Publications by authors named "Martin Englund"

177 Publications

Agreement Between Clinical Examination and Magnetic Resonance Imaging in Acute Knee Trauma With Hemarthrosis.

Clin J Sport Med 2021 Jun 9. Epub 2021 Jun 9.

Department of Orthopaedics, NU-Hospital Group, Uddevalla/Trollhättan, Sweden; Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden; and Department of Orthopaedics, Helsingborg Hospital, Helsingborg, Sweden.

Objective: Hemarthrosis after knee trauma often indicates serious joint injury. Few studies have evaluated agreement between clinical examination and findings from magnetic resonance imaging (MRI). We aimed to describe the agreement between acute clinical examination and subacute MRI findings after acute knee trauma with hemarthrosis and the importance of the subspecialty of the examiner.

Design: Longitudinal cohort study. Agreement with MRI findings was evaluated by logistic regression.

Setting: Helsingborg hospital.

Patients: Thousand one hundred forty-five consecutive patients with hemarthrosis after knee trauma.

Interventions: Clinical examination and MRI.

Main Outcome Measures: agreement between clinical examination and findings from MRI. We considered the radiologist's report as the gold standard.

Results: Median time (25th, 75th percentile) from injury to clinical examination was 2 (1, 7) days, and from injury to imaging was 8 (5, 15) days. The overall sensitivity and specificity of clinical examination versus MRI for major ligament injury or lateral patella dislocation (LPD) were 70% [95% confidence interval 67-73) and 66% (61-72), respectively. Orthopedic subspecialist knee had the highest agreement with anterior cruciate ligament rupture (adjusted odds ratios were 1.7 (95% confidence interval 1.2-2.3), 1.9 (1.2-3.0) and 5.9 (3.7-9.5) for orthopedic trainees, orthopedic subspecialists other, and orthopedic subspecialist knee, respectively]. For other ligament injuries and LPD, we did not find statistically significant differences.

Conclusions: Clinical diagnosis after acute knee injury is relatively unreliable versus MRI findings even when performed by orthopedic specialists. However, the agreement is improved when the examination is performed by an orthopedic knee subspecialist.
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http://dx.doi.org/10.1097/JSM.0000000000000950DOI Listing
June 2021

Risk of comorbidities following physician-diagnosed knee or hip osteoarthritis: a register-based cohort study.

Arthritis Care Res (Hoboken) 2021 Jun 4. Epub 2021 Jun 4.

Clinical Epidemiology Unit, Orthopedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.

Objective: To estimate the risk of developing comorbidities in patients after physician-diagnosed knee or hip osteoarthritis (OA).

Design: Cohort study using Swedish longitudinal healthcare register data; we studied residents in the Skåne region aged ≥35 years at January 1, 2010 free from diagnosed hip or knee OA (n= 548,681). We then identified subjects with at least one new diagnosis of knee or hip OA (incident OA) between 2010 and 2017 (n=50,942 considered exposed). Subjects without diagnosed OA were considered unexposed. From January 2010 both unexposed and exposed subjects were observed for the occurrence of 18 different pre-defined comorbidities until either relocation outside of the region, death, occurrence of the comorbidity, or December 2017, whichever came first. We calculated unadjusted and adjusted hazard ratios (HR, aHR) of comorbidities using Cox models with knee and hip OA as time-varying exposures.

Results: Subjects with incident knee or hip OA had 7% to 60% higher adjusted hazards (aHR between 1.07 to 1.60), of depression, cardiovascular diseases, back pain, and osteoporosis than individuals without an OA diagnosis. An increased risk of diabetes was found only for knee OA (aHR 1.19, 95% CI 1.13-1.26). For the rest of the diagnoses, we found either no increased risk or estimates with wide confidence intervals, excluding clear interpretations of the direction or size of effects.

Conclusions: Incident physician-diagnosed knee and hip OA is associated with increased risk of depression, cardiovascular diseases, back pain, osteoporosis, and diabetes. However, the latter only for knee OA.
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http://dx.doi.org/10.1002/acr.24717DOI Listing
June 2021

What Are the Patient-reported Outcomes of Trapeziectomy and Tendon Suspension at Long-term Follow-up?

Clin Orthop Relat Res 2021 05 20. Epub 2021 May 20.

J. M. Wolf, I. Atroshi, Department of Clinical Sciences Lund - Orthopedics, Lund University, Lund, Sweden.

Background: There are multiple options for the treatment of thumb carpometacarpal joint osteoarthritis (CMC1 OA), with evidence for pain relief and improved function. Although simple trapeziectomy has the lowest complication risk, tendon suspension of the first metacarpal and interposition is still the most commonly used surgical procedure in patients with CMC1 OA. Although there are several reports of good short-term results after trapeziectomy and tendon suspension-interposition arthroplasty, few studies have evaluated long-term outcomes. This study is one of the largest and longest follow-up evaluations of a cohort of patients with CMC1 OA who were treated with trapeziectomy and suspension-interposition arthroplasty, capturing 96% of the original cohort for evaluation.

Questions/purposes: (1) After trapeziectomy and tendon suspension surgery, what are the long-term, patient-reported outcomes and clinical measurements (strength and ROM); and in unilateral procedures, how do these parameters compare with those of the contralateral hand that was not operated on? (2) What is the mean subsidence (unloaded trapezial space), and does pinch strength correlate with the amount of subsidence?

Methods: From 1998 to 2005, 130 patients underwent trapeziectomy and abductor pollicis longus (APL) suspension-interposition arthroplasty for CMC1 OA at one orthopaedic department. During this period, 15 patients were treated with CMC1 arthrodesis and four were treated with implant arthroplasty, for a total of 149 patients. The surgeons used APL suspensionplasty for most patients, based on age and expected postoperative function; they also employed this procedure to avoid hardware or implant failure issues. The 100 living patients were asked to participate in this retrospective study, 96% (96) of whom were enrolled. The mean age at surgery was 58 ± 7 years. The patients completed a two-item thumb pain scale (modified from the SF-36 body pain scale), a hand pain VAS (average level of pain experienced over the week preceding measurement), and the 11-item QuickDASH. Patient-reported outcomes data were obtained from all 96 patients, and 83% (80) of patients underwent bilateral hand radiography and a physical examination at a mean follow-up of 17 ± 2.4 years. We calculated outcome data for each patient, and in 39 patients with unilateral surgery and intact contralateral CMC1 joint, we compared the operated side with the contralateral side. We compared our outcome data with that from the Swedish National Quality Registry for Hand Surgery (HAKIR), noting comparable outcomes for pain and QuickDASH scores.

Results: At long-term follow-up after trapeziectomy and APL suspension surgery, the mean thumb pain score was 19 ± 26, hand pain VAS score 23 ± 25, and QuickDASH score 26 ± 21. In the patients with unilateral surgery and intact contralateral CMC1 joint, the thumb pain score for the operated side was lower than the contralateral side, specifically 19 ± 25 compared with 29 ± 30 (mean difference -9.8 [95% CI -19.5 to -0.2]; p = 0.045); hand pain VAS score was 24 ± 23 versus 30 ± 25 (mean difference -6.1 [95% CI -15.2 to 3.1]; p = 0.19), and the QuickDASH score was 27 ± 19. Grip strength showed no differences between the operated and contralateral sides (mean 16.7 ± 7.3 kg versus 16.6 ± 6.9 kg, mean difference 0.1 [95% CI -1.6 to 1.8]; p = 0.90), while pinch was different (4.4 ± 1.4 versus 5.0 ± 1.5 kg, mean difference -0.6 [95% CI -0.9 to -0.3]; p = 0.001). The mean trapezial space was 4.4 ± 2.2 mm, and there was no association between the trapezial space and pinch strength (0.07 kg [95% CI -0.04 to 0.18] per mm of space; p = 0.17).

Conclusion: The finding of comparable pain and function between operated and unoperated sides at long-term follow-up suggests that trapeziectomy and tendon suspension-interposition arthroplasty provides predictable outcomes, and surgeons can use these data to counsel patients that surgery can potentially return them to comparable use. However, as patients often have asymptomatic radiographic OA on the contralateral side, future studies are needed to examine the impact of asymptomatic disease on function.

Level Of Evidence: Level IV, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000001795DOI Listing
May 2021

ProteoMill: Efficient network-based functional analysis portal for proteomics data.

Bioinformatics 2021 May 12. Epub 2021 May 12.

Faculty of Medicine, Department of Clinical Sciences Lund, Rheumatology and Molecular Skeletal Biology, Lund University, Lund, Sweden.

Summary: Functional analysis has become a common approach to incorporate biological knowledge into the analysis of omics data, and to explore molecular events that govern a disease state. It is though only one step in a wider analytical pipeline that typically requires use of multiple individual analysis software. There is currently a need for a well-integrated omics analysis tool that performs all the steps. The ProteoMill portal is developed as an R Shiny application and integrates all necessary steps from data-upload, converting identifiers, to quality control, differential expression and network-based functional analysis into a single fast, interactive easy to use workflow. Further, it maintains annotation data sources up to date, overcoming a common problem with use of outdated information, and seamlessly integrates multiple R-packages for an improved user-experience. The functionality provided in this software can benefit researchers by facilitating the exploratory analysis of proteomics data.

Availability: ProteoMill is available at https://proteomill.com.
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http://dx.doi.org/10.1093/bioinformatics/btab373DOI Listing
May 2021

Relating MR relaxation times of meniscus to tissue degeneration through comparison with histopathology.

Osteoarthr Cartil Open 2020 Jun 3;2(2). Epub 2020 Apr 3.

Clinical Epidemiology Unit, Orthopedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.

Background: Quantitative magnetic resonance imaging (MRI), e.g. relaxation parameter mapping, may be sensitive to structural and compositional tissue changes, and could potentially be used to non-invasively detect and monitor early meniscus degeneration related to knee osteoarthritis.

Objective: To investigate MR relaxation times as potential biomarkers for meniscus degeneration through comparisons with histopathology.

Methods: We measured MR relaxation parameters in the posterior horn of 40 menisci (medial and lateral) at a wide range of degenerative stages. T1, T2 and T2* were mapped using standard and ultrashort echo time sequences at 9.4 T and compared to gold standard histology using Pauli's histopathological scoring system, including assessment of surface integrity, collagen organization, cellularity and Safranin-O staining.

Results: All three relaxation times increased with total Pauli score (mean difference per score (95% CI) for T2*: 0.62 (0.37, 0.86), T2: 0.83 (0.53, 1.1) and T1: 24.7 (16.5, 32.8) ms/score). Clear associations were seen with scores of surface integrity (mean difference per score for T2*: 3.0 (1.8, 4.2), T2: 4.0 (2.5, 5.5) and T1: 116 (75.6, 156) ms/score) and collagen organization (mean difference between highest and lowest score for T2*: 5.3 (1.6, 8.9), T2: 6.1 (1.7, 11) and T1: 204 (75.9, 332) ms). The results were less clear for the remaining histopathological measures.

Conclusions: MR relaxation times T1, T2 and T2* of human menisci are associated with histologically verified degenerative processes, in particular related to surface integrity and collagen organization. If confirmed MR relaxation times may thus be potential biomarkers for meniscus degeneration.
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http://dx.doi.org/10.1016/j.ocarto.2020.100061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610736PMC
June 2020

Less improvement following meniscal repair compared with arthroscopic partial meniscectomy: a prospective cohort study of patient-reported outcomes in 150 young adults at 1- and 5-years' follow-up.

Acta Orthop 2021 Apr 30:1-8. Epub 2021 Apr 30.

Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.

Background and purpose - Meniscal repair may reduce long-term risk of knee osteoarthritis compared with arthroscopic partial meniscectomy (APM), whereas patient-reported outcomes may be poorer at short term than for APM. We compared patient-reported outcomes in young adults undergoing meniscal repair or APM up to ∼5 years after surgery.Patients and methods - We included 150 patients aged 18-40 years from the Knee Arthroscopy Cohort Southern Denmark (KACS) undergoing meniscal repair or APM. Between-group differences in change in a composite of 4 of 5 Knee injury and Osteoarthritis Outcome Score (KOOS) subscales (pain, symptoms, sport and recreation, and quality of life-KOOS) from baseline, 12, and 52 weeks, and a median of 5 years (range 4-6 years) were analyzed using adjusted mixed linear models, with 52 weeks being the primary endpoint.Results - 32 patients had meniscal repair (mean age 26 [SD 6]), and 118 patients underwent APM (mean age 32 [SD 7]). The repair and APM groups improved in KOOS from before to 52 weeks after surgery (least square means 7 and 19, respectively; adjusted mean difference -12, [95% CI -19 to -4] in favor of APM). Both groups improved further from 52 weeks to 5 years after surgery with the difference in KOOS scores between the groups remaining similar.Interpretation - Patients having meniscal repair experienced less improvements in patient-reported outcomes from baseline to 52 weeks and 5 years post-surgery. The findings highlight the need for randomized trials comparing these interventions in terms of patient-reported outcomes and knee OA development.
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http://dx.doi.org/10.1080/17453674.2021.1917826DOI Listing
April 2021

Socioeconomic inequalities in all-cause and cause-specific mortality among patients with osteoarthritis in the Skåne region, Sweden.

Arthritis Care Res (Hoboken) 2021 Apr 3. Epub 2021 Apr 3.

Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Clinical Epidemiology Unit, Sweden.

Objective: To assess the association between education and all-cause and cause-specific mortality among patients with osteoarthritis (OA) in comparison to an OA-free reference cohort.

Methods: Using data from the Skåne healthcare register, we identified all residents aged ≥45 years in the region of Skåne, with doctor-diagnosed OA of peripheral joints between 1998 and 2013 (n=123,993). We created an age and sex-matched reference cohort without OA diagnosis (n=121,318). Subjects were followed until death, relocation outside Skåne, or the end of 2014. The relative index of inequality (RII) and the slope index of inequality (SII) were estimated by the Cox model and Aalen´s additive hazard model, respectively.

Results: We found an inverse association between education and mortality. The magnitude of relative inequalities in all-cause mortality were comparable in the OA (RII 1.53, 95% CI:1.46, 1.61) and reference cohorts (RII:1.54, 95% CI:1.47, 1.62). The absolute inequalities were smaller in the OA (SII 937 all-cause deaths per 100,000 person-years, 95% CI:811, 1063) compared with the reference cohort (SII 1265, 95% CI:1109, 1421). Cardiovascular mortality contributed more to the absolute inequalities in the OA than in the reference cohort (60.1% vs. 48.1%) while the opposite was observed for cancer mortality (8.5% vs. 22.3%).

Conclusion: We found higher all-cause and cause-specific mortality in OA patients with lower education. The observed inequalities in the OA cohort reflect the inequalities in the population at large. The greater burden of cardiovascular diseases in OA patients suggests that proper management of cardiovascular risk factors in OA patients is important.
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http://dx.doi.org/10.1002/acr.24613DOI Listing
April 2021

Epidemiology of biopsy-confirmed giant cell arteritis in southern Sweden - an update on incidence and first prevalence estimate.

Rheumatology (Oxford) 2021 Mar 18. Epub 2021 Mar 18.

Department of Clinical Sciences Lund, Rheumatology, Lund University, Sweden.

Objective: To characterize the epidemiology of temporal artery biopsy-positive (TAB+) giant cell arteritis (GCA), including trends in incidence, seasonal variation, and prevalence in Skåne, the southernmost region of Sweden.

Methods: All histopathology reports of TABs from 1997 through 2019 were reviewed to identify patients diagnosed with TAB+ GCA. Incidence rates based on the 23-year period and the point-prevalence at 31 December, 2014 were determined. An alternative prevalence calculation included only TAB+ GCA patients living in the study area and receiving immunosuppressant therapy on the point-prevalence date.

Results: 1360 patients were diagnosed with TAB+ GCA (71% female). The average annual incidence 1997-2019 was 13.3 (95% CI 12.6-14.0) per 100 000 inhabitants aged ≥50 years and was higher in females (17.8; 95% CI 16.7-18.9) than in males (8.2; 95% CI 7.4-9.0). The age- and sex- standardized incidence declined from 17.3 in 1997-8.7 in 2019, with incidence ratio (IR) of 0.98 per year (95% CI 0.98-0.99). A seasonal variation was observed with higher incidence during spring than winter [IR 1.19 (95% CI 1.03-1.39)]. The overall point-prevalence of TAB+ GCA was 127.1 per 100 000 (95% CI 117-137.3) and was 75.5 (95% CI 67.7-83.3) when including only patients receiving immunosuppressants.

Conclusions: Over the past two decades, the incidence of biopsy-confirmed GCA has decreased by ∼2% per year. Still, a high prevalence of GCA on current treatment was observed. More cases are diagnosed during spring and summer than in the winter.
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http://dx.doi.org/10.1093/rheumatology/keab269DOI Listing
March 2021

Factors associated with longitudinal change of meniscal extrusion in overweight women without clinical signs of osteoarthritis.

Rheumatology (Oxford) 2021 Mar 10. Epub 2021 Mar 10.

Dept. of General Practice, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.

Objectives: To identify variables associated with longitudinal change in meniscal extrusion, which might be used as possible targets for knee osteoarthritis (KOA) prevention.

Methods: In a high-risk population of middle-aged overweight women, meniscal extrusion was assessed with magnetic resonance imaging (1.5 T, coronal proton density, in-plane resolution 0.5 mm2, Sante DICOM Editor) at baseline and after 30 months. Outcomes were the absolute change in medial and lateral extrusion (mm) and relative change in extrusion (%). Based upon literature, eleven factors were hypothesized to be associated with longitudinal change. Generalized estimating equations were used to model the effect on meniscal change (p< 0.05).

Results: 677 knees of 343 women were available for analysis, with a mean age of 55.7 years (+/- 3.2) and a mean body mass index (BMI) of 32.3 kg/m2 (+/- 4.2). The greatest change in meniscal extrusion appeared medially with incident meniscal tear (4.4%; absolute 0.9 mm (95% CI: 0.3, 1.5; p= 0.004); relative 14.5% (4.4, 24.7; 0.005)). Varus malalignment was associated with an increase of medial extrusion of 0.6 mm (37.6%; 0.1, 1.0; 0.009)). A 5 kg/m2 higher baseline BMI was associated with absolute and relative increase of medial extrusion of 0.2 mm and 2.96% (0.1, 0.3; <0.001 and 1.3, 4.8; 0.002). Less explicit but significant changes in extrusion appeared with longitudinal change in BMI.

Conclusion: Meniscal tears, varus malalignment and BMI were significantly associated with change in meniscal extrusion in middle-aged overweight women, providing viable therapeutic targets to prevent or reduce extrusion and thereby decelerate KOA development.
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http://dx.doi.org/10.1093/rheumatology/keab228DOI Listing
March 2021

Development of MRI-defined Structural Tissue Damage after Anterior Cruciate Ligament Injury over 5 Years: The KANON Study.

Radiology 2021 05 9;299(2):383-393. Epub 2021 Mar 9.

From the Department of Radiology, Friedrich-Alexander University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany (F.W.R.); Quantitative Imaging Center, Department of Radiology, Boston University School of Medicine, FGH Building, 4th Floor, 820 Harrison Avenue, Boston, MA 02118 (F.W.R., A.G.); Department of Clinical Sciences Lund, Orthopaedics (F.W.R., L.S.L., R.F.), and Clinical Epidemiology Unit, Orthopaedics, Department of Clinical Sciences Lund (M.E.), Lund University, Lund, Sweden; Department of Radiology, VA Boston Healthcare System, West Roxbury, Mass (A.G.); and Clinical Studies Sweden-Forum South, Skåne University Hospital, Lund, Sweden (A.Å.).

Background MRI is used to evaluate structural joint changes after anterior cruciate ligament (ACL) injury, but no long-term data are available for comparing different treatment approaches. Purpose To describe structural joint damage with MRI over a 5-year period in the Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON) study and to compare frequencies of such tissue damage for a nonsurgical versus a surgical treatment strategy. Materials and Methods In this secondary analysis of a prospective trial (ISRCTN 84752559), 119 participants with an acute ACL injury were evaluated. Participants were enrolled from 2002 through 2006, the 2-year follow-up started in 2008, and the 5-year follow-up started in 2011. A 1.5-T MRI examination was performed at baseline and at 2- and 5-year follow-up. MRI scans were read according to a validated scoring instrument. Kruskal-Wallis tests were used to assess whether the frequencies of structural damage differed between the three as-treated groups. Results Of 119 participants (mean age, 26 years ± 5 [standard deviation]), 91 men were evaluated. At 2- and 5-year follow-up, respectively, 13% (15 of 117) and 13% (15 of 115) of knees showed incident cartilage damage in the medial tibiofemoral joint, 11% (13 of 117) and 17% (20 of 115) of knees showed incident cartilage damage in the lateral tibiofemoral joint, and 4% (five of 117) and 8% (nine of 115) of knees showed incident cartilage damage in the patellofemoral joint. Osteophyte development was seen in 23% (27 of 117) and 29% (33 of 115) of knees in the medial tibiofemoral joint, in 36% (42 of 117) and 43% (49 of 115) of knees in the lateral tibiofemoral joint, and in 35% (41 of 117) and 37% (42 of 115) of knees in the patellofemoral joint. No major differences between the groups were found for incident or worsening cartilage damage, bone marrow lesions, and osteophytes at 2 or 5 years. The rehabilitation-alone group showed less Hoffa-synovitis at 2 ( = .02) and 5 ( = .008) years. Conclusion Young adults with anterior cruciate ligament injury showed no major difference in frequency of structural tissue damage on MRI scans at 2 and 5 years regardless of treatment. However, the rehabilitation-alone group had less inflammation at 2 and 5 years. © RSNA, 2021 See also the editorial by Andreisek in this issue.
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http://dx.doi.org/10.1148/radiol.2021202954DOI Listing
May 2021

Trajectory of Healthcare Resource Utilization in Giant Cell Arteritis: A Population-based Study.

J Rheumatol 2021 Mar 1. Epub 2021 Mar 1.

This study was supported by grants from the Swedish Research Council (Vetenskapsrådet: 2019-01655), Stiftelsen Konung Gustaf V:s 80-årsfond, Alfred Österlunds Foundation, and Swedish Medical Association (Svenska Läkarsällskapet). A.J. Mohammad, MD, MPH, PhD, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, and Department of Medicine, University of Cambridge, Cambridge, UK; A. Turkiewicz, PhD, M. Englund, MD, PhD, Clinical Epidemiology Unit, Lund University, Lund, Sweden; P. Stamatis, MD, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden; C. Turesson, MD, PhD, Department of Clinical Sciences, Rheumatology, Lund University, Malmö, Sweden; A. Kiadaliri, PhD, Clinical Epidemiology Unit, and Centre for Economic Demography, Lund University, Lund, Sweden. There are no competing interests for any of the authors. Address correspondence to Dr. A.J. Mohammad, Department of Rheumatology, Skåne University Hospital, 221 85 Lund, Sweden. Email: Accepted for publication February 17, 2021.

Objective: To estimate the healthcare resource utilization (HRU) in patients with giant cell arteritis (GCA) compared with the general population in southern Sweden.

Methods: The study sample comprised 653 patients with GCA along with 10 age-, sex-, and residency area-matched reference subjects per patient. Data on public and private healthcare consultations and hospitalizations were extracted from the Skåne Healthcare Register. We assessed trajectories of primary and specialist healthcare visits, as well as hospital admissions and inpatient days from 3 years before through 5 years after the date of GCA diagnosis for patients and matched references. HRU was analyzed using generalized estimating equations adjusted for sex, age at the index year, calendar year of diagnosis, education, income, marital status, place of birth, and Charlson Comorbidity Index. Inverse probability weighting was used to account for dropout during study.

Results: Patients with GCA had higher rates of healthcare visits than the references from the year before GCA diagnosis and up to 4 years after diagnosis, with the largest relative (rate ratio 1.85, 95% CI 1.68-2.05) and absolute (mean difference 10.2, 95% CI 8.1-12.3 visits per person) differences in the year of diagnosis. Similar trajectories were observed for primary and specialist healthcare visits. For hospital admissions and inpatient days, the differences disappeared 1 year after diagnosis date.

Conclusion: Patients with GCA utilized healthcare services at a significantly higher rate than the reference population. The increased utilization among Swedish patients with GCA was evident 1 year before and prolonged up to 4 years after diagnosis date.
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http://dx.doi.org/10.3899/jrheum.201131DOI Listing
March 2021

Osteoarthritis and risk of hospitalization for ambulatory care sensitive conditions: A general population-based cohort study.

Rheumatology (Oxford) 2021 Feb 16. Epub 2021 Feb 16.

Clinical Epidemiology Unit, Department of Clinical Sciences Lund, Orthopaedics, Lund University, Sweden, Lund.

Objective: To determine the association between osteoarthritis (OA) and risk of hospitalization for ambulatory care sensitive conditions (HACSCs).

Methods: We included all individuals aged 40-85 years who resided in Skåne, Sweden on 31st December 2005 with at least one healthcare consultation during 1998-2005 (n = 515 256). We identified those with a main diagnosis of OA between January 1, 1998 and December 31, 2016. People were followed from January 1st 2006 until an HACSC, death, relocation outside Skåne, or December 31st 2016 (whichever occurred first). OA status was treated as a time-varying covariate (those diagnosed before January 1, 2006 considered as exposed for whole study period). We assessed relative (hazard ratios (HRs) using Cox proportional hazard model) and absolute (hazard difference using additive hazard model) effects of OA on HACSCs adjusted for potential confounders.

Results: Crude incidence rates of HACSCs were 239 (95% CI 235, 242) and 151 (150, 152) per 10 000 person-years among OA and non-OA persons, respectively. The OA persons had an increased risk of HACSCs (HR [95% CI] 1.11 [1.09, 1.13]) and its subcategories of medical conditions except chronic obstructive pulmonary disease (HR [95% CI] 0.86 [0.81, 0.90]). There were 20 (95% CI 16, 24) more HACSCs per 10 000 person-years in OA compared with non-OA persons. While HRs for knee and hip OA were generally comparable, only knee OA was associated with increased risk of hospitalization for diabetes.

Conclusion: OA is associated with an increased risk of HACSCs, highlighting the urgent need to improve outpatient care for OA patients.
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http://dx.doi.org/10.1093/rheumatology/keab161DOI Listing
February 2021

Temporal relationship between osteoarthritis and comorbidities: a combined case control and cohort study in the UK primary care setting.

Rheumatology (Oxford) 2021 Jan 28. Epub 2021 Jan 28.

Academic Rheumatology, Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, UK.

Objective: To determine the burden of comorbidities in osteoarthritis (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 multimorbidity (≥2 comorbidities excluding OA) both before and after OA diagnosis were estimated, adjusting for covariates, using odds ratios (aOR) and hazard ratios (aHR) 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 SLE) were associated with OA only following the diagnosis of OA. People with OA had 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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http://dx.doi.org/10.1093/rheumatology/keab067DOI Listing
January 2021

Prevention of posttraumatic osteoarthritis at the time of injury: Where are we now, and where are we going?

J Orthop Res 2021 Jun 4;39(6):1152-1163. Epub 2021 Mar 4.

Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK.

This overview of progress made in preventing post-traumatic osteoarthritis (PTOA) was delivered in a workshop at the Orthopaedics Research Society Annual Conference in 2019. As joint trauma is a major risk factor for OA, defining the molecular changes within the joint at the time of injury may enable the targeting of biological processes to prevent later disease. Animal models have been used to test therapeutic targets to prevent PTOA. A review of drug treatments for PTOA in rodents and rabbits between 2016 and 2018 revealed 11 systemic interventions, 5 repeated intra-articular or topical interventions, and 5 short-term intra-articular interventions, which reduced total Osteoarthritis Research Society International scores by 30%-50%, 20%-70%, and 0%-40%, respectively. Standardized study design, reporting of effect size, and quality metrics, alongside a "whole joint" approach to assessing efficacy, would improve the translation of promising new drugs. A roadblock to translating preclinical discoveries has been the lack of guidelines on the design and conduct of human trials to prevent PTOA. An international workshop addressing this in 2016 considered inclusion criteria and study design, and advocated the use of experimental medicine studies to triage candidate treatments and the development of early biological and imaging biomarkers. Human trials for the prevention of PTOA have tested anakinra after anterior cruciate ligament rupture and dexamethasone after radiocarpal injury. PTOA offers a unique opportunity for defining early mechanisms of OA to target therapeutically. Progress in trial design and high-quality preclinical research, and allegiance with patients, regulatory bodies, and the pharmaceutical industry, will advance this field.
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http://dx.doi.org/10.1002/jor.24982DOI Listing
June 2021

High genetic contribution to anterior cruciate ligament rupture: Heritability ~69.

Br J Sports Med 2020 Dec 7. Epub 2020 Dec 7.

Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden.

Objectives: We aimed to determine the lifetime genetic risk for anterior cruciate ligament (ACL) rupture.

Methods: We used a twin study approach, linking the Swedish Twin Register with national healthcare data to form a 30 year, population wide, longitudinal twin cohort. We studied ACL rupture in this cohort of 88 414 identical and fraternal twins, aged ≥17 years, to determine the familial risk and heritability of ACL rupture.

Results: The incidence rate of ACL rupture was 70 (95% CI 66 to 74) per 100 000 person years. The familial risk, which is the excess risk ratio (RR) of the second twin having ACL rupture given that the first twin has had such a rupture, was higher in identical twin pairs (RR=8.6, 95% CI 6.2 to 11.0) than in fraternal twin pairs (RR=1.9, 95% CI 0.9 to 3.0). The overall heritability of ACL rupture was high, 69% (95% CI 47 to 91), increasing from 60% at age 17 years to 80% at age 60 years. Women and men had similar familial risk and heritability of ACL rupture.

Conclusion: The genetic contribution to ACL rupture of ~69% is high and suggests strong familial clustering. If clinicians recognise the high genetic risk of such injury, they may be better able to counsel athletes whose near relatives have had ACL rupture.
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http://dx.doi.org/10.1136/bjsports-2020-102392DOI Listing
December 2020

Willingness to Undergo Joint Surgery Following a First-Line Intervention for Osteoarthritis: Data From the Better Management of People With Osteoarthritis Register.

Arthritis Care Res (Hoboken) 2021 Jun;73(6):818-827

Lund University, Lund, Sweden.

Objective: To assess the proportion of participants reconsidering their willingness to undergo surgery after 3 and 12 months. Secondary aims were to analyze and compare the characteristics of individuals willing and unwilling to undergo joint surgery for osteoarthritis (OA) before a first-line intervention, and to study the association between pain intensity, walking difficulties, self-efficacy, and fear of movement with the willingness to undergo surgery.

Methods: This was an observational study based on Swedish register data. We included 30,578 individuals with knee or hip OA who participated in a first-line intervention including education and exercise.

Results: Individuals willing to undergo surgery at baseline showed a higher proportion of men (40% versus 27%) and more severe symptoms and disability. Respectively, 45% and 30% of the individuals with knee and hip OA who were willing to undergo surgery at baseline became unwilling after the intervention. At the end of the study period (12 months), 35% and 19% of those with knee and hip OA, respectively, who were willing to undergo surgery at baseline became unwilling. High pain intensity, walking difficulties, and fear of movement were associated with higher odds of being willing to undergo surgery at both follow-ups, while increased self-efficacy showed the opposite association.

Conclusion: A first-line intervention for OA is associated with reduced willingness to undergo surgery, with a greater proportion among patients with knee OA than hip OA. Due to its temporal variability, willingness to undergo surgery should be used with care to deem surgery eligibility.
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http://dx.doi.org/10.1002/acr.24486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251860PMC
June 2021

Complex sociodemographic inequalities in consultations for low back pain: lessons from multilevel intersectional analysis.

Pain 2021 04;162(4):1135-1143

Clinical Epidemiology Unit, Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden.

Abstract: Sociodemographic inequalities in the occurrence of low back pain (LBP) are well-studied. This study aimed to examine complex sociodemographic inequalities in the risk of LBP consultation in the population from a socioeconomical intersectional perspective. Using register data, we identified 458,852 individuals aged 35 to 75 years residing in Skåne in 2013, with no previous LBP consultation since 2006. We created 108 strata using categories of age, sex, education, income, and nativity. With individuals nested within strata, we modelled the absolute risk of LBP consultation during 2014 in a series of multilevel logistic regression models. We quantified discriminatory accuracy (DA) of these variables by computing the variance partition coefficient and area under the receiver operating characteristic curve (AUC). We identified 13,657 (3.0%) people with an LBP consultation. The absolute risk ranged from 2.1% (95% credible interval: 1.9%-2.3%) among young native men with high education and high income to 4.8% (4.3%-5.5%) among young foreign-born women with medium education and low income (2.3-fold relative difference). Discriminatory accuracy of intersectional strata was very low (variance partition coefficient 1.1% (0.7-1.6); and AUC 0.56 [0.55-0.56]). Sex (35.6%) and nativity (19.2%) had the largest contributions in explaining the initially small between-strata variation in risk of LBP. The low DA of the intersectional strata indicates the existence of limited intersectional inequalities in LBP consultation. Therefore, interventions to reduce LBP risk should be universal rather than targeted to specific socioeconomic groups with a higher average risk. Before planning targeted intervention, other risk factors with higher DA need to be identified.
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http://dx.doi.org/10.1097/j.pain.0000000000002081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977617PMC
April 2021

Arthroscopic partial meniscectomy for a degenerative meniscus tear: a 5 year follow-up of the placebo-surgery controlled FIDELITY (Finnish Degenerative Meniscus Lesion Study) trial.

Br J Sports Med 2020 Nov 27;54(22):1332-1339. Epub 2020 Aug 27.

Finnish Centre for Evidence-Based Orthopedics (FICEBO), University of Helsinki, Helsinki, Finland

Objectives: To assess the long-term effects of arthroscopic partial meniscectomy (APM) on the development of radiographic knee osteoarthritis, and on knee symptoms and function, at 5 years follow-up.

Design: Multicentre, randomised, participant- and outcome assessor-blinded, placebo-surgery controlled trial.

Setting: Orthopaedic departments in five public hospitals in Finland.

Participants: 146 adults, mean age 52 years (range 35-65 years), with knee symptoms consistent with degenerative medial meniscus tear verified by MRI scan and arthroscopically, and no clinical signs of knee osteoarthritis were randomised.

Interventions: APM or placebo surgery (diagnostic knee arthroscopy).

Main Outcome Measures: We used two indices of radiographic knee osteoarthritis (increase in Kellgren and Lawrence grade ≥1, and increase in Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing and osteophyte sum score, respectively), and three validated patient-relevant measures of knee symptoms and function (Western Ontario Meniscal Evaluation Tool (WOMET), Lysholm, and knee pain after exercise using a numerical rating scale).

Results: There was a consistent, slightly greater risk for progression of radiographic knee osteoarthritis in the APM group as compared with the placebo surgery group (adjusted absolute risk difference in increase in Kellgren-Lawrence grade ≥1 of 13%, 95% CI -2% to 28%; adjusted absolute mean difference in OARSI sum score 0.7, 95% CI 0.1 to 1.3). There were no relevant between-group differences in the three patient-reported outcomes: adjusted absolute mean differences (APM vs placebo surgery), -1.7 (95% CI -7.7 to 4.3) in WOMET, -2.1 (95% CI -6.8 to 2.6) in Lysholm knee score, and -0.04 (95% CI -0.81 to 0.72) in knee pain after exercise, respectively. The corresponding adjusted absolute risk difference in the presence of mechanical symptoms was 18% (95% CI 5% to 31%); there were more symptoms reported in the APM group. All other secondary outcomes comparisons were similar.

Conclusions: APM was associated with a slightly increased risk of developing radiographic knee osteoarthritis and no concomitant benefit in patient-relevant outcomes, at 5 years after surgery.

Trial Registration: ClinicalTrials.gov (NCT01052233 and NCT00549172).
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http://dx.doi.org/10.1136/bjsports-2020-102813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606577PMC
November 2020

The relationship between MRI features and knee pain over 6 years in knees without radiographic osteoarthritis at baseline.

Arthritis Care Res (Hoboken) 2020 Aug 2. Epub 2020 Aug 2.

Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden.

Aim: To explore whether MRI features suggestive of knee OA are associated with presence of knee pain in possible early-stage OA development.

Methods: We included 294 participants from the Osteoarthritis Initiative (mean [SD] age 50 (3) years, 50% women), with baseline Kellgren and Lawrence grade=0 in both knees, and who had all obtained knee MRIs from 4 different time points over 6 years (baseline, 24, 48 and 72 months). Using a linear mixed model (knees matched within individuals), we studied whether MRI features: meniscal body extrusion (millimeter), cartilage area loss (score 0 to 39), cartilage full thickness loss (0-16), osteophytes (0-29), meniscal integrity (0-10), bone marrow lesions (BML) including bone marrow cysts (0-20), Hoffa or effusion synovitis (absent/present) and popliteal cysts (absent/present) were associated with knee-specific pain as reported on the Knee injury and Osteoarthritis Outcomes Score (KOOS) questionnaire on 0-100 scale (worst-best).

Results: The difference in KOOS knee pain for a knee with a one unit higher score on MRI feature was: for meniscal extrusion -1.52 (95% CI -2.35,-0.69), cartilage area loss -0.23 (-0.48,0.02), cartilage full thickness loss: -1.04 (-1.58,-0.50), osteophytes -0.32 (-0.61,-0.03), meniscal integrity -0.28 (-0.58,0.02), BMLs including potential cysts -0.19 (-0.55,0.16), synovitis 0.23 (-1.14,1.60) and popliteal cysts 0.86 (-0.56,2.29).

Conclusion: Meniscal extrusion, full thickness cartilage loss and osteophytes are associated with having more knee pain. Although these features may be relevant targets for future trials, the clinical relevance of our findings is unclear because no feature was associated with a clinically important difference in knee pain.
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http://dx.doi.org/10.1002/acr.24394DOI Listing
August 2020

Infections Are Associated With Increased Risk of Giant Cell Arteritis: A Population-based Case-control Study from Southern Sweden.

J Rheumatol 2021 02 15;48(2):251-257. Epub 2020 May 15.

A.J. Mohammad, MD, MPH, PhD, Associate Professor of Rheumatology, Senior Consultant Rheumatologist, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Department of Clinical Sciences Lund, Clinical Epidemiology Unit, Lund University, Lund, Sweden, Department of Medicine, University of Cambridge, Cambridge, UK.

Objective: To investigate the association between infections and the subsequent development of giant cell arteritis (GCA) in a large population-based cohort from a defined geographic area in Sweden.

Methods: Patients diagnosed with biopsy-confirmed GCA between 2000 and 2016 were identified through the database of the Department of Pathology in Skåne, the southernmost region of Sweden. For each GCA case, 10 controls matched for age, sex, and area of residence were randomly selected from the general population. Using the Skåne Healthcare Register, we identified all infection events prior to patients' date of GCA diagnosis and controls' index date. With infection as exposure, a conditional logistic regression model was employed to estimate the OR for developing GCA. The types of infections contracted nearest in time to the GCA diagnosis/index date were identified.

Results: A total of 1005 patients with biopsy-confirmed GCA (71% female) and 10,050 controls were included in the analysis. Infections were more common among patients subsequently diagnosed with GCA compared to controls (51% vs 41%, OR 1.78, 95% CI 1.53-2.07). Acute upper respiratory tract infection (OR 1.77, 95% CI 1.47-2.14), influenza and pneumonia (OR 1.72, 95 % CI 1.35-2.19), and unspecified infections (OR 5.35, 95 % CI 3.46-8.28) were associated with GCA. Neither skin nor gastrointestinal infections showed a correlation.

Conclusion: Infections, especially those of the respiratory tract, were associated with subsequent development of biopsy-confirmed GCA. Our findings support the hypothesis that a range of infections may trigger GCA.
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http://dx.doi.org/10.3899/jrheum.200211DOI Listing
February 2021

Arthroscopic meniscectomy versus non-surgical or sham treatment in patients with MRI confirmed degenerative meniscus lesions: a protocol for an individual participant data meta-analysis.

BMJ Open 2020 03 8;10(3):e031864. Epub 2020 Mar 8.

Department of Operating Rooms, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

Introduction: Arthroscopic partial meniscectomy (APM) after degenerative meniscus tears is one of the most frequently performed surgeries in orthopaedics. Although several randomised controlled trials (RCTs) have been published that showed no clear benefit compared with sham treatment or non-surgical treatment, the incidence of APM remains high. The common perception by most orthopaedic surgeons is that there are subgroups of patients that need APM to improve, and they argue that each study sample of the existing trials is not representative for the day-to-day patients in the clinic. Therefore, the objective of this individual participant data meta-analysis (IPDMA) is to assess whether there are subgroups of patients with degenerative meniscus lesions who benefit from APM in comparison with non-surgical or sham treatment.

Methods And Analysis: An existing systematic review will be updated to identify all RCTs worldwide that evaluated APM compared with sham treatment or non-surgical treatment in patients with knee symptoms and degenerative meniscus tears. Time and effort will be spent in contacting principal investigators of the original trials and encourage them to collaborate in this project by sharing their trial data. All individual participant data will be validated for missing data, internal data consistency, randomisation integrity and censoring patterns. After validation, all datasets will be combined and analysed using a one-staged and two-staged approach. The RCTs' characteristics will be used for the assessment of clinical homogeneity and generalisability of the findings. The most important outcome will be the difference between APM and control groups in knee pain, function and quality of life 2 years after the intervention. Other outcomes of interest will include the difference in adverse events and mental health.

Ethics And Dissemination: All trial data will be anonymised before it is shared with the authors. The data will be encrypted and stored on a secure server located in the Netherlands. No major ethical concerns remain. This IPDMA will provide the evidence base to update and tailor diagnostic and treatment protocols as well as (international) guidelines for patients for whom orthopaedic surgeons consider APM. The results will be submitted for publication in a peer-reviewed journal.

Prospero Registration Number: CRD42017067240.
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http://dx.doi.org/10.1136/bmjopen-2019-031864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064080PMC
March 2020

Proteomic characterization of the normal human medial meniscus body using data-independent acquisition mass spectrometry.

J Orthop Res 2020 08 31;38(8):1735-1745. Epub 2020 Jan 31.

Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund University, Lund, Sweden.

Recent research suggests an important role of the meniscus in the development of knee osteoarthritis. We, therefore, aimed to analyze the proteome of the normal human meniscus body, and specifically to gain new knowledge on global protein expression in the different radial zones. Medial menisci were retrieved from the right knees of 10 human cadaveric donors, from which we cut a 2 mm radial slice from the mid-portion of the meniscal body. This slice was further divided into three zones: inner, middle, and peripheral. Proteins were extracted and prepared for mass spectrometric analysis using data-independent acquisition. We performed subsequent data searches using Spectronaut Pulsar and used fixed-effect linear regression models for statistical analysis. We identified 638 proteins and after statistical analysis, we observed the greatest number of differentially expressed proteins between the inner and peripheral zones (163 proteins) and the peripheral and middle zones (136 proteins), with myocilin being the protein with the largest fold-change in both comparisons. Chondroadherin was one of eight proteins that differed between the inner and middle zones. Functional enrichment analyses showed that the peripheral one-third of the medial meniscus body differed substantially from the two more centrally located zones, which were more similar to each other. This is probably related to the higher content of cells and vascularization in the peripheral zone, whereas the middle and inner zones of the meniscal body appear to be more similar to hyaline cartilage, with high levels of extracellular matrix proteins such as aggrecan and collagen type II.
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http://dx.doi.org/10.1002/jor.24602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610686PMC
August 2020

Early tibial subchondral bone texture changes after arthroscopic partial meniscectomy in knees without radiographic OA: A prospective cohort study.

J Orthop Res 2020 08 28;38(8):1819-1825. Epub 2020 Jan 28.

Tribology Laboratory, School of Civil and Mechanical Engineering, Curtin University, Australia.

Arthroscopic partial meniscectomy (APM) may lead to changes in underlying trabecular bone (TB) structure potentially promoting the development of knee joint osteoarthritis. Our aim was to investigate if there are early changes occurring in tibial subchondral TB texture in the leg undergoing medial APM compared with the unoperated non-injured contra-lateral leg. The bone texture was measured as the medial-to-lateral ratio of fractal dimensions (FD) calculated for regions selected on weight-bearing anteroposterior tibiofemoral x-rays. Twenty-one subjects before and 12 months after APM were included from 374 patients scheduled for unilateral medial APM. The medial-to-lateral ratio was calculated for horizontal, vertical, and roughest FDs respectively. Higher FD means higher bone roughness. Each FD was calculated over a range of scales using a variance orientation transform method. Mean values of medial-to-lateral horizontal FD calculated for APM knees at follow-up were higher than those at baseline. For unoperated knees the values were lower. The difference in the horizontal FD change from baseline to follow-up between APM and contra-lateral legs was 0.028 (95% CI, 0.004-0.052). The bone roughness changes may reflect the increase in peak knee adduction moment (KAM) and KAM impulse during walking reported for the same cohort in a previous study. They may also reflect early signs of osteoarthritis development and thus, we speculate that individuals with increased bone texture roughness ratio after APM might be at higher risk of knee osteoarthritis development.
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http://dx.doi.org/10.1002/jor.24593DOI Listing
August 2020

Occupational load as a risk factor for clinically relevant base of thumb osteoarthritis.

Occup Environ Med 2020 03 20;77(3):168-171. Epub 2020 Jan 20.

Clinical Sciences Lund, Orthopedics, Lund University, Lund, Sweden.

Objective: It is postulated that increased load from pinch and grasp in occupational tasks increases the risk of thumb carpometacarpal (CMC1) osteoarthritis (OA). We sought to characterise the relationship between doctor-diagnosed CMC1 OA and occupation in a large working population.

Methods: We performed a matched case-control study using a Swedish healthcare register. We identified residents aged 30-65 years in 2013 with physician-diagnosed CMC1 OA from 1998 to 2013. We matched four controls per person with CMC1 OA by age, sex, education and postcode. Swedish Standard Classification of Occupations was used to assign occupation. Occupation was categorised as light, light-moderate, moderate and heavy labour. We used conditional logistic regression to estimate ORs with 95% CIs.

Results: We identified 3462 patients with CMC1 OA and matched 13 211 controls. The mean age of the CMC1 OA group was 63 (SD 7) years, with 81% women. The ORs for CMC1 OA in men were 1.31 (95% CI 0.96 to 1.79) for light-moderate, 1.76 (95% CI 1.29 to 2.40) for moderate and 2.00 (95% CI 1.59 to 2.51) for heavy compared with light work. Women had ORs for CMC1 OA of 1.46 (95% CI 1.32 to 1.61) for light-moderate, 1.27 (95% CI 1.10 to 1.46) for moderate and 1.31 (95% CI 1.07 to 1.59) for heavy compared with light work.

Conclusions: The association between increased manual load in occupation and risk of CMC1 OA is more pronounced in men than in women, likely due to higher workload in the heavy labour category.
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http://dx.doi.org/10.1136/oemed-2019-106184DOI Listing
March 2020

Statistical analysis plan for the 5-year and 10-year follow-up assessments of the FIDELITY trial.

Trials 2020 Jan 14;21(1):76. Epub 2020 Jan 14.

Finnish Center for Evidence-Based Orthopedics (FICEBO), Department of Orthopedics and Traumatology, University of Helsinki and Helsinki University Hospital, Töölö hospital, Topeliuksenkatu 5, Building B, 00260, Helsinki, Finland.

Background: The research objectives of the 5-year and 10-year assessments in the Finnish degenerative meniscal lesion study (FIDELITY) are twofold: (1) to assess the long-term efficacy of arthroscopic partial meniscectomy (APM) in adults (age 35 to 65 years) with a degenerative meniscus tear and (2) to determine the respective effects of APM and degenerative meniscus tear on the development of radiographic and clinical knee osteoarthritis (OA).

Methods And Design: FIDELITY is an ongoing multi-center, randomized, participant and outcome assessor blinded, placebo-surgery-controlled trial in 146 patients. This statistical analysis plan (SAP) article describes the overall principles for analysis of long-term outcomes (5-year and 10-year follow up), including how participants will be included in each analysis, the primary and secondary outcomes and their respective analyses, adjustments for covariates, and the presentation of the results. In addition, we will present the planned sensitivity and subgroup analyses.

Discussion: To assess the long-term efficacy of APM on knee symptoms and function we are carrying out a long-term (5-year and 10-year) follow up of our placebo-surgery-controlled FIDELITY trial according to statistical principles outlined in detail in this document. As our second primary objective, whether APM (resection of torn meniscus tear) accelerates or delays the development of knee osteoarthritis in patients with an arthroscopically verified degenerative tear of the medial meniscus, a pre-registered follow-up is also carried out.

Trial Registration: ClinicalTrials.gov, NCT00549172 (Arthroscopy in the Treatment of Degenerative Medial Meniscus Tear). Registered on 25 October 2007 (NCT00549172). ClinicalTrials.gov, NCT01052233 (Development of Knee Osteoarthritis After Arthroscopic Partial Resection of Degenerative Meniscus Tear). Registered on 20 January 2010.
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http://dx.doi.org/10.1186/s13063-019-3833-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961384PMC
January 2020

Understanding the role of diabetes in the osteoarthritis disease and treatment process: a study protocol for the Swedish Osteoarthritis and Diabetes (SOAD) cohort.

BMJ Open 2019 12 17;9(12):e032923. Epub 2019 Dec 17.

Faculty of medicine, Department of Clinical Sciences, Orthopedics, Clinical Epidemiology Unit, Lund University, Lund, Sverige, Sweden.

Introduction: Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Metabolic comorbidities such as type II diabetes occur with a higher rate in people with OA than in the general population. Several factors including obesity, hyperglycaemia toxicity and physical inactivity have been suggested as potential links between diabetes and OA, and have been shown to negatively impact patients' health and quality of life. However, little is known on the role of diabetes in determining the outcome of non-surgical and surgical management of OA, and at the same time, how different OA interventions may affect diabetes control. Thus, the overall aim of this project is to explore (1) the impact of diabetes on the outcome of non-surgical and surgical OA treatments and (2) the impact of non-surgical and surgical OA treatments on diabetes control.

Methods And Analysis: The study cohort is based on prospectively ascertained register data on a national level in Sweden. Data from OA patients who received a first-line non-surgical intervention and are registered in the National Quality Register for Better Management of Patients with Osteoarthritis will be merged with data from the Swedish Knee and Hip Arthroplasty Registers and the National Diabetes Register. Additional variables regarding patients' use of prescribed drugs, comorbidities, socioeconomic status and cause of death will be obtained through other national health and population data registers. The linkage will be performed on an individual level using unique personal identity numbers.

Ethics And Dissemination: This study received ethical approval (2019-02570) from the Swedish Ethical Review Authority. Results from this cohort will be submitted to peer-reviewed scientific journals and reported at the leading national and international meetings in the field.
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http://dx.doi.org/10.1136/bmjopen-2019-032923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937096PMC
December 2019

Prevalence and incidence of non-gout crystal arthropathy in southern Sweden.

Arthritis Res Ther 2019 12 17;21(1):291. Epub 2019 Dec 17.

Department of Clinical Sciences, Lund, Section for Rheumatology, Lund University, Lund and Skåne University Hospital, Lund, Sweden.

Objective: To estimate the prevalence and incidence of non-gout crystal arthropathy in relation to socioeconomic factors in southern Sweden.

Methods: All patients (age ≥ 18 years) with at least one visit to a physician with the diagnosis of interest in the Skåne region (population of 1.3 million) in 1998-2014 were identified. Non-gout crystal arthropathy (ICD-10 codes M11.0-M11.9) was subclassified in four different groups: calcium pyrophosphate crystal deposition related arthropathy (CPPD), unspecified non-gout arthropathies, chondrocalcinosis, and hydroxyapatite crystal deposition disease. The crude and age-adjusted point prevalence on December 31, 2014, and the cumulative incidence during 2014 were calculated for all non-gout crystal arthropathies, CPPD, and other unspecified non-gout arthropathies overall and in relation to occupation, income, and level of education.

Results: The crude 2014 point prevalence (95% CI) and 2014 cumulative incidence (95% CI) of all non-gout crystal arthropathies were 0.23% (0.23-0.24) and 21.5 (19-25) cases/100,000 persons. Mean age (range) among all prevalent cases in 2014 was 71 (20-102) years and 56% were males. The point prevalence and cumulative incidence of CPPD were 0.09% (0.08-0.09) and 8 (7-10)/100,000 persons, respectively. The corresponding data for unspecified non-gout crystal deposition disease was 0.16% (0.16-0.17) and 15.6 (13-18)/100,000 persons, respectively. The prevalence and incidence of CPPD and unspecified non-gout crystal arthropathies were slightly higher in men and increased with age irrespective of gender. Unspecified non-gout crystal arthropathy but not CPPD was less prevalent in persons with ≥ 15 years of education, whereas there were no clear associations with occupation and income.

Conclusion: The prevalence of all diagnosed non-gout crystal arthropathies was 0.23%, thus considerably less prevalent than gout in southern Sweden. CPPD and other unspecified non-gout crystal arthropathies are the predominant diagnoses, increasing with age and in men. With the exception for unspecified non-gout crystal arthropathies being inversely correlated to a higher level of education, no convincing association with the socioeconomic factors was found.
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http://dx.doi.org/10.1186/s13075-019-2077-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918617PMC
December 2019

Risk of knee osteoarthritis after different types of knee injuries in young adults: a population-based cohort study.

Br J Sports Med 2020 Jun 11;54(12):725-730. Epub 2019 Dec 11.

Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund University, Faculty of Medicine, Lund, Sweden.

Objectives: To estimate the risk of clinically diagnosed knee osteoarthritis (OA) after different types of knee injuries in young adults.

Methods: In a longitudinal cohort study based on population-based healthcare data from Skåne, Sweden, we included all persons aged 25-34 years in 1998-2007 (n=149 288) with and without diagnoses of knee injuries according to International Classification of Diseases (ICD)-10. We estimated the HR of future diagnosed knee OA in injured and uninjured persons using Cox regression, adjusted for potential confounders. We also explored the impact of type of injury (contusion, fracture, dislocation, meniscal tear, cartilage tear/other injury, collateral ligament tear, cruciate ligament tear and injury to multiple structures) on diagnosed knee OA risk.

Results: We identified 5247 persons (mean (SD) age 29.4 (2.9) years, 67% men) with a knee injury and 142 825 persons (mean (SD) age 30.2 (3.0) years, 45% men) without. We found an adjusted HR of 5.7 (95% CI 5.0 to 6.6) for diagnosed knee OA in injured compared with uninjured persons during the first 11 years of follow-up and 3.4 (95% CI 2.9 to 4.0) during the following 8 years. The corresponding risk difference (RD) after 19 years of follow-up was 8.1% (95% CI 6.7% to 9.4%). Cruciate ligament injury, meniscal tear and fracture of the tibia plateau/patella were associated with greatest increase in risk (RD of 19.6% (95% CI 13.2% to 25.9%), 10.5% (95% CI 6.4% to 14.7%) and 6.6% (95% CI 1.1% to 12.2%), respectively).

Conclusion: In young adults, knee injury increases the risk of future diagnosed knee OA about sixfold with highest risks found after cruciate ligament injury, meniscal tear and intra-articular fracture.
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http://dx.doi.org/10.1136/bjsports-2019-100959DOI Listing
June 2020

Intersectional Inequalities and Individual Heterogeneity in Chronic Rheumatic Diseases: An Intersectional Multilevel Analysis.

Arthritis Care Res (Hoboken) 2021 02;73(2):296-304

Lund University, Lund, Sweden, and Boston University School of Medicine, Boston, Massachusetts.

Objective: To examine how intersections of multiple sociodemographic variables explain the individual heterogeneity in risk of being diagnosed with any of following chronic rheumatic diseases (CRDs): osteoarthritis (OA), gout, rheumatoid arthritis (RA), or spondyloarthritis (SpA).

Methods: We identified individuals ages 40-65 years residing in Skåne, Sweden by December 31, 2013 and having done so from January 1, 2000 (n = 342,542). We used a Skåne health care register to identify those with a diagnosis of the CRD of interest between January 1, 2014 and December 31, 2015, with no previous such diagnosis during 2000-2013. We created 144 intersectional social strata (ISS) using categories of age, sex, education, income, civil status, and immigration. For individuals nested within ISS, we applied multilevel logistic regression models to estimate the variance partition coefficient (VPC) as a measure of discriminatory accuracy of the ISS and the predicted absolute risks and 95% credible intervals for each stratum.

Results: Overall, 3.5%, 0.5%, 0.2%, and 0.2% of the study population were diagnosed with OA, gout, RA, and SpA, respectively. The VPC ranged from 16.2% for gout to 0.5% for SpA. Sex explained the largest proportion of between-strata variation in risk of RA, gout, and SpA, while age was the most important factor for OA. The most between-strata differences in risk of these CRDs were due to the additive main effects.

Conclusion: Despite meaningful between-strata inequalities in the risk of being diagnosed with CRDs (except SpA), there were substantial within-strata heterogeneities that remain unexplained. There was limited evidence of intersectional interaction effects.
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http://dx.doi.org/10.1002/acr.24109DOI Listing
February 2021
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