Myocardial infarction in a population-based cohort of patients with biopsy-confirmed giant cell arteritis in southern Sweden.

OBJECTIVES: To determine the incidence rate (IR) of myocardial infarction (MI), relative risk of MI, and impact of incident MI on mortality in individuals with biopsy-confirmed giant cell arteritis (GCA). METHODS: MIs in individuals diagnosed with GCA 1998-2016 in Skåne, Sweden were identified by searching the SWEDEHEART register, a record of all patients receiving care for MI in a coronary care unit (CCU). The regional diagnosis database, with subsequent case review, identified GCA patients receiving care for MI outside of a CCU. A cohort of 10 reference subjects for each GCA case, matched for age, sex and area of residence, was used to calculate the incidence rate ratio (IRR) of MI in GCA to that in the general population. RESULTS: The GCA cohort comprised 1134 individuals. During 7958 person-years of follow-up, 102 were diagnosed with incident MI, yielding an IR of 12.8 per 1000 person-years (95% CI 10.3 to 15.3). The IR was highest in the 30 days following GCA diagnosis and declined thereafter. The IRR of MI in GCA to that of the background population was 1.29 (95% CI 1.05 to 1.59). Mortality was higher in GCA patients who experienced incident MI than in those without MI (HR 2.8; 95% CI 2.2 to 3.6). CONCLUSIONS: The highest incidence of MI occurs within the 30 days following diagnosis of GCA. Individuals with GCA have a moderately increased risk of MI compared with a reference population. Incident MI has a major impact on mortality in GCA.

Deep Learning for Predicting Progression of Patellofemoral Osteoarthritis Based on Lateral Knee Radiographs, Demographic Data, and Symptomatic Assessments.

OBJECTIVE: In this study, we propose a novel framework that utilizes deep learning and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of 7 years. MATERIAL AND METHODS: This study included subjects (1,832 subjects, 3,276 knees) from the baseline of the Multicenter Osteoarthritis Study (MOST). Patellofemoral joint regions of interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end deep learning method was developed for predicting PFOA progression based on imaging data in a five-fold cross-validation setting. To evaluate the performance of the models, a set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, body mass index, and Western Ontario and McMaster Universities Arthritis Index score, and the radiographic osteoarthritis stage of the tibiofemoral joint (Kellgren and Lawrence [KL] score). Finally, to increase predictive power, we trained an ensemble model using both imaging and clinical data. RESULTS: Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an area under the receiver operating characteristic curve (AUC) of 0.856 and average precision (AP) of 0.431, slightly outperforming the deep learning approach without attention (AUC = 0.832, AP = 0.4) and the best performing reference GBM model (AUC = 0.767, AP = 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP = 0.447), although the clinical significance of this minor performance gain remains unknown. The spatial attention module improved the predictive performance of the backbone model, and the visual interpretation of attention maps focused on the joint space and the regions where osteophytes typically occur. CONCLUSION: This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.

Changes in educational inequalities in knee and hip osteoarthritis surgery and non-surgery specialist care visits over time in Sweden.

Objective: To examine changes in prevalence and socioeconomic inequalities in knee and hip OA outcomes, in more specific surgery and non-surgery specialist care visits, from 2001 to 2011 in Sweden and to what extent sociodemographic factors can explain the changes. Design: We included all individuals aged ≥35 years resident in Sweden from 2001 to 2011. Individual-level data was retrieved from the Swedish Interdisciplinary Panel. Highest educational attainment was used as socioeconomic measure and the concentration index was used to assess relative and absolute educational inequalities. We used decomposition method to examine changes in prevalence and relative educational inequalities. Results: A total of 4,794,693 and 5,359,186 people were included for the years 2001 and 2011, respectively. The crude prevalence of surgery and specialist visits for knee and hip OA was 36-83% higher in 2011 than in 2001. The increase in hip OA outcomes was largely explained by changes in the sociodemographic composition of the population, whereas for knee OA outcomes, changes in the strength of the associations with sociodemographic factors appeared more important. All outcomes were concentrated among people with lower education in all study years. The relative inequalities declined over the study period, while the absolute inequalities increased for knee OA outcomes and remained stable for hip OA. Conclusion: Our findings show an increasing burden of all studied OA outcomes. Moreover, our findings suggest persistent educational inequalities with more surgeries and specialist visits among lower-educated individuals. Future research should incorporate additional variables to better understand and address these inequalities.

Toward designing human intervention studies to prevent osteoarthritis after knee injury: A report from an interdisciplinary OARSI 2023 workshop.

Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.

Exploratory neutron tomography of articular cartilage.

OBJECTIVE: To investigate the feasibility of using neutron tomography to gain new knowledge of human articular cartilage degeneration in osteoarthritis (OA). Different sample preparation techniques were evaluated to identify maximum intra-tissue contrast. DESIGN: Human articular cartilage samples from 14 deceased donors (18-75 years, 9 males, 5 females) and 4 patients undergoing total knee replacement due to known OA (all female, 61-75 years) were prepared using different techniques: control in saline, treated with heavy water saline, fixed and treated in heavy water saline, and fixed and dehydrated with ethanol. Neutron tomographic imaging (isotropic voxel sizes from 7.5 to 13.5 µm) was performed at two large scale facilities. The 3D images were evaluated for gradients in hydrogen attenuation as well as compared to images from absorption X-ray tomography, magnetic resonance imaging, and histology. RESULTS: Cartilage was distinguishable from background and other tissues in neutron tomographs. Intra-tissue contrast was highest in heavy water-treated samples, which showed a clear gradient from the cartilage surface to the bone interface. Increased neutron flux or exposure time improved image quality but did not affect the ability to detect gradients. Samples from older donors showed high variation in gradient profile, especially from donors with known OA. CONCLUSIONS: Neutron tomography is a viable technique for specialized studies of cartilage, particularly for quantifying properties relating to the hydrogen density of the tissue matrix or water movement in the tissue.

Exercise for knee osteoarthritis pain: Association or causation?

Exercise is universally recommended as a primary strategy for the management of knee osteoarthritis (OA) pain. The recommendations are based on results from more than 100 randomized controlled trials (RCTs) that compare exercise to no-attention control groups. However, due to the inherent difficulties with adequate placebo control, participant blinding and the use of patient-reported outcomes, the existing RCT evidence is imperfect. To better understand the evidence used to support a causal relationship between exercise and knee OA pain relief, we examined the existing evidence through the Bradford Hill considerations for causation. The Bradford Hill considerations, first proposed in 1965 by Sir Austin Bradford Hill, provide a framework for assessment of possible causal relationships. There are 9 considerations by which the evidence is reviewed: Strength of association, Consistency, Specificity, Temporality, Biological Gradient (Dose-Response), Plausibility, Coherence, Experiment, and Analogy. Viewing the evidence from these 9 viewpoints did neither bring forward indisputable evidence for nor against the causal relationship between exercise and improved knee OA pain. Rather, we conclude that the current evidence is not sufficient to support claims about (lack of) causality. With our review, we hope to advance the continued global conversation about how to improve the evidence-based management of patients with knee OA.

Use of prescribed analgesics before and after exercise therapy and patient education in patients with knee or hip osteoarthritis.

The aim of this study was to investigate utilisation patterns of prescribed analgesics before, during, and after an exercise therapy and patient education program among patients with knee or hip osteoarthritis. This cohort study is based on data from the nationwide Good Life with osteoarthritis in Denmark (GLA:D®) patient-register linked with national health registries including data on prescribed analgesics. GLA:D® consists of 8-12 weeks of exercise and patient education. We included 35,549 knee/hip osteoarthritis patients starting the intervention between January 2013 and November 2018. Utilisation patterns the year before, 3 months during, and the year after the intervention were investigated using total dispensed defined daily doses (DDDs) per month per 1000 population as outcome. During the year before the intervention, use of prescribed paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids increased with 85%, 79% and 22%, respectively. During the intervention, use of paracetamol decreased with 16% with a stable use the following year. Use of NSAIDs and opioids decreased with 38% and 8%, respectively, throughout the intervention and the year after. Sensitivity analyses indicated that the prescription of most analgesics changed over time. For paracetamol, NSAIDs, and opioids, 10% of analgesic users accounted for 45%, 50%, and 70%, respectively, of the total DDDs dispensed during the study period. In general, analgesic use increased the year before the intervention followed by a decrease during the intervention and the year after. A small proportion of analgesic users accounted for half or more of all paracetamol, NSAIDs, and opioids dispensed during the study period.

Inflammatory rheumatic diseases and the risk of drug use disorders: a register-based cohort study in Sweden.

To investigate the association between chronic inflammatory rheumatic diseases (CIRD) and drug use disorder (DUD). Individuals aged ≥ 30 years in 2009 that met the following conditions were included: residing in the Skåne region, Sweden, with at least one healthcare contact in person and no history of DUD (ICD-10 codes F11-F16, F18-F19) during 1998-2009 (N = 649,891). CIRD was defined as the presence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), or systemic lupus erythematosus. Treating CIRD as a time-varying exposure, we followed people from January 1, 2010 until a diagnosis of DUD, death, relocation outside the region, or December 31, 2019, whichever occurred first. We used flexible parametric survival models adjusted for attained age, sociodemographic characteristics, and coexisting conditions for data analysis. There were 64 (95% CI 62-66) and 104 (88-123) incident DUD per 100,000 person-years among those without and with CIRD, respectively. CIRD was associated with an increased risk of DUD in age-adjusted analysis (hazard ratio [HR] 1.77, 95% CI 1.49-2.09). Almost identical HR (1.71, 95% CI 1.45-2.03) was estimated after adjustment for sociodemographic characteristics, and it slightly attenuated when coexisting conditions were additionally accounted for (1.47, 95% CI 1.24-1.74). Fully adjusted HRs were 1.49 (1.21-1.85) for RA, 2.00 (1.38-2.90) for AS, and 1.58 (1.16-2.16) for PsA. More stringent definitions of CIRD didn't alter our findings. CIRD was associated with an increased risk of DUD independent of sociodemographic factors and coexisting conditions. Key Points • A register-based cohort study including 649,891 individuals aged≥30 residing in the Skåne region, Sweden, was conducted. • Chronic inflammatory rheumatic diseases were associated with higher risks of drug use disorder independent of sociodemographic factors and coexisting conditions.

Diagnostic Accuracy of Candidate Magnetic Resonance Imaging Knee Osteoarthritis Definitions Versus Radiograph in an Acute Anterior Cruciate Ligament Injury Cohort.

OBJECTIVE: We tested the diagnostic accuracy of previously proposed magnetic resonance imaging (MRI) osteoarthritis (OA) definitions in a cohort after acute anterior cruciate ligament (ACL) injury. METHODS: We studied participants with posteroanterior and lateral knee radiographs and MRI 5 years after ACL injury, scored using the Anterior Cruciate Ligament Osteoarthritis Score. Radiographic OA (ROA) was defined using Osteoarthritis Research Society International scoring of osteophytes and joint space narrowing considering medial/lateral tibiofemoral and patellofemoral compartments. We tested three candidate MRI OA definitions that performed well in an older adult cohort. "Multicenter Osteoarthritis Study (MOST) simple" required cartilage score ≥2 (range 0-6) and osteophyte score ≥2 (0-7); "MOST optional" included cartilage score ≥2, osteophyte score ≥2, and either bone marrow lesions (BMLs) ≥1 (0-3) or synovitis ≥2 (0-3). The third, a Delphi panel definition, included nonzero scores for cartilage, osteophyte, BMLs, meniscus, and other structures. We calculated sensitivity and specificity with 95% confidence intervals (95% CIs) for each MRI definition versus ROA. RESULTS: We included 113 participants (mean age 26 years, 26% female). At 5 years, 29 participants (26%) had ROA. "MOST simple" had a sensitivity of 52% (95% CI 33%-71%), and specificity of 76% (95% CI 66%-85%). Sensitivity and specificities for "MOST optional" were 28% (95% CI 29%-67%) and 83% (95% CI 74%-91%), respectively. The Delphi panel definition had a sensitivity of 48% (95% CI 29%-67%) and specificity of 77% (95% CI 67%-86%). CONCLUSION: Simple MRI-based OA definitions requiring at least cartilage damage and an osteophyte have low sensitivity and high specificity in young persons after knee injury.

Genetic Influence on Osteoarthritis Versus Other Rheumatic Diseases.

OBJECTIVE: We aimed to compare the genetic contribution to osteoarthritis (OA) versus other rheumatic/musculoskeletal diseases (RMDs) in the same population and to explore the role for any shared genetics between OA and other RMDs. METHODS: In 59,970 Swedish twins aged 35 years or older, we estimated the heritability (the variance explained by genetic factors) of OA in peripheral joints, back and neck pain, shoulder pain (adhesive capsulitis, impingement syndrome, etc), rheumatoid arthritis, spondyloarthritis (SpA) and psoriatic arthritis, myalgia, and osteoporosis diagnosed in specialist and inpatient care. We also studied how much covariance between OA and each of the RMDs could be explained by genetics by studying phenotypic correlations in bivariate classical twin models. RESULTS: Any-site OA and hip OA (50% and 64%) were among the most heritable RMDs (as compared with 23% for fibromyalgia [lowest] and 63% for SpA [highest]). The highest phenotypic correlations were between OA (any joint site) and shoulder pain in the same individual (r = 0.33, 95% confidence interval 0.31-0.35), of which 70% (95% confidence interval 52-88) could be explained by shared genetics. The phenotypic correlation between OA and back/neck pain was r = 0.25, with 25% to 75% explained by genetics. Phenotypic correlations between OA and each of the other RMDs were lower (r ~ 0.1 to r ~ 0.2), with inconclusive sources of variation. CONCLUSION: OA has relatively large heritability as compared with other RMDs. The coexistence of OA and shoulder pain, as well as back pain, was common and could often be explained by genetic factors. Findings imply similar etiologies of OA and several pain conditions.

Income-Related Inequality Changes in Osteoarthritis First-Line Interventions: A Cohort Study.

OBJECTIVE: To examine income-related inequality changes in the outcomes of an osteoarthritis (OA) first-line intervention. DESIGN: Retrospective cohort study. SETTING: Swedish health care system. PARTICIPANTS: We included 115,403 people (age: 66.2±9.7 years; females 67.8%; N=115,403) with knee (67.8%) or hip OA (32.4%) recorded in the "Swedish Osteoarthritis Registry" (SOAR). INTERVENTIONS: Exercise and education. MAIN OUTCOME MEASURES: Erreygers' concentration index (E) measured income-related inequalities in "Pain intensity," "Self-efficacy," "Use of NSAIDs," and "Desire for surgery" at baseline, 3-month, and 12-month follow-ups and their differences over time. E-values range from -1 to +1 if the health variables are more concentrated among people with lower or higher income. Zero represents perfect equality. We used entropy balancing to address demographic and outcome imbalances and bootstrap replications to estimate confidence intervals for E differences over time. RESULTS: Comparing baseline to 3 months, "pain" concentrated more among individuals with lower income initially (E=-0.027), intensifying at 3 months (difference with baseline: E=-0.011 [95% CI: -0.014; -0.008]). Similarly, the "Desire for surgery" concentrated more among individuals with lower income initially (E=-0.009), intensifying at 3 months (difference with baseline: E=-0.012 [-0.018; -0.005]). Conversely, "Self-efficacy" concentrated more among individuals with higher income initially (E=0.058), intensifying at 3 months (difference with baseline: E=0.008 [0.004; 0.012]). Lastly, the "Use of NSAIDs" concentrated more among individuals with higher income initially (E=0.068) but narrowed at 3 months (difference with baseline: E=-0.029 [-0.038; -0.021]). Comparing baseline with 12 months, "pain" concentrated more among individuals with lower income initially (E=-0.024), intensifying at 12 months (difference with baseline: E=-0.017 [-0.022; -0.012]). Similarly, the "Desire for surgery" concentrated more among individuals with lower income initially (E=-0.016), intensifying at 12 months (difference with baseline: E=-0.012 [-0.022; -0.002]). Conversely, "Self-efficacy" concentrated more among individuals with higher income initially (E=0.059), intensifying at 12 months (difference with baseline: E=0.016 [0.011; 0.021]). The variable 'Use of NSAIDs' was not recorded in the SOAR at 12-month follow-up. CONCLUSION: Our results highlight the increase of income-related inequalities in the SOAR over time.

Arthroscopic partial meniscectomy for the degenerative meniscus tear: a comparison of patients included in RCTs and prospective cohort studies.

BACKGROUND AND PURPOSE: Concerns exist regarding the generalizability of results from randomized controlled trials (RCTs) evaluating arthroscopic partial meniscectomy (APM) to treat degenerative meniscus tears. It has been suggested that study populations are not representative of subjects selected for surgery in daily clinical practice. Therefore, we aimed to compare patients included in trials and prospective cohort studies that received APM for a degenerative meniscus tear. PATIENTS AND METHODS: Individual participant data from 4 RCTs and 2 cohort studies undergoing APM were collected. 1,970 patients were analyzed: 605 patients included in RCTs and 1,365 included in the cohorts. We compared patient and disease characteristics, knee pain, overall knee function, and health-related quality of life at baseline between the RCT and cohort groups using standardized differences, ratios comparing the variance of continuous covariates, and graphical methods such as quantile-quantile plots, side-by-side boxplots, and non-parametric density plots. RESULTS: Differences between RCT and the cohort were observed primarily in age (younger patients in the cohort; standardized difference: 0.32) and disease severity, with the RCT group having more severe symptoms (standardized difference: 0.38). While knee pain, overall knee function, and quality of life generally showed minimal differences between the 2 groups, it is noteworthy that the largest observed difference was in knee pain, where the cohort group scored 7 points worse (95% confidence interval 5-9, standardized difference: 0.29). CONCLUSION: Patients in RCTs were largely representative of those in cohort studies regarding baseline scores, though variations in age and disease severity were observed. Younger patients with less severe osteoarthritis were more common in the cohort; however, trial participants still appear to be broadly representative of the target population.

Proteomic profiling of human menisci from mild joint degeneration and end-stage osteoarthritis versus healthy controls.

Objective: To gain new insight into the molecular changes of the meniscus by comparing the proteome profiles of healthy controls with mild degeneration and end-stage osteoarthritis (OA). Method: We obtained tissue plugs from lateral and medial menisci of 37 individuals (central part of the posterior horn) classified as healthy (n â€‹= â€‹12), mild signs of joint damage (n â€‹= â€‹13) and end-stage OA (n â€‹= â€‹12). The protein profile was analysed by nano-liquid chromatography-mass spectrometry using data-independent acquisition and quantified by Spectronaut. Linear-mixed effects modelling was applied to extract the between-group comparisons. Results: A similar protein profile was observed for the mild group as compared to healthy controls while the most different group was end-stage OA mainly for the medial compartment. When a pattern of gradual change in protein levels from healthy to end-stage OA was required, a 42-proteins panel was identified, suggesting a potential role in OA development. The levels of QSOX1 were lower and G6PD higher in the mild group following the proposed protein abundance pattern. Qualitative protein changes suggest lower levels of CYTL1 as a potential biomarker of early joint degradation. Conclusion: For future targeted proteomic approaches, we propose a candidate panel of 42 proteins based on gradually altered meniscal posterior horn protein abundance patterns associated with joint degradation.

Sensitivity of simulated knee joint mechanics to selected human and bovine fibril-reinforced poroelastic material properties.

Fibril-reinforced poroviscoelastic material models are considered state-of-the-art in modeling articular cartilage biomechanics. Yet, cartilage material parameters are often based on bovine tissue properties in computational knee joint models, although bovine properties are distinctly different from those of humans. Thus, we aimed to investigate how cartilage mechanical responses are affected in the knee joint model during walking when fibril-reinforced poroviscoelastic properties of cartilage are based on human data instead of bovine. We constructed a finite element knee joint model in which tibial and femoral cartilages were modeled as fibril-reinforced poroviscoelastic material using either human or bovine data. Joint loading was based on subject-specific gait data. The resulting mechanical responses of knee cartilage were compared between the knee joint models with human or bovine fibril-reinforced poroviscoelastic cartilage properties. Furthermore, we conducted a sensitivity analysis to determine which fibril-reinforced poroviscoelastic material parameters have the greatest impact on cartilage mechanical responses in the knee joint during walking. In general, bovine cartilage properties yielded greater maximum principal stresses and fluid pressures (both up to 30%) when compared to the human cartilage properties during the loading response in both femoral and tibial cartilage sites. Cartilage mechanical responses were very sensitive to the collagen fibril-related material parameter variations during walking while they were unresponsive to proteoglycan matrix or fluid flow-related material parameter variations. Taken together, human cartilage material properties should be accounted for when the goal is to compare absolute mechanical responses of knee joint cartilage as bovine material parameters lead to substantially different cartilage mechanical responses.

Two-year MRI-defined structural damage and patient-reported outcomes following surgery or exercise for meniscal tears in young adults.

OBJECTIVE: To investigate potential differences in structural knee joint damage assessed by MRI and patient-reported outcomes (PROMs) at 2-year follow-up between young adults randomised to early surgery or exercise and education with optional delayed surgery for a meniscal tear. METHODS: A secondary analysis of a multicentre randomised controlled trial including 121 patients (18-40 years) with an MRI-verified meniscal tear. For this study, only patients with 2-year follow-up were included. The main outcomes were the difference in worsening of structural knee damage, assessed by MRI using the Anterior Cruciate Ligament OsteoArthrits Score, and the difference in change in the mean score of four Knee Injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sport and recreation, and quality of life, from baseline to 2 years. RESULTS: In total, 82/121 (68%) patients completed the 2-year follow-up (39 from the surgical group and 43 from the exercise group). MRI-defined cartilage damage had developed or progressed in seven (9.1%) patients and osteophytes developed in two (2.6%) patients. The worsening of structural damage from baseline to 2-year follow-up was similar between groups. The mean (95% CI) adjusted differences in change in KOOS4 between intervention groups from baseline to 2 years was -1.4 (-9.1, 6.2) points. The mean improvement in KOOS4 was 16.4 (10.4, 22.4) in the surgical group and 21.5 (15.0, 28.0) in the exercise group. No between group differences in improvement were found in the KOOS subscales. CONCLUSIONS: The 2-year worsening of MRI-defined structural damage was limited and similar in young adult patients with a meniscal tear treated with surgery or exercise with optional delayed surgery. Both groups had similar clinically relevant improvements in KOOS4, suggesting the choice of treatment strategy does not impact 2-year structural knee damage or PROMs. TRIAL REGISTRATION NUMBER: NCT02995551.

Use of non-surgical treatments on the journey to knee replacement in patients with knee osteoarthritis: a 10-year population-based case-control study.

AIM: To investigate temporal trends in primary care visits, physiotherapy visits, dispensed non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in knee osteoarthritis (OA) patients who have and have not undergone knee replacement. METHODS: We analysed 5665 OA patients from the Skåne Healthcare Register, Sweden, who underwent knee replacement between 2015 and 2019. Controls were OA patients without knee replacement, matched 1:1 by sex, age, time and healthcare level of initial OA diagnosis, and assigned a pseudo-index date corresponding to their case's knee replacement date. Annual prevalence and prevalence ratio of primary care and physiotherapy visits, dispensed NSAIDs and opioids (all for any cause) in the 10 years before knee replacement were estimated using Poisson regression. RESULTS: The annual prevalence of all-cause primary care visits, physiotherapy visits and opioid use was similar between cases and controls until 3 years before the index date when it started to increase among the cases. The year before the index date, the prevalence ratio (cases vs controls) for physiotherapy use was 1.8 (95% CI 1.7, 1.8), while for opioid use 1.6 (1.5, 1.7). NSAID use was consistently higher among cases, even 10 years before the index date when the prevalence ratio versus controls was 1.3 (1.2, 1.3), increasing to 1.8 (1.7, 1.9) in the year preceding the index date. CONCLUSIONS: Management of OA patients who have and have not undergone knee replacement appears largely similar except for higher use of NSAIDs in knee replacement cases. Symptomatic treatments start to increase a few years before the surgery in knee replacement cases.

Opioid dispensing in relation to arthroscopic knee surgery in Denmark from 2006 to 2018.

INTRODUCTION: In the US, opioids are commonly prescribed after arthroscopic knee surgery. We aimed to investigate opioid dispensing in relation to arthroscopic knee surgeries from 2006 to 2018 in Denmark. METHODS: In Danish registries, we identified patients (≥ 15 years old) having arthroscopic knee surgery (anterior cruciate ligament (ACL) reconstruction; meniscal surgery; cartilage resection; synovectomy and diagnostic arthroscopy) between 1 January 2006 and 31 December 2018 and opioid dispensing (oral morphine equivalents (OMEQ)) within seven days after discharge from surgery. RESULTS: Among 218,940 patients, 15,263 (7%) had an opioid dispensed within seven days after being discharged following surgery. The opioid dispensing incidence (per 1,000 persons/year) increased during the study period for all procedures. This trend was more pronounced for ACL reconstruction, which recorded an increase from 86 (95% confidence interval (CI): 75-99) in 2006 to 278 (95% CI: 255-301) in 2018, corresponding to 9% and 28% of ACL patients, respectively. In the same period, the average amount of opioids dispensed within the first seven days after discharge decreased (change: 70.0 OMEQ (95% CI: 12.4-127.5)). Tramadol and oxycodone were the most commonly dispensed opioids. CONCLUSION: About 7% of patients had an opioid dispensed within the first seven days after discharge following arthroscopic knee surgery. The incidence of opioids dispensed increased for all investigated procedures from 2006 to 2018. In the same period, the average amount of opioids dispensed within the first seven days after discharge decreased. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Comorbidity in incident osteoarthritis cases and matched controls using electronic health record data.

BACKGROUND: Comorbidities are common in patients with osteoarthritis (OA). This study aimed to determine the association of a wide range of previously diagnosed comorbidities in adults with newly diagnosed OA compared with matched controls without OA. METHODS: A case-control study was conducted. The data were derived from an electronic health record database that contains the medical records of patients from general practices throughout the Netherlands. Incident OA cases were defined as patients with one or more diagnostic codes recorded in their medical records that correspond to knee, hip, or other/peripheral OA. Additionally, the first OA code had to be recorded between January 1, 2006, and December 31, 2019. The date of cases' first OA diagnosis was defined as the index date. Cases were matched (by age, sex, and general practice) to up to 4 controls without a recorded OA diagnosis. Odds ratios were derived for each 58 comorbidities separately by dividing the comorbidity prevalence of cases by that of their matched controls at the index date. RESULTS: 80,099 incident OA patients were identified of whom 79,937 (99.8%) were successfully matched with 318,206 controls. OA cases had higher odds for 42 of the 58 studied comorbidities compared with matched controls. Musculoskeletal diseases and obesity showed large associations with incident OA. CONCLUSIONS: Most of the comorbidities under study had higher odds in patients with incident OA at the index date. While previously known associations were confirmed in this study, some associations were not described earlier.