ABSTRACT
BACKGROUND: Treatments for osteoarthritis (OA) are limited. Previous small studies suggest that the antirheumatic drug methotrexate may be a potential treatment for OA pain. OBJECTIVE: To assess symptomatic benefits of methotrexate in knee OA (KOA). DESIGN: A multicenter, randomized, double-blind, placebo-controlled trial done between 13 June 2014 and 13 October 2017. (ISRCTN77854383; EudraCT: 2013-001689-41). SETTING: 15 secondary care musculoskeletal clinics in the United Kingdom. PARTICIPANTS: A total of 207 participants with symptomatic, radiographic KOA and knee pain (severity ≥4 out of 10) on most days in the past 3 months with inadequate response to current medication were approached for inclusion. INTERVENTION: Participants were randomly assigned 1:1 to oral methotrexate once weekly (6-week escalation 10 to 25 mg) or matched placebo over 12 months and continued usual analgesia. MEASUREMENTS: The primary end point was average knee pain (numerical rating scale [NRS] 0 to 10) at 6 months, with 12-month follow-up to assess longer-term response. Secondary end points included knee stiffness and function outcomes and adverse events (AEs). RESULTS: A total of 155 participants (64% women; mean age, 60.9 years; 50% Kellgren-Lawrence grade 3 to 4) were randomly assigned to methotrexate (n = 77) or placebo (n = 78). Follow-up was 86% (n = 134; methotrexate: 66, placebo: 68) at 6 months. Mean knee pain decreased from 6.4 (SD, 1.80) at baseline to 5.1 (SD, 2.32) at 6 months in the methotrexate group and from 6.8 (SD, 1.62) to 6.2 (SD, 2.30) in the placebo group. The primary intention-to-treat analysis showed a statistically significant pain reduction of 0.79 NRS points in favor of methotrexate (95% CI, 0.08 to 1.51; P = 0.030). There were also statistically significant treatment group differences in favor of methotrexate at 6 months for Western Ontario and McMaster Universities Osteoarthritis Index stiffness (0.60 points [CI, 0.01 to 1.18]; P = 0.045) and function (5.01 points [CI, 1.29 to 8.74]; P = 0.008). Treatment adherence analysis supported a dose-response effect. Four unrelated serious AEs were reported (methotrexate: 2, placebo: 2). LIMITATION: Not permitting oral methotrexate to be changed to subcutaneous delivery for intolerance. CONCLUSION: Oral methotrexate added to usual medications demonstrated statistically significant reduction in KOA pain, stiffness, and function at 6 months. PRIMARY FUNDING SOURCE: Versus Arthritis.
ABSTRACT
Introduction: Interprofessional education (IPE) is essential in pharmacy training, providing students with vital collaborative skills for real-world healthcare. Advanced Pharmacy Practice Experience (APPE) is integral to IPE, allowing students to apply their knowledge in diverse healthcare settings. The COVID-19 pandemic has disrupted healthcare education and raised concerns about its impact on IPE during APPE rotations. Our study investigates the pandemic's influence on pharmacy students' interprofessional interactions and APPE performance. Objective: To assess the interprofessional experiences of fourth-year pharmacy students before and during the COVID-19 pandemic in the context of APPE. Methods: This retrospective observational study examined the experiences of P4 pharmacy students in the United States during APPEs before and during the pandemic. We employed electronic surveys with 21 questions to gauge interactions and interprofessional team effectiveness, employing Likert scale response options. We compared responses between the 2019-2020 and 2020-2021 APPE rotations using statistical tests. Results: Our study encompassed 83 and 86 students for the 2019-2020 and 2020-2021 APPE rotations, respectively, achieving a 100% response rate. Amid the pandemic, written communications between pharmacy students and healthcare providers in general medicine rotations increased, while in-person engagement decreased. Pre-COVID, students reported higher colleague referrals and greater interprofessional utilization during ambulatory care rotations. Conclusion: COVID-19 shifted interactions from in-person to written communication between pharmacy students and healthcare providers. Students reported decreased satisfaction with their interprofessional experiences. This research offers insights into the changing landscape of pharmacy education, helping students prepare for evolving challenges in healthcare delivery and education.
ABSTRACT
Introduction: Older adults are not protected from obesity, which has been linked to frailty, cognitive impairment, and other aging-related factors. Intensive lifestyle interventions have been shown to be effective for weight loss in older adults; however, these have typically been highly intensive and less feasible for dissemination. This analysis describes weight loss in a large-scale, commercially available, digital intervention in a subset of older adults. Methods: Older adults (N = 20,443, males = 6,238; females = 14,205) between 65 and 85 years of age with overweight (43.3%) or obesity (46.7%) participated in an online, self-directed weight loss program. Behavioral-based content was delivered through weekly video lessons within an online platform that included weight and physical activity tracking, an online community, a reference library, and access to coaching support. Self-reported measures taken at the time of entry into the program were used for this analysis (demographics, height, body weight, and health status). Weight was reported across weeks of engagement in the curriculum. Results: The average weight loss was -3.15 kg (95% CI: [-3.20, -3.11]) at 15.5 weeks. Weight loss was significantly greater in male individuals (-3.79 kg [95% CI: -3.89, -3.71]) versus female individuals (-2.87 kg [95% CI: -2.94, -2.82]) (p < 0.001), with a similar engagement in curriculum weeks. Percent weight loss was statistically significant for all age categories (p < 0.05) and self-reported health conditions (p < 0.05). Discussion: Short-term weight loss was observed in older adults exposed to a low-touch, self-guided, and digital behavioral-based weight loss program. Weight loss was also observed even in the presence of various chronic health conditions.
ABSTRACT
OBJECTIVES: Knee synovial abnormalities, potentially treatment targets for knee pain and osteoarthritis, are common in middle-aged and older population, but its etiology remains unclear. We examined the associations between hyperuricemia and knee synovial abnormalities detected by ultrasound in a general population sample. METHODS: Participants aged ≥ 50 years were from a community-based observational study. Hyperuricemia was defined as serum urate (SU) level > 416 µmol/L in men and > 357 µmol/L in women. Ultrasound of both knees was performed to determine the presence of synovial abnormalities, i.e., synovial hypertrophy, effusion, or Power Doppler signal (PDS). We examined the relation of hyperuricemia to prevalence of knee synovial abnormalities and its laterality, and the dose-response relationships between SU levels and the prevalence of knee synovial abnormalities. RESULTS: In total, 3,405 participants were included in the analysis. Hyperuricemia was associated with higher prevalence of knee synovial abnormality (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]: 1.02 to 1.43), synovial hypertrophy (aOR = 1.33, 95% CI: 1.05 to 1.68), and effusion (aOR = 1.21, 95% CI: 1.02 to 1.44), respectively. There were dose-response relationships between SU levels and synovial abnormalities. Additionally, the hyperuricemia was more associated with prevalence of bilateral than with that of unilateral knee synovial abnormality, synovial hypertrophy, or effusion; however, no significant association was observed between hyperuricemia and PDS. CONCLUSION: In this population-based study we found that hyperuricemia was associated with higher prevalence of knee synovial abnormality, synovial hypertrophy and effusion, suggesting that hyperuricemia may play a role in pathogenesis of knee synovial abnormalities.
Subject(s)
Hyperuricemia , Osteoarthritis, Knee , Synovitis , Aged , Female , Humans , Male , Middle Aged , Cross-Sectional Studies , Hyperuricemia/complications , Hyperuricemia/diagnostic imaging , Hyperuricemia/epidemiology , Osteoarthritis, Knee/complications , Synovitis/diagnostic imaging , Synovitis/epidemiology , UltrasonographyABSTRACT
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.
Subject(s)
Hyperuricemia , Synovitis , Humans , Hyperuricemia/epidemiology , Hyperuricemia/blood , Male , Synovitis/diagnostic imaging , Synovitis/epidemiology , Female , Middle Aged , Cross-Sectional Studies , Aged , Prevalence , China/epidemiology , Hand Joints/diagnostic imaging , Adult , Ultrasonography, Doppler , Risk Factors , Uric Acid/bloodABSTRACT
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.
Subject(s)
Arthralgia , Disease Progression , Osteoarthritis, Knee , Humans , Female , Male , Osteoarthritis, Knee/blood , Middle Aged , Cross-Sectional Studies , Aged , Arthralgia/blood , Longitudinal Studies , Cohort Studies , Oxylipins/blood , Knee Joint , Hydroxyeicosatetraenoic Acids/blood , Arachidonic Acids/blood , Biomarkers/blood , Pain Measurement , Arachidonic Acid/bloodABSTRACT
OBJECTIVES: Early-onset osteoarthritis (OA) is an emerging health issue amidst the escalating prevalence of overweight and obesity. However, there are scant data on its disease, economic burden and attributable burden due to high body mass index (BMI). METHODS: Using data from the Global Burden of Diseases Study 2019, we examined the numbers of incident cases, prevalent cases, years lived with disability (YLDs) and corresponding age-standardised rates for early-onset OA (diagnosis before age 55) from 1990 to 2019. The case definition was symptomatic and radiographically confirmed OA in any joint. The average annual percentage changes (AAPCs) of the age-standardised rates were calculated to quantify changes. We estimated the economic burden of early-onset OA and attributable burden to high BMI. RESULTS: From 1990 to 2019, the global incident cases, prevalent cases and YLDs of early-onset OA were doubled. 52.31% of incident OA cases in 2019 were under 55 years. The age-standardised rates of incidence, prevalence and YLDs increased globally and for countries in all Sociodemographic Index (SDI) quintiles (all AAPCs>0, p<0.05), with the fastest increases in low-middle SDI countries. 98.04% of countries exhibited increasing trends in all age-standardised rates. Early-onset OA accounts for US$46.17 billion in healthcare expenditure and US$60.70 billion in productivity loss cost in 2019. The attributable proportion of high BMI for early-onset OA increased globally from 9.41% (1990) to 15.29% (2019). CONCLUSIONS: Early-onset OA is a developing global health problem, causing substantial economic costs in most countries. Targeted implementation of cost-effective policies and preventive intervention is required to address the growing health challenge.
Subject(s)
Age of Onset , Body Mass Index , Global Burden of Disease , Global Health , Osteoarthritis , Humans , Global Burden of Disease/trends , Osteoarthritis/epidemiology , Osteoarthritis/economics , Middle Aged , Male , Female , Prevalence , Adult , Incidence , Global Health/economics , Cost of Illness , Young Adult , Obesity/epidemiology , Obesity/economics , Disability-Adjusted Life Years/trendsABSTRACT
Melatonin exhibits potential for pain relief and long-term safety profile. We examined the analgesic effects of oral melatonin on osteoarthritis (OA) and investigated the underlying mechanism. Using data from a UK primary care database, we conducted a cohort study in individuals with OA to compare the number of oral analgesic prescriptions and the risk of knee/hip replacement between melatonin initiators and hypnotic benzodiazepines (i.e., active comparator) initiators using quantile regression models and Cox-proportional hazard models, respectively. To elucidate causation, we examined the effects of melatonin on pain behaviors and explored several metabolites that may serve as potential regulatory agents of melatonin in the monoiodoacetate rat model of OA. Using data from another community-based cohort study, that is, the Xiangya OA Study, we verified the association between the key serum metabolite and incident symptomatic knee OA. Compared with the hypnotic benzodiazepines cohort (n = 8135), the melatonin cohort (n = 813) had significantly fewer subsequent prescriptions of oral analgesics (50th percentile: 5 vs. 7, 75th percentile: 19 vs. 29, and 99th percentile: 140 vs. 162) and experienced a lower risk of knee/hip replacement (hazard ratio = 0.47, 95% Cl: 0.30-0.73) during the follow-up period. In rats, oral melatonin alleviated pain behaviors and increased serum levels of glycine. There was an inverse association between baseline serum glycine levels and the risk of incident symptomatic knee OA in humans (n = 760). In conclusion, our findings indicate that oral melatonin shows significant potential to be a novel treatment for OA pain. The potential role of glycine in its analgesic mechanism warrants further investigation.
Subject(s)
Melatonin , Osteoarthritis, Hip , Osteoarthritis, Knee , Humans , Animals , Rats , Cohort Studies , Melatonin/pharmacology , Melatonin/therapeutic use , Osteoarthritis, Hip/drug therapy , Analgesics/pharmacology , Analgesics/therapeutic use , Osteoarthritis, Knee/drug therapy , Pain/drug therapy , Benzodiazepines/therapeutic use , Glycine , Hypnotics and Sedatives/therapeutic useABSTRACT
ABSTRACT: Our aim was to investigate relative contributions of central and peripheral mechanisms to knee osteoarthritis (OA) diagnosis and their independent causal association with knee OA. We performed longitudinal analysis using data from UK-Biobank participants. Knee OA was defined using International Classification of Diseases manual 10 codes from participants' hospital records. Central mechanisms were proxied using multisite chronic pain (MCP) and peripheral mechanisms using body mass index (BMI). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated, and proportional risk contribution (PRC) was estimated from receiver-operator-characteristic (ROC) analysis. To estimate the causal effects, we performed 2-sample multivariable Mendelian Randomisation (MR) analysis. We selected genetic instruments from the largest Genome Wide Association Study of BMI (N = 806,834) and MCP (N = 387,649) and estimated the instruments genetic associations with knee OA in the largest available dataset (62,497 cases and 333,557 control subjects). The multivariable MR was performed using modified inverse-variance weighting methods. Of the 203,410 participants, 6% developed knee OA. Both MCP (OR 1.23, 95% CI; 1.21-1.24) and BMI (1.10, 95% CI; 1.10-1.11) were associated with knee OA diagnosis. The PRC was 6.9% (95% CI; 6.7%-7.1%) for MCP and 21.9% (95% CI; 21.4%-22.5%) for BMI; the combined PRC was 38.8% (95% CI; 37.9%-39.8%). Body mass index and MCP had independent causal effects on knee OA (OR 1.76 [95% CI, 1.64-1.88] and 1.83 [95% CI, 1.54-2.16] per unit change, respectively). In conclusion, peripheral risk factors (eg, BMI) contribute more to the development of knee OA than central risk factors (eg, MCP). Peripheral and central factors are independently causal on knee OA.
Subject(s)
Biological Specimen Banks , Body Mass Index , Genome-Wide Association Study , Mendelian Randomization Analysis , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/genetics , Osteoarthritis, Knee/epidemiology , Mendelian Randomization Analysis/methods , Female , Male , United Kingdom/epidemiology , Longitudinal Studies , Risk Factors , Middle Aged , Aged , Chronic Pain/genetics , Chronic Pain/epidemiology , Adult , UK BiobankABSTRACT
INTRODUCTION: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an update is needed. METHODS: The Standardised Operating Procedures for EULAR recommendations were followed. A multidisciplinary Task Force with 25 members representing 14 European countries was established. The Task Force agreed on an updated search strategy of 11 research questions. The systematic literature review encompassed dates from 1 January 2012 to 27 May 2022. Retrieved evidence was discussed, updated recommendations were formulated, and research and educational agendas were developed. RESULTS: The revised recommendations include two overarching principles and eight evidence-based recommendations including (1) an individualised, multicomponent management plan; (2) information, education and self-management; (3) exercise with adequate tailoring of dosage and progression; (4) mode of exercise delivery; (5) maintenance of healthy weight and weight loss; (6) footwear, walking aids and assistive devices; (7) work-related advice and (8) behaviour change techniques to improve lifestyle. The mean level of agreement on the recommendations ranged between 9.2 and 9.8 (0-10 scale, 10=total agreement). The research agenda highlighted areas related to these interventions including adherence, uptake and impact on work. CONCLUSIONS: The 2023 updated recommendations were formulated based on research evidence and expert opinion to guide the optimal management of hip and knee OA.
Subject(s)
Exercise Therapy , Osteoarthritis, Hip , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/therapy , Osteoarthritis, Knee/rehabilitation , Osteoarthritis, Hip/therapy , Osteoarthritis, Hip/rehabilitation , Exercise Therapy/methods , Patient Education as Topic/methods , Europe , Self-Management/methods , Self-Help Devices , Evidence-Based Medicine , Weight LossABSTRACT
OBJECTIVE: Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. METHODS: We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue. RESULTS: Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. CONCLUSION: An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.
Subject(s)
Gout , Obesity , Proof of Concept Study , Weight Loss , Aged , Female , Humans , Male , Middle Aged , Body Mass Index , Diet, Reducing , Fatigue/etiology , Gout/complications , Gout/diet therapy , Obesity/complications , Uric Acid/bloodABSTRACT
OBJECTIVES: The incidence of gout in the UK appears to have declined since 2013; however, whether such a trend occurred across participants born in different years (ie, birth cohort) is unknown. We aimed to examine the effects of the birth cohort on gout incidence using an age-period-cohort (APC) model. DESIGN: Cross-sectional study. SETTING: Nationwide data from the UK primary care database. PARTICIPANTS: Individuals between 30 and 89 years of age were included. We excluded individuals who had gout history when entering the database and individuals with less than 1 year of continuous follow-up between 1 January 1999 and 31 December 2019. PRIMARY AND SECONDARY OUTCOME MEASURES: Gout was identified using READ codes assigned by general practitioners. The incidence of gout between 1999-2013 and 2011-2019 was analysed with APC model. RESULTS: The incidence of gout between 1999 and 2013 increased with birth cohorts. Compared with those born in 1949-1953 (reference), the age-adjusted and period-adjusted rate ratios (RRs) of incident gout increased from 0.39 (95% CI 0.34 to 0.46) in participants born in 1910-1914 to 2.36 (95% CI 2.09 to 2.66) in participants born in 1979-1983 (p for trend <0.001). In contrast, the incidence of gout between 2011 and 2019 decreased with birth cohorts. Compared with those born in 1949-1953 (reference), the age-adjusted and period-adjusted RRs of incident gout declined from 2.75 (95% CI 2.30 to 3.28) in participants born in 1922-1926 to 0.75 (95% CI 0.65 to 0.87) in participants born in 1976-1980 but then increased slightly to 0.95 (95% CI 0.77 to 1.17) in participants born in 1985-1989. CONCLUSIONS: The gout incidence between 1999 and 2013 in the UK increased with the birth cohorts and then decreased between 2011 and 2019 except for those born after 1980. Future monitoring is needed to help identify aetiological factors and guide preventive and treatment strategies for gout.
Subject(s)
Gout , Humans , Incidence , Cross-Sectional Studies , Gout/epidemiology , Cohort Studies , United Kingdom/epidemiology , Risk FactorsABSTRACT
OBJECTIVE: The pathogenesis of hand osteoarthritis (OA) remains unknown. Hyperuricaemia, which is related to inflammation, may play a role in hand OA, but evidence is lacking. In a large population-based study, we examined the association between hyperuricaemia and hand OA. METHODS: Participants were from the Xiangya OA Study, a community-based observational study. Hyperuricaemia was defined as serum urate >416 µmol/L in men and >357 µmol/L in women. Radiographic hand OA (RHOA) was defined as presence of the modified Kellgren-Lawrence grade ≥2 in any hand joint. Symptomatic hand OA (SHOA) was defined as presence of both self-reported symptoms and RHOA in the same hand. The associations of hyperuricaemia with RHOA or SHOA were examined using generalised estimating equations. RESULTS: Among 3628 participants, the prevalence of RHOA was higher in participants with hyperuricaemia than those with normouricaemia (26.9% vs 20.9%), with an adjusted OR (aOR) of 1.34 (95% CI 1.11 to 1.61). The associations were consistent in men (aOR 1.33, 95% CI 1.01 to 1.74) and women (aOR 1.35, 95% CI 1.05 to 1.74). Hyperuricaemia was mainly associated with bilateral RHOA (aOR 1.54, 95% CI 1.18 to 2.01) but not unilateral RHOA (aOR 1.13, 95% CI 0.89 to 1.45). Prevalence of SHOA was higher, although statistically insignificant, in participants with hyperuricaemia (aOR 1.39, 95% CI 0.94 to 2.07). CONCLUSION: In this population-based study, hyperuricaemia was associated with a higher prevalence of hand OA. Future prospective studies are required to investigate the temporal relationship. TRIAL REGISTRATION NUMBER: NCT04033757.
Subject(s)
Hand Joints , Hyperuricemia , Osteoarthritis , Male , Humans , Female , Hyperuricemia/complications , Hyperuricemia/epidemiology , Osteoarthritis/epidemiology , Osteoarthritis/etiology , Hand Joints/diagnostic imaging , Hand , Prospective StudiesABSTRACT
Bayes' Theorem provides a rationality-standard for information search when there are two mutually exclusive hypotheses and one or more statistical cues pertaining to the likelihoods of the hypotheses. Prior research shows that when people already have a cue pertaining to a hypothesis and are asked to seek additional information to help decide which hypothesis is correct, they tend to exhibit a specific form of pseudodiagnosticity: Rather than seek information that would assess the same cue relative to an alternative hypothesis, they tend to seek information about how a second cue would pertain to the first hypothesis. For example, if people are told that 70% of genuine paintings are landscapes, they then seek to know the percentage of genuine paintings that are watercolor rather than the percentage of fake paintings that are landscapes. However, this response pattern has sometimes been violated in a way that may depend on the cues' numerical values (e.g., 70% vs. 30%), thus raising a question as to the nature of the bias: Does the selection bias characterize the search process per se, or does it reflect the manner in which people utilize already-obtained percentage information? To address these issues, we employed a novel, search-only judgment paradigm in which people were asked to search for cues and to select them without ever obtaining the cues' percentage values. The results confirmed a tendency toward same-hypothesis pseudodiagnosticity both in primary (i.e., most-preferred) and secondary preference, and supported a model in which pseudodiagnosticity can proceed with or without numerical cue data.
ABSTRACT
OBJECTIVES: Knee synovitis is a highly prevalent and potentially curable condition for knee pain; however, its pathogenesis remains unclear. We sought to assess the associations of the gut fungal microbiota and the fungi-bacteria correlation network with knee synovitis. METHODS: Participants were derived from a community-based cross-sectional study. We performed an ultrasound examination of both knees. A knee was defined as having synovitis if its synovium was ≥4 mm and/or Power Doppler (PD) signal was within the knee synovium area (PD synovitis). We collected faecal specimens from each participant and assessed gut fungal and bacterial microbiota using internal transcribed spacer 2 and shotgun metagenomic sequencing. We examined the relation of α-diversity, ß-diversity, the relative abundance of taxa and the interkingdom correlations to knee synovitis. RESULTS: Among 977 participants (mean age: 63.2 years; women: 58.8%), 191 (19.5%) had knee synovitis. ß-diversity of the gut fungal microbiota, but not α-diversity, was significantly associated with prevalent knee synovitis. The fungal genus Schizophyllum was inversely correlated with the prevalence and activity (ie, control, synovitis without PD signal and PD synovitis) of knee synovitis. Compared with those without synovitis, the fungi-bacteria correlation network in patients with knee synovitis was smaller (nodes: 93 vs 153; edges: 107 vs 244), and the average number of neighbours was fewer (2.3 vs 3.2). CONCLUSION: Alterations of gut fungal microbiota and the fungi-bacteria correlation network are associated with knee synovitis. These novel findings may help understand the mechanisms of the gut-joint axis in knee synovitis and suggest potential targets for future treatment.
Subject(s)
Dysbiosis , Synovitis , Humans , Female , Middle Aged , Dysbiosis/microbiology , Cross-Sectional Studies , Synovitis/pathology , Fungi , Bacteria/geneticsABSTRACT
Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs. In this study, we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulation-specific gene expression between cartilage with macroscopically confirmed osteoarthritis (n = 5) and cartilage without osteoarthritis (n = 5) from the interphalangeal joints of five donors. Of 105 142 cells, we identified 13 subpopulations, including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes. Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage. Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage. In these two subpopulations from osteoarthritic cartilage, the ferroptosis pathway was enriched, and expression of iron overload-related genes, e.g., FTH1, was elevated. To verify these findings, we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study. Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis (odds ratio = 1.07, 95% confidence interval: 1.02-1.11) among participants (n = 332 668) in UK Biobank. High levels of serum ferritin (encoded by FTH1), a biomarker of body iron overload, were significantly associated with a high prevalence of hand osteoarthritis among participants (n = 1 241) of Xiangya Osteoarthritis Study (P-for-trend = 0.037). In conclusion, our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis, providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.
Subject(s)
Cartilage, Articular , Iron Overload , Osteoarthritis , Humans , Chondrocytes/metabolism , Cross-Sectional Studies , Cartilage, Articular/metabolism , Osteoarthritis/genetics , Iron Overload/metabolism , Sequence Analysis, RNAABSTRACT
BACKGROUND: Since gut microbiome dysbiosis can cause inflammatory disorders by affecting host metabolism, we postulate that the gut microbiome and related metabolites could play a role in hand osteoarthritis. We characterised gut microbiome-related metabolites in people with symptomatic hand osteoarthritis (SHOA) in two independent cohorts. METHODS: Using data collected from a large-sample community-based observational study (discovery cohort), we assessed the relations of the microbial function and plasma key metabolites related to altered microbial function with SHOA. Finally, we verified the relations of plasma metabolites to SHOA in an independent observational study (validation cohort). FINDINGS: In the discovery cohort (n = 1359), compared to those without SHOA, participants with SHOA had significantly altered microbial functions related to tryptophan metabolism (Q = 0.025). Therefore we measured the plasma tryptophan metabolites and found that participants with SHOA had higher levels of 5-hydroxyindoleacetic acid (odds ratio [OR] = 1.25, 95% confidence interval [CI]: 1.09-1.42) and 5-hydroxytryptophol (OR = 1.13, 95% CI: 1.04-1.23), but lower levels of indole-3-lactic acid (ILA) (OR = 0.85, 95% CI: 0.72-1.00), skatole (OR = 0.93, 95% CI: 0.88-0.99) and 3-hydroxyanthranilic acid (OR = 0.90, 95% CI: 0.85-0.96). Findings from the validation cohort (n = 142) verified that lower levels of ILA were related to SHOA (OR = 0.70, 95% CI: 0.53-0.92). INTERPRETATION: Alterations of the microbial function of tryptophan biosynthesis and tryptophan metabolites, especially lower levels of ILA, are associated with SHOA. These findings suggest the role of the microbiome and tryptophan metabolites in developing of SHOA and may contribute to future translational opportunities. FUNDING: National Key Research and Development Plan and National Natural Science Foundation of China.
Subject(s)
Gastrointestinal Microbiome , Microbiota , Osteoarthritis , Humans , China , Tryptophan/metabolism , Observational Studies as TopicABSTRACT
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.