Distinct myofibre domains of the human myotendinous junction revealed by single-nucleus RNA sequencing.

The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre that is faced with the challenge of maintaining robust cell-matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,124 nuclei in semitendinosus muscle-tendon samples from three healthy males by using single-nucleus RNA sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei represented by 47 enriched transcripts, of which the presence of ABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1 and FREM2 was confirmed at the MTJ at the protein level in immunofluorescence assays. Four distinct subclusters of MTJ myonuclei were apparent, comprising two COL22A1-expressing subclusters and two subclusters lacking COL22A1 expression but with differing fibre type profiles characterized by expression of either MYH7 or MYH1 and/or MYH2. Our findings reveal distinct myonuclei profiles of the human MTJ, which represents a weak link in the musculoskeletal system that is selectively affected in pathological conditions ranging from muscle strains to muscular dystrophies.

Nestin and osteocrin mRNA increases in human semitendinosus myotendinous junction 7 days after a single bout of eccentric exercise.

The myotendinous junction (MTJ), a specialized interface for force transmission between muscle and tendon, has a unique transcriptional activity and is highly susceptible to muscle strain injury. Eccentric exercise training is known to reduce this risk of injury, but knowledge of the influence of exercise on the MTJ at the molecular and cellular levels is limited. In this study, 30 subjects were randomized to a single bout of eccentric exercise 1 week prior to tissue sampling (exercised) or no exercise (control). Samples were collected from the semitendinosus as part of reconstruction of the anterior cruciate ligament and divided into fractions containing muscle, MTJ and tendon, respectively. The concentrations of macrophages and satellite cells were counted, and the expression of genes previously known to be active at the MTJ were analyzed by real-time-quantitative PCR. An effect of the single bout of exercise was found on the expression of nestin (NES) and osteocrin (OSTN) mRNA in the MTJ and tendon fractions. Genes earlier identified at the MTJ (COL22A1, POSTN, ADAMTS8, MNS1, NCAM1) were confirmed to be expressed at a significantly higher level in the MTJ compared to muscle and tendon but were unaffected by exercise. In the exercise group a higher concentration of macrophages, but not of satellite cells, was seen in muscle close to the MTJ. The expression of NES and OSTN was higher in human semitendinosus MTJ 1 week after a single session of heavy eccentric exercise. Based on these results, NES and OSTN could have a part in explaining how the MTJ adapts to eccentric exercise.

RNA sequencing and immunofluorescence of the myotendinous junction of mature horses and humans.

The myotendinous junction (MTJ) is a specialized interface for transmitting high forces between the muscle and tendon and yet the MTJ is a common site of strain injury with a high recurrence rate. The aim of this study was to identify previously unknown MTJ components in mature animals and humans. Samples were obtained from the superficial digital flexor (SDF) muscle-tendon interface of 20 horses, and the tissue was separated through a sequential cryosectioning approach into muscle, MTJ (muscle tissue enriched in myofiber tips attached to the tendon), and tendon fractions. RT-PCR was performed for genes known to be expressed in the three tissue fractions and t-distributed stochastic neighbor embedding (t-SNE) plots were used to select the muscle, MTJ, and tendon samples from five horses for RNA sequencing. The expression of previously known and unknown genes identified through RNA sequencing was studied by immunofluorescence on human hamstring MTJ tissue. The main finding was that RNA sequencing identified the expression of a panel of 61 genes enriched at the MTJ. Of these, 48 genes were novel for the MTJ and 13 genes had been reported to be associated with the MTJ in earlier studies. The expression of known [COL22A1 (collagen XXII), NCAM (neural cell adhesion molecule), POSTN (periostin), NES (nestin), OSTN (musclin/osteocrin)] and previously undescribed [MNS1 (meiosis-specific nuclear structural protein 1), and LCT (lactase)] MTJ genes was confirmed at the protein level by immunofluorescence on tissue sections of human MTJ. In conclusion, in muscle-tendon interface tissue enriched with myofiber tips, we identified the expression of previously unknown MTJ genes representing diverse biological processes, which may be important in the maintenance of the specialized MTJ.

Collagens in primary frozen shoulder: expression of collagen mRNA isoforms in the different phases of the disease.

OBJECTIVES: Primary frozen shoulder (pFS) has three phases that differ in clinical presentation. It is characterized by contracture of the joint capsule. We hypothesized that there is a general upregulation of collagens in pFS, and that this is highest in the first phase of the disease. The aims of this study were to investigate the expression of various collagens and degradation of collagens in patients with primary pFS and relate this to the three phases of the condition. METHODS: From twenty-six patients with pFS and eight control patients with subacromial impingement, biopsies were obtained during shoulder arthroscopy from the middle glenohumeral ligament and the anterior capsule, and mRNA levels for collagens, MMP-2 and -14 and TGF-ß1, - ß2 and -ß3 in the tissue were analysed using real-time PCR. RESULTS: Genes for collagens type I, III, IV, V, VI and XIV, were activated in pFS, and the total mRNA for all collagens was increased (P < 0.05). This upregulation was independent of disease phases in pFS. In addition, MMP-2, MMP-14, TGF-ß1 and TGF-ß3 were upregulated in all phases of the disease. CONCLUSION: There is a general upregulation and an increased degradation of collagens in pFS in all three phases of the disease. This indicates a constantly increased turnover of the fibrotic tissue in the capsule from pFS. The difference in clinical presentation of pFS observed in the three phases of the disease is not primarily a result of variations in collagen production.

Choosing the most appropriate PROM for clinical studies in sports medicine.

Choosing the most appropriate patient-reported outcome measure (PROM) for a clinical study is essential in order to achieve trustworthy results. This choice will depend on (a) the objective of the study and hence the research question; (b) the choice of a theoretical framework, such as the World Health Organization's International Classification of Functioning, Disability, and Health (ICF); (c) whether there currently is a PROM that possesses high content validity and high construct validity for the specific patient group and objective, and if not; (d) the decision on whether to use a suboptimal PROM or develop and validate a new PROM. This paper presents the steps that should be followed in order to assess the relevance of PROMs and suggests ways to enhance the choice depending on the goal of the study.

A catalogue of PROMs in sports science: Quality assessment of PROM development and validation.

Choosing the most adequate PROM for a study is a non-trivial process. The aim of this study was to provide a catalogue with analyses of content and construct validity of PROMs relevant to research in sports science, including all published local translations. The most commonly used PROMs in sports research were selected from a PubMed search "patient reported outcome measures sports", identifying 439 articles and 194 different PROMs. Articles describing development of the 61 selected PROMs were assessed for content validity, and all articles regarding construct validity of each PROM and all published translations (in total 622 articles) were analyzed. A catalogue with assessments of the 61 PROMs was produced. The majority were of inferior validity, with few exceptions. The most common reason for this was that the PROM had not been developed by methods that ensure high content validity. Another major reason for inferior validity was that construct validity had not been secured by adequate statistical methods. In conclusion, this catalogue provides a tool for researchers to facilitate choosing the most valid PROM for studies in sports research. Furthermore, it shows for popular PROMs where further validation is needed, and for fields in musculoskeletal medicine where valid PROMs are lacking. It is suggested that a targeted effort is made to develop valid PROMs for major conditions in musculoskeletal research. The current method is easier to practice compared with assessment after COSMIN guidelines.

Are adequate PROMs used as outcomes in randomized controlled trials? an analysis of 54 trials.

Results by patient-reported outcome measures (PROMs) from randomized controlled trials (RCTs) in musculoskeletal research often influence healthcare strategies. We aimed to evaluate to which extent these RCTs use adequate PROMs, and how this influences the results and conclusions. We identified RCTs of sports research relevance with PROMs as primary outcomes published in 13 preselected journals between January 1, 2008, and November 1, 2019; all journals regularly publish results from musculoskeletal research. Five journals have a high impact factor (>15), and eight with lower impact factors are widely read journals. It was assessed whether the RCTs had used PROMs with high content validity and whether the most adequate PROMs were used (ie, the most well developed and well validated for the patients enrolled in the study). We registered journal impact factor, year of publication, existence of a registered protocol, and whether the study showed significant difference between interventions. A total of 54 RCTs with 56 primary outcomes comprising 26 different PROMs were identified. For 13 RCTs (24%), a protocol was not published. In only 24 of RCTs (44%), the most appropriate PROM had been used as primary outcome, independent of a registered protocol, ranking of the journal, and year of publication. In seven cases, PROMs were used to evaluate a condition that they had not been developed for. RCTs that used the most adequate PROM showed significantly more often (46%) difference in outcomes in contrast to RCTs that used inadequate PROMs (22%) (P = 0.0483). In conclusion, in the majority of RCTs, the most adequate PROM had not been used. Studies, in which the most adequate PROM had been used as outcome, were significantly more likely to show significant difference between interventions. The extent to which protocols were not available was surprisingly high. Journals should request that adequate PROMs are used in RCTs, and if this is not the case that it is discussed how it might influence the results and conclusions. Likewise, it should be requested that a protocol is published or registered.

Potential problems in the use of patient reported outcome measures (PROMs) and reporting of PROM data in sports science.

To use an inadequate patient reported outcome measure (PROM) or use a PROM in an inappropriate way potentially influences the quality of measurement. The objectives of this study were to define potential inadequate uses of PROMs in sports research studies and estimate how often they occur. A consensus group consisting of medical researchers, statisticians, and psychometricians identified and defined potentially irregular applications of PROMs. Occurrence of these in 349 consecutive articles in sports medicine in which PROMs were used as primary outcomes was reviewed. In all, 14 different potential problems were defined, and one or several occurred in 172 of the articles (49%). These were as follows: using a PROM that was developed for a different patient group (100 cases), using two or more PROMs with identical questions (94), aggregation of domain sum scores (82), combinations of subjective and objective measures (27), using a PROM to diagnose or evaluate the individual patient (7), using a PROM for a single limb (3), recall bias (3), exclusion of domains or items (3), construction of a PROM for a specific occasion (2), categorization of the scale (2), and mixing different versions of a PROM (1). Adaption of scale scores (e. g., to percentage) when results are reported (144) carries a risk of miscalculation and distorted impression of results. Data related to uncertainty about completing the PROM and the handling of missing data were not provided in the manuscripts. In conclusion, potential problems in the use and reporting of PROMs are common in sports research, and this can influence the validity of reported results.

How to develop a condition-specific PROM.

Developing new patient-reported outcome measures (PROMs) for application in clinical studies can be necessary if an adequate PROM does not exist. For adequate measurement, it is essential that the PROM has face validity (ie, is perceived to be relevant by clinicians and researchers) and has high content validity (ie, content relevance and content coverage for the targeted patient group). The steps needed to create PROMs that possess face and content validity for a specific condition are described in this paper. Face validity is achieved by item identification and generation through literature review. Content validity is confirmed through repetitive cognitive interviews of patients from the targeted patient group in order to generate a consensus-based pilot-version of the new PROM. This qualitative process ensures that items are appropriately worded, understandable, and minimizes doubts about how items should be answered. A practical example of this process is presented, which shows the development of the Knee Numeric-Entity Evaluation Score (KNEES-ACL), a condition-specific PROM for patients with deficiency of the anterior cruciate ligament (ACL).

Responsiveness, minimal important difference, minimal relevant difference, and optimal number of patients for a study.

Several terms are used to describe changes in PROM scores in relation to treatments. Whether the change is small, large, or relevant is defined in different ways, yet these change scores are used to recommend or oppose treatments. They are also used to calculate the necessary number of patients for a study. This article offers a theoretical explanation behind the terms responsiveness, minimal important difference (MID), minimal important change (MIC), minimal relevant difference (MIREDIF), and threshold of clinical importance. It also gives instructions on how these and the optimal number of patients for a study are calculated. Responses to two domains of the Knee Injury and Osteoarthritis Outcome Score (KOOS), before and 1 year after reconstruction of the anterior cruciate ligament of 164 patients, are used to illustrate the calculations. This paper presents the most common methods used to calculate and interpret MID. Results vary substantially across domains, patient location on the scale, and health conditions. The optimal number of patients depends on the minimal relevant difference (MIREDIF), the standard error of the measure (SEM), the desired statistical power for the measurement, and the responsiveness of the measurement instrument (the PROM). There is often uncertainty surrounding the calculation and interpretation of responsiveness, MID, and MIREDIF, as these concepts are complex. When MID is used to evaluate research results, authors should specify how the MID was calculated, and its relevance for the study population. These measures should only be used after thorough consideration to justify healthcare decisions.

Psychometric validation of PROM instruments.

The aim was to provide an overview of the different statistical methods for validation of patient-reported outcome measures, ranging from simple statistical methods available in all software packages to advanced statistical models that require specialized software. A non-technical summary of classical test theory (CTT) and modern test theory (MTT) is provided. Specifically, confirmatory factor analysis, item response theory, and Rasch analysis is outlined. One CTT and three MTT methods were used to validate the two subscales (Symptoms and Quality of Life) from the Knee Injury and Osteoarthritis Outcome Score (KOOS). For each methodology, two analyses were considered: (i) a unidimensional analysis ignoring the pre-specified dimensionality, and (ii) a two-dimensional analysis using the pre-specified dimensionality. While CTT did not adequately address central issues regarding the validity of the KOOS subscales, the three MTT methods yielded very similar results. In conclusion, MTT methods offer analysis of all relevant properties related to the validity of patient-reported outcome measures, while this is not the case for CTT. Claims about sufficient validity based on CTT methods are inadequate and should not be trusted.

What is a PROM and why do we need it?

The purpose of this article was to introduce the reader to the nature of patient-reported outcome measures (PROMs) and pitfalls in their use. PROMs collect subjective information directly from the patient regarding specific or general conditions and add to clinical and functional outcomes, and turn unmeasurable subjective qualities into quantitative measures. PROMs are questionnaires consisting of items: questions or statements with predefined response options. The items in an adequate PROM have been developed by involvement of patients with the condition in focus, and the PROM has been validated for these patients using suitable statistical methods. An adequate well-targeted PROM is more responsive than an inadequate PROM. Unfortunately, many studies use inadequate PROMs as outcomes. The methods used to generate PROMs should be described as thoroughly as those used to develop any other types of measurement instruments, and the choice of PROM should always be explained and thereby justified. If the PROM used is not adequate, the consequences for the interpretation of the results should be discussed. In many cases, an adequate PROM does not exist. If the best available PROM is chosen, there are methods to validate the adequacy of the chosen PROM, which make an interpretation of the study results possible.

How to translate and locally adapt a PROM. Assessment of cross-cultural differential item functioning.

Translating patient-reported outcome measures (PROMs) can alter the meaning of items and undermine the PROM's psychometric properties (quantified as cross-cultural differential item functioning [DIF]). The aim of this paper was to present the theoretical background for PROM translation, adaptation, and cross-cultural validation, and assess how PROMs used in sports medicine research have been translated and adapted. We also assessed DIF for the Knee Injury and Osteoarthritis Outcome Score (KOOS) across Danish, Norwegian, and Swedish versions. We conducted a search in PubMed and Scopus to identify the method of translation, adaptation, and validation of PROMs relevant to musculoskeletal research. Additionally, 150 preoperative KOOS questionnaires were obtained from the Scandinavian knee ligament reconstruction registries, and cross-cultural DIF was evaluated using confirmatory factor analysis and Rasch analysis. There were 392 studies identified, describing the translation of 61 PROMs. Ninety-four percent were performed with forward-backward technique. Forty-nine percent used cognitive interviews to ensure appropriate wording, understandability, and adaptation to the target culture. Only two percent were validated according to modern test theory. No study assessed cross-cultural DIF. One KOOS subscale showed no cross-cultural DIF, two had DIF with respect to some (but not all) items, and thus conversion tables could be constructed, and two KOOS subscales could not be pooled. Most PROM translations are of undocumented quality, despite the common conclusion that they are valid and reliable. Scores from three of five KOOS subscales can be pooled across the Danish, Norwegian, and Swedish versions, but two of these must be adjusted for DIF.

Measurement properties of UCLA Activity Scale for hip and knee arthroplasty patients and translation and cultural adaptation into Danish.

Background and purpose - The UCLA Activity Scale (UCLA) is a questionnaire assessing physical activity level from 1 (low) to 10 (high) in patients undergoing hip or knee arthroplasty (HA/KA). After translation and cultural adaptation, we evaluated the measurement properties of the Danish UCLA.Patients and methods - After dual panel translation, cognitive interviews were performed among 55 HA/KA patients. An orthopedic surgeon and a physiotherapist estimated UCLA scores for 80 KA patients based on short interviews. Measurement properties were evaluated in 130 HA and 134 KA patients preoperatively and 1-year postoperatively.Results - To suit Danish patients of today, several adaptations were required. Prior to interviews, 4 patients were excluded, and 11 misinterpreted the answer options. Examiners rated the remaining 65 patients (mean age 67 years) 0.2-1.6 UCLA levels lower than patients themselves. The 130 HA and 134 KA patients (mean age 71/68 years) changed from 4.3 (SD 1.9)/4.5 (1.8) preoperatively to 6.6 (1.8)/6.2 (1.0) at 1-year follow-up. 103 (79%) HA and 89 (66%) KA patients reported increased activity. Effect sizes were large (1.2/0.96). Knee patients reaching minimal important change (MIC, ≥ 8 Oxford Knee Score points) had higher 1-year UCLA scores than patients not reaching MIC.Interpretation - Original scale development was undocumented. Content validity was questionable, and there was discrepancy between patient and examiner estimates. UCLA appears valuable for measuring change in self-reported physical activity on a group level. 4 out of 5 HA patients and 2 out of 3 KA patients were more physically active 1 year after joint replacement surgery.

Predicting post-operative functional ability from pre-operative measures in ACL-injured individuals.

PURPOSE: This study aimed to quantify the relationship between objective and subjective measures of functional ability and determine if measures in the deficient (ACLd) state were correlated to, and capable of predicting a patient's objective and subjective measures in the reconstructed (ACLr) state. METHODS: Twenty ACL-injured participants completed hop and side cut movements prior to and 10 months post-reconstruction. Their subjective measures (Tegner, Lysholm, IKDC, KOOS, and KNEEs) were related to objective measures of functional ability (peak knee flexion, peak knee extensor moment, stiffness, knee joint center excursion (KJCE), and knee joint center boundary). Correlations were used to determine relationships between variables whereas regressions were used to identify ACLd score's predictive ability of an ACLr score. RESULTS: Relationships between objective and subjective measures were task and ACL status dependent with KJCE and stiffness most commonly being related to subjective scores. The greatest correlation was between knee stiffness and Tegner in the ACLr group during the side cut (r = 0.69). Peak knee flexion angle (adj. R2  = 0.4-0.66) was the best objective predictor between ACLd and ACLr states while KOOS-ADL had the strongest correlations (r = 0.70-0.77) and Tegner had the greatest predictive power (odds ratio: 1.46-1.86) between states in both tasks. CONCLUSION: Objective measures show a wide range of correlation to subjective measures with some being quite strong. Furthermore, objective measures in the ACLd state are more correlated and more often capable of predicting ACLr scores than the subjective measures of functional ability.

Heterotopic Ossification After an Achilles Tendon Rupture Cannot Be Prevented by Early Functional Rehabilitation: A Cohort Study.

BACKGROUND: Tendon loading might play a role in the development of heterotopic ossification after Achilles tendon ruptures. Early heavy loading on a healing tendon in animals has been shown to prolong the proinflammatory response, and inflammatory cells are thought to drive heterotopic ossification formation. Taken together, this suggests that early rehabilitation might influence heterotopic ossification development. QUESTIONS/PURPOSES: The purposes of this study were to investigate (1) whether the presence of heterotopic ossification after Achilles tendon ruptures influences clinical outcome and (2) whether early mobilization or weightbearing prevents the development of heterotopic ossification. METHODS: This was a retrospective analysis of 69 patients from a previous clinical trial. All patients were treated surgically, but with three different early rehabilitation protocols after surgery: late weightbearing and ankle immobilization, late weightbearing and ankle mobilization, and early weightbearing and ankle mobilization. Plain radiographs taken 2, 6, 12, 26, and 52 weeks postoperatively were analyzed for heterotopic ossification, which was detected in 19% of patients (13 of 69) at 52 weeks. Heterotopic ossification was measured, scored, and correlated to clinical outcomes; heel-raise index (HRI), ankle joint ROM, tendon strain, Achilles tendon rupture score (ATRS), and Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire scores at 26 and 52 weeks postoperatively. RESULTS: Heterotopic ossification had no adverse effects on patient-reported outcomes (ATRS or VISA-A), tendon strain, or ROM. In fact, patients with heterotopic ossification tended to have a better HRI at 52 weeks compared with patients without (mean difference 14% [95% CI -0.2 to 27]; p = 0.053). Neither the occurrence (heterotopic ossification/no heterotopic ossification) nor the heterotopic ossification severity (ossification score) differed between the three rehabilitation groups. Seventeen percent of the patients (four of 24) with early functional rehabilitation (early weightbearing and ankle joint mobilization exercise) had heterotopic ossification (score, 2-3) while late weightbearing and immobilization resulted in heterotopic ossification in 13% of the patients (score, 3-4). CONCLUSIONS: Heterotopic ossification occurs relatively frequently after Achilles tendon ruptures but appears to have no adverse effects on functional outcomes. Furthermore, heterotopic ossification develops during the first 6 weeks after rupture, and weightbearing or ankle-joint mobilization does not prevent this from occurring. LEVEL OF EVIDENCE: Level III, prognostic study.

No detectable remodelling in adult human menisci: an analysis based on the C14 bomb pulse.

OBJECTIVES: Bone and other human tissues remodel through life, for example, as a response to increasing load, and this prevents permanent destruction of the tissue. Non-traumatic meniscal rupture is a common musculoskeletal disease, but it is unknown if it is caused by inability of the menisci to remodel. The aim of this study was to determine whether meniscal collagen is remodelling throughout life. METHODS: The life-long turnover of the human meniscal collagens was explored by the 14C bomb pulse method. 14C levels were determined in menisci from 18 patients with osteoarthritis and 7 patients with healthy knees. RESULTS: There was a negligible turnover of the meniscal collagen in adults. This low turnover was observed in menisci from patients with knee osteoarthritis and in healthy menisci. CONCLUSION: This study provides evidence that essentially no remodelling occurs in the adult human meniscal collagen structure and explains the clinical degeneration that is often seen in menisci of middle-aged and elderly persons. It suggests that strengthening of the collagen structure of menisci, as response to physical activity, may occur during childhood, while it is not possible in the adult population.

Anterior cruciate ligament reconstruction improves subjective ability but not neuromuscular biomechanics during dynamic tasks.

PURPOSE: The purpose of this study was to identify high-functioning anterior cruciate ligament-deficient patients and assess the effects of reconstruction on their self-reported functionality, muscle activations and biomechanical properties. METHODS: Twenty young and active patients participated pre- (11.5 ± 14.3 months post-injury) and again 10.5 ± 1.7 months post-reconstruction and were individually matched to 20 healthy controls. Participants completed hop and side cut movements while patient-related outcome measures, lower limb electromyography, kinetic, and whole body kinematic data were collected. One-dimensional statistical parametric mapping was used to test for group differences (healthy vs deficient; deficient vs reconstructed; reconstructed vs healthy). RESULTS: When comparing healthy to anterior cruciate ligament-deficient participants, all questionnaires indicated significant lower subjective function while the only substantial biomechanical difference between these participants was a decreased knee extensor moment in both the hop (peak difference: 0.63 Nm/kg, p < 0.001) and side cut (peak difference: 0.76 Nm/kg, p < 0.001). When comparing patients' pre- and post-reconstruction, no biomechanical differences were observed whereas only half of the questionnaires (Tegner, Lysholm, KNEES-ADL, KNEES-Slackness, KNEES-Looseness, KNEES-Sport Behaviour, IKDC, and KOOS-QoL) indicated higher function in the reconstructed state. When comparing the reconstructed patients to the healthy participants, all questionnaires were still significantly higher in the healthy controls. The reconstructed group also had a smaller flexion angle (peak difference: 14.5°, p = 0.007) and knee extensor moment (peak difference: 0.62 Nm/kg, p < 0.001) during the hop and a smaller knee extensor moment (peak difference: 0.90 Nm/kg, p < 0.001) during the side-cut task. CONCLUSION: At 10-months post-reconstruction, the current results indicate that in high-functioning anterior cruciate ligament-deficient patients, reconstruction had little impact on objective measures of functional ability during dynamic tasks although self-reported function was improved. LEVEL OF EVIDENCE: Therapeutic prospective cohort study, Level II.

Knee Osteoarthritis Patients Can Provide Useful Estimates of Passive Knee Range of Motion: Development and Validation of the Copenhagen Knee ROM Scale.

BACKGROUND: Knee arthroplasty does not always require extensive long-term follow-up. If knee range of motion (ROM) could be assessed reliably by patients, some follow-up visits might be replaced by patient-reported outcome measures, and this additional information could be reported directly to registers. We developed and tested the validity and reliability of a simple scale for patients to self-report their passive knee ROM. METHODS: Through an iterative process, we created a 2-item scale with 11 illustrations of knee motion in 15° increments. The validity and reliability was tested in knee osteoarthritis and arthroplasty patients at different treatment stages, many with poor ROM. Patient estimates were compared to passive goniometer measurements performed blindly by a physiotherapist and a junior orthopedic surgeon. RESULTS: The mean difference between 100 patients' (70.9 years) estimates and goniometer measurements was -0.7° (standard deviation, 12.3°) for flexion and 1.1° (standard deviation, 11.6°) for extension, both not significant. Correlation was 0.79 and 0.63, and kappa values at retest were 0.84 and 0.66. For flexion < 110°, sensitivity of patient estimates was 88% and specificity was 88%. For a limit of 100°, values were 95% and 81%. For extension deficits >10°, sensitivity was 78% and specificity 70%. Values were 100% and 66% for a 15° limit. CONCLUSION: The Copenhagen Knee ROM Scale is a patient-friendly and feasible alternative to passive ROM measurement for registers, research, and selected clinical use. This scale appears reliable and valid compared to reports of similar tools, and patient estimates are better correlated to goniometer measurements.

Risk Factors for Post-treatment Complex Regional Pain Syndrome (CRPS): An Analysis of 647 Cases of CRPS from the Danish Patient Compensation Association.

OBJECTIVES: Complex regional pain syndrome is a challenging condition that includes a broad spectrum of sensory, autonomic, and motor features predominantly in extremities recovering from a trauma. Few large-scale studies have addressed occurrence of and factors associated with complex regional pain syndrome (CRPS) following orthopedic treatment. The present study aimed to identify factors associated with post-treatment development of CRPS. METHODS: Using the Danish Patient Compensation Association's database, we identified 647 patients claiming post-treatment CRPS between 1992 and 2015. Age, gender, initial diagnosis, treatment, and amount of compensation were extracted. Multivariate logistic regressions were performed to identify variables associated with approval of the claim. For carpal tunnel syndrome (CTS) patients, we registered whether symptoms were bilateral or unilateral and if neurophysiology prior to treatment was pathologic. RESULTS: The following ratios were found: women:men was 4:1, primary diagnosis to the upper limb:lower limb was 2.5:1, and surgical:nonsurgical treatment was 3:1. Mean age was 47.5 ± 13.7 years, and no intergender difference was detected. Antebrachial fracture (23%) and CTS (9%) were the most common primary conditions. Surgical treatment was associated with approval of the claim (odds ratio 3.5, 95% confidence interval 2.3 to 5.3; P < 0.001). Half of CTS patients had normal neurophysiology prior to surgery; among patients with unilateral symptoms, 71.4% had normal neurophysiology. CONCLUSIONS: Female gender, surgical treatment, and treatment to the upper limb were risk factors. Elective surgery accounted for a large number of post-treatment CRPS patients. In CTS patients developing CRPS, normal neurophysiological examination findings were common, and it could be suspected that these patients were suffering from an pre-clinical stage of CRPS, not CTS.