), gall stones, liver diseases, cancer, and hearing impairment. Five multimorbidity clusters were identified in OA. These clusters were led by both pain and hypertension, hypertension only, depression, back pain only, and relative healthy group (lowest number of any conditions). Over time, comorbidity clusters changed after the diagnosis of OA. About 30% of people changed from the cluster driven by either back pain or hypertension to the cluster driven by both back pain and hypertension. The accumulation of multimorbidity in people with OA happens in five different ways, and 17.5% of people develop multimorbidity quicker compared to relative healthy group. Obesity, smoking and alcohol use during the diagnosis of OA are strongly associated with the faster development of multimorbidity. People with OA were 1.2 times more likely to consult with general practitioners (GP),1.1 times more likely to be hospitalised, 3.25 times likely to get higher DALYs and 1.9 times more likely to die. Within OA, people with multimorbidity had higher mortality, burden, and health utilisations. Conclusions OA affects one in ten people aged 20 years or more in the UK. The burden of both GP diagnosed OA and joint pain in primary care is consistently high and increasing further. People with OA are more likely to develop other chronic conditions. Five different comorbidity clusters have been identified. While younger people are likely to have pain and depression, the elderly are likely to have CV-MSK comorbidities. The growth of multimorbidity in people with OA differs with 17.5% developing it faster than others. People with OA and CV-MSK and CV comorbidity have worse health outcomes. This information from this study can be used to develop personalised care in primary care. Further research is needed to understand the causality between OA and comorbidity

Comorbidities in Osteoarthritis: a systematic review and meta-analysis of observational studies

ObjectivesOsteoarthritis (OA) is a common chronic condition in older people but its association with other chronic conditions is largely unknown. This study aimed to systematically review the literature on comorbidities in people with OA compared to those without.MethodsWe searched four databases for observational studies on comorbidities in people with OA. Studies of OA only or in comparison with non‐OA controls were included. Risk of bias and study quality was assessed using the Newcastle‐Ottawa Scale (NOS). The prevalence of comorbidities in the OA group and prevalence ratio (PR) and 95% confidence interval (CI) between OA and non‐OA groups were calculated.ResultsForty‐two studies from 16 countries (27 case‐only and 15 comparative studies) met the inclusion criteria. Mean age of participants varied from 51 to 76 years. Pooled prevalence of any comorbidity was 67% (95%CI: 57%‐74%) in people with OA versus 56% (95%CI: 44%‐68%) in people without OA. The pooled PR for any comorbidity was 1.21 (95%CI: 1.02‐1.45). The PR increased from 0.73 (95%CI: 0.43‐1.25) for one comorbidity, to 1.58 (95%CI: 1.03‐2.42) for two, and 1.94 (95%CI 1.45‐ 2.59) for three or more comorbidities. The key comorbidities associated with OA were stroke (PR 2.61; 95%CI: 2.13‐3.21), peptic ulcer (PR 2.36; 95%CI: 1.71‐3.27) and metabolic syndrome (PR 1.94; 95%CI 1.21‐3.12).ConclusionsPeople with OA are more likely to have other chronic conditions. The association is dose‐dependent in terms of the number of comorbidities, suggesting multimorbidities. Further studies on the causality of this association and clinical implications are needed

A Study on the Prevalence of Alcohol Consumption, Tobacco Use and Sexual Behaviour among Adolescents in Urban Areas of the Udupi District, Karnataka, India

Objectives: The aim of this study was to assess the prevalence of alcohol consumption, tobacco use and risky sexual behaviour among adolescents, and to evaluate the socioeconomic factors potentially influencing these behaviours. Methods: This cross-sectional study was conducted from January to April 2011 among 376 adolescents (15–19 years old) studying in different schools and colleges in Udupi, India. The Youth Risk Behavior Survey questionnaire and guidelines were followed for data collection. Participants’ alcohol consumption, smoking habits and sexual behaviour patterns were explored. Univariate analysis followed by multivariate logistic regression was done. Results: The prevalence of alcohol consumption, tobacco use and sexual activity was found to occur in 5.7%, 7.2% and 5.5% of participants, respectively. The mean age of the participants’ first sexual activity, consumption of alcohol and tobacco use was reported to be approximately 16.8 years. Multivariate analysis showed that males were more likely to have used alcohol and tobacco. Other factors, such as religion and tobacco use among family members, were found to be influential. Conclusion: The potential coexistence of multiple risk behaviours in a student demands an integrated approach. Emphasis should be placed on health education in schools and an increased awareness among parents in order to prevent adolescents’ behaviours from becoming a risk to their health

Barriers and facilitators to physical activity among ethnic Chinese children in school, home and community settings: a qualitative systematic review

Objective: The review aimed to synthesize the barriers and facilitators from the available studies that dealt with physical activity among ethnic Chinese children and uncover any differences or similarities in these barriers and facilitators.Introduction: Physical activity promotes overall health, fitness, and well-being in children, yet prevalence of this has been low among ethnic Chinese children who reside in both Chinese and non-Chinese territories. Research has been conducted to explore the barriers and facilitators to physical activity among ethnic Chinese children. However, no qualitative systematic review has been conducted to synthesize these barriers and facilitators.Inclusion criteria: This review synthesized the barriers and facilitators to physical activity among ethnic Chinese children aged six to 17 years, or among people who had responsibility for them in school, home, and community settings or country (Chinese or non-Chinese territories). The review included studies that focused on their views, experiences, attitudes, understandings, perceptions, and perspectives. Studies were included if they focused on qualitative data including, but not limited to, designs such as phenomenology, ethnography, grounded theory and action research. In addition, the authors considered cross-sectional surveys to find any free-text relating to the review question.Methods: MEDLINE, Embase, CINAHL, PsycINFO, BNI, AMED, Web of Science, Scopus, CNKI, Wanfang and VIP databases were searched to identify published studies. The search for unpublished studies included EthOS, OpenGrey, ProQuest Dissertations and Theses, CNKI and Wanfang. Databases were searched from their inception dates till 10 December 2018 and no language restrictions were applied. The Joanna Briggs Institute (JBI) guidelines for qualitative systematic reviews were followed in conducting the review. The JBI process of meta-aggregation was used to identify categories and synthesize findings.Results: Out of 9460 records identified, 11 qualitative studies met the eligibility criteria and were included in the review. Regarding critical appraisal, using the JBI checklist for qualitative research (10 criteria), the scores ranged from a moderate score of six (n=2) to a high score of seven and above (n=9). Seven studies were from China, two from Australia, one each from the UK and US. The sample size ranged from 12 to 115 participants. A total of 56 findings were extracted and aggregated into 24 categories, based on the similarity of meaning. Fourteen categories described perceived barriers and 10 categories described perceived facilitators, while one category described both barriers and facilitators. From studies conducted in the Chinese territories, four synthesized findings (personal, socio-cultural, environmental, and policy- and program-related barriers and facilitators) were aggregated from 37 extracted findings and 16 aggregated categories. From studies conducted in the non-Chinese territories, only two synthesized findings (personal and socio-cultural barriers and facilitators) were derived from 19 extracted findings and eight aggregated categories.Conclusions: In terms of barriers and facilitators to physical activity, four broad themes emerged from the participants’ accounts, namely personal, socio-cultural, environmental, and policy- and program-related factors. Barriers and facilitators at the personal and socio-cultural level (e.g., parents and teachers) were most frequently cited, reflecting the importance of children's self-influence and the role of adults. Future interventions are needed to address the identified barriers and enhance the facilitators

Reliability of detection of ultrasound and MRI features of hand osteoarthritis: a systematic review and meta-analysis

OBJECTIVES: To systematically review the literature on inter- and intra-rater reliability of scoring US and MRI changes in hand OA. METHODS: MEDLINE, EMBASE, CINHAL, Web of Science and AMED were searched from inception to January 2020. Kappa (κ), weighted kappa (κw) and intra-class correlation coefficients for dichotomous, semi-quantitative and summated scores, respectively, and their 95% CI were pooled using a random-effects model. Heterogeneity between studies was assessed and reliability estimates were interpreted using the Landis-Koch classification. RESULTS: Fifty studies met the inclusion criteria (29 US, 17 MRI, 4 involving both modalities). The pooled κ (95% CI) for inter-rater reliability was substantial for US-detected osteophytes [0.66 (0.54, 0.79)], grey-scale synovitis [0.64 (0.32, 0.97)] and power Doppler [0.76, (0.47, 1.05)], whereas intra-rater reliability was almost perfect for osteophytes [0.82 (0.80, 0.84)], central bone erosions (CBEs) [0.83 (0.78, 0.89)] and effusion [0.83 (0.74, 0.91)], and substantial for grey-scale synovitis [0.64 (0.49, 0.79)] and power Doppler [0.70 (0.59, 0.80)]. Inter-rater reliability for dichotomous assessment was substantial for MRI-detected CBEs [0.75 (0.67, 0.83)] and synovitis [0.69 (0.51, 0.87)], slight for osteophytes [0.14 (0.04, 0.25)], and almost perfect for sum score of osteophytes, CBEs, joint space narrowing (JSN), and bone marrow lesions (BMLs) (0.81-0.89). Intra-rater reliability was almost perfect for sum score of MRI synovitis [0.92 (0.87, 0.96)], BMLs [0.88 (0.78, 0.98)], osteophytes [0.86 (0.74, 0.98)], CBEs [0.83 (0.66, 1.00)] and JSN [0.91 (0.87, 0.91)]. CONCLUSION: US and MRI are reliable in detecting hand OA features. US may be preferred due to low cost and increasing availability

Constitutional morphological features and risk of hip osteoarthritis: A case-control study using standard radiographs

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: To evaluate the risk of association with hip osteoarthritis (OA) of 14 morphological features measured on standard antero-posterior pelvis radiographs. Methods: A case-control study of 566 symptomatic unilateral hip OA cases and 1108 controls without hip OA, using the Genetics of OA and Lifestyle database. Unaffected hips of cases were assumed to reflect pre-OA morphology of the contralateral affected hip. ORs with 95% CI adjusted for confounding factors were calculated using logistic regression. Hierarchical clustering on principal component method was used to identify clusters of morphological features. Proportional risk contribution (PRC) of these morphological features in the context of other risk factors of hip OA was estimated using receiver operating characteristic analysis. Results: All morphological features showed right-left symmetry in controls. Each feature was associated with hip OA after adjusting for age, gender and body mass index. Increased sourcil angle had the strongest association (OR: 6.93, 95% CI 5.16 to 9.32). Three clusters were identified. The PRC varied between individual features, as well as between clusters. It was 35% (95% CI 31% to 40%) for all 14 morphological features, compared to 21% (95% CI 19% to 24%) for all other well-established risk factors. Conclusions: Constitutional morphological variation strongly associates with hip OA development and may explain much of its heritability. Relevant morphological measures can be assessed readily on standard radiographs to help predict risk of hip OA. Prospective studies are required to provide further support for causality

The Causal Association Between Osteoarthritis and Common Comorbidities: A Mendelian Randomisation Study

ObjectiveTo investigate the causal association between Osteoarthritis (OA) and five comorbidities: depression, tiredness, multisite chronic pain, irritable bowel syndrome (IBS) and gout.DesignThis study used two-sample Mendelian Randomisation (MR). To select the OA genetic instruments, we used data from the largest recent genome-wide association study (GWAS) of OA (GO Consortium), with a focus on OA of the knee (62,497 cases, 333,557 controls), hip (35,445 cases, 316,943 controls) and hand (20,901 cases, 282,881 controls). Genetic associations for comorbidities were selected from GWAS for depression (246,363 cases, 561,190 controls), tiredness (449,019 participants), multisite chronic pain (387,649 participants), IBS (53,400 cases, 433,201 controls) and gout (6543 cases, 456,390 controls). We performed a bidirectional MR analysis using the inverse variance weighted method, for both joint specific and overall OA.ResultsHip OA had a causal effect on multisite chronic pain (per unit change 0.02, 95% CI 0.01 to 0.04). Multisite chronic pain had a causal effect on knee (odd ratio (OR) 2.74, 95% CI 2.20 to 3.41), hip (OR 2.12, 95% CI 1.54 to 2.92), hand (OR 2.24, 95% CI 1.59 to 3.16) and overall OA (OR 2.44, 95% CI, 2.06 to 2.86). In addition, depression and tiredness had causal effects on knee and hand, but not hip, OA.ConclusionsApart from Hip OA to multisite chronic pain, other joint OA did not have causal effects on these comorbidities. In contrast, multisite chronic pain had a causal effect on any painful OA

Comorbidities and use of analgesics in people with knee pain: a study in the Nottingham Knee Pain and Health in the Community (KPIC) cohort

Objectives: The aims were to examine the prevalence of comorbidities and role of oral analgesic use in people with knee pain (KP) compared with those without. Methods: The Knee Pain and related health In the Community (KPIC) cohort comprises community-derived adults aged ≥40 years, irrespective of knee pain. Thirty-six comorbidities across 10 systems were compared between people with KP and controls without KP or knee OA. Multivariable logistic regression analysis was used to determine the adjusted odds ratio (aOR) and 95% CI for multimorbidity (at least two chronic conditions) and each specific comorbidity. Both prescribed and over-the-counter analgesics were included in the model, and their interactions with KP for comorbidity outcomes were examined. Results: Two thousand eight hundred and thirty-two cases with KP and 2518 controls were selected from 9506 baseline participants. The mean age of KP cases was 62.2 years, and 57% were women. Overall, 29% of the total study population had multimorbidity (KP cases 34.4%; controls 23.8%). After adjustment for age, sex, BMI and analgesic use, KP was significantly associated with multimorbidity (aOR 1.35; 95% CI 1.17, 1.56) and with cardiovascular (aOR 1.25; 95% CI 1.08, 1.44), gastrointestinal (aOR 1.34; 95% CI 1.04, 1.92), chronic widespread pain (aOR 1.54; 95% CI 1.29, 1.86) and neurological (aOR 1.32; 95% CI 1.01, 1.76) comorbidities. For multimorbidity, the use of paracetamol and opioids interacted positively with KP, whereas the use of NSAIDs interacted negatively for seven comorbidities. Conclusion: People with KP are more likely to have other chronic conditions. The long-term benefits and harms of this change remain to be investigated. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02098070

Causal association between subtypes of osteoarthritis and common comorbidities: A Mendelian randomisation study

Objective To investigate the causal association between Osteoarthritis (OA) and five comorbidities: depression, tiredness, multisite chronic pain, irritable bowel syndrome (IBS) and gout. Design This study used two-sample Mendelian Randomisation (MR). To select the OA genetic instruments, we used data from the largest recent genome-wide association study (GWAS) of OA (GO Consortium), with a focus on OA of the knee (62,497 cases, 333,557 controls), hip (35,445 cases, 316,943 controls) and hand (20,901 cases, 282,881 controls). Genetic associations for comorbidities were selected from GWAS for depression (246,363 cases, 561,190 controls), tiredness (449,019 participants), multisite chronic pain (387,649 participants), IBS (53,400 cases, 433,201 controls) and gout (6543 cases, 456,390 controls). We performed a bidirectional MR analysis using the inverse variance weighted method, for both joint specific and overall OA. Results Hip OA had a causal effect on multisite chronic pain (per unit change 0.02, 95% CI 0.01 to 0.04). Multisite chronic pain had a causal effect on knee (odd ratio (OR) 2.74, 95% CI 2.20 to 3.41), hip (OR 2.12, 95% CI 1.54 to 2.92), hand (OR 2.24, 95% CI 1.59 to 3.16) and overall OA (OR 2.44, 95% CI, 2.06 to 2.86). In addition, depression and tiredness had causal effects on knee and hand, but not hip, OA. Conclusions Apart from Hip OA to multisite chronic pain, other joint OA did not have causal effects on these comorbidities. In contrast, multisite chronic pain had a causal effect on any painful OA