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OBJECTIVE: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up. METHOD: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community (KPIC) cohort study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas OA scores were collected at baseline. Oxylipin levels were quantified using liquid chromatography coupled with mass spectrometry. Associations were measured by linear regression and receiver operating characteristics (ROC). RESULTS: Serum levels of 8,9-epoxyeicosatrienoic acid (EET) (ß(95% confidence intervals (CI)) = 1.809 (-0.71 to 2.91)), 14,15-dihydroxyeicosatrienoic acid (DHET) (ß(95%CI) = 0.827 (0.34-1.31)), and 12-hydroxyeicosatetraenoic acid (HETE) (ß(95%CI) = 4.090 (1.92-6.26)) and anandamide (ß(95%CI) = 3.060 (1.35-4.77)) were cross-sectionally associated with current self-reported knee pain scores (numerical rating scale (NRS) item 3, average pain). Serum levels of 9- (ß(95%CI) = 0.467 (0.18-0.75)) and 15-HETE (ß(95%CI) = 0.759 (0.29-1.22)), 14-hydroxydocosahexaenoic acid (ß(95%CI) = 0.483(0.24-0.73)), and the ratio of 8,9-EET:DHET (ß(95%CI) = 0.510(0.19-0.82)) were cross-sectionally associated with KL scores. Baseline serum concentrations of 8,9-EET (ß(95%CI) = 2.166 (0.89-3.44)), 5,6-DHET (ß(95%CI) = 152.179 (69.39-234.97)), and 5-HETE (ß(95%CI) = 1.724 (0.677-2.77) showed positive longitudinal associations with follow-up knee pain scores (NRS item 3, average pain). Combined serum 8,9-EET and 5-HETE concentration showed the strongest longitudinal association (ß(95%CI) = 1.156 (0.54-1.77) with pain scores at 3 years, and ROC curves distinguished between participants with no pain and high pain scores at follow-up (area under curve (95%CI) = 0.71 (0.61-0.82)). CONCLUSIONS: Serum levels of a combination of hydroxylated metabolites of arachidonic acid may have prognostic utility for knee pain, providing a potential novel approach to identify people who are more likely to have debilitating pain in the future.
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Artralgia , Progressão da Doença , Osteoartrite do Joelho , Humanos , Feminino , Masculino , Osteoartrite do Joelho/sangue , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Artralgia/sangue , Estudos Longitudinais , Estudos de Coortes , Oxilipinas/sangue , Articulação do Joelho , Ácidos Hidroxieicosatetraenoicos/sangue , Ácidos Araquidônicos/sangue , Biomarcadores/sangue , Medição da Dor , Ácido Araquidônico/sangueRESUMO
OBJECTIVE: Clinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol-the most commonly used analgesics for OA, remains unknown. DESIGN: Network meta-analysis. DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA. RESULTS: A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs). CONCLUSIONS: Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166.
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Osteoartrite do Quadril , Osteoartrite do Joelho , Idoso , Humanos , Acetaminofen/uso terapêutico , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides , Terapia por Exercício , Metanálise em Rede , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: Synovial abnormalities are modifiable targets for hand pain and osteoarthritis. We examined the prevalence and distribution of ultrasound-detected hand synovial abnormalities in a community-derived sample of older people in China. METHODS: Within the Xiangya Osteoarthritis Study, a community-based study, we assessed synovial hypertrophy (SH), joint effusion, and Power Doppler signal (PDS) on all fingers and thumbs of both hands using standardized ultrasound examinations (score: 0-3). We assessed distribution patterns of SH and effusion using χ2-test and interrelationships of SH and effusion in different joints and hands by generalized estimating equations. RESULTS: Among 3,623 participants (mean age: 64.4 years; women: 58.1%), prevalence of SH, effusion and PDS were 85.5%, 87.3% and 1.5%, respectively. Prevalence of SH, effusion and PDS increased with age, was higher in the right hand than in the left hand and was more common in proximal than in distal hand joints. SH and effusion often occurred in multiple joints (P < 0.001). SH in one joint was strongly associated with presence of SH in the same joint of the opposite hand (odds ratio [OR]= 6.60, 95% confidence interval [CI]: 6.19-7.03) followed by SH in other joints in the same row, (OR=5.70, 95%CI: 5.32-6.11), and then other joints in the same ray of the same hand (OR=1.49, 95%CI: 1.39-1.60). Similar patterns were observed for effusion. CONCLUSION: Hand synovial abnormalities are common among older people, often affect multiple hand joints and present a unique pattern. These findings suggest both systemic and mechanical factors play roles in their occurrence.
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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.
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Osteoartrite do Quadril , Estudos de Casos e Controles , Articulação do Quadril/diagnóstico por imagem , Humanos , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/etiologia , Estudos Prospectivos , Radiografia , Fatores de RiscoRESUMO
OBJECTIVES: To determine individual responses to ibuprofen gel or capsaicin cream for painful, radiographic knee OA using a series of n-of-1 trials. METHODS: Twenty-two participants were allocated 5% ibuprofen gel (A) and 0.025% capsaicin cream (B) in random sequence (AB or BA). Patients underwent up to 3 treatment cycles, each comprising one treatment for 4 weeks, an individualized washout period (maximum 4 weeks), then the other treatment for 4 weeks. Differential (ibuprofen or capsaicin) response was defined when change-from-baseline pain intensity scores (0-10 NRS) differed by ≥1 between treatments in ≥2 cycles within a participant. RESULTS: A total of 104 treatment periods were aggregated. Mean pain reduction was 1.2 (95% CI: 0.5, 1.8) on ibuprofen and 1.6 (95% CI: 0.9, 2.4) on capsaicin (P = 0.221). Of 22 participants, 4 (18%) had a greater response to ibuprofen, 9 (41%) to capsaicin, 4 (18%) had similar responses, and 5 (23%) were undetermined. CONCLUSION: Irrespective of equal efficacy overall, 59% of people displayed a greater response to one treatment over the other. Patients who do not benefit from one type of topical treatment should be offered to try another, which may be more effective. N-of-1 trials are useful to identify individual response to treatment. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT03146689.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Capsaicina/uso terapêutico , Ibuprofeno/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Capsaicina/administração & dosagem , Feminino , Humanos , Ibuprofeno/administração & dosagem , Masculino , Pessoa de Meia-Idade , Medição da Dor , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the burden of comorbidities in OA and their temporal relationships in the UK. METHODS: The Clinical Practice Research Datalink (CPRD) GOLD was used to identify people with incident OA and age, gender and practice matched non-OA controls from UK primary care. Controls were assigned the same index date as matched cases (date of OA diagnosis). Associations between OA and 49 individual comorbidities and multimorbidities (two or more comorbidities excluding OA) both before and after OA diagnosis were estimated, adjusting for covariates, using odds ratios (aORs) and hazard ratios (aHRs), respectively. RESULTS: During 1997-2017, we identified 221 807 incident OA cases and 221 807 matched controls. Of 49 comorbidities examined, 38 were associated with OA both prior to and following the diagnosis of OA and 2 (dementia and systemic lupus erythematosus) were associated with OA only following the diagnosis of OA. People with OA had a higher risk of developing heart failure [aHR 1.63 (95% CI 1.56, 1.71)], dementia [aHR 1.62 (95% CI 1.56, 1.68)], liver diseases [aHR 1.51 (95% CI 1.37, 1.67)], irritable bowel syndrome [aHR 1.51 (95% CI 1.45, 1.58)], gastrointestinal bleeding [aHR 1.49 (95% CI 1.39, 1.59)], 10 musculoskeletal conditions and 25 other conditions following OA diagnosis. The aOR for multimorbidity prior to the index date was 1.71 (95% CI 1.69, 1.74), whereas the aHR for multimorbidity after the index date was 1.29 (95% CI 1.28, 1.30). CONCLUSIONS: People with OA are more likely to have other chronic conditions both before and after the OA diagnosis. Further study on shared aetiology and causality of these associations is needed.
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Demência/epidemiologia , Gastroenteropatias/epidemiologia , Insuficiência Cardíaca/epidemiologia , Hepatopatias/epidemiologia , Osteoartrite/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Risco , Reino UnidoRESUMO
OBJECTIVE: Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether statins associate with reduction in the risk for joint replacement due to OA and RA. METHODS: This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed statins and people never prescribed statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21-28%), medium (32-38%) or high (42-55%) intensity. RESULTS: A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75-0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63-0.94) but not OA (0.97, 0.94-1.01). CONCLUSION: Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted.
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Artrite Reumatoide/cirurgia , Artroplastia de Quadril , Artroplastia do Joelho , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Lipoproteínas LDL/sangue , Estudos Longitudinais , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Risco , Fatores SexuaisRESUMO
BACKGROUND: In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community. METHODS: Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 µmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346. FINDINGS: 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 µmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42-4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years. INTERPRETATION: Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes. FUNDING: Arthritis Research UK.
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Gota/economia , Gota/enfermagem , Padrões de Prática em Enfermagem , Anos de Vida Ajustados por Qualidade de Vida , Ácido Úrico/sangue , Idoso , Alopurinol/administração & dosagem , Análise Custo-Benefício , Gerenciamento Clínico , Inglaterra , Feminino , Medicina Geral/métodos , Gota/tratamento farmacológico , Supressores da Gota/administração & dosagem , Humanos , Estudos Longitudinais , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Objectives: The role of inflammation in OA is controversial and it is unclear whether suppressing inflammation with conventional or biologic DMARDs is effective. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to compare DMARDs with placebo in participants with symptomatic OA. Methods: Databases (Medline, Embase, Allied and Complementary Medicine Database, Web of Science and Cochrane Library), conference abstracts and ClinicalTrials.gov were searched to end of November 2017 for placebo-controlled RCTs of DMARDs, including biologics, in symptomatic OA. Pain data at treatment peak time point were extracted and combined using a random-effects meta-analysis. Markers of inflammation and adverse events were extracted and reviewed. Risk of bias assessment was conducted using Cochrane's tool. Results: Eleven RCTs (1205 participants) were meta-analysed, including six for conventional DMARDs (757 participants) and five for biologics (448 participants). Overall, DMARDs were statistically superior to placebo [effect size (ES) = 0.18, 95% CI: 0.03, 0.34], although the difference was not clinically significant (0.5 ES threshold). Furthermore, no statistically significant differences were observed in sub-analysis of high-quality trials (ES = 0.11, 95% CI : -0.06, 0.28), biologics (ES = 0.16, 95% CI: -0.02, 0.34) or conventional DMARDs (ES = 0.24, 95% CI: -0.05, 0.54). No difference was found between erosive vs non-erosive hand OA, hand vs knee OA or anti-IL1 vs anti-TNF biologics. Conclusion: DMARDs did not offer clinically significant pain relief above placebo in OA. This poor efficacy indicates that inflammation may not be a prime driver for OA pain.
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Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Osteoartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
OBJECTIVES: To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA). METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies. RESULTS: 43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=-0.30, 95% CI -0.40 to -0.20) and improving function (SMD=-0.35, 95% CI -0.45 to -0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=-0.81, 95% CI -1.12 to -0.52) and piroxicam was most effective for functional improvement (SMD=-1.04, 95% CI -1.60 to -0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs. CONCLUSIONS: Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Administração Cutânea , Anti-Inflamatórios não Esteroides/efeitos adversos , Teorema de Bayes , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Salicilatos/efeitos adversos , Salicilatos/uso terapêutico , Adesivo TransdérmicoRESUMO
Objective: We aimed to create an imaging biomarker for knee shape using knee dual-energy x-ray absorptiometry (DXA) scans and investigate its potential association with subsequent total knee replacement (TKR), independently of radiographic features of knee osteoarthritis and established risk factors. Methods: Using a 129-point statistical shape model, knee shape (expressed as a B-score) and minimum joint space width (mJSW) of the medial joint compartment (binarized as above or below the first quartile) were derived. Osteophytes were manually graded in a subset of images and an overall score was assigned. Cox proportional hazards models were used to examine the associations of B-score, mJSW and osteophyte score with TKR risk, adjusting for age, sex, height and weight. Results: The analysis included 37,843 individuals (mean age 63.7 years). In adjusted models, B-score was associated with TKR: each unit increase in B-score, reflecting one standard deviation from the mean healthy shape, corresponded to a hazard ratio (HR) of 2.25 (2.08, 2.43), while a lower mJSW had a HR of 2.28 (1.88, 2.77). Among the 6719 images scored for osteophytes, mJSW was replaced by osteophyte score in the most strongly predictive model for TKR. In ROC analyses, a model combining B-score, osteophyte score, and demographics outperformed a model including demographics alone (AUC â= â0.87 vs 0.73). Conclusions: Using statistical shape modelling, we derived a DXA-based imaging biomarker for knee shape that was associated with kOA progression. When combined with osteophytes and demographic data, this biomarker may help identify individuals at high risk of TKR, facilitating targeted interventions.
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OBJECTIVE: Although hand synovitis is prevalent in the older population, the etiology remains unclear. Hyperuricemia, a modifiable metabolic disorder, may serve as an underlying mechanism of hand synovitis, but little is known about their relationship. We assessed the association between hyperuricemia and hand synovitis in a large population-based sample. METHODS: We performed a cross-sectional study in Longshan County, Hunan Province, China. Hyperuricemia was defined as a serum urate level >420 µmol/L in men and >360 µmol/L in women. Ultrasound examinations were performed on both hands of 4,080 participants, and both gray-scale synovitis and the Power Doppler signal (PDS) were assessed using semiquantitative scores (grades 0-3). We evaluated the association of hyperuricemia with hand gray-scale synovitis (grade ≥2) and PDS (grade ≥1), respectively, adjusting for age, sex, and body mass index. RESULTS: All required assessments for analysis were available for 3,286 participants. The prevalence of hand gray-scale synovitis was higher among participants with hyperuricemia (30.0%) than those with normouricemia (23.3%), with an adjusted odds ratio (aOR) of 1.28 (95% confidence interval [CI] 1.00-1.62). Participants with hyperuricemia also had a higher prevalence of PDS (aOR 2.36; 95% CI 1.15-4.81). Furthermore, hyperuricemia positively associated, both at the hand and joint levels, with the presence of gray-scale synovitis (aOR 1.27; 95% CI 1.00-1.60 and adjusted prevalence ratio [aPR] 1.26; 95% CI 1.10-1.44, respectively) and PDS (aOR 2.35; 95% CI 1.15-4.79 and aPR 2.34; 95% CI 1.28-4.30, respectively). CONCLUSION: This population-based study provides more evidence for a positive association between hyperuricemia and prevalent hand synovitis.
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Hiperuricemia , Sinovite , Humanos , Hiperuricemia/epidemiologia , Hiperuricemia/sangue , Masculino , Sinovite/diagnóstico por imagem , Sinovite/epidemiologia , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Prevalência , China/epidemiologia , Articulação da Mão/diagnóstico por imagem , Adulto , Ultrassonografia Doppler , Fatores de Risco , Ácido Úrico/sangueRESUMO
BACKGROUND: The burden of osteoarthritis (OA) in UK primary care has not been investigated thoroughly. AIM: To estimate healthcare use and mortality in people with OA (overall and joint specific). DESIGN AND SETTING: A matched cohort study of adults with an incident diagnosis of OA in primary care were selected for the study using UK national Clinical Practice Research Datalink (CPRD) electronic records. METHOD: Healthcare utilisation was measured as the annual average number of primary care consultations and admissions to hospital after the index date for any cause and all-cause mortality data in 221 807 people with OA and an equal number of controls (with no OA diagnosis) who were matched to the case patients by age (standard deviation 2 years), sex, practice, and year of registration. The associations between OA and healthcare utilisation and all-cause mortality were estimated using multinomial logistic regression and Cox regression, respectively, adjusting for covariates. RESULTS: The mean age of the study population was 61 years and 58% were female. In the OA group, the median number of primary care consultations per year after the index date was 10.91 compared with 9.43 in the non-OA control group (P = 0.001) OA was associated with an increased risk of GP consultation and admission to hospital. The adjusted hazard ratio for all-cause mortality was 1.89 (95% confidence interval [CI] = 1.85 to 1.93) for any OA, 2.09 (95% CI = 2.01 to 2.19) for knee OA, 2.08 (95% CI = 1.95 to 2.21) for hip OA, and 1.80 (95% CI = 1.58 to 2.06) for wrist/hand OA, compared with the respective non-OA control group. CONCLUSION: People with OA had increased rates of GP consultations, admissions to hospital, and all-cause mortality that varied across joint sites.
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Osteoartrite do Quadril , Osteoartrite do Joelho , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Pré-Escolar , Masculino , Estudos de Coortes , Osteoartrite do Joelho/epidemiologia , Atenção à Saúde , Osteoartrite do Quadril/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Atenção Primária à Saúde , Reino Unido/epidemiologiaRESUMO
Knee pain is associated with lower muscle strength, and both contribute to disability. Peripheral and central neurological mechanisms contribute to OA pain. Understanding the relative contributions of pain mechanisms to muscle strength might help future treatments. The Knee Pain and related health In the Community (KPIC) cohort provided baseline and year 1 data from people with early knee pain (n = 219) for longitudinal analyses. A cross-sectional analysis was performed with baseline data from people with established knee pain (n = 103) and comparative data from people without knee pain (n = 98). Quadriceps and handgrip strength indicated local and general muscle weakness, respectively. The indices of peripheral nociceptive drive were knee radiographic and ultrasound scores. The indices associated with central pain mechanisms were Pressure Pain detection Threshold (PPT) distal to the knee, and a validated self-report Central Aspects of Pain Factor (CAPF). The associations were explored using correlation and multivariable regression. Weaker quadriceps strength was associated with both high CAPF and low PPT at baseline. Year 1 quadriceps weakness was predicted by higher baseline CAPF (ß = -0.28 (95% CI: -0.55, -0.01), p = 0.040). Weaker baseline and year 1 handgrip strength was also associated with higher baseline CAPF. Weaker baseline quadriceps strength was associated with radiographic scores in bivariate but not adjusted analyses. Quadriceps strength was not significantly associated with total ultrasound scores. Central pain mechanisms might contribute to muscle weakness, both locally and remote from the knee.
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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.
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BACKGROUND: Use of serum urate as a treatment target and outcome measure has become controversial in view of the 2017 American College of Physicians guidelines, which advocated a treat-to-symptom rather than a treat-to-target serum urate approach to gout management. The relevance of serum urate as a treatment target measure implies that achievement of target serum urate is causally associated with improvement in patient-important outcomes such as reduction in the number of gout flares. The aim of this study was to assess the causal relationship between achieving target serum urate and the occurrence of gout flares. METHODS: We analysed individual patient-level data from two randomised trials on urate-lowering therapies in people with gout conducted in Nottingham, UK, and New Zealand. We included participants randomly assigned to immediate dose escalation in the New Zealand study and all participants in the Nottingham study (a nurse-led gout care group and a general practitioner-led usual care group). Individuals who on average achieved a serum urate concentration less than 6 mg/dL (0·36 mmol/L) based on data at 6, 9, and 12 months post-baseline were defined as serum urate responders. The primary outcome was the proportion of participants having at least one gout flare, and the secondary outcome was the mean number of flares per participant per month, from 12 to 24 months after baseline, compared between serum urate responders and non-responders. In adjusted logistic regression models, serum urate at baseline, previous flare history (in the year preceding study entry), presence of tophi at baseline, and, for the Nottingham dataset, the original randomisation group, were included as covariates. The Nottingham study was registered with ClinicalTrials.gov, NCT01477346. The New Zealand study was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000845932. FINDINGS: From the combined individual data from both trials, we identified 343 serum urate responders and 245 serum urate non-responders. Significantly fewer serum urate responders had a gout flare than did serum urate non-responders between 12 and 24 months (91 [27%] of 343 vs 156 [64%] of 245; adjusted odds ratio [OR] 0·29 [95% CI 0·17 to 0·51], p<0·0001). The mean number of flares per participant per month between 12 and 24 months was significantly lower in serum urate responders than in serum urate non-responders (adjusted mean difference -1·41 [95% CI -1·77 to -1·04], p<0·0001). This association was independent of the original randomised treatment allocation. INTERPRETATION: Achieving an average serum urate concentration less than 6 mg/dL is associated with an absence of gout flares and a reduction in the number of flares in the subsequent 12 months in people with gout. These results support a treat-to-target serum urate approach in the management of gout. FUNDING: None.
RESUMO
INTRODUCTION: Osteoarthritis (OA) is one of the leading chronic conditions in the older population. People with OA are more likely to have one or more other chronic conditions than those without. However, the temporal associations, clusters of the comorbidities, role of analgesics and the causality and variation between populations are yet to be investigated. This paper describes the protocol of a multinational study in four European countries (UK, Netherlands, Sweden and Spain) exploring comorbidities in people with OA. METHODS AND ANALYSIS: This multinational study will investigate (1) the temporal associations of 61 identified comorbidities with OA, (2) the clusters and trajectories of comorbidities in people with OA, (3) the role of analgesics on incidence of comorbidities in people with OA, (4) the potential biomarkers and causality between OA and the comorbidities, and (5) variations between countries.A combined case-control and cohort study will be conducted to find the temporal association of OA with the comorbidities using the national or regional health databases. Latent class analysis will be performed to identify the clusters at baseline and joint latent class analysis will be used to examine trajectories during the follow-up. A cohort study will be undertaken to evaluate the role of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and paracetamol on the incidence of comorbidities. Mendelian randomisation will be performed to investigate the potential biomarkers for causality between OA and the comorbidities using the UK Biobank and the Rotterdam Study databases. Finally, a meta-analyses will be used to examine the variations and pool the results from different countries. ETHICS AND DISSEMINATION: Research ethics was obtained according to each database requirement. Results will be disseminated through the FOREUM website, scientific meetings, publications and in partnership with patient organisations.