- Email: [email protected]
The Upper Limb Hypermobility Assessment Tool: A novel validated measure of adult joint mobility
Accepted Manuscript The Upper Limb Hypermobility Assessment Tool: A novel validated measure of adult joint mobility Leslie L. Nicholson, Cliffton Chan PII:
S2468-7812(18)30046-8
DOI:
10.1016/j.msksp.2018.02.006
Reference:
MSKSP 167
To appear in:
Musculoskeletal Science and Practice
Received Date: 3 October 2017 Revised Date:
8 January 2018
Accepted Date: 19 February 2018
Please cite this article as: Nicholson, L.L., Chan, C., The Upper Limb Hypermobility Assessment Tool: A novel validated measure of adult joint mobility, Musculoskeletal Science and Practice (2018), doi: 10.1016/j.msksp.2018.02.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT The Upper Limb Hypermobility Assessment Tool: A novel validated measure of adult joint mobility
Short running title: The Upper Limb Hypermobility Assessment Tool
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Associate Professor Leslie L Nicholsona,b 75 East St Lidcombe, NSW 2141 (Australia) Email: [email protected]
75 East St Lidcombe, NSW 2141 (Australia)
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Email: [email protected]
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Dr Cliffton Chana,b
a
The University of Sydney, Discipline of Biomedical Science, Sydney Medical School
b
The Hypermobility and Performance Laboratory, Bosch Institute, The University of Sydney
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Corresponding Author: Associate Professor Leslie L Nicholson
ACCEPTED MANUSCRIPT The Upper Limb Hypermobility Assessment Tool: A novel validated measure of adult joint mobility
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Short running title: The Upper Limb Hypermobility Assessment Tool
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ACCEPTED MANUSCRIPT ABSTRACT Background: Existing measures of generalized joint hypermobility do not include commonly affected upper limb joints.
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Objective: To evaluate the reliability of a novel clinically-applicable measure of upper limb joint mobility, its ability to discriminate between varying extents of hypermobility, identify generalized joint hypermobility, and to establish a cut-point for hypermobility classification.
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Design: Validation of a diagnostic tool
Method: Participants were sought from three groups - healthy controls, likely and known
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hypermobiles, and assessed using the Upper Limb Hypermobility Assessment Tool (ULHAT), Beighton score and clinical opinion. Pearson's correlation coefficient examined individual group and whole cohort relationships between upper limb hypermobility, age, gender and ethnicity. MANOVA investigated between-group differences in ULHAT scores.
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Median interquartile ranges and ROC Curve analysis identified the cut-off score for identification of upper limb hypermobility. Percent agreement with clinical opinion assessed the ability of the ULHAT to identify generalized joint hypermobility.
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Results: 112 adult participants (mean age 24.3 ± 5.5years) across the three groups were assessed. Inter-rater reliability of the tool was high (ICC2,1= 0.92). The cut-point was
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established at ≥7/12 (sensitivity 0.84, specificity 0.77, +LR 3.7, -LR 0.2). Upper limb hypermobility did not vary with age or ethnicity (both p>0.12), but was greater in females (p<0.001). The ULHAT discriminated between the three groups and identified generalized hypermobility.
Conclusions: The 12-item ULHAT measures mobility of multiple upper limb joints in all movement planes. Using a cut-off of ≥7/12 in adults, the ULHAT is a reliable and valid tool for identifying upper limb hypermobility and generalized joint hypermobility.
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ACCEPTED MANUSCRIPT Key Words: Generalized Joint Hypermobility, Ehlers-Danlos Syndrome, measurement, clinical assessment
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1. Introduction Generalized joint hypermobility (GJH) is an asymptomatic condition characterized by
greater than normal passive and active range, in at least four joints and in at least one plane of motion (1). The extent of GJH varies with respect to age, gender and ethnicity.
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By describing an individual as “hypermobile”, the assumption is that their joint mobility is
uppermost 5% of the population (2).
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greater than 95% of the population, or that their joint mobility places them in the
Since 1973, the Beighton scoring system has been used for classification of an individual’s joint mobility (3). One point is allocated for extension of the knees and elbows (bilaterally) past 10º (4 possible points), extension of the 5th metacarpophalangeal (MCP)
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joints (bilaterally) past 90º (2 possible points), apposition of the left and right thumbs to the flexor surface of the ipsilateral radius (2 possible points), and forward trunk and hip flexion to place the palms on the floor (1 possible point), for a total of 9 points. While a range of
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cut-off scores from ≥4/9 to ≥8/9 has been used to classify individuals as hypermobile, the most commonly cited cut-off in adults is ≥4/9 (4-6). A 2017 international consensus
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classification proposes a cut-off of ≥5/9 for GJH, suggesting a traditional overestimation of its prevalence (7).
Hypermobility is a key trait of people with Ehlers-Danlos Syndrome Hypermobility Type (EDS-HT) and Joint Hypermobility Syndrome (JHS), where it is associated with joint instability and pain. While hypermobility may be an inherited trait, it can also be acquired through training (8, 9). Ballet dancers have a high prevalence of spine, hip, knee, ankle and shoulder hypermobility thought to be, at least in part, related to their training (10). Inherited and Page | 3
ACCEPTED MANUSCRIPT acquired hypermobility affects multiple joints of the upper limbs, in all three anatomical planes. Nearly ten percent of adolescents with a Beighton score of ≥6/9 report troublesome shoulder pain, a prevalence second only to low back pain in a sample population of 2,901 (11). In a study of 1,311 military academy freshmen, a significant
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relationship was found between GJH and glenohumeral instability; those defined as
having GJH using the Beighton scoring system were 2.5 times more likely to report a history of shoulder instability (12). Most commonly, this instability occurs in the coronal
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and horizontal planes. Indeed, failing to recognize hypermobility as a cause of
multidirectional glenohumeral instability sometimes results in inappropriate management
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and prolonged prognosis, especially detrimental to the rehabilitation of the throwing athlete (13). The shoulder is most commonly identified as unstable in people with symptomatic hypermobility disorders such as EDS-HT and JHS (14), with pain most frequently localized to the neck, shoulder and forearms (15). Another affected body region is the radioulnar (wrist) joint where hand pain in musicians is suggested to be related to
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multi-planar hypermobility (16). Immediately evident is that the Beighton, despite its upper more than lower limb joint representation, does not include any tests of the shoulder or radioulnar joints. Although a reliable measure (17, 18), the validity of the Beighton scoring
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system as a means of identifying generalized or whole body hypermobility is questionable. Not only does it fail to test commonly hypermobile joints, it assesses joint
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motion in only the sagittal plane. The Lower Limb Assessment Scale (LLAS) developed by Ferrari and colleagues is a reliable and valid measure of lower limb hypermobility and it has been found to correlate highly with clinical opinion of generalized joint hypermobility in both children and adults (19, 20). The LLAS comprises 12 bilateral tests of mobility of the hip, knee, tibiofibular, ankle and foot joints in all 3 planes of motion. The cut-off score for the LLAS has been established as ≥7/12 unilaterally, in both adults and children (19, 20).
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ACCEPTED MANUSCRIPT Currently there is no joint mobility scoring system that focusses on the shoulder, radioulnar, wrist and finger joints (other than the 5th MCP) of the upper limb. The aim of this study was firstly to develop a reliable and clinically-applicable tool to quantify upper limb joint mobility based on the LLAS, to establish a cut-point for classification of upper
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limb hypermobility and finally to validate this tool as a discriminator of both upper limb and generalized joint hypermobility.
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2. Materials and methods
To determine whether the Upper Limb Hypermobility Assessment Tool (ULHAT) can
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identify people with varying extents of upper limb hypermobility, participants were sought from three groups as convenience series, in 2015/2016. The cohort in this study was the same as that reported in a validation study of the LLAS in adults (20). See Figure 1 for a
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graphical representation of the group allocation and recruitment strategies.
EDS-HT: Ehlers-Danlos Syndrome – hypermobility type; JHS: Joint Hypermobility Syndrome.
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ACCEPTED MANUSCRIPT Figure 1: A diagrammatic representation of the inclusion criteria, recruitment process and allocation of participants into the three cohorts
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Participants of either gender were included in the study. Volunteers older than 40 years of age were excluded due to the confounding effect of age-related joint degeneration (24). Participants were excluded if they did not meet the inclusion criteria, had another
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diagnosed rheumatological condition (e.g. Marfans, Stickler’s or Loeys Dietz syndromes), or had an orthopaedic condition with pain, disability or previous trauma that might restrict
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normal range of motion.
Participants were surveyed to collect demographical data (age, gender, ethnicity), clinical history related to joint mobility (perceived instability, occurrence of subluxations/ dislocations), and self-perceived hypermobility (Hakim 5-part questionnaire (25)). All
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participants underwent a single physical testing session that included the Beighton scoring system, the Lower Limb Assessment Scale (LLAS)(19), and the ULHAT.
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The ULHAT was designed as an upper limb analogue of the 12 composite tests of the LLAS, to test the mobility of many joints of the upper limb in multiple planes of motion. These tests
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include passive physiological, passive accessory and active range of motion. For ease of clinical decision making and in keeping with the format of all existing hypermobility assessment tools, (1,3,19) the individual ULHAT tests require only yes/no judgements. The upper limb joints assessed reflect those most commonly affected by instability and the planes in which that instability most frequently occurs (12-16). The twelve tests that comprise the ULHAT and the descriptors for each are found in Table 1, while the rationale for the cut-off values chosen for each test is summarised in Table 2.
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Test Description
1. Shoulder Flexion
Supine: hand of non-tested arm under lumbar spine. Patient gently pushes spine into their hand and maintains position. Examiner raises arm over the head. Can the whole humerus rest easily on the plinth? Supine: shoulder placed at 90° abduction supported by plinth with forearm neutral. Arm is passively rotated from maximal internal to maximal external rotation, with mild pressure applied at end of range. Is there >180° in total? *an inclinometer can be applied against the medial border of the distal ulna where rotation is close to 180° Supine: shoulder placed at 90° abduction supported by plinth, forearm supinated. Patient actively extends elbow. Is there >10° extension? *an inclinometer can be used over the medial epicondyle of the humerus, arms aligned with the ulna and humerus where elbow extension is close to 10° Supine: tested arm is placed at 90° shoulder abduct ion with forearm supinated. Examiner tests for valgus/varus elbow joint play in 0° extension with fingers of one hand palpating the respective medial/lateral joint lines while simultaneously applying counterpressure to the distal humerus with the other hand. Do the joint lines open / is there excessive laxity in either direction? Supine: shoulder placed at 0° flexion/abduction, el bow flexed to 90°. Examiner passively moves the for earm from maximal supination to maximal pronation, looking down the forearm, visualising the line between the epicondyles of the humerus as a reference point. Is there >180° in total? Sitting: upright with hand on lap, examiner grasps lower humerus with one hand, while palpating the greater tubercle of the humerus proximally and stabilising the trunk with the other hand. A moderate to strong downwards pressure is applied to distract the humeral head from the acromion. Is there a visual or palpable sulcus between the acromion and humeral head? Sitting: patient's forearm supinated resting on the desk, the examiner stabilizes the distal radius and performs a volarly-directed passive accessory glide to the head of ulna. Repeat in forearm pronation. Is there equal or more glide in pronation compared to supination? Sitting: elbow resting on the plinth/table flexed to 90°, forearm pronated and wrist flexed, the patie nt takes their thumb towards the volar surface of their radius. Can more than just the tip of the thumb approximate the forearm? Sitting: forearm and hand resting on the desk, the examiner passively extends digits 2, 3, 4 and 5 at the MCP one at a time, allowing the interphalangeal joints to flex. Do any of the four MCPs extend >90°? * An inclinometer can be used where the MCP extension is close to 90° rd Sitting: pronated forearm arm resting on the plinth, the middle of the head of the 3 metacarpal, and the midline of the proximal forearm are marked. The axis of the goniometer is placed at the midpoint of the radiocarpal joint dorsally, and its arms are aligned with the two marks. The examiner passively moves the hand from maximal radial to maximal ulnar deviation. Is there >60° in total? Sitting: with forearm pronated, rest patient’s hand on paper. Patient is encouraged to spread their fingers maximally. Mark the paper at Length st th Span1 the tips of the 1 and 5 digits recording span in millimetres (numerator). Repeat x2. The distance from the centre of the distal wrist Span2 crease to the tip of the middle finger is measured in mm (denominator). The ratio is calculated as Span / Length. Is the result >1.2? Standing: patient standing beside table, carpals and metacarpals of tested wrist on the desk, MCP and interphalangeal joints and thumb flexed over the edge of the desk. Patient moves the forearm over the fixed hand by slowly lunging forward, ensuring heel of hand is in full contact with desk, to extend the wrist. Is there >90° wrist extension? *an inclinometer can be used where the wrist extension is close to 90° L=
8. Wrist Flexion & Thumb Abduction nd th 9. 2 - 5 Metacarpophalangeal (MCP) Extension 10. Wrist Radial/Ulnar Deviation 11. Handspan: Hand Length 12. Wrist Extension
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7. Distal Radioulnar Joint Play
Table 1: The Upper Limb Hypermobility Assessment Tool Page | 7
RIGHT Yes No
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4. Elbow Varus/Valgus Joint Play 5. Radioulnar Joint Supination/ Pronation 6. Sulcus Sign
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3. Elbow Extension
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2. Shoulder Rotation
LEFT Yes No
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Test Name
Length Span1 Span2
R=
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Performed by Patient
Plane of Standardised by movement Sagittal • Thoracolumbar stabilization • Gravity - allow 10 seconds at ends of range
Cut point used 180°
Shoulder Rotation
Passive Physiological
Examiner
180°
Elbow Extension
Passive Physiological
Patient
Transverse • Maintaining supported shoulder in 90° abduction • Gravity - allow 10 seconds at ends of range Sagittal • Gravity - allow 10 seconds at ends of range
Elbow Valgus/Varus
Passive Accessory
Examiner
Radioulnar Joint Supination/ Pronation
Passive Physiological
Examiner
Sulcus Sign
Passive Accessory Passive Accessory
Examiner
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• Moderate force only is used • Ensure patient is relaxed Transverse • Ensure good stabilisation of the distal radius • If equivocal score as negative
Visual or palpable sulcus Joint play in pronation ≥ supination
• Elbow flexed so ECRL and ECRB do not limit wrist flexion • Patient asked to not cause discomfort • PIP joint and elbow are flexed so FDS does not limit range
More than tip of thumb contacts forearm
N/A
Wrist Flexion & Thumb Abduction
Passive physiological
Patient
Sagittal
2nd-5th MCP Extension
Passive Physiological
Examiner
Sagittal
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Joint line opening minimal force >180°
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Examiner
>10°
• Perform in 0° elbow extension, neutral forearm • Apply force along joint line Transverse • Perform in 90° elbow flexion • Moderate overpressure applied Coronal
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Distal Radioulnar Joint (DRUJ) play
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Shoulder Flexion
Type of movement Passive Physiological
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Test
>90°
“Normal” range in adults 164°±12.5 (26) 167°±5 (27) 180° (28) 170° (29) 90° MR + 90° ER = 180° total (30) 69° MR + 104° ER = 173° (27) 90° MR + 90° LR = 180° (28) 70° MR + 90° LR = 160° (29) 0° (30) 0° (28) 0.6°±3 (27) 10° (29) Minimal joint line opening should occur in either direction 80° P + 80° S = 160° total (30) 76°P + 82° S = 158° (27) 90° P +90° S = 180° (28) 90° P + 90° S = 180° (29) No sulcus should appear between the acromion and humeral head The Interosseous Membrane is less taut in supination compared to the pronation position, so less volar and dorsal DRUJ accessory motion should occur in pronation (31-33) Wrist Flexion 90° (28) Wrist Flexion 80° (29) No thumb to forearm contact Beighton – apposition thumb tip constitutes a point 30° (28) 45° (29) <90 (3)
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Active Physiological
Patient
Coronal
• Moderate force is used • Patient needs to keep the hand flat
>180°
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Wrist Radial/Ulnar Deviation
20° RD + 30° UD 50° total (30) 22° RD + 36° UD 58° total (27) 25° RD + 35° UD 60° (28) 20° RD + 40° UD 60° (29) Mean ratio was determined by the current study was 1.14 (0.04)
>1.2 • Wrist maintained in neutral deviation • Patient encouraged to spread as wide as possible Wrist Passive Patient Sagittal • Heel of hand to be kept in >90° 60° (30) Extension Physiological contact with the table top 75° ± 6.5 (27) • Fingers and thumb flexed so 70° (28) their muscles/tendons do not 60° (29) limit wrist extension MR Medial Rotation; LR Lateral Rotation; ECRL Extensor Carpi Radialis Longus; ECRB Extensor Carpi Radialis Brevis; MCP Metacarpophalangeal Joint; PIP Proximal Interphalangeal Joint; FDS Flexor Digitorum Superficialis; RD Radial Deviation; UD Ulnar Deviation. Active Physiological
Patient
Coronal
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Handspan: Hand Length
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Table 2: Rationale for criterion cut-offs
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ACCEPTED MANUSCRIPT The supplement provides a photographic explanation of each test to enable standardized use by clinicians and researchers. The only component test that has not been documented previously is the handspan test. To determine “normal” span, we tested 43 healthy adult participants whose Beighton score was less than 4/9 and LLAS less than 7/12. None of the
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participants had a reason to have acquired hand hypermobility (such as musical instrument playing). The mean (SD) handspan to length ratio was 1.14 (0.04). The ULHAT is performed on both upper limbs, each providing a score to a maximum of 12. The reliability of the
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ULHAT was assessed in a pilot study of the initial 20 participants (10 control and 10 known hypermobile participants), where inter-rater reliability was assessed using a two-way random
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absolute agreement, single measures intraclass correlation coefficient. This revealed excellent inter-rater reliability (ICC2,1= 0.92, 95% CI = 0.89 to 0.97, p <0.001)(34). Therefore, a single examiner assessed the remaining participants.
To enable validation of the ULHAT, a gold standard against which to test its ability to identify
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GJH was required. Both researchers, experienced musculoskeletal physiotherapists, individually allocated each participant to one of three clinical opinion groups (normal, borderline hypermobile and hypermobile). The allocation was based on their history of
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instability episodes, whether they met the ≥2/5 self-perceived hypermobility criterion of the historical Hakim 5-part questionnaire and their clinical presentation including the
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comprehensive physical assessment of lower limb joint mobility (LLAS) in line with current best practice (1, 35). Any disagreement on group allocation were discussed and resolved. Participants provided written informed consent prior to data collection. Ethical approval was gained from the Human Research Ethics Committees of XXXXXXXXXXX [Protocol No. 2015/465] and XXXXXXXXXXXXXXXXXXXXXX [Protocol No. 13174].
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ACCEPTED MANUSCRIPT Statistical Analysis Data were anonymized, coded and analyzed having been inspected for outliers and tested for normality using calculations of skewness to determine whether parametric or non-
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parametric tests were to be carried out. Analysis was performed using SPSS Version 21 (IBM, NY, USA). Between-group demographic variables of age, gender and ethnicity were subject to descriptive analysis. The associations between the continuous variables of age, and Beighton and ULHAT scores were tested with Pearson’s correlation coefficient (r). A
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correlation of r ≤0.35 was considered to be weak, 0.36-0.67 moderate, and ≥0.68 a strong correlation (36). While the literature reports no significant side-to-side difference in many
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lower limb range of motion tests (19, 37, 38), upper limb dominance may confer side-to-side differences. If the correlation coefficient between sides is strong and significant, we can infer hypermobility from a single side.
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To test the null hypothesis of no significant difference between the three cohorts (control, likely and known hypermobile participants) when using the Beighton score or the ULHAT, a multivariate analysis of variance (MANOVA) was performed, followed by post-hoc analyses
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(Tukey HSD). Effect sizes (partial η2) greater than 0.01 were considered small differences, greater than 0.06 were considered medium differences, and values greater than 0.14 were
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representative of a large difference between groups (39).
Median and inter-quartile ranges for each clinical opinion group (normal, borderline and hypermobile) estimated the cut-off score to represent hypermobility when using the ULHAT. The sensitivity and specificity for each level of the ULHAT were determined using Receiver Operator Characteristic (ROC) curve analysis. The optimal cut-off score on the ROC curve was considered to be the point closest to the top left hand side of the y-axis, maximising the true positive rate and minimizing the false positive rate (40). Positive and negative likelihood ratios were calculated for the determined cut-off point, combining the utility of sensitivity and Page | 11
ACCEPTED MANUSCRIPT specificity (40). Clinical opinion was used as the gold standard for this analysis, and because McNemar’s Test analysis required dichotomous classification, the participants who were initially categorized as “borderline hypermobile,” were reclassified as normally mobile. This reclassification was based on the conclusion that if the clinicians were uncertain of the
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diagnosis, then the participant was less likely to be generally hypermobile. Finally, the ULHAT, Beighton score, and clinical opinion were compared to determine if either the ULHAT or Beighton score could be used to accurately predict GJH. Cut-off scores of ≥4/9
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and ≥5/9 were used for the diagnosis of GJH when using the Beighton score (41). To test the null hypothesis of no difference in identification of GJH between the measures, percentage
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agreement between the tools was calculated and the significance was determined using McNemar’s test. For this study, a p-value <0.05 was considered significant and the power was set at 0.95 to minimise the possibility of type II errors.
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3. Results
Participant demographic data is detailed in Table 3. The ethnic breakdown of each group revealed that the majority of participants were Caucasian (79%). While participants ranged in
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age between 18 and 40 years, the known hypermobile group was significantly older than both the controls and the likely hypermobile group (both p<0.001). Gender n (%)
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Cohort
Age (years) ± SD
Ethnicity n (%)
Control
M: 11 (28%)
22.6 ± 2.8
Caucasian: 24 (60%)
(n = 40)
F: 29 (72%)
Range:19-32
Asian: 12 (30%) Other: 4 (10%)
Likely
M: 16 (40%)
22.6 ± 4.4
Caucasian: 34 (85%)
Hypermobile
F: 24 (60%)
Range:18-33
Asian: 4 (10%)
(n = 40) Known
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Other: 2 (5%) M: 1 (3%)
28.4 ± 6.9
Caucasian: 30 (94%)
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F: 31 (97%)
Range:18-40
Asian: 0 (0%)
(n = 32)
Other: 2 (6%)
Total cohort
M: 28 (25%)
24.3 ± 5.5
Caucasian: 88 (79%)
(n = 112)
F: 84 (75%)
Range:18-40
Asian: 16 (14%)
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Other: 8 (7%)
Table 3: Demographic data of the three subgroups and the entire cohort
The ULHAT score for the left and right limbs of the whole cohort were highly and significantly
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correlated (r=0.87, p=0.001). As a result, the ULHAT was recorded as a score out of 12 for a
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randomly chosen limb, rather than out of a total of 24 for both limbs of all participants (42). The correlation between limbs was lower in the known hypermobile group; whilst still demonstrating a strong correlation, it did not reach significance (Table 4).
Control Likely Hypermobile
Whole Cohort
ULHAT
Pearson’s
Significance
Left
Right
Correlation
Level
4.1(2.3)
3.5(2.6)
0.85
0.01
5.8(1.6)
5.3(2.0)
0.79
0.01
7.8(2.0)
7.6(2.0)
0.69
0.43
5.3(2.8)
0.87
0.001
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Known Hypermobile
ULHAT
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Group
5.8 (2.5)
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Table 4: Side to side mean (SD) scores for the ULHAT across the three groups and entire cohort
3.1 Does the ULHAT discriminate between extents of hypermobility? The proportion of participants who achieved a total ULHAT score between 0 and 12 was examined (Figure 2). The distribution of the scores suggests that the ULHAT discriminated between the three groups with the largest overlap at 5 of the possible 12. The MANOVA confirmed a statistically significant difference between the three groups (Pillai’s Trace = 0.38, Page | 13
ACCEPTED MANUSCRIPT F(4.0, 218.0) = 13.0, p<0.001), with an effect size (partial η2) of 0.36 meaning that 36% of the variability in the ULHAT score is explained by group allocation. Statistically significant differences in the mean ULHAT score between all three groups was revealed with post-hoc analysis (Tukey HSD). The mean difference between control and likely hypermobile
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participants was -1.7 (95%CI -2.78 to -0.62; p=0.001), between control and hypermobile participants was -3.72 (95%CI -4.87 to -2.57; p< 0.001) and between likely and known
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hypermobile participants was -2.02 (95%CI -3.17 to -0.87; p<0.001).
Figure 2: Number of participants who scored each of the 12 levels of the Upper Limb Hypermobility Assessment Tool 3.2 Is upper limb mobility measured using the ULHAT associated with age, gender or ethnicity? A weak and non-significant correlation between age of the whole cohort and the extent of their upper limb mobility was found. With participants self-categorized as Caucasian or nonCaucasian, weak correlation was found between ethnicity and upper limb mobility.
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ACCEPTED MANUSCRIPT Conversely, moderate correlation was found between upper limb mobility and gender across the whole cohort. However, when the correlation was considered for each of the three groups, the moderate correlation was found only for the controls and likely hypermobile
Ethnicity
Significance
Correlation
Level
Control
-0.11
0.52
Likely Hypermobile
-0.23
Known Hypermobile
-0.14
Entire Cohort
0.15
0.12
0.25
0.12
0.01
0.99
0.02
0.91
Control Likely Hypermobile
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Known Hypermobile
0.16
0.46
Entire Cohort
0.08
0.38
Control
0.55
<0.001
Likely Hypermobile
0.48
0.002
Known Hypermobile
0.17
0.35
Entire Cohort
0.46
<0.001
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Gender
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Age
Pearson’s
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Demographic Group
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groups but not for the known hypermobile group (Table 5).
Table 5: Correlation between upper limb joint mobility and age, ethnicity and gender for each subgroup and the entire cohort.
3.3 Establishing a cut-off score for the identification of upper limb hypermobility The median and interquartile ranges for the ULHAT total score across the three clinically defined groups are represented in Figure 3. This figure suggests that a cut-off score of seven to eight would differentiate the controls from the known hypermobile participants, with Page | 15
ACCEPTED MANUSCRIPT minimal overlap with the borderline hypermobile individuals. This observation was confirmed by the ROC Curve presented in Figure 4 where the point on the curve closest to the top lefthand corner corresponded to a cut off score of 7. At this point the sensitivity and specificity were highest at 0.84 and 0.77 respectively, producing a positive likelihood ratio of 3.7 and a
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negative likelihood ratio of 0.2.
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Figure 3: Median and interquartile ranges of the Upper Limb Hypermobility Assessment Tool
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across the clinically defined groups. The dotted line represents the score of 8/12.
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Figure 4: Receiver Operator Characteristic Curve for the Upper Limb Hypermobility
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Assessment Tool
Given that the majority of the participants were Caucasian and only a weak correlation was
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observed between upper limb mobility and ethnicity, the analysis was repeated excluding the 24 non-Caucasians. This resulted in a cohort of 88 participants (24 controls, 34 likely hypermobile and 30 known hypermobile participants). The ROC analysis revealed the same cut-off score of 7/12, with a higher sensitivity of 0.86, specificity of 0.84, positive likelihood
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ratio of 5.4 and a negative likelihood ratio of 0.2.
3.4 Comparing the Upper Limb Hypermobility Assessment Tool Score with clinical opinion:
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Can the ULHAT be used to accurately identify GJH? On the basis of clinical opinion, 3% of control, 23% of likely hypermobile and 94% of known
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hypermobile participants were identified as generally hypermobile. Having identified a cut-off score of ≥7/12 for the identification of upper limb hypermobility, the ULHAT identified upper limb hypermobility in 15% control, 35% likely hypermobile and 81% known hypermobile participants. High levels of agreement were found between the ULHAT and clinical opinion across each group, especially in the control group at 88% agreement, followed by the known hypermobile group at 81% and the likely hypermobile group at 78%. McNemar’s Test confirmed no significant difference in agreement between clinical opinion of generalized hypermobility and the ULHAT at this cut-off score for all three subgroups (all p>0.06). By comparison, a Beighton score cut-off of ≥4/9 revealed low to moderate levels of agreement Page | 17
ACCEPTED MANUSCRIPT with clinical opinion for the control and likely hypermobile groups (48% and 45% respectively), and high levels of agreement only with the known hypermobile group at 91%. Utilizing a Beighton cut-off score of ≥5/9 improved the moderate levels of agreement with clinical opinion for the control and likely hypermobile groups (58% for both), while
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maintaining high levels of agreement with the known hypermobile group at 88%. Having identified a cut-off score of ≥5/9 for the identification of GJH, the Beighton scoring system identified GJH in 45% control, 60% likely hypermobile and 94% known hypermobile
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participants. With the more stringent cut-off of ≥5/9 and higher agreement with clinical opinion, the McNemar’s test still revealed a significant difference in the agreement between
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clinical opinion of generalized hypermobility and the Beighton score for the control and likely hypermobile participants (p<0.001), but not in the known hypermobile group (p=1.0).
4. Discussion
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The newly developed Upper Limb Hypermobility Assessment Tool is a reliable and valid instrument for the identification of both upper limb and generalized hypermobility in an adult population. A cut-off point of ≥7/12 was identified as the score that best identifies those with
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upper limb hypermobility from those without. The high sensitivity and specificity results in a positive likelihood ratio greater than 3 and a negative likelihood ratio less than 0.3,
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suggesting that the ULHAT is useful in determining an accurate post-test probability of a person having upper limb hypermobility (43). When using the ULHAT score as a continuous measure, from 0 to 12, upper limb hypermobility was not demonstrated to decrease with age. This finding is in contrast to the hypermobility of the lower limb, where the LLAS was found to decrease with age in those with normal joint mobility (20). Similarly, generalized joint hypermobility as identified using the Beighton scoring system has been reported to decrease with age (6, 44). We pose two hypotheses to explain the different findings. The first relates to the age range of the sample Page | 18
ACCEPTED MANUSCRIPT in the current study. The participants in this study were aged between 18 and 40 years. It is possible that hypermobility of the upper limb decreases after the 5th decade of life. This hypothesis is supported by a study of 1000 healthy Australians, aged 3 to 101 suggesting that the Beighton cut-off reduces after 40 years of age, particularly in males (2). The second
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hypothesis relates to load. Joints of the lower limb are subject to greater and more frequent sustained loading associated with weight bearing and ambulation, and may therefore be prone to stiffening associated with degeneration (45). Indeed, 65% of joints affected by
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osteoarthritis are found in the lower limb (46). The upper limb may be less susceptible to high sustained joint loading, hence less resultant stiffening.
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A significant difference in the extent of upper limb hypermobility was found between sides of the body with the left demonstrating greater mobility than the right. We hypothesize that this might be due to dominance of the right upper limb whereby greater use may confer stiffness. This hypothesis agrees with the findings of other researchers who report reduced range in
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the dominant limb of normal participants (47, 48). We did not record dominance however and are assuming that most participants, possibly up to 90%, were right hand dominant as this is consistent with the population normative data (49). While the entire cohort exhibited this
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reduced right-sided joint mobility, when groups were considered individually, the known hypermobile group did not demonstrate a side-to-side difference (p = 0.43). Our hypothesis
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for this finding is that their symptomatic hypermobility, manifesting as joint pain and instability, has resulted in equivocal use of both sides and consequently more bilaterallydistributed joint micro-trauma. 4.1 Clinical Relevance and Impact The ULHAT was used as a dichotomous screening tool to identify the presence or absence of generalized joint hypermobility, compared with the gold-standard of clinical opinion. A positive ULHAT score (≥7/12) appeared to concur with identification of generalized joint hypermobility across the three recruited subgroups. The high agreement between the
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ACCEPTED MANUSCRIPT identification of generalized hypermobility using the ULHAT and that of clinical opinion was significant, suggesting that the two criteria are measuring the same dimension. Surprisingly, this was not the case when clinical opinion was compared with the Beighton Scoring system, where the latter significantly overestimated the prevalence of GJH in controls and likely
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hypermobile participants even at a cut-point of ≥5/9. This suggests that they are not
measuring the same dimension and that identifying GJH on the basis of the Beighton alone may be insufficient. Consequently, we recommend that researchers and clinicians can
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confidently use the Beighton score to rule out the presence of GJH while using the ULHAT to rule in the presence of upper limb specific and generalized joint hypermobility. Finally, the
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intended use of the ULHAT extends to screening in occupational and sporting populations, early identification of possible risk factors for injury and provision of joint specific data enabling targeted management.
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4.2 Limitations and directions for future research
There is no gold standard test for generalised joint hypermobility. Traditionally, a participant’s Beighton score has been used however, the low number of joints tested in only one plane
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and the inconsistency in reported prevalence, raise questions as to its validity. Following current best practice recommendations, this study employed the consensus clinical opinion
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of two experienced musculoskeletal physiotherapists who undertook thorough subjective and physical assessments of participants, as the gold standard against which the ULHAT and Beighton scoring system were tested. Future research will determine the ideal test or combination of tests to optimally identify GJH. As some of the individual ULHAT tests require manual therapy skills and clinical judgement, the reliability of the ULHAT needs to be established using less experienced examiners. Since the majority of our participants were female and all were between the ages of 18-40 years, future research should determine the validity of the ULHAT and a cut-point in a more gender-balanced adult and paediatric
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ACCEPTED MANUSCRIPT population. Twenty-one percent of our cohort were non-Caucasian and this represents the typical Australian population (50). Given that ethnicity has been previously proposed to be a contributing factor to joint mobility, we determined the cut-off score excluding the nonCaucasian participants, hypothesising that the cut-off score would be lower. However, this
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was not the case resulting in the same cut-off value, with a similarly high sensitivity and specificity. Hence, we cautiously suggest that a cut-off score of ≥7/12 is applicable to the general Australian population but possibly ≥8/12 in a non-Caucasian population. Finally,
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whether all 12 items of the ULHAT are necessary, measuring different dimensions of upper limb hypermobility is currently unknown. Accordingly, the tool’s internal construct validity
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8. 9. 10. 11.
12.
13.
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16.
17.
18.
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HAKIM A, GRAHAME R: Joint hypermobility. Best Practice & Research Clinical Rheumatology 2003; 17: 989-1004. SINGH H, MCKAY M, BALDWIN J et al.: Beighton scores and cut-offs across the lifespan: cross-sectional study of an Australian population. Rheumatology (Oxford) 2017kex043. BEIGHTON P, SOLOMON L, SOSKOLNE C: Articular mobility in an African population. Annals of the rheumatic diseases 1973; 32: 413. JANSSON A, SAARTOK T, WERNER S, RENSTRÖM P: General joint laxity in 1845 Swedish school children of different ages: age-and gender-specific distributions. Acta paediatrica 2004; 93: 1202-06. CLINCH J, DEERE K, SAYERS A et al.: Epidemiology of generalized joint laxity (hypermobility) in fourteen-year-old children from the UK: A population-based evaluation. Arthritis & Rheumatism 2011; 63: 2819-27. REMVIG L, JENSEN DV, WARD RC: Epidemiology of general joint hypermobility and basis for the proposed criteria for benign joint hypermobility syndrome: review of the literature. The Journal of rheumatology 2007; 34: 804-09. MALFAIT F, FRANCOMANO C, BYERS P et al.: The 2017 international classification of the Ehlers–Danlos syndromes. In: American Journal of Medical Genetics Part C: Seminars in Medical Genetics: 2017: Wiley Online Library; 2017: 8-26. KLEMP P, STEVENS J, ISAACS S: A hypermobility study in ballet dancers. The Journal of rheumatology 1984; 11: 692-96. GRAHAME R: Joint hypermobility and genetic collagen disorders: are they related? Archives of disease in childhood 1999; 80: 188-91. GANNON L, BIRD H: The quantification of joint laxity in dancers and gymnasts. J Sports Sci 1999; 17: 743-50. TOBIAS JH, DEERE K, PALMER S, CLARK EM, CLINCH J: Joint hypermobility is a risk factor for musculoskeletal pain during adolescence: findings of a prospective cohort study. Arthritis & Rheumatology 2013; 65: 1107-15. CAMERON KL, DUFFEY ML, DEBERARDINO TM, STONEMAN PD, JONES CJ, OWENS BD: Association of generalized joint hypermobility with a history of glenohumeral joint instability. Journal of athletic training 2010; 45: 253-58. ELLENBECKER TS, COOLS A: Rehabilitation of shoulder impingement syndrome and rotator cuff injuries: an evidence-based review. British journal of sports medicine 2010; 44: 319-27. HAKIM AJ, MALFAIT F, DE PAEPE A: The heritable disorders of connective tissue: epidemiology, nosology and clinical features. In HAKIM AJ, KEER R, GRAHAME R (Eds.): Hypermobility, fibromyalgia and chronic pain. Churchill Livingstone/Elsevier 2010: 3-17. VOERMANS NC, KNOOP H, BLEIJENBERG G, VAN ENGELEN BG: Pain in Ehlers-Danlos syndrome is common, severe, and associated with functional impairment. Journal of pain and symptom management 2010; 40: 370-78. QUARRIER NF: Is hypermobility syndrome (HMS) a contributing factor for chronic unspecific wrist pain in a musician? If so, how is it evaluated and managed? Work 2011; 40: 325-33. EVANS AM, ROME K, PEET L: The foot posture index, ankle lunge test, Beighton scale and the lower limb assessment score in healthy children: a reliability study. Journal of foot and ankle research 2012; 5: 1. CASTORI M, TINKLE B, LEVY H, GRAHAME R, MALFAIT F, HAKIM A: A framework for the classification of joint hypermobility and related conditions. In: American Journal of Medical Genetics Part C: Seminars in Medical Genetics: 2017: Wiley Online Library; 2017.
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1.
Page | 22
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25.
26.
27. 28. 29. 30. 31. 32.
33.
34. 35.
36. 37.
38.
RI PT
24.
SC
23.
M AN U
22.
TE D
21.
EP
20.
FERRARI J, PARSLOW C, LIM E, HAYWARD A: Pediatric rheumatology joint hypermobility: The use of a new assessment tool to measure lower limb hypermobility. Clin Exp Rheumatol 2005; 23: 413-20. MEYER K, CHAN C, HOPPER L, NICHOLSON LL: Identifying lower limb specific and generalised joint hypermobility in adults: validation of the Lower Limb Assessment Score. BMC Musculoskeletal Disorders 2017; 18: 1-9. TINKLE BT, BIRD HA, GRAHAME R, LAVALLEE M, LEVY HP, SILLENCE D: The lack of clinical distinction between the hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome (aka hypermobility syndrome). Am J Med Genet A 2009; 149: 2368-70. BEIGHTON P, DE PAEPE A, STEINMANN B, TSIPOURAS P, WENSTRUP RJ: Ehlers-Danlos syndromes: revised nosology. am J Med genet 1998; 77: 31-37. SCHEPER MC, DE VRIES JE, DE VOS R, VERBUNT J, NOLLET F, ENGELBERT RH: Generalized joint hypermobility in professional dancers: a sign of talent or vulnerability? Rheumatology (Oxford) 2012kes220. ANDERSON AS, LOESER RF: Why is osteoarthritis an age-related disease? Best Practice & Research Clinical Rheumatology 2010; 24: 15-26. HAKIM A, GRAHAME R: A simple questionnaire to detect hypermobility: an adjunct to the assessment of patients with diffuse musculoskeletal pain. International journal of clinical practice 2003; 57: 163-66. SABARI JS, MALTZEV I, LUBARSKY D, LISZKAY E, HOMEL P: Goniometric assessment of shoulder range of motion: comparison of testing in supine and sitting positions. Archives of physical medicine and rehabilitation 1998; 79: 647-51. BOONE DC, AZEN SP: Normal range of motion of joints in male subjects. JBJS 1979; 61: 756-59. PALMER ML, EPLER ME, EPLER MF: Fundamentals of musculoskeletal assessment techniques: Lippincott Williams & Wilkins; 1998. SCHÜNKE M, SCHULTE E, SCHUMACHER U, ROSS LM, LAMPERTI ED: Thieme atlas of anatomy: general anatomy and musculoskeletal system, vol. 1: Thieme Stuttgart; 2006. ASSOCIATION AM: Guides to the evaluation of permanent impairment: American Medical Association Press; 1990. SKAHEN JR, PALMER AK, WERNER FW, FORTINO MD: Reconstruction of the interosseous membrane of the forearm in cadavers. The Journal of hand surgery 1997; 22: 986-94. WATANABE H, BERGER RA, BERGLUND LJ, ZOBITZ ME, AN K-N: Contribution of the interosseous membrane to distal radioulnar joint constraint. The Journal of hand surgery 2005; 30: 1164-71. GABL M, ZIMMERMANN R, ANGERMANN P et al.: The interosseous membrane and its influence on the distal radioulnar joint: an anatomical investigation of the distal tract. The Journal of Hand Surgery: British & European Volume 1998; 23: 179-82. FLEISS JL: Design and analysis of clinical experiments, vol. 73: John Wiley & Sons; 2011. CASTORI M, TINKLE B, LEVY H, GRAHAME R, MALFAIT F, HAKIM A: A framework for the classification of joint hypermobility and related conditions. In: American Journal of Medical Genetics Part C: Seminars in Medical Genetics: 2017: Wiley Online Library; 2017: 148-57. TAYLOR R: Interpretation of the correlation coefficient: a basic review. Journal of diagnostic medical sonography 1990; 6: 35-39. BENNELL K, KHAN K, MATTHEWS B, SINGLETON C: Changes in hip and ankle range of motion and hip muscle strength in 8–11 year old novice female ballet dancers and controls: a 12 month follow up study. British journal of sports medicine 2001; 35: 54-59. MORRISON SC, FERRARI J: Inter-rater reliability of the Foot Posture Index (FPI-6) in the assessment of the paediatric foot. Journal of foot and ankle research 2009; 2: 1.
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19.
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44.
45. 46.
47.
48.
49.
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EP
50.
RI PT
43.
SC
41. 42.
M AN U
40.
COHEN J: Statistical power analysis for the behavioral sciences, vol. 2nd. Hillsdale, N.J: L. Erlbaum Associates; 1988. PEAT J, BARTON B: Medical statistics: A guide to data analysis and critical appraisal: John Wiley & Sons; 2008. GRAHAME R: Joint hypermobility syndrome pain. Current Science Inc 2009; 13: 427-33. GRAY K, GIBBONS P, LITTLE D, BURNS J: Bilateral clubfeet are highly correlated: a cautionary tale for researchers. Clinical orthopaedics and related research 2014; 472: 3517. SACKETT DL: Evidence-based Medicine How to practice and teach EBM: WB Saunders Company; 1997. KWON J-W, LEE W-J, PARK S-B, KIM MJ, JANG SH, CHOI CK: Generalized joint hypermobility in healthy female Koreans: prevalence and age-related differences. Annals of rehabilitation medicine 2013; 37: 832-38. ARDEN N, NEVITT MC: Osteoarthritis: epidemiology. Best practice & research Clinical rheumatology 2006; 20: 3-25. CUSHNAGHAN J, DIEPPE P: Study of 500 patients with limb joint osteoarthritis. I. Analysis by age, sex, and distribution of symptomatic joint sites. Annals of the rheumatic diseases 1991; 50: 8-13. ALLANDER E, BJÖRNSSON O, OLAFSSON O, SIGFUSSON N, THORSTEINSSON J: Normal range of joint movements in shoulder, hip, wrist and thumb with special reference to side: a comparison between two populations. International Journal of Epidemiology 1974; 3: 253-61. GÜNAL I, KÖSE N, ERDOGAN O, GÖKTÜRK E, SEBER S: Normal range of motion of the joints of the upper extremity in male subjects, with special reference to side. JBJS 1996; 78: 1401-4. MCMANUS C: Right hand, left hand: The origins of asymmetry in brains, bodies, atoms and cultures: Harvard University Press; 2004. BALDWIN JN, MCKAY MJ, MOLONEY N et al.: Reference values and factors associated with musculoskeletal symptoms in healthy adolescents and adults. Musculoskeletal Science and Practice 2017; 29: 99-107.
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ACCEPTED MANUSCRIPT Acknowledgements The authors would like to acknowledge the invaluable assistance of Dr Luke Hopper and Jenny Woods who were responsible for participant recruitment at the West Australian Academy of the Arts and the West Australian Ballet respectively. Thanks also to Dr Claire
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Hiller, Dr Verity Pacey, Feili Zhang and Kaitlin Meyer who assisted with data collection and entry. This study was funded by a BRIG grant from the Discipline of Biomedical Science at
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The University of Sydney.
ACCEPTED MANUSCRIPT Highlights •
Targeted quantification of upper limb hypermobility has eluded practitioners The Beighton score lacks face validity to identify upper limb hypermobility The Upper Limb Hypermobility Assessment Tool is described and validated
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The tool comprises 12 passive accessory and physiological joint mobility tests
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A cut-off point of 7/12 identifies upper limb and generalised joint hypermobility
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S2468-7812(18)30046-8
DOI:
10.1016/j.msksp.2018.02.006
Reference:
MSKSP 167
To appear in:
Musculoskeletal Science and Practice
Received Date: 3 October 2017 Revised Date:
8 January 2018
Accepted Date: 19 February 2018
Please cite this article as: Nicholson, L.L., Chan, C., The Upper Limb Hypermobility Assessment Tool: A novel validated measure of adult joint mobility, Musculoskeletal Science and Practice (2018), doi: 10.1016/j.msksp.2018.02.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT The Upper Limb Hypermobility Assessment Tool: A novel validated measure of adult joint mobility
Short running title: The Upper Limb Hypermobility Assessment Tool
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Associate Professor Leslie L Nicholsona,b 75 East St Lidcombe, NSW 2141 (Australia) Email: [email protected]
75 East St Lidcombe, NSW 2141 (Australia)
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Email: [email protected]
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Dr Cliffton Chana,b
a
The University of Sydney, Discipline of Biomedical Science, Sydney Medical School
b
The Hypermobility and Performance Laboratory, Bosch Institute, The University of Sydney
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Corresponding Author: Associate Professor Leslie L Nicholson
ACCEPTED MANUSCRIPT The Upper Limb Hypermobility Assessment Tool: A novel validated measure of adult joint mobility
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Short running title: The Upper Limb Hypermobility Assessment Tool
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ACCEPTED MANUSCRIPT ABSTRACT Background: Existing measures of generalized joint hypermobility do not include commonly affected upper limb joints.
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Objective: To evaluate the reliability of a novel clinically-applicable measure of upper limb joint mobility, its ability to discriminate between varying extents of hypermobility, identify generalized joint hypermobility, and to establish a cut-point for hypermobility classification.
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Design: Validation of a diagnostic tool
Method: Participants were sought from three groups - healthy controls, likely and known
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hypermobiles, and assessed using the Upper Limb Hypermobility Assessment Tool (ULHAT), Beighton score and clinical opinion. Pearson's correlation coefficient examined individual group and whole cohort relationships between upper limb hypermobility, age, gender and ethnicity. MANOVA investigated between-group differences in ULHAT scores.
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Median interquartile ranges and ROC Curve analysis identified the cut-off score for identification of upper limb hypermobility. Percent agreement with clinical opinion assessed the ability of the ULHAT to identify generalized joint hypermobility.
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Results: 112 adult participants (mean age 24.3 ± 5.5years) across the three groups were assessed. Inter-rater reliability of the tool was high (ICC2,1= 0.92). The cut-point was
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established at ≥7/12 (sensitivity 0.84, specificity 0.77, +LR 3.7, -LR 0.2). Upper limb hypermobility did not vary with age or ethnicity (both p>0.12), but was greater in females (p<0.001). The ULHAT discriminated between the three groups and identified generalized hypermobility.
Conclusions: The 12-item ULHAT measures mobility of multiple upper limb joints in all movement planes. Using a cut-off of ≥7/12 in adults, the ULHAT is a reliable and valid tool for identifying upper limb hypermobility and generalized joint hypermobility.
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ACCEPTED MANUSCRIPT Key Words: Generalized Joint Hypermobility, Ehlers-Danlos Syndrome, measurement, clinical assessment
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1. Introduction Generalized joint hypermobility (GJH) is an asymptomatic condition characterized by
greater than normal passive and active range, in at least four joints and in at least one plane of motion (1). The extent of GJH varies with respect to age, gender and ethnicity.
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By describing an individual as “hypermobile”, the assumption is that their joint mobility is
uppermost 5% of the population (2).
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greater than 95% of the population, or that their joint mobility places them in the
Since 1973, the Beighton scoring system has been used for classification of an individual’s joint mobility (3). One point is allocated for extension of the knees and elbows (bilaterally) past 10º (4 possible points), extension of the 5th metacarpophalangeal (MCP)
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joints (bilaterally) past 90º (2 possible points), apposition of the left and right thumbs to the flexor surface of the ipsilateral radius (2 possible points), and forward trunk and hip flexion to place the palms on the floor (1 possible point), for a total of 9 points. While a range of
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cut-off scores from ≥4/9 to ≥8/9 has been used to classify individuals as hypermobile, the most commonly cited cut-off in adults is ≥4/9 (4-6). A 2017 international consensus
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classification proposes a cut-off of ≥5/9 for GJH, suggesting a traditional overestimation of its prevalence (7).
Hypermobility is a key trait of people with Ehlers-Danlos Syndrome Hypermobility Type (EDS-HT) and Joint Hypermobility Syndrome (JHS), where it is associated with joint instability and pain. While hypermobility may be an inherited trait, it can also be acquired through training (8, 9). Ballet dancers have a high prevalence of spine, hip, knee, ankle and shoulder hypermobility thought to be, at least in part, related to their training (10). Inherited and Page | 3
ACCEPTED MANUSCRIPT acquired hypermobility affects multiple joints of the upper limbs, in all three anatomical planes. Nearly ten percent of adolescents with a Beighton score of ≥6/9 report troublesome shoulder pain, a prevalence second only to low back pain in a sample population of 2,901 (11). In a study of 1,311 military academy freshmen, a significant
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relationship was found between GJH and glenohumeral instability; those defined as
having GJH using the Beighton scoring system were 2.5 times more likely to report a history of shoulder instability (12). Most commonly, this instability occurs in the coronal
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and horizontal planes. Indeed, failing to recognize hypermobility as a cause of
multidirectional glenohumeral instability sometimes results in inappropriate management
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and prolonged prognosis, especially detrimental to the rehabilitation of the throwing athlete (13). The shoulder is most commonly identified as unstable in people with symptomatic hypermobility disorders such as EDS-HT and JHS (14), with pain most frequently localized to the neck, shoulder and forearms (15). Another affected body region is the radioulnar (wrist) joint where hand pain in musicians is suggested to be related to
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multi-planar hypermobility (16). Immediately evident is that the Beighton, despite its upper more than lower limb joint representation, does not include any tests of the shoulder or radioulnar joints. Although a reliable measure (17, 18), the validity of the Beighton scoring
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system as a means of identifying generalized or whole body hypermobility is questionable. Not only does it fail to test commonly hypermobile joints, it assesses joint
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motion in only the sagittal plane. The Lower Limb Assessment Scale (LLAS) developed by Ferrari and colleagues is a reliable and valid measure of lower limb hypermobility and it has been found to correlate highly with clinical opinion of generalized joint hypermobility in both children and adults (19, 20). The LLAS comprises 12 bilateral tests of mobility of the hip, knee, tibiofibular, ankle and foot joints in all 3 planes of motion. The cut-off score for the LLAS has been established as ≥7/12 unilaterally, in both adults and children (19, 20).
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ACCEPTED MANUSCRIPT Currently there is no joint mobility scoring system that focusses on the shoulder, radioulnar, wrist and finger joints (other than the 5th MCP) of the upper limb. The aim of this study was firstly to develop a reliable and clinically-applicable tool to quantify upper limb joint mobility based on the LLAS, to establish a cut-point for classification of upper
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limb hypermobility and finally to validate this tool as a discriminator of both upper limb and generalized joint hypermobility.
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2. Materials and methods
To determine whether the Upper Limb Hypermobility Assessment Tool (ULHAT) can
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identify people with varying extents of upper limb hypermobility, participants were sought from three groups as convenience series, in 2015/2016. The cohort in this study was the same as that reported in a validation study of the LLAS in adults (20). See Figure 1 for a
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graphical representation of the group allocation and recruitment strategies.
EDS-HT: Ehlers-Danlos Syndrome – hypermobility type; JHS: Joint Hypermobility Syndrome.
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ACCEPTED MANUSCRIPT Figure 1: A diagrammatic representation of the inclusion criteria, recruitment process and allocation of participants into the three cohorts
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Participants of either gender were included in the study. Volunteers older than 40 years of age were excluded due to the confounding effect of age-related joint degeneration (24). Participants were excluded if they did not meet the inclusion criteria, had another
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diagnosed rheumatological condition (e.g. Marfans, Stickler’s or Loeys Dietz syndromes), or had an orthopaedic condition with pain, disability or previous trauma that might restrict
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normal range of motion.
Participants were surveyed to collect demographical data (age, gender, ethnicity), clinical history related to joint mobility (perceived instability, occurrence of subluxations/ dislocations), and self-perceived hypermobility (Hakim 5-part questionnaire (25)). All
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participants underwent a single physical testing session that included the Beighton scoring system, the Lower Limb Assessment Scale (LLAS)(19), and the ULHAT.
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The ULHAT was designed as an upper limb analogue of the 12 composite tests of the LLAS, to test the mobility of many joints of the upper limb in multiple planes of motion. These tests
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include passive physiological, passive accessory and active range of motion. For ease of clinical decision making and in keeping with the format of all existing hypermobility assessment tools, (1,3,19) the individual ULHAT tests require only yes/no judgements. The upper limb joints assessed reflect those most commonly affected by instability and the planes in which that instability most frequently occurs (12-16). The twelve tests that comprise the ULHAT and the descriptors for each are found in Table 1, while the rationale for the cut-off values chosen for each test is summarised in Table 2.
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Test Description
1. Shoulder Flexion
Supine: hand of non-tested arm under lumbar spine. Patient gently pushes spine into their hand and maintains position. Examiner raises arm over the head. Can the whole humerus rest easily on the plinth? Supine: shoulder placed at 90° abduction supported by plinth with forearm neutral. Arm is passively rotated from maximal internal to maximal external rotation, with mild pressure applied at end of range. Is there >180° in total? *an inclinometer can be applied against the medial border of the distal ulna where rotation is close to 180° Supine: shoulder placed at 90° abduction supported by plinth, forearm supinated. Patient actively extends elbow. Is there >10° extension? *an inclinometer can be used over the medial epicondyle of the humerus, arms aligned with the ulna and humerus where elbow extension is close to 10° Supine: tested arm is placed at 90° shoulder abduct ion with forearm supinated. Examiner tests for valgus/varus elbow joint play in 0° extension with fingers of one hand palpating the respective medial/lateral joint lines while simultaneously applying counterpressure to the distal humerus with the other hand. Do the joint lines open / is there excessive laxity in either direction? Supine: shoulder placed at 0° flexion/abduction, el bow flexed to 90°. Examiner passively moves the for earm from maximal supination to maximal pronation, looking down the forearm, visualising the line between the epicondyles of the humerus as a reference point. Is there >180° in total? Sitting: upright with hand on lap, examiner grasps lower humerus with one hand, while palpating the greater tubercle of the humerus proximally and stabilising the trunk with the other hand. A moderate to strong downwards pressure is applied to distract the humeral head from the acromion. Is there a visual or palpable sulcus between the acromion and humeral head? Sitting: patient's forearm supinated resting on the desk, the examiner stabilizes the distal radius and performs a volarly-directed passive accessory glide to the head of ulna. Repeat in forearm pronation. Is there equal or more glide in pronation compared to supination? Sitting: elbow resting on the plinth/table flexed to 90°, forearm pronated and wrist flexed, the patie nt takes their thumb towards the volar surface of their radius. Can more than just the tip of the thumb approximate the forearm? Sitting: forearm and hand resting on the desk, the examiner passively extends digits 2, 3, 4 and 5 at the MCP one at a time, allowing the interphalangeal joints to flex. Do any of the four MCPs extend >90°? * An inclinometer can be used where the MCP extension is close to 90° rd Sitting: pronated forearm arm resting on the plinth, the middle of the head of the 3 metacarpal, and the midline of the proximal forearm are marked. The axis of the goniometer is placed at the midpoint of the radiocarpal joint dorsally, and its arms are aligned with the two marks. The examiner passively moves the hand from maximal radial to maximal ulnar deviation. Is there >60° in total? Sitting: with forearm pronated, rest patient’s hand on paper. Patient is encouraged to spread their fingers maximally. Mark the paper at Length st th Span1 the tips of the 1 and 5 digits recording span in millimetres (numerator). Repeat x2. The distance from the centre of the distal wrist Span2 crease to the tip of the middle finger is measured in mm (denominator). The ratio is calculated as Span / Length. Is the result >1.2? Standing: patient standing beside table, carpals and metacarpals of tested wrist on the desk, MCP and interphalangeal joints and thumb flexed over the edge of the desk. Patient moves the forearm over the fixed hand by slowly lunging forward, ensuring heel of hand is in full contact with desk, to extend the wrist. Is there >90° wrist extension? *an inclinometer can be used where the wrist extension is close to 90° L=
8. Wrist Flexion & Thumb Abduction nd th 9. 2 - 5 Metacarpophalangeal (MCP) Extension 10. Wrist Radial/Ulnar Deviation 11. Handspan: Hand Length 12. Wrist Extension
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7. Distal Radioulnar Joint Play
Table 1: The Upper Limb Hypermobility Assessment Tool Page | 7
RIGHT Yes No
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4. Elbow Varus/Valgus Joint Play 5. Radioulnar Joint Supination/ Pronation 6. Sulcus Sign
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3. Elbow Extension
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2. Shoulder Rotation
LEFT Yes No
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Test Name
Length Span1 Span2
R=
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Performed by Patient
Plane of Standardised by movement Sagittal • Thoracolumbar stabilization • Gravity - allow 10 seconds at ends of range
Cut point used 180°
Shoulder Rotation
Passive Physiological
Examiner
180°
Elbow Extension
Passive Physiological
Patient
Transverse • Maintaining supported shoulder in 90° abduction • Gravity - allow 10 seconds at ends of range Sagittal • Gravity - allow 10 seconds at ends of range
Elbow Valgus/Varus
Passive Accessory
Examiner
Radioulnar Joint Supination/ Pronation
Passive Physiological
Examiner
Sulcus Sign
Passive Accessory Passive Accessory
Examiner
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• Moderate force only is used • Ensure patient is relaxed Transverse • Ensure good stabilisation of the distal radius • If equivocal score as negative
Visual or palpable sulcus Joint play in pronation ≥ supination
• Elbow flexed so ECRL and ECRB do not limit wrist flexion • Patient asked to not cause discomfort • PIP joint and elbow are flexed so FDS does not limit range
More than tip of thumb contacts forearm
N/A
Wrist Flexion & Thumb Abduction
Passive physiological
Patient
Sagittal
2nd-5th MCP Extension
Passive Physiological
Examiner
Sagittal
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Joint line opening minimal force >180°
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Examiner
>10°
• Perform in 0° elbow extension, neutral forearm • Apply force along joint line Transverse • Perform in 90° elbow flexion • Moderate overpressure applied Coronal
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Distal Radioulnar Joint (DRUJ) play
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Shoulder Flexion
Type of movement Passive Physiological
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Test
>90°
“Normal” range in adults 164°±12.5 (26) 167°±5 (27) 180° (28) 170° (29) 90° MR + 90° ER = 180° total (30) 69° MR + 104° ER = 173° (27) 90° MR + 90° LR = 180° (28) 70° MR + 90° LR = 160° (29) 0° (30) 0° (28) 0.6°±3 (27) 10° (29) Minimal joint line opening should occur in either direction 80° P + 80° S = 160° total (30) 76°P + 82° S = 158° (27) 90° P +90° S = 180° (28) 90° P + 90° S = 180° (29) No sulcus should appear between the acromion and humeral head The Interosseous Membrane is less taut in supination compared to the pronation position, so less volar and dorsal DRUJ accessory motion should occur in pronation (31-33) Wrist Flexion 90° (28) Wrist Flexion 80° (29) No thumb to forearm contact Beighton – apposition thumb tip constitutes a point 30° (28) 45° (29) <90 (3)
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Active Physiological
Patient
Coronal
• Moderate force is used • Patient needs to keep the hand flat
>180°
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Wrist Radial/Ulnar Deviation
20° RD + 30° UD 50° total (30) 22° RD + 36° UD 58° total (27) 25° RD + 35° UD 60° (28) 20° RD + 40° UD 60° (29) Mean ratio was determined by the current study was 1.14 (0.04)
>1.2 • Wrist maintained in neutral deviation • Patient encouraged to spread as wide as possible Wrist Passive Patient Sagittal • Heel of hand to be kept in >90° 60° (30) Extension Physiological contact with the table top 75° ± 6.5 (27) • Fingers and thumb flexed so 70° (28) their muscles/tendons do not 60° (29) limit wrist extension MR Medial Rotation; LR Lateral Rotation; ECRL Extensor Carpi Radialis Longus; ECRB Extensor Carpi Radialis Brevis; MCP Metacarpophalangeal Joint; PIP Proximal Interphalangeal Joint; FDS Flexor Digitorum Superficialis; RD Radial Deviation; UD Ulnar Deviation. Active Physiological
Patient
Coronal
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Handspan: Hand Length
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Table 2: Rationale for criterion cut-offs
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ACCEPTED MANUSCRIPT The supplement provides a photographic explanation of each test to enable standardized use by clinicians and researchers. The only component test that has not been documented previously is the handspan test. To determine “normal” span, we tested 43 healthy adult participants whose Beighton score was less than 4/9 and LLAS less than 7/12. None of the
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participants had a reason to have acquired hand hypermobility (such as musical instrument playing). The mean (SD) handspan to length ratio was 1.14 (0.04). The ULHAT is performed on both upper limbs, each providing a score to a maximum of 12. The reliability of the
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ULHAT was assessed in a pilot study of the initial 20 participants (10 control and 10 known hypermobile participants), where inter-rater reliability was assessed using a two-way random
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absolute agreement, single measures intraclass correlation coefficient. This revealed excellent inter-rater reliability (ICC2,1= 0.92, 95% CI = 0.89 to 0.97, p <0.001)(34). Therefore, a single examiner assessed the remaining participants.
To enable validation of the ULHAT, a gold standard against which to test its ability to identify
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GJH was required. Both researchers, experienced musculoskeletal physiotherapists, individually allocated each participant to one of three clinical opinion groups (normal, borderline hypermobile and hypermobile). The allocation was based on their history of
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instability episodes, whether they met the ≥2/5 self-perceived hypermobility criterion of the historical Hakim 5-part questionnaire and their clinical presentation including the
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comprehensive physical assessment of lower limb joint mobility (LLAS) in line with current best practice (1, 35). Any disagreement on group allocation were discussed and resolved. Participants provided written informed consent prior to data collection. Ethical approval was gained from the Human Research Ethics Committees of XXXXXXXXXXX [Protocol No. 2015/465] and XXXXXXXXXXXXXXXXXXXXXX [Protocol No. 13174].
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ACCEPTED MANUSCRIPT Statistical Analysis Data were anonymized, coded and analyzed having been inspected for outliers and tested for normality using calculations of skewness to determine whether parametric or non-
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parametric tests were to be carried out. Analysis was performed using SPSS Version 21 (IBM, NY, USA). Between-group demographic variables of age, gender and ethnicity were subject to descriptive analysis. The associations between the continuous variables of age, and Beighton and ULHAT scores were tested with Pearson’s correlation coefficient (r). A
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correlation of r ≤0.35 was considered to be weak, 0.36-0.67 moderate, and ≥0.68 a strong correlation (36). While the literature reports no significant side-to-side difference in many
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lower limb range of motion tests (19, 37, 38), upper limb dominance may confer side-to-side differences. If the correlation coefficient between sides is strong and significant, we can infer hypermobility from a single side.
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To test the null hypothesis of no significant difference between the three cohorts (control, likely and known hypermobile participants) when using the Beighton score or the ULHAT, a multivariate analysis of variance (MANOVA) was performed, followed by post-hoc analyses
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(Tukey HSD). Effect sizes (partial η2) greater than 0.01 were considered small differences, greater than 0.06 were considered medium differences, and values greater than 0.14 were
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representative of a large difference between groups (39).
Median and inter-quartile ranges for each clinical opinion group (normal, borderline and hypermobile) estimated the cut-off score to represent hypermobility when using the ULHAT. The sensitivity and specificity for each level of the ULHAT were determined using Receiver Operator Characteristic (ROC) curve analysis. The optimal cut-off score on the ROC curve was considered to be the point closest to the top left hand side of the y-axis, maximising the true positive rate and minimizing the false positive rate (40). Positive and negative likelihood ratios were calculated for the determined cut-off point, combining the utility of sensitivity and Page | 11
ACCEPTED MANUSCRIPT specificity (40). Clinical opinion was used as the gold standard for this analysis, and because McNemar’s Test analysis required dichotomous classification, the participants who were initially categorized as “borderline hypermobile,” were reclassified as normally mobile. This reclassification was based on the conclusion that if the clinicians were uncertain of the
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diagnosis, then the participant was less likely to be generally hypermobile. Finally, the ULHAT, Beighton score, and clinical opinion were compared to determine if either the ULHAT or Beighton score could be used to accurately predict GJH. Cut-off scores of ≥4/9
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and ≥5/9 were used for the diagnosis of GJH when using the Beighton score (41). To test the null hypothesis of no difference in identification of GJH between the measures, percentage
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agreement between the tools was calculated and the significance was determined using McNemar’s test. For this study, a p-value <0.05 was considered significant and the power was set at 0.95 to minimise the possibility of type II errors.
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3. Results
Participant demographic data is detailed in Table 3. The ethnic breakdown of each group revealed that the majority of participants were Caucasian (79%). While participants ranged in
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age between 18 and 40 years, the known hypermobile group was significantly older than both the controls and the likely hypermobile group (both p<0.001). Gender n (%)
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Cohort
Age (years) ± SD
Ethnicity n (%)
Control
M: 11 (28%)
22.6 ± 2.8
Caucasian: 24 (60%)
(n = 40)
F: 29 (72%)
Range:19-32
Asian: 12 (30%) Other: 4 (10%)
Likely
M: 16 (40%)
22.6 ± 4.4
Caucasian: 34 (85%)
Hypermobile
F: 24 (60%)
Range:18-33
Asian: 4 (10%)
(n = 40) Known
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Other: 2 (5%) M: 1 (3%)
28.4 ± 6.9
Caucasian: 30 (94%)
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F: 31 (97%)
Range:18-40
Asian: 0 (0%)
(n = 32)
Other: 2 (6%)
Total cohort
M: 28 (25%)
24.3 ± 5.5
Caucasian: 88 (79%)
(n = 112)
F: 84 (75%)
Range:18-40
Asian: 16 (14%)
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Other: 8 (7%)
Table 3: Demographic data of the three subgroups and the entire cohort
The ULHAT score for the left and right limbs of the whole cohort were highly and significantly
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correlated (r=0.87, p=0.001). As a result, the ULHAT was recorded as a score out of 12 for a
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randomly chosen limb, rather than out of a total of 24 for both limbs of all participants (42). The correlation between limbs was lower in the known hypermobile group; whilst still demonstrating a strong correlation, it did not reach significance (Table 4).
Control Likely Hypermobile
Whole Cohort
ULHAT
Pearson’s
Significance
Left
Right
Correlation
Level
4.1(2.3)
3.5(2.6)
0.85
0.01
5.8(1.6)
5.3(2.0)
0.79
0.01
7.8(2.0)
7.6(2.0)
0.69
0.43
5.3(2.8)
0.87
0.001
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Known Hypermobile
ULHAT
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Group
5.8 (2.5)
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Table 4: Side to side mean (SD) scores for the ULHAT across the three groups and entire cohort
3.1 Does the ULHAT discriminate between extents of hypermobility? The proportion of participants who achieved a total ULHAT score between 0 and 12 was examined (Figure 2). The distribution of the scores suggests that the ULHAT discriminated between the three groups with the largest overlap at 5 of the possible 12. The MANOVA confirmed a statistically significant difference between the three groups (Pillai’s Trace = 0.38, Page | 13
ACCEPTED MANUSCRIPT F(4.0, 218.0) = 13.0, p<0.001), with an effect size (partial η2) of 0.36 meaning that 36% of the variability in the ULHAT score is explained by group allocation. Statistically significant differences in the mean ULHAT score between all three groups was revealed with post-hoc analysis (Tukey HSD). The mean difference between control and likely hypermobile
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participants was -1.7 (95%CI -2.78 to -0.62; p=0.001), between control and hypermobile participants was -3.72 (95%CI -4.87 to -2.57; p< 0.001) and between likely and known
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hypermobile participants was -2.02 (95%CI -3.17 to -0.87; p<0.001).
Figure 2: Number of participants who scored each of the 12 levels of the Upper Limb Hypermobility Assessment Tool 3.2 Is upper limb mobility measured using the ULHAT associated with age, gender or ethnicity? A weak and non-significant correlation between age of the whole cohort and the extent of their upper limb mobility was found. With participants self-categorized as Caucasian or nonCaucasian, weak correlation was found between ethnicity and upper limb mobility.
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ACCEPTED MANUSCRIPT Conversely, moderate correlation was found between upper limb mobility and gender across the whole cohort. However, when the correlation was considered for each of the three groups, the moderate correlation was found only for the controls and likely hypermobile
Ethnicity
Significance
Correlation
Level
Control
-0.11
0.52
Likely Hypermobile
-0.23
Known Hypermobile
-0.14
Entire Cohort
0.15
0.12
0.25
0.12
0.01
0.99
0.02
0.91
Control Likely Hypermobile
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Known Hypermobile
0.16
0.46
Entire Cohort
0.08
0.38
Control
0.55
<0.001
Likely Hypermobile
0.48
0.002
Known Hypermobile
0.17
0.35
Entire Cohort
0.46
<0.001
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Gender
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Age
Pearson’s
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Demographic Group
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groups but not for the known hypermobile group (Table 5).
Table 5: Correlation between upper limb joint mobility and age, ethnicity and gender for each subgroup and the entire cohort.
3.3 Establishing a cut-off score for the identification of upper limb hypermobility The median and interquartile ranges for the ULHAT total score across the three clinically defined groups are represented in Figure 3. This figure suggests that a cut-off score of seven to eight would differentiate the controls from the known hypermobile participants, with Page | 15
ACCEPTED MANUSCRIPT minimal overlap with the borderline hypermobile individuals. This observation was confirmed by the ROC Curve presented in Figure 4 where the point on the curve closest to the top lefthand corner corresponded to a cut off score of 7. At this point the sensitivity and specificity were highest at 0.84 and 0.77 respectively, producing a positive likelihood ratio of 3.7 and a
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negative likelihood ratio of 0.2.
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Figure 3: Median and interquartile ranges of the Upper Limb Hypermobility Assessment Tool
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across the clinically defined groups. The dotted line represents the score of 8/12.
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Figure 4: Receiver Operator Characteristic Curve for the Upper Limb Hypermobility
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Assessment Tool
Given that the majority of the participants were Caucasian and only a weak correlation was
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observed between upper limb mobility and ethnicity, the analysis was repeated excluding the 24 non-Caucasians. This resulted in a cohort of 88 participants (24 controls, 34 likely hypermobile and 30 known hypermobile participants). The ROC analysis revealed the same cut-off score of 7/12, with a higher sensitivity of 0.86, specificity of 0.84, positive likelihood
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ratio of 5.4 and a negative likelihood ratio of 0.2.
3.4 Comparing the Upper Limb Hypermobility Assessment Tool Score with clinical opinion:
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Can the ULHAT be used to accurately identify GJH? On the basis of clinical opinion, 3% of control, 23% of likely hypermobile and 94% of known
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hypermobile participants were identified as generally hypermobile. Having identified a cut-off score of ≥7/12 for the identification of upper limb hypermobility, the ULHAT identified upper limb hypermobility in 15% control, 35% likely hypermobile and 81% known hypermobile participants. High levels of agreement were found between the ULHAT and clinical opinion across each group, especially in the control group at 88% agreement, followed by the known hypermobile group at 81% and the likely hypermobile group at 78%. McNemar’s Test confirmed no significant difference in agreement between clinical opinion of generalized hypermobility and the ULHAT at this cut-off score for all three subgroups (all p>0.06). By comparison, a Beighton score cut-off of ≥4/9 revealed low to moderate levels of agreement Page | 17
ACCEPTED MANUSCRIPT with clinical opinion for the control and likely hypermobile groups (48% and 45% respectively), and high levels of agreement only with the known hypermobile group at 91%. Utilizing a Beighton cut-off score of ≥5/9 improved the moderate levels of agreement with clinical opinion for the control and likely hypermobile groups (58% for both), while
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maintaining high levels of agreement with the known hypermobile group at 88%. Having identified a cut-off score of ≥5/9 for the identification of GJH, the Beighton scoring system identified GJH in 45% control, 60% likely hypermobile and 94% known hypermobile
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participants. With the more stringent cut-off of ≥5/9 and higher agreement with clinical opinion, the McNemar’s test still revealed a significant difference in the agreement between
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clinical opinion of generalized hypermobility and the Beighton score for the control and likely hypermobile participants (p<0.001), but not in the known hypermobile group (p=1.0).
4. Discussion
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The newly developed Upper Limb Hypermobility Assessment Tool is a reliable and valid instrument for the identification of both upper limb and generalized hypermobility in an adult population. A cut-off point of ≥7/12 was identified as the score that best identifies those with
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upper limb hypermobility from those without. The high sensitivity and specificity results in a positive likelihood ratio greater than 3 and a negative likelihood ratio less than 0.3,
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suggesting that the ULHAT is useful in determining an accurate post-test probability of a person having upper limb hypermobility (43). When using the ULHAT score as a continuous measure, from 0 to 12, upper limb hypermobility was not demonstrated to decrease with age. This finding is in contrast to the hypermobility of the lower limb, where the LLAS was found to decrease with age in those with normal joint mobility (20). Similarly, generalized joint hypermobility as identified using the Beighton scoring system has been reported to decrease with age (6, 44). We pose two hypotheses to explain the different findings. The first relates to the age range of the sample Page | 18
ACCEPTED MANUSCRIPT in the current study. The participants in this study were aged between 18 and 40 years. It is possible that hypermobility of the upper limb decreases after the 5th decade of life. This hypothesis is supported by a study of 1000 healthy Australians, aged 3 to 101 suggesting that the Beighton cut-off reduces after 40 years of age, particularly in males (2). The second
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hypothesis relates to load. Joints of the lower limb are subject to greater and more frequent sustained loading associated with weight bearing and ambulation, and may therefore be prone to stiffening associated with degeneration (45). Indeed, 65% of joints affected by
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osteoarthritis are found in the lower limb (46). The upper limb may be less susceptible to high sustained joint loading, hence less resultant stiffening.
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A significant difference in the extent of upper limb hypermobility was found between sides of the body with the left demonstrating greater mobility than the right. We hypothesize that this might be due to dominance of the right upper limb whereby greater use may confer stiffness. This hypothesis agrees with the findings of other researchers who report reduced range in
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the dominant limb of normal participants (47, 48). We did not record dominance however and are assuming that most participants, possibly up to 90%, were right hand dominant as this is consistent with the population normative data (49). While the entire cohort exhibited this
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reduced right-sided joint mobility, when groups were considered individually, the known hypermobile group did not demonstrate a side-to-side difference (p = 0.43). Our hypothesis
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for this finding is that their symptomatic hypermobility, manifesting as joint pain and instability, has resulted in equivocal use of both sides and consequently more bilaterallydistributed joint micro-trauma. 4.1 Clinical Relevance and Impact The ULHAT was used as a dichotomous screening tool to identify the presence or absence of generalized joint hypermobility, compared with the gold-standard of clinical opinion. A positive ULHAT score (≥7/12) appeared to concur with identification of generalized joint hypermobility across the three recruited subgroups. The high agreement between the
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ACCEPTED MANUSCRIPT identification of generalized hypermobility using the ULHAT and that of clinical opinion was significant, suggesting that the two criteria are measuring the same dimension. Surprisingly, this was not the case when clinical opinion was compared with the Beighton Scoring system, where the latter significantly overestimated the prevalence of GJH in controls and likely
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hypermobile participants even at a cut-point of ≥5/9. This suggests that they are not
measuring the same dimension and that identifying GJH on the basis of the Beighton alone may be insufficient. Consequently, we recommend that researchers and clinicians can
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confidently use the Beighton score to rule out the presence of GJH while using the ULHAT to rule in the presence of upper limb specific and generalized joint hypermobility. Finally, the
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intended use of the ULHAT extends to screening in occupational and sporting populations, early identification of possible risk factors for injury and provision of joint specific data enabling targeted management.
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4.2 Limitations and directions for future research
There is no gold standard test for generalised joint hypermobility. Traditionally, a participant’s Beighton score has been used however, the low number of joints tested in only one plane
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and the inconsistency in reported prevalence, raise questions as to its validity. Following current best practice recommendations, this study employed the consensus clinical opinion
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of two experienced musculoskeletal physiotherapists who undertook thorough subjective and physical assessments of participants, as the gold standard against which the ULHAT and Beighton scoring system were tested. Future research will determine the ideal test or combination of tests to optimally identify GJH. As some of the individual ULHAT tests require manual therapy skills and clinical judgement, the reliability of the ULHAT needs to be established using less experienced examiners. Since the majority of our participants were female and all were between the ages of 18-40 years, future research should determine the validity of the ULHAT and a cut-point in a more gender-balanced adult and paediatric
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ACCEPTED MANUSCRIPT population. Twenty-one percent of our cohort were non-Caucasian and this represents the typical Australian population (50). Given that ethnicity has been previously proposed to be a contributing factor to joint mobility, we determined the cut-off score excluding the nonCaucasian participants, hypothesising that the cut-off score would be lower. However, this
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was not the case resulting in the same cut-off value, with a similarly high sensitivity and specificity. Hence, we cautiously suggest that a cut-off score of ≥7/12 is applicable to the general Australian population but possibly ≥8/12 in a non-Caucasian population. Finally,
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whether all 12 items of the ULHAT are necessary, measuring different dimensions of upper limb hypermobility is currently unknown. Accordingly, the tool’s internal construct validity
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needs to be determined using Rasch analysis.
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HAKIM A, GRAHAME R: Joint hypermobility. Best Practice & Research Clinical Rheumatology 2003; 17: 989-1004. SINGH H, MCKAY M, BALDWIN J et al.: Beighton scores and cut-offs across the lifespan: cross-sectional study of an Australian population. Rheumatology (Oxford) 2017kex043. BEIGHTON P, SOLOMON L, SOSKOLNE C: Articular mobility in an African population. Annals of the rheumatic diseases 1973; 32: 413. JANSSON A, SAARTOK T, WERNER S, RENSTRÖM P: General joint laxity in 1845 Swedish school children of different ages: age-and gender-specific distributions. Acta paediatrica 2004; 93: 1202-06. CLINCH J, DEERE K, SAYERS A et al.: Epidemiology of generalized joint laxity (hypermobility) in fourteen-year-old children from the UK: A population-based evaluation. Arthritis & Rheumatism 2011; 63: 2819-27. REMVIG L, JENSEN DV, WARD RC: Epidemiology of general joint hypermobility and basis for the proposed criteria for benign joint hypermobility syndrome: review of the literature. The Journal of rheumatology 2007; 34: 804-09. MALFAIT F, FRANCOMANO C, BYERS P et al.: The 2017 international classification of the Ehlers–Danlos syndromes. In: American Journal of Medical Genetics Part C: Seminars in Medical Genetics: 2017: Wiley Online Library; 2017: 8-26. KLEMP P, STEVENS J, ISAACS S: A hypermobility study in ballet dancers. The Journal of rheumatology 1984; 11: 692-96. GRAHAME R: Joint hypermobility and genetic collagen disorders: are they related? Archives of disease in childhood 1999; 80: 188-91. GANNON L, BIRD H: The quantification of joint laxity in dancers and gymnasts. J Sports Sci 1999; 17: 743-50. TOBIAS JH, DEERE K, PALMER S, CLARK EM, CLINCH J: Joint hypermobility is a risk factor for musculoskeletal pain during adolescence: findings of a prospective cohort study. Arthritis & Rheumatology 2013; 65: 1107-15. CAMERON KL, DUFFEY ML, DEBERARDINO TM, STONEMAN PD, JONES CJ, OWENS BD: Association of generalized joint hypermobility with a history of glenohumeral joint instability. Journal of athletic training 2010; 45: 253-58. ELLENBECKER TS, COOLS A: Rehabilitation of shoulder impingement syndrome and rotator cuff injuries: an evidence-based review. British journal of sports medicine 2010; 44: 319-27. HAKIM AJ, MALFAIT F, DE PAEPE A: The heritable disorders of connective tissue: epidemiology, nosology and clinical features. In HAKIM AJ, KEER R, GRAHAME R (Eds.): Hypermobility, fibromyalgia and chronic pain. Churchill Livingstone/Elsevier 2010: 3-17. VOERMANS NC, KNOOP H, BLEIJENBERG G, VAN ENGELEN BG: Pain in Ehlers-Danlos syndrome is common, severe, and associated with functional impairment. Journal of pain and symptom management 2010; 40: 370-78. QUARRIER NF: Is hypermobility syndrome (HMS) a contributing factor for chronic unspecific wrist pain in a musician? If so, how is it evaluated and managed? Work 2011; 40: 325-33. EVANS AM, ROME K, PEET L: The foot posture index, ankle lunge test, Beighton scale and the lower limb assessment score in healthy children: a reliability study. Journal of foot and ankle research 2012; 5: 1. CASTORI M, TINKLE B, LEVY H, GRAHAME R, MALFAIT F, HAKIM A: A framework for the classification of joint hypermobility and related conditions. In: American Journal of Medical Genetics Part C: Seminars in Medical Genetics: 2017: Wiley Online Library; 2017.
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ACCEPTED MANUSCRIPT
25.
26.
27. 28. 29. 30. 31. 32.
33.
34. 35.
36. 37.
38.
RI PT
24.
SC
23.
M AN U
22.
TE D
21.
EP
20.
FERRARI J, PARSLOW C, LIM E, HAYWARD A: Pediatric rheumatology joint hypermobility: The use of a new assessment tool to measure lower limb hypermobility. Clin Exp Rheumatol 2005; 23: 413-20. MEYER K, CHAN C, HOPPER L, NICHOLSON LL: Identifying lower limb specific and generalised joint hypermobility in adults: validation of the Lower Limb Assessment Score. BMC Musculoskeletal Disorders 2017; 18: 1-9. TINKLE BT, BIRD HA, GRAHAME R, LAVALLEE M, LEVY HP, SILLENCE D: The lack of clinical distinction between the hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome (aka hypermobility syndrome). Am J Med Genet A 2009; 149: 2368-70. BEIGHTON P, DE PAEPE A, STEINMANN B, TSIPOURAS P, WENSTRUP RJ: Ehlers-Danlos syndromes: revised nosology. am J Med genet 1998; 77: 31-37. SCHEPER MC, DE VRIES JE, DE VOS R, VERBUNT J, NOLLET F, ENGELBERT RH: Generalized joint hypermobility in professional dancers: a sign of talent or vulnerability? Rheumatology (Oxford) 2012kes220. ANDERSON AS, LOESER RF: Why is osteoarthritis an age-related disease? Best Practice & Research Clinical Rheumatology 2010; 24: 15-26. HAKIM A, GRAHAME R: A simple questionnaire to detect hypermobility: an adjunct to the assessment of patients with diffuse musculoskeletal pain. International journal of clinical practice 2003; 57: 163-66. SABARI JS, MALTZEV I, LUBARSKY D, LISZKAY E, HOMEL P: Goniometric assessment of shoulder range of motion: comparison of testing in supine and sitting positions. Archives of physical medicine and rehabilitation 1998; 79: 647-51. BOONE DC, AZEN SP: Normal range of motion of joints in male subjects. JBJS 1979; 61: 756-59. PALMER ML, EPLER ME, EPLER MF: Fundamentals of musculoskeletal assessment techniques: Lippincott Williams & Wilkins; 1998. SCHÜNKE M, SCHULTE E, SCHUMACHER U, ROSS LM, LAMPERTI ED: Thieme atlas of anatomy: general anatomy and musculoskeletal system, vol. 1: Thieme Stuttgart; 2006. ASSOCIATION AM: Guides to the evaluation of permanent impairment: American Medical Association Press; 1990. SKAHEN JR, PALMER AK, WERNER FW, FORTINO MD: Reconstruction of the interosseous membrane of the forearm in cadavers. The Journal of hand surgery 1997; 22: 986-94. WATANABE H, BERGER RA, BERGLUND LJ, ZOBITZ ME, AN K-N: Contribution of the interosseous membrane to distal radioulnar joint constraint. The Journal of hand surgery 2005; 30: 1164-71. GABL M, ZIMMERMANN R, ANGERMANN P et al.: The interosseous membrane and its influence on the distal radioulnar joint: an anatomical investigation of the distal tract. The Journal of Hand Surgery: British & European Volume 1998; 23: 179-82. FLEISS JL: Design and analysis of clinical experiments, vol. 73: John Wiley & Sons; 2011. CASTORI M, TINKLE B, LEVY H, GRAHAME R, MALFAIT F, HAKIM A: A framework for the classification of joint hypermobility and related conditions. In: American Journal of Medical Genetics Part C: Seminars in Medical Genetics: 2017: Wiley Online Library; 2017: 148-57. TAYLOR R: Interpretation of the correlation coefficient: a basic review. Journal of diagnostic medical sonography 1990; 6: 35-39. BENNELL K, KHAN K, MATTHEWS B, SINGLETON C: Changes in hip and ankle range of motion and hip muscle strength in 8–11 year old novice female ballet dancers and controls: a 12 month follow up study. British journal of sports medicine 2001; 35: 54-59. MORRISON SC, FERRARI J: Inter-rater reliability of the Foot Posture Index (FPI-6) in the assessment of the paediatric foot. Journal of foot and ankle research 2009; 2: 1.
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ACCEPTED MANUSCRIPT
44.
45. 46.
47.
48.
49.
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50.
RI PT
43.
SC
41. 42.
M AN U
40.
COHEN J: Statistical power analysis for the behavioral sciences, vol. 2nd. Hillsdale, N.J: L. Erlbaum Associates; 1988. PEAT J, BARTON B: Medical statistics: A guide to data analysis and critical appraisal: John Wiley & Sons; 2008. GRAHAME R: Joint hypermobility syndrome pain. Current Science Inc 2009; 13: 427-33. GRAY K, GIBBONS P, LITTLE D, BURNS J: Bilateral clubfeet are highly correlated: a cautionary tale for researchers. Clinical orthopaedics and related research 2014; 472: 3517. SACKETT DL: Evidence-based Medicine How to practice and teach EBM: WB Saunders Company; 1997. KWON J-W, LEE W-J, PARK S-B, KIM MJ, JANG SH, CHOI CK: Generalized joint hypermobility in healthy female Koreans: prevalence and age-related differences. Annals of rehabilitation medicine 2013; 37: 832-38. ARDEN N, NEVITT MC: Osteoarthritis: epidemiology. Best practice & research Clinical rheumatology 2006; 20: 3-25. CUSHNAGHAN J, DIEPPE P: Study of 500 patients with limb joint osteoarthritis. I. Analysis by age, sex, and distribution of symptomatic joint sites. Annals of the rheumatic diseases 1991; 50: 8-13. ALLANDER E, BJÖRNSSON O, OLAFSSON O, SIGFUSSON N, THORSTEINSSON J: Normal range of joint movements in shoulder, hip, wrist and thumb with special reference to side: a comparison between two populations. International Journal of Epidemiology 1974; 3: 253-61. GÜNAL I, KÖSE N, ERDOGAN O, GÖKTÜRK E, SEBER S: Normal range of motion of the joints of the upper extremity in male subjects, with special reference to side. JBJS 1996; 78: 1401-4. MCMANUS C: Right hand, left hand: The origins of asymmetry in brains, bodies, atoms and cultures: Harvard University Press; 2004. BALDWIN JN, MCKAY MJ, MOLONEY N et al.: Reference values and factors associated with musculoskeletal symptoms in healthy adolescents and adults. Musculoskeletal Science and Practice 2017; 29: 99-107.
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ACCEPTED MANUSCRIPT Acknowledgements The authors would like to acknowledge the invaluable assistance of Dr Luke Hopper and Jenny Woods who were responsible for participant recruitment at the West Australian Academy of the Arts and the West Australian Ballet respectively. Thanks also to Dr Claire
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Hiller, Dr Verity Pacey, Feili Zhang and Kaitlin Meyer who assisted with data collection and entry. This study was funded by a BRIG grant from the Discipline of Biomedical Science at
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ACCEPTED MANUSCRIPT Highlights •
Targeted quantification of upper limb hypermobility has eluded practitioners The Beighton score lacks face validity to identify upper limb hypermobility The Upper Limb Hypermobility Assessment Tool is described and validated
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The tool comprises 12 passive accessory and physiological joint mobility tests
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A cut-off point of 7/12 identifies upper limb and generalised joint hypermobility
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