- Email: [email protected]
Early Intra-articular Corticosteroid Injection Improves Pain and Function in Adhesive Capsulitis of the Shoulder: 1-Year Retrospective Longitudinal Study
Accepted Manuscript Early intra-articular corticosteroid injection improves pain and function in adhesive capsulitis of shoulder: 1-year retrospective longitudinal study Jung Hwan Ahn, MD, Doo-Hyung Lee, MD, PhD, Hyuncheol Kang, PhD, Michael Y. Lee, MD, MHA, Dae Ryong Kang, PhD, Seung-Hyun Yoon, MD, PhD PII:
S1934-1482(17)30662-7
DOI:
10.1016/j.pmrj.2017.06.004
Reference:
PMRJ 1917
To appear in:
PM&R
Received Date: 27 June 2016 Revised Date:
25 May 2017
Accepted Date: 3 June 2017
Please cite this article as: Ahn JH, Lee D-H, Kang H, Lee MY, Kang DR, Yoon S-H, Early intraarticular corticosteroid injection improves pain and function in adhesive capsulitis of shoulder: 1-year retrospective longitudinal study, PM&R (2017), doi: 10.1016/j.pmrj.2017.06.004. 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.
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Title: Early intra-articular corticosteroid injection improves pain and function in adhesive
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capsulitis of shoulder: 1-year retrospective longitudinal study
Authors: Jung Hwan Ahn, MD, Doo-Hyung Lee, MD, PhD, Hyuncheol Kang, PhD, Michael Y. Lee, MD, MHA, Dae Ryong Kang, PhD, Seung-Hyun Yoon, MD, PhD
Affiliation: Department of Emergency Medicine (J.H. Ahn), Department of Orthopedic
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Surgery (D.-H. Lee), Medical Humanities and Social Medicine (D.R. Kang), and Physical Medicine and Rehabilitation (S.-H. Yoon), Ajou University School of Medicine, Suwon,
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Republic of Korea
Department of Applied Statistics (H. Kang), Hoseo University, Asan, Republic of Korea Department of Physical Medicine and Rehabilitation (M.Y. Lee), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC
Correspondence: Seung-Hyun Yoon, MD, PhD, Department of Physical Medicine and
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Rehabilitation, Ajou University School of Medicine, 164, World Cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea E-mail: [email protected]
Telephone: +82-31-219-5279
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Fax: +82-31-219-5209
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Conflict of interest: none declared. This manuscript contains original material only that has not previously been published, and is not currently under consideration elsewhere, nor will be submitted elsewhere until a final decision has been made by the journal.
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Title: Early intra-articular corticosteroid injection improves pain and function in
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adhesive capsulitis of shoulder: 1-year retrospective longitudinal study
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Background: Intra-articular corticosteroid injection is a commonly used therapy for
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adhesive capsulitis, but not enough studies exist on the optimal timing of the injection.
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Objective: To determine whether intra-articular corticosteroid injection has better
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outcomes in patients with earlier stage than later stage of adhesive capsulitis.
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Study design: Retrospective longitudinal study
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Setting: University-affiliated tertiary care hospital.
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Participants: Primary adhesive capsulitis patients (n=339) who were unresponsive to at
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least 1 month of conservative treatment and who had ultrasound-guided corticosteroid
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injection.
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Interventions: Not applicable.
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Main Outcome Measurements: Visual analog scale, Shoulder Pain and Disability Index,
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and passive range of motion (flexion, abduction, external rotation, and internal rotation
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and extension) were evaluated at pretreatment, month 1 and 12 after the first injection.
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Results: The result of the multiple regressions, which considered the main and the
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interaction effect of confounding variables, showed that the differences of all outcomes
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in both short-term effect at month 1 and long-term effect at month 12 are greater when
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the duration of pain prior to injection is shorter. Among the confounders, the injection
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number in the difference of internal rotation and extension between month 0 and 12
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(IRE ∆(0-12)) was statistically significant. IRE ∆(0-12) was also greater when the pain
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duration was shorter, though the decrease in IRE ∆(0-12) differed depending on the
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number of injections.
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Conclusions: Early injection improves outcomes of adhesive capsulitis at both short-
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and long-term follow-ups. If pain persists despite non-invasive and conservative
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treatments, early injection may be considered to shorten its natural history.
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Keywords: periarthritis; shoulder pain; treatment outcome; prognosis; intra-articular
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injections; adhesive capsulitis; frozen shoulder
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Introduction
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Adhesive capsulitis is a long-lasting, painful shoulder condition commonly known as
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frozen shoulder or painful stiff shoulder. The condition results from progressive fibrosis
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and eventual contracture of the capsule of the glenohumeral joint, which causes pain
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and stiffness [1,2]. The treatment for adhesive capsulitis includes supervised exercise,
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physical modalities, nonsteroidal anti-inflammatory drugs, oral corticosteroid, intra-
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articular corticosteroid injection (IACI), suprascapular nerve block, hydraulic
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arthrographic capsular distension, manipulation and arthroscopic capsular release [1-8].
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IACI is one of the conservative treatments for adhesive capsulitis. It is effective in
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rapidly reducing the pain[3], but there is a paucity of studies that define the optimal
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timing of the injection. It is in the early stages of adhesive capsulitis that a
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hypervascular synovial hyperplasia is present and this may eventually lead to the
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fibrosis of the capsule. It has been contended that if given at an early (e.g. freezing)
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stage, IACI may possibly minimize the morbidity of the disorder. Early treatment with
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IACI may provide a chemical ablation of the synovitis which can help prevent the
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development of the fibrosis and shorten the natural history of the disease [2,4,9,10].
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However, not enough studies exist to prove the effectiveness of early injection. The aim
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of this study is to evaluate whether early IACI is beneficial for pain and function.
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Methods
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Patients
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This is a 1-year retrospective longitudinal study based on the shoulder disease registry
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data from the university-affiliated tertiary care hospital. Informed consent was waived
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for this retrospective study as part of an exemption approved by the institutional review
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board. 661 patients diagnosed with primary adhesive capsulitis were reviewed
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retrospectively between January 1st, 2011 and December 31st, 2014. They were
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outpatients at rehabilitation and orthopedic clinics. All the patients underwent a
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standardized history-taking, physical examination and ultrasonographic evaluation by
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the lead author; passive and active range of motion, painful arc and impingement test,
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resisted test, strength of muscles in the affected shoulder at the initial workup.
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Inclusion criteria were patients who had adhesive capsulitis with a normal radiograph
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finding of the affected shoulder and restriction of passive motion of greater than 30˚ in 2
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or more planes of movement by goniometric measurement with scapula rotation
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restrained [11,12]; pain duration ranging from 3 to 12 months (freezing and frozen stage
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of adhesive capsulitis); and average pain intensity during a week defined as a score of 6
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points or more on a 10-cm visual analog scale (VAS) rated from “no pain” to “the worst
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imaginable pain”. Abnormal limits of passive motion were defined as forward flexion
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<150˚, extension <20˚, abduction <150˚, external rotation <60˚, and internal rotation
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<60˚. External rotation and internal rotation were measured at shoulder 90˚ abduction. If
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abduction measured was less than 90°, maximum possible abduction was achieved
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before measuring the external rotation. To restrict the contribution of scapular rotation,
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the patient was asked to relax, and the evaluator held the clavicle and scapular spine
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with the hand. Passive elevation of the upper arm was stopped, and goniometric angles
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were taken when it was no longer possible to prevent the scapula from rotating [13].
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Patients were excluded if they had any of the following: secondary adhesive capsulitis
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(secondary to other causes including inflammatory or infectious arthritis, stroke, tumor,
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trauma, or fracture); history of diabetes and/or thyroid dysfunction; rotator cuff disease
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on both physical and ultrasonographic examinations; medium to large sized (≥3cm)
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partial- or full-thickness tear of the rotator cuff on ultrasonography [14,15]; calcific
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tendinitis; primary osteoarthritis of the glenohumeral joint in a simple radiograph; and
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previous corticosteroid injection on the affected shoulder. Magnetic resonance imaging
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was not undertaken routinely, but those with either muscle weakness or a sign of
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positive impingement were excluded on the basis of a high likeliness of rotator cuff tear.
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A minimum of 1 month conservative treatment was provided without any IACI. The
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conservative treatment included analgesics (nonsteroidal anti-inflammatory drugs,
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acetaminophen/tramadol, opioids, tricyclic antidepressants, and fentanyl patch),
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flexibility exercise, and physical modalities (heat and electrical therapies). Patients
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received an institutional flexibility exercise of glenohumeral joint with physical
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therapists once or two times a week for 2-4 weeks, and were educated to do the same
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exercise at home. Patients who complained about persistent shoulder pain of VAS≥6
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even after 1 month of conservative treatment were recommended to take the IACI.
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Ultrasound-guided corticosteroid injection and exercise education
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Patients sat in a seated position with their hands on their thighs. After aseptic 4
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preparation, the lead author inserted a 23-gauge, 6 cm long needle parallel to the
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transducer from the posterior side of the shoulder. The needle was advanced under a
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real-time ultrasound equipment (Logiq P6, GE Healthcare, Buckinghamshire, United
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Kingdom) using 10-12MHz, linear array transducers until the needle tip entered the
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glenohumeral joint. The lead author injected 2mL of 10mg/mL triamcinolone acetonide
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and 8mL of 1% lidocaine. After injection, the patients were instructed about the home
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exercise program for increasing the range of motion including stretching forward and
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bending down to a desk, Codman exercise, wall-climbing exercise, external and internal
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rotation with bar, and posterior shoulder stretch [16]. Exercises were to be performed 3
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times a day lasting 10 minutes each round. No nonsteroidal anti-inflammatory drugs,
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analgesics, or opioids were prescribed after injection. Patients were asked to visit the
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hospital again at month 1, 2, and 3 after the injection and recommended to have a
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second or third injection if their pain persisted over 50%.
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Outcome measurements
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VAS, Shoulder Pain and Disability Index score (SPADI), passive range of motion were
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compared for pre-, 1 month (short-term effect of IACI), and 12 month (long-term effect)
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after the first injection. All outcome measurements were evaluated by the lead author. A
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VAS as primary outcome measurement was used to assess shoulder pain. SPADI is a
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self-reporting questionnaire for patients with shoulder pain, which consists of 13
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questions that are divided into 2 domains: pain (5 items) and disability (8 items) [17].
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Each domain score is equally weighted and added to obtain a total percentage score
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between the ranges of 0 (best) to 100 (worst). Passive range of motion of forward
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flexion, abduction and external rotation were measured by goniometer in supine
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position. External rotation was measured in 0° abduction of shoulder and 90° flexion of
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elbow position. Internal rotation and extension was measured as the distance (cm) from
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the spinous process of 7th cervical vertebra to the tip of the fully extended thumb in
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standing position [18]. This methodology shows high intrarater reliability [19] and is a
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useful method that is also relevant with the activities of daily living, such as dressing,
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bathing, and toileting [20].
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Statistical analysis 5
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All the data were analyzed by using the SPSS version 23 statistics software (IBM,
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Armonk, NY). Continuous data are expressed as means ± standard deviation.
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Categorical data are shown as absolute values, together with the frequency distribution.
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The number of injections were reclassified into two groups, single-injection (injection
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number 1) group and double- or triple-injection (injection number 2 or 3) group; the two
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latter were combined since only 7 (2.1%) out of 339 patients opted for triple-injection.
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The multiple regression analysis was conducted to determine the relationship between
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the differences of outcomes and pain duration while controlling the confounding
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variables (gender, age, injection number, or arm dominance). Simple regression was
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also conducted between the differences of outcomes and other variables (age, gender,
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the group according to injection number, arm dominance or pain duration) in order to
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select the variables which were put into multiple regression. The variables with P ≤ .05
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in the simple regression were entered into the multiple regression with main and
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interaction effects. P <.05 was considered significant in multiple regression analysis. In
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the multiple regression analysis, it was considered significant if P <.05.
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Results
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General characteristics
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Medical records of a total of 661 patients were reviewed. Of them, 246 had pain that
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improved after conservative treatment (figure 1). IACI was recommended to the rest of
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the patients (415) with pain of VAS ≥6; 40 refused and 375 accepted the
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recommendation. Of the 375 who accepted, 36 were not included in the 12-month
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follow-up; 17 did not attend the follow-up, 8 were treated at other clinics, and 11 could
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not be reached. Finally, 339 patients completed the follow-up at month 1 (short-term
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effects) and 12 (long-term) after IACI. The mean (range) age was 54.5±6.0 (39 to 69)
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years old; ratio of male to female 111 (32.7%): 228 (67.3%); ratio of dominant to non-
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dominant arm 129 (38.1%): 210 (61.9%); pain duration 8.2±3.0 (3 to 12) months; and
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ratio of injection (single- versus double- and triple-injection) 146 (43.1%): 193 (56.9%).
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Outcome measurements and complications
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Table 1 shows the value and changes of outcome measurements after IACI. Apart from
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facial flushing on days 2 to 6 after injection (12 patients), there were no serious
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complications such as infection.
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Selection of confounders
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Table 2 shows the results of simple regression analysis. In case of short-term effects, or
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the difference in month 0 to 1 (∆(0-1) or ∆(1-0)), arm dominance was the confounder in
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only VAS ∆(0-1), while no confounders were found in other outcomes (SPADI ∆(0-1),
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flexion ∆(1-0), abduction ∆(1-0), external rotation ∆(1-0), internal rotation and
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extension ∆(0-1)). In long-term effects, or the difference in month 0 to 12 (∆(0-12) or
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∆(12-0)), the confounders were injection number and arm dominance in VAS ∆(0-12),
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injection number and gender in SPADI ∆(0-12), while no confounder was found in
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flexion ∆(12-0), injection number and gender in abduction ∆(12-0), injection number in
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external rotation ∆(12-0), and injection number and gender in internal rotation and
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extension ∆(0-12) (P <.05).
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Relation between the differences of outcomes and pain duration controlling confounders
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Table 3 shows the results of multiple regression for short-term effects. Pain duration
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was statistically significant in all the differences of outcomes (flexion, P =.016; others,
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P <.001). Beta (regression coefficient) of pain duration in all the differences of
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outcomes was negative. Arm dominance as confounder in VAS ∆(0-1) was not
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statistically significant considering the main and the interaction effect with pain
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duration (P >.05). Table 4 shows the results of multiple regression for long-term effects.
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Pain duration was statistically significant in all the differences of outcomes (flexion, P
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=.001; others, P <.001). Beta of pain duration in all the differences of outcomes was
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negative. Among the confounders in the differences of outcomes, the main and the
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interaction effect of injection number in IRE ∆(0-12) was statistically significant
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(injection number, P =.002; interaction between pain duration and injection number, P
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=.001), while the other confounders were not statistically significant. The slopes which
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represent the different injection number groups were negative, x axis being pain
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duration and y axis IRE ∆(0-12) (figure 2).
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Discussion
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This 1-year retrospective longitudinal study reveals that the improvement in outcomes,
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which considered the main and the interaction effect of the confounding variables, are
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greater when the pain duration prior to IACI is shorter in both short-term effect at
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month 1 and long-term effect at month 12. Among the confounders in the improvement 7
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in outcomes, only the injection number in IRE ∆(0-12) resulted in a statistically
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significant confounder resulting in better outcomes with more injections. Though the
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decrease in IRE ∆(0-12) differed depending on the number of injections, IRE ∆(0-12)
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was also greater when the pain duration was shorter. These results suggest that early
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IACI will have a greater improvement in pain and function than late IACI.
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Many researchers have dismissed adhesive capsulitis as a benign condition, with most
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being self-resolving [1,21]. However, it is now widely accepted that up to 50% of the
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patients may not fully recover from the symptoms and disability, even with long-term
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follow-ups [22-24]. Some investigators have advocated the use of IACI in the treatment
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of early adhesive capsulitis and suggested that patients treated with injection at an early
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stage of the disorder respond better than later stage. Their rationale for early IACI is that
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it would reduce inflammation of synovium, decreasing capsular fibrosis and shortening
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the natural history of the disease [2,4,9,10,25,26]. However, not enough studies exist to
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prove the effects of early injection. In a previous retrospective case series, the authors
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showed that IACI may be more efficacious in the freezing stage (stage 1 and 2 based on
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the classification by Neviaser and Neviaser’s four staging system [27]) before the
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development of a significant capsular contracture [25]. In the same study, the result
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showed that an early IACI for adhesive capsulitis may have allowed patients to recover
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motion at a median time of 3 months. But the study had several limitations, including
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patients in stage 1 (n=5) who would be difficult to diagnose if not for the support of an
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arthroscopic or histologic evaluation; no control group of frozen stage (stage 3 and 4)
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patients to compare the effectiveness of IACI; relatively few samples (n=44 in total);
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and a short mean follow-up period of 6.7 months. Our study overcame previous
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limitations by including frozen stage patients, a relatively large sample (n=339), and a
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long enough follow-up (1-yr) to observe the effect of IACI.
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The natural history of adhesive capsulitis is commonly described in three stages [4,5,21];
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freezing, frozen and thawing stages. The first or the freezing stage is marked by
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progressive pain and loss of motion lasting up to 9 months. The second or the frozen
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stage lasts from 4 to 12 months. In this stage, pain improves but stiffness persists and
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continues to impact patients’ ability to perform activities of daily living. The third and
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final thawing stage is a period of recovery marked by gradual improvement in the range
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of motion that can take up to 12 to 42 months. Since the purpose of IACI is to reduce
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pain caused by capsular inflammation, many authors claim that IACI is effective in
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freezing or early frozen stages with moderate to severe pain [2,28]. We included patients
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with pain duration of up to 12 months, which is considered to be long enough to include
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patients with freezing to frozen stages.
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IACI is considered to be a well-known and accepted treatment for adhesive capsulitis.
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Based on the concept of synovial inflammation for the pathology of adhesive capsulitis,
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the joint capsule can be the main pathology, and IACI can be justified for its treatment
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[29]. However, not enough evidences exist to conclude which injection method (intra-
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articular versus subacromial injection) is superior for the treatment of adhesive
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capsulitis. There are three studies that compared the location of injection. Oh et al [29]
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found that an intra-articular injection did not have a significantly greater decrease in the
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VAS score compared with a subacromial injection. Another study reported similar
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improvements in range of motion between intra-articular and subacromial injections
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[30]. A more recent study compared the efficacy of 3 injection methods, subacromial
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injection, intra-articular injection, and hydrodilatation in the treatment of primary
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adhesive capsulitis. Although hydrodilatation yielded more rapid improvement, the 3
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injection methods resulted in similar improvement in the final follow-up at 6 months
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[31].
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Ultrasound was used as guidance for IACI in this study. Traditionally, IACI for the
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treatment of adhesive capsulitis has been performed guided by anatomical landmarks
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alone. With the advent of readily available imaging tools such as ultrasound, image-
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guided injections have increasingly become accepted into routine care. While there is
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some evidence that the use of imaging improves accuracy, it is unclear from current
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evidence whether or not it improves patient-relevant outcomes [32]. Lee et al [33]
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compared ultrasound-guided injections of corticosteroid with blind injections for
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adhesive capsulitis during 6 weeks. The improvement in pain intensity, range of motion,
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and shoulder function score was significantly greater in the ultrasound-guided injection
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group than in the blind injection group by the second week post-injection. However,
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there were no further significant differences in the improvement between the 2 groups
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beyond the third week. Raeissadat et al [34] also compared ultrasound-guided injections
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with blind injections for a 4-week period. Improvements in pain intensity, range of
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motion, and functional score after 1 and 4 weeks were more prominent in the
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ultrasound-guided group, but the differences were not statistically significant, except for
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the changes in extension where the improvements were significantly higher in the
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ultrasound-guided group. The accuracy of injections was also higher in the ultrasound-
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guided group (90 % vs. 76 %), but the differences were not found to be significant.
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Overall, ultrasound-guided injections in adhesive capsulitis are more accurate. However,
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there were either no statistically significant correlations between the accuracy of
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injection and improvement of patients’ symptoms [34], or, even if found, the differences
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were insignificant after the third week [33].
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In this study, we used a sufficient amount of local anesthetic (8 mL of 1% lidocaine) to
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reduce pain during and after the injection. Several in vitro studies reported the
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chondrotoxic effect of local anesthetics [35,36]. And another study reported that the
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osteoarthritic articular cartilage is more vulnerable to local anesthetics than normal
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articular cartilage [37]. However, a more recent study investigated the in vivo effects of
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local anesthetics on the articular cartilage of the knees in rats. The experiment was first
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performed on normal knees, and then repeated on joints affected by experimentally
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induced osteoarthritis by transection of the anterior cruciate ligament. Results showed
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that intra-articular injections with 10 mL of 0.5% bupivacaine repeated once a week for
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5 consecutive weeks did not have a significant effect on the viability and density of
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chondrocytes, nor on the histological features of articular cartilage when compared with
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saline solution injections. The effects of local anesthetic were nonsignificant at different
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time points, regardless of whether osteoarthritic changes were induced [38]. However,
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these effects are limited to 0.5% bupivacaine, and further studies are needed for other
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types of local anesthetics. Since the toxic effect to chondrocyte of local anesthetics is
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still under investigation, it would be appropriate to use as little anesthetic volume as
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possible.
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We adopted widely-applied diagnostic criteria of adhesive capsulitis, commonly used
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also in previous studies [11,12,39,40]. According to this criteria, a patient will be
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diagnosed as adhesive capsulitis when his/her range of motion is decreased more than
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30˚ on 2 planes based on normal range of motion (forward flexion 180˚, extension 50˚,
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abduction 180˚, external rotation 90˚, internal rotation 90˚). Primary adhesive capsulitis
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is caused by global capsular inflammation and fibrosis, which results in a global
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limitation of range of motion. Recent studies have, however, argued that an
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anterosuperior or anteroinferior capsular tightening is another characteristic [6] and
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included a limitation of external rotation in the diagnostic criteria of adhesive capsulitis;
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external rotation to less than one half of normal [28] or less than 20° of external rotation
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[13,41]. Considering these changes, it would be more ideal to use a diagnostic criteria
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that would include the limitation of external rotation in the future studies on adhesive
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capsulitis.
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Longer pain duration will most probably push the number of injections up, which can be
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another reason for advocating early injection. We conducted an additional statistical
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analysis to explore the relationship between pain duration and the number of injections.
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The result showed a trend of longer pain leading to increased number of injections.
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However, factors (dominant arm, gender, and VAS 1) other than pain duration should be
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considered before drawing any conclusions based merely on injection counts. Further
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study that considers other factors (e.g. socioeconomic status or personal preference for
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injection et al) not included in this study will be needed to clarify the correlation
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between pain duration and number of injections.
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The greatest limitation of this study lies in the fact that it is a retrospective study.
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Nonetheless, it has a low drop-out rate (9.6% in total) and includes at least 4 rounds of
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follow-ups (at month 1, 2, 3, and 12) after IACI to monitor any patients that have
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received other treatments in a great effort to reduce bias. Second, we excluded patients
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with diabetes or thyroid dysfunction. However, adhesive capsulitis is often associated
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with diabetes or thyroid dysfunction [42,43]; the presence of these diseases may be an
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important prognostic factor for adhesive capsulitis. Therefore, it would be necessary to
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have further research that would include these patients. Third, this study included
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patients with pain duration ranging from 3 to 12 months. However, the duration of pain
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was determined entirely based on the patient’s memory, possibly leading to a recall bias.
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Conclusion
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This 1-year follow-up retrospective study reveals that an early IACI shows greater
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improvement in pain and function than late IACI. If pain persists despite non-invasive
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and conservative treatments, an early injection may be considered to shorten its natural
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history.
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Acknowledgment
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The authors thank Aeree Park, MA, for the English translation of the Korean manuscript.
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Figure 1. Flow diagram indicating progress of patients through the study.
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IACI, intra-articular corticosteroid injection
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Figure 2. The multiple linear regression graph showing the difference of internal
430
rotation and extension between month 0 and 12 (IRE ∆(0-12)), pain duration, and the
431
groups according to the injection number. Dotted line represents the single-injection
432
group (injection number 1, IRE ∆(0-12) = 31.36 + (-1.40) x pain duration). Solid line
433
represents the double- or triple-injection group (injection number 2 or 3, IRE ∆(0-12) =
434
41.98 + (-2.67) x pain duration). IRE ∆(0-12) is greater when the pain duration is
435
shorter, though the decrease in the IRE ∆(0-12) differs depending on the number of the
436
injection.
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ACCEPTED MANUSCRIPT Table 1. Changes of outcome measurements after intra-articular corticosteroid injection Month 1
Month 12
∆(0-1)
∆(0-12)
VAS score
7.6±1.0
3.2±1.4
1.9±1.3
4.4±1.8
5.7±1.7
SPADI score
59.5±5.6
30.6±11.0
24.1±9.9
28.9±12.5
35.5±11.4
Flexion, degree
144.9±18.7
153.4±18.2
166.4±13.5
Abduction, degree
72.4±14.7
115.7±33.8
148.9±33.8
ER, degree
32.4±10.8
40.5±8.0
73.5±15.8
IRE, cm
51.7±7.4
42.2±7.7
31.6±8.3
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∆(a-b) means difference of month a to b.
-8.5±14.3
-21.5±21.7
-43.3±34.0
-76.5±32.7
-8.1±11.1
-41.1±21.4
9.5±8.2
20.0±11.0
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Values are expressed as mean ± standard deviation.
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Month 0
VAS=visual analogue scale; SPADI=Shoulder Pain and Disability Index; ER=external
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rotation; IRE= internal rotation and extension.
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Table 2. Results of simple linear regressions. Gender
Beta
SE
P
Beta
SE
P
Beta
SE
∆(0-1)
-.33
.03
<.001
.01
.02
.759
-.35
.21
∆(0-12)
-.24
.03
<.001
-.01
.02
.681
.36
∆(0-1)
-1.84
.21
<.001
.01
.11
.963
-2.64
∆(0-12)
-1.68
.19
<.001
.05
.10
.632
∆(1-0)
-.63
.26
.016
.09
.13
.490
∆(12-0)
-1.35
.39
.001
.29
∆(1-0)
-5.16
.56
<.001
.11
∆(12-0)
-4.74
.54
<.001
∆(1-0)
-1.67
.18
∆(12-0)
-4.82
.29
∆(0-1)
-1.26
∆(0-12)
-2.06
Abduction
.24
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ER
Beta
SE
P
Beta
SE
P
.089
-
-
-
.72
.20
<.001
.067
-1.21
.17
<.001
.37
.19
.047
1.45
.069
-
-
-
1.27
1.40
.368
-3.40
1.31
.010
-7.10
1.19
<.001
-.16
1.27
.902
-.43
1.67
.797
-
-
-
2.47
1.60
.124
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Flexion
Arm dominance
P
VAS
SPADI
Injection number
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Age
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Pain duration
.20
.147
-.91
2.51
.718
-3.66
2.37
.124
3.97
2.42
.102
.31
.732
-5.50
3.93
.162
-
-
-
-1.24
3.81
.745
.30
.416
-7.46
3.77
.049
-20.91
3.41
<.001
4.87
3.66
.184
<.001
-.12
.10
.256
-2.24
1.28
.081
-
-
-
.99
1.24
.425
<.001
-.08
.20
.699
-1.77
2.48
.477
-16.69
2.17
<.001
2.87
2.39
.231
.13
<.001
-.10
.08
.173
-.86
.95
.369
-
-
-
-1.10
.92
.232
.17
<.001
-.06
.10
.570
-3.07
1.27
.016
-6.57
1.16
<.001
-.54
1.24
.664
IRE
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∆(a-b) means difference of month a to b.
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VAS=visual analogue scale; SPADI=Shoulder Pain and Disability Index; ER= external rotation; IRE= internal rotation and extension.
ACCEPTED MANUSCRIPT Table 3. Short-term effects by multiple linear regressions. Response variables VAS ∆(0-1)
Effects Intercept *
Pain duration
B
SE
t
P
7.22
.29
24.56
<.001
-.30
.03
-90.3
<.001
-.15
.48
-.30
.763
Dominant Non-dominant
0
Pain duration x arm dominance Dominant
-.07
Non-dominant SPADI ∆(0-1)
Intercept
44.10
Pain duration Intercept
*
Intercept *
Pain duration ER ∆(1-0)
Intercept Pain duration*
IRE ∆(0-1)
Intercept
.
.06
-1.30
.196
.
.
.
1.81
24.41
<.001
.21
-8.91
<.001
13.64
2.28
5.99
<.001
-.63
.26
-2.42
.016
85.78
4.86
17.66
<.001
-5.16
.56
-9.30
<.001
21.86
1.59
13.72
<.001
-1.67
.18
-9.18
<.001
19.84
1.18
16.87
<.001
-1.26
.13
-9.35
<.001
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Pain duration*
.
-1.84
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Pain duration Abduction ∆(1-0)
.
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*
Flexion ∆(1-0)
0
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Arm dominance
* The effects were statistically significant (P <.05).
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∆(a-b) means difference of month a to b.
VAS=visual analogue scale; SPADI=Shoulder Pain and Disability Index; ER=external
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rotation; IRE=internal rotation and extension.
ACCEPTED MANUSCRIPT Table 4. Long-term effects by multiple linear regressions. Response variables VAS ∆(0-12)
Effects Intercept
Pain duration
*
B
SE
t
P
7.18
.50
14.34
<.001
-.19
.05
-3.77
<.001
.23
.55
.41
.681
1 2 or 3
0
.
.
.
.50
.17
.864
.06
-.80
.426
.04
.07
.68
.496
0
.
.
.
51.26
2.99
17.15
<.001
-2.09
.31
-6.75
<.001
-4.16
3.72
-1.12
.265
0
.
.
.
-2.31
3.49
-.66
.508
.40
1.68
.093
.78
.44
1.78
.076
0
.
.
.
Intercept
32.60
3.41
9.57
<.001
Pain duration*
-1.35
.39
-3.47
.001
120.71
8.67
13.92
<.001
-5.81
.90
-6.48
<.001
-13.04
10.80
-1.21
.228
0
.
.
.
-5.80
10.11
-.57
.567
Arm dominance Dominant
.07
Non-dominant
0
Dominant
-.05
Non-dominant
0
2 or 3 Intercept
Pain duration
*
Injection number 1
Gender
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2 or 3
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Pain duration x injection number 1
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Pain duration x arm dominance
SPADI ∆(0-12)
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Injection number
Male
Female
0
Pain duration x gender
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Male
Female
.67 0
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Pain duration x injection number 1
2 or 3
Flexion ∆(12-0)
Abduction ∆(12-0)
Intercept
Pain duration
*
Injection number 1 2 or 3 Gender Male
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0
Pain duration x gender Male
1.51
Female
1.15
1.31
.190
2.56
1.27
2.02
.045
0
.
.
.
4.63
17.63
<.001
.47
-10.64
<.001
5.79
-.63
.528
.
.
.
.73
.68
1.07
.284
0
.
.
.
41.98
2.68
15.69
<.001
-2.67
.28
-9.65
<.001
-10.62
3.33
-3.19
.002
0
.
.
.
4.22
3.12
1.35
.177
.35
-.31
.760
1.27
.39
3.25
.001
0
.
.
.
0
1 2 or 3 ER ∆(12-0)
Intercept
81.57
Pain duration*
-4.97
Injection number 1
-3.66 0
Pain duration x injection number 2 or 3 IRE ∆(0-12)
Intercept
Pain duration
*
Injection number 1* 2 or 3 Gender
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1
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2 or 3
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Pain duration x injection number
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Male
Female
0
Pain duration x gender Male
Female
-.11 0
EP
Pain duration x injection number 1*
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2 or 3
* The effects were statistically significant (P <.05). ∆(a-b) means difference of month a to b. VAS=visual analogue scale; SPADI=Shoulder Pain and Disability Index; ER=external rotation; IRE=internal rotation and extension.
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S1934-1482(17)30662-7
DOI:
10.1016/j.pmrj.2017.06.004
Reference:
PMRJ 1917
To appear in:
PM&R
Received Date: 27 June 2016 Revised Date:
25 May 2017
Accepted Date: 3 June 2017
Please cite this article as: Ahn JH, Lee D-H, Kang H, Lee MY, Kang DR, Yoon S-H, Early intraarticular corticosteroid injection improves pain and function in adhesive capsulitis of shoulder: 1-year retrospective longitudinal study, PM&R (2017), doi: 10.1016/j.pmrj.2017.06.004. 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.
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Title: Early intra-articular corticosteroid injection improves pain and function in adhesive
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capsulitis of shoulder: 1-year retrospective longitudinal study
Authors: Jung Hwan Ahn, MD, Doo-Hyung Lee, MD, PhD, Hyuncheol Kang, PhD, Michael Y. Lee, MD, MHA, Dae Ryong Kang, PhD, Seung-Hyun Yoon, MD, PhD
Affiliation: Department of Emergency Medicine (J.H. Ahn), Department of Orthopedic
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Surgery (D.-H. Lee), Medical Humanities and Social Medicine (D.R. Kang), and Physical Medicine and Rehabilitation (S.-H. Yoon), Ajou University School of Medicine, Suwon,
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Republic of Korea
Department of Applied Statistics (H. Kang), Hoseo University, Asan, Republic of Korea Department of Physical Medicine and Rehabilitation (M.Y. Lee), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC
Correspondence: Seung-Hyun Yoon, MD, PhD, Department of Physical Medicine and
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Rehabilitation, Ajou University School of Medicine, 164, World Cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea E-mail: [email protected]
Telephone: +82-31-219-5279
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Fax: +82-31-219-5209
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Conflict of interest: none declared. This manuscript contains original material only that has not previously been published, and is not currently under consideration elsewhere, nor will be submitted elsewhere until a final decision has been made by the journal.
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Title: Early intra-articular corticosteroid injection improves pain and function in
2
adhesive capsulitis of shoulder: 1-year retrospective longitudinal study
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Background: Intra-articular corticosteroid injection is a commonly used therapy for
4
adhesive capsulitis, but not enough studies exist on the optimal timing of the injection.
5
Objective: To determine whether intra-articular corticosteroid injection has better
6
outcomes in patients with earlier stage than later stage of adhesive capsulitis.
7
Study design: Retrospective longitudinal study
8
Setting: University-affiliated tertiary care hospital.
9
Participants: Primary adhesive capsulitis patients (n=339) who were unresponsive to at
10
least 1 month of conservative treatment and who had ultrasound-guided corticosteroid
11
injection.
12
Interventions: Not applicable.
13
Main Outcome Measurements: Visual analog scale, Shoulder Pain and Disability Index,
14
and passive range of motion (flexion, abduction, external rotation, and internal rotation
15
and extension) were evaluated at pretreatment, month 1 and 12 after the first injection.
16
Results: The result of the multiple regressions, which considered the main and the
17
interaction effect of confounding variables, showed that the differences of all outcomes
18
in both short-term effect at month 1 and long-term effect at month 12 are greater when
19
the duration of pain prior to injection is shorter. Among the confounders, the injection
20
number in the difference of internal rotation and extension between month 0 and 12
21
(IRE ∆(0-12)) was statistically significant. IRE ∆(0-12) was also greater when the pain
22
duration was shorter, though the decrease in IRE ∆(0-12) differed depending on the
23
number of injections.
24
Conclusions: Early injection improves outcomes of adhesive capsulitis at both short-
25
and long-term follow-ups. If pain persists despite non-invasive and conservative
26
treatments, early injection may be considered to shorten its natural history.
27
Keywords: periarthritis; shoulder pain; treatment outcome; prognosis; intra-articular
28
injections; adhesive capsulitis; frozen shoulder
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Introduction
30
Adhesive capsulitis is a long-lasting, painful shoulder condition commonly known as
31
frozen shoulder or painful stiff shoulder. The condition results from progressive fibrosis
32
and eventual contracture of the capsule of the glenohumeral joint, which causes pain
33
and stiffness [1,2]. The treatment for adhesive capsulitis includes supervised exercise,
34
physical modalities, nonsteroidal anti-inflammatory drugs, oral corticosteroid, intra-
35
articular corticosteroid injection (IACI), suprascapular nerve block, hydraulic
36
arthrographic capsular distension, manipulation and arthroscopic capsular release [1-8].
37
IACI is one of the conservative treatments for adhesive capsulitis. It is effective in
38
rapidly reducing the pain[3], but there is a paucity of studies that define the optimal
39
timing of the injection. It is in the early stages of adhesive capsulitis that a
40
hypervascular synovial hyperplasia is present and this may eventually lead to the
41
fibrosis of the capsule. It has been contended that if given at an early (e.g. freezing)
42
stage, IACI may possibly minimize the morbidity of the disorder. Early treatment with
43
IACI may provide a chemical ablation of the synovitis which can help prevent the
44
development of the fibrosis and shorten the natural history of the disease [2,4,9,10].
45
However, not enough studies exist to prove the effectiveness of early injection. The aim
46
of this study is to evaluate whether early IACI is beneficial for pain and function.
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Methods
49
Patients
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This is a 1-year retrospective longitudinal study based on the shoulder disease registry
51
data from the university-affiliated tertiary care hospital. Informed consent was waived
52
for this retrospective study as part of an exemption approved by the institutional review
53
board. 661 patients diagnosed with primary adhesive capsulitis were reviewed
54
retrospectively between January 1st, 2011 and December 31st, 2014. They were
55
outpatients at rehabilitation and orthopedic clinics. All the patients underwent a
56
standardized history-taking, physical examination and ultrasonographic evaluation by
57
the lead author; passive and active range of motion, painful arc and impingement test,
58
resisted test, strength of muscles in the affected shoulder at the initial workup.
59
Inclusion criteria were patients who had adhesive capsulitis with a normal radiograph
60
finding of the affected shoulder and restriction of passive motion of greater than 30˚ in 2
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or more planes of movement by goniometric measurement with scapula rotation
62
restrained [11,12]; pain duration ranging from 3 to 12 months (freezing and frozen stage
63
of adhesive capsulitis); and average pain intensity during a week defined as a score of 6
64
points or more on a 10-cm visual analog scale (VAS) rated from “no pain” to “the worst
65
imaginable pain”. Abnormal limits of passive motion were defined as forward flexion
66
<150˚, extension <20˚, abduction <150˚, external rotation <60˚, and internal rotation
67
<60˚. External rotation and internal rotation were measured at shoulder 90˚ abduction. If
68
abduction measured was less than 90°, maximum possible abduction was achieved
69
before measuring the external rotation. To restrict the contribution of scapular rotation,
70
the patient was asked to relax, and the evaluator held the clavicle and scapular spine
71
with the hand. Passive elevation of the upper arm was stopped, and goniometric angles
72
were taken when it was no longer possible to prevent the scapula from rotating [13].
73
Patients were excluded if they had any of the following: secondary adhesive capsulitis
74
(secondary to other causes including inflammatory or infectious arthritis, stroke, tumor,
75
trauma, or fracture); history of diabetes and/or thyroid dysfunction; rotator cuff disease
76
on both physical and ultrasonographic examinations; medium to large sized (≥3cm)
77
partial- or full-thickness tear of the rotator cuff on ultrasonography [14,15]; calcific
78
tendinitis; primary osteoarthritis of the glenohumeral joint in a simple radiograph; and
79
previous corticosteroid injection on the affected shoulder. Magnetic resonance imaging
80
was not undertaken routinely, but those with either muscle weakness or a sign of
81
positive impingement were excluded on the basis of a high likeliness of rotator cuff tear.
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A minimum of 1 month conservative treatment was provided without any IACI. The
83
conservative treatment included analgesics (nonsteroidal anti-inflammatory drugs,
84
acetaminophen/tramadol, opioids, tricyclic antidepressants, and fentanyl patch),
85
flexibility exercise, and physical modalities (heat and electrical therapies). Patients
86
received an institutional flexibility exercise of glenohumeral joint with physical
87
therapists once or two times a week for 2-4 weeks, and were educated to do the same
88
exercise at home. Patients who complained about persistent shoulder pain of VAS≥6
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even after 1 month of conservative treatment were recommended to take the IACI.
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Ultrasound-guided corticosteroid injection and exercise education
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Patients sat in a seated position with their hands on their thighs. After aseptic 4
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preparation, the lead author inserted a 23-gauge, 6 cm long needle parallel to the
94
transducer from the posterior side of the shoulder. The needle was advanced under a
95
real-time ultrasound equipment (Logiq P6, GE Healthcare, Buckinghamshire, United
96
Kingdom) using 10-12MHz, linear array transducers until the needle tip entered the
97
glenohumeral joint. The lead author injected 2mL of 10mg/mL triamcinolone acetonide
98
and 8mL of 1% lidocaine. After injection, the patients were instructed about the home
99
exercise program for increasing the range of motion including stretching forward and
100
bending down to a desk, Codman exercise, wall-climbing exercise, external and internal
101
rotation with bar, and posterior shoulder stretch [16]. Exercises were to be performed 3
102
times a day lasting 10 minutes each round. No nonsteroidal anti-inflammatory drugs,
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analgesics, or opioids were prescribed after injection. Patients were asked to visit the
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hospital again at month 1, 2, and 3 after the injection and recommended to have a
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second or third injection if their pain persisted over 50%.
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Outcome measurements
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VAS, Shoulder Pain and Disability Index score (SPADI), passive range of motion were
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compared for pre-, 1 month (short-term effect of IACI), and 12 month (long-term effect)
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after the first injection. All outcome measurements were evaluated by the lead author. A
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VAS as primary outcome measurement was used to assess shoulder pain. SPADI is a
112
self-reporting questionnaire for patients with shoulder pain, which consists of 13
113
questions that are divided into 2 domains: pain (5 items) and disability (8 items) [17].
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Each domain score is equally weighted and added to obtain a total percentage score
115
between the ranges of 0 (best) to 100 (worst). Passive range of motion of forward
116
flexion, abduction and external rotation were measured by goniometer in supine
117
position. External rotation was measured in 0° abduction of shoulder and 90° flexion of
118
elbow position. Internal rotation and extension was measured as the distance (cm) from
119
the spinous process of 7th cervical vertebra to the tip of the fully extended thumb in
120
standing position [18]. This methodology shows high intrarater reliability [19] and is a
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useful method that is also relevant with the activities of daily living, such as dressing,
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bathing, and toileting [20].
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Statistical analysis 5
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All the data were analyzed by using the SPSS version 23 statistics software (IBM,
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Armonk, NY). Continuous data are expressed as means ± standard deviation.
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Categorical data are shown as absolute values, together with the frequency distribution.
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The number of injections were reclassified into two groups, single-injection (injection
129
number 1) group and double- or triple-injection (injection number 2 or 3) group; the two
130
latter were combined since only 7 (2.1%) out of 339 patients opted for triple-injection.
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The multiple regression analysis was conducted to determine the relationship between
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the differences of outcomes and pain duration while controlling the confounding
133
variables (gender, age, injection number, or arm dominance). Simple regression was
134
also conducted between the differences of outcomes and other variables (age, gender,
135
the group according to injection number, arm dominance or pain duration) in order to
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select the variables which were put into multiple regression. The variables with P ≤ .05
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in the simple regression were entered into the multiple regression with main and
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interaction effects. P <.05 was considered significant in multiple regression analysis. In
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the multiple regression analysis, it was considered significant if P <.05.
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Results
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General characteristics
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Medical records of a total of 661 patients were reviewed. Of them, 246 had pain that
144
improved after conservative treatment (figure 1). IACI was recommended to the rest of
145
the patients (415) with pain of VAS ≥6; 40 refused and 375 accepted the
146
recommendation. Of the 375 who accepted, 36 were not included in the 12-month
147
follow-up; 17 did not attend the follow-up, 8 were treated at other clinics, and 11 could
148
not be reached. Finally, 339 patients completed the follow-up at month 1 (short-term
149
effects) and 12 (long-term) after IACI. The mean (range) age was 54.5±6.0 (39 to 69)
150
years old; ratio of male to female 111 (32.7%): 228 (67.3%); ratio of dominant to non-
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dominant arm 129 (38.1%): 210 (61.9%); pain duration 8.2±3.0 (3 to 12) months; and
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ratio of injection (single- versus double- and triple-injection) 146 (43.1%): 193 (56.9%).
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Outcome measurements and complications
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Table 1 shows the value and changes of outcome measurements after IACI. Apart from
155
facial flushing on days 2 to 6 after injection (12 patients), there were no serious
156
complications such as infection.
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Selection of confounders
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Table 2 shows the results of simple regression analysis. In case of short-term effects, or
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the difference in month 0 to 1 (∆(0-1) or ∆(1-0)), arm dominance was the confounder in
160
only VAS ∆(0-1), while no confounders were found in other outcomes (SPADI ∆(0-1),
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flexion ∆(1-0), abduction ∆(1-0), external rotation ∆(1-0), internal rotation and
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extension ∆(0-1)). In long-term effects, or the difference in month 0 to 12 (∆(0-12) or
163
∆(12-0)), the confounders were injection number and arm dominance in VAS ∆(0-12),
164
injection number and gender in SPADI ∆(0-12), while no confounder was found in
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flexion ∆(12-0), injection number and gender in abduction ∆(12-0), injection number in
166
external rotation ∆(12-0), and injection number and gender in internal rotation and
167
extension ∆(0-12) (P <.05).
168
Relation between the differences of outcomes and pain duration controlling confounders
169
Table 3 shows the results of multiple regression for short-term effects. Pain duration
170
was statistically significant in all the differences of outcomes (flexion, P =.016; others,
171
P <.001). Beta (regression coefficient) of pain duration in all the differences of
172
outcomes was negative. Arm dominance as confounder in VAS ∆(0-1) was not
173
statistically significant considering the main and the interaction effect with pain
174
duration (P >.05). Table 4 shows the results of multiple regression for long-term effects.
175
Pain duration was statistically significant in all the differences of outcomes (flexion, P
176
=.001; others, P <.001). Beta of pain duration in all the differences of outcomes was
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negative. Among the confounders in the differences of outcomes, the main and the
178
interaction effect of injection number in IRE ∆(0-12) was statistically significant
179
(injection number, P =.002; interaction between pain duration and injection number, P
180
=.001), while the other confounders were not statistically significant. The slopes which
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represent the different injection number groups were negative, x axis being pain
182
duration and y axis IRE ∆(0-12) (figure 2).
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Discussion
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This 1-year retrospective longitudinal study reveals that the improvement in outcomes,
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which considered the main and the interaction effect of the confounding variables, are
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greater when the pain duration prior to IACI is shorter in both short-term effect at
188
month 1 and long-term effect at month 12. Among the confounders in the improvement 7
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in outcomes, only the injection number in IRE ∆(0-12) resulted in a statistically
190
significant confounder resulting in better outcomes with more injections. Though the
191
decrease in IRE ∆(0-12) differed depending on the number of injections, IRE ∆(0-12)
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was also greater when the pain duration was shorter. These results suggest that early
193
IACI will have a greater improvement in pain and function than late IACI.
194
Many researchers have dismissed adhesive capsulitis as a benign condition, with most
195
being self-resolving [1,21]. However, it is now widely accepted that up to 50% of the
196
patients may not fully recover from the symptoms and disability, even with long-term
197
follow-ups [22-24]. Some investigators have advocated the use of IACI in the treatment
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of early adhesive capsulitis and suggested that patients treated with injection at an early
199
stage of the disorder respond better than later stage. Their rationale for early IACI is that
200
it would reduce inflammation of synovium, decreasing capsular fibrosis and shortening
201
the natural history of the disease [2,4,9,10,25,26]. However, not enough studies exist to
202
prove the effects of early injection. In a previous retrospective case series, the authors
203
showed that IACI may be more efficacious in the freezing stage (stage 1 and 2 based on
204
the classification by Neviaser and Neviaser’s four staging system [27]) before the
205
development of a significant capsular contracture [25]. In the same study, the result
206
showed that an early IACI for adhesive capsulitis may have allowed patients to recover
207
motion at a median time of 3 months. But the study had several limitations, including
208
patients in stage 1 (n=5) who would be difficult to diagnose if not for the support of an
209
arthroscopic or histologic evaluation; no control group of frozen stage (stage 3 and 4)
210
patients to compare the effectiveness of IACI; relatively few samples (n=44 in total);
211
and a short mean follow-up period of 6.7 months. Our study overcame previous
212
limitations by including frozen stage patients, a relatively large sample (n=339), and a
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long enough follow-up (1-yr) to observe the effect of IACI.
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The natural history of adhesive capsulitis is commonly described in three stages [4,5,21];
215
freezing, frozen and thawing stages. The first or the freezing stage is marked by
216
progressive pain and loss of motion lasting up to 9 months. The second or the frozen
217
stage lasts from 4 to 12 months. In this stage, pain improves but stiffness persists and
218
continues to impact patients’ ability to perform activities of daily living. The third and
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final thawing stage is a period of recovery marked by gradual improvement in the range
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of motion that can take up to 12 to 42 months. Since the purpose of IACI is to reduce
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pain caused by capsular inflammation, many authors claim that IACI is effective in
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freezing or early frozen stages with moderate to severe pain [2,28]. We included patients
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with pain duration of up to 12 months, which is considered to be long enough to include
224
patients with freezing to frozen stages.
225
IACI is considered to be a well-known and accepted treatment for adhesive capsulitis.
226
Based on the concept of synovial inflammation for the pathology of adhesive capsulitis,
227
the joint capsule can be the main pathology, and IACI can be justified for its treatment
228
[29]. However, not enough evidences exist to conclude which injection method (intra-
229
articular versus subacromial injection) is superior for the treatment of adhesive
230
capsulitis. There are three studies that compared the location of injection. Oh et al [29]
231
found that an intra-articular injection did not have a significantly greater decrease in the
232
VAS score compared with a subacromial injection. Another study reported similar
233
improvements in range of motion between intra-articular and subacromial injections
234
[30]. A more recent study compared the efficacy of 3 injection methods, subacromial
235
injection, intra-articular injection, and hydrodilatation in the treatment of primary
236
adhesive capsulitis. Although hydrodilatation yielded more rapid improvement, the 3
237
injection methods resulted in similar improvement in the final follow-up at 6 months
238
[31].
239
Ultrasound was used as guidance for IACI in this study. Traditionally, IACI for the
240
treatment of adhesive capsulitis has been performed guided by anatomical landmarks
241
alone. With the advent of readily available imaging tools such as ultrasound, image-
242
guided injections have increasingly become accepted into routine care. While there is
243
some evidence that the use of imaging improves accuracy, it is unclear from current
244
evidence whether or not it improves patient-relevant outcomes [32]. Lee et al [33]
245
compared ultrasound-guided injections of corticosteroid with blind injections for
246
adhesive capsulitis during 6 weeks. The improvement in pain intensity, range of motion,
247
and shoulder function score was significantly greater in the ultrasound-guided injection
248
group than in the blind injection group by the second week post-injection. However,
249
there were no further significant differences in the improvement between the 2 groups
250
beyond the third week. Raeissadat et al [34] also compared ultrasound-guided injections
251
with blind injections for a 4-week period. Improvements in pain intensity, range of
252
motion, and functional score after 1 and 4 weeks were more prominent in the
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ultrasound-guided group, but the differences were not statistically significant, except for
254
the changes in extension where the improvements were significantly higher in the
255
ultrasound-guided group. The accuracy of injections was also higher in the ultrasound-
256
guided group (90 % vs. 76 %), but the differences were not found to be significant.
257
Overall, ultrasound-guided injections in adhesive capsulitis are more accurate. However,
258
there were either no statistically significant correlations between the accuracy of
259
injection and improvement of patients’ symptoms [34], or, even if found, the differences
260
were insignificant after the third week [33].
261
In this study, we used a sufficient amount of local anesthetic (8 mL of 1% lidocaine) to
262
reduce pain during and after the injection. Several in vitro studies reported the
263
chondrotoxic effect of local anesthetics [35,36]. And another study reported that the
264
osteoarthritic articular cartilage is more vulnerable to local anesthetics than normal
265
articular cartilage [37]. However, a more recent study investigated the in vivo effects of
266
local anesthetics on the articular cartilage of the knees in rats. The experiment was first
267
performed on normal knees, and then repeated on joints affected by experimentally
268
induced osteoarthritis by transection of the anterior cruciate ligament. Results showed
269
that intra-articular injections with 10 mL of 0.5% bupivacaine repeated once a week for
270
5 consecutive weeks did not have a significant effect on the viability and density of
271
chondrocytes, nor on the histological features of articular cartilage when compared with
272
saline solution injections. The effects of local anesthetic were nonsignificant at different
273
time points, regardless of whether osteoarthritic changes were induced [38]. However,
274
these effects are limited to 0.5% bupivacaine, and further studies are needed for other
275
types of local anesthetics. Since the toxic effect to chondrocyte of local anesthetics is
276
still under investigation, it would be appropriate to use as little anesthetic volume as
277
possible.
278
We adopted widely-applied diagnostic criteria of adhesive capsulitis, commonly used
279
also in previous studies [11,12,39,40]. According to this criteria, a patient will be
280
diagnosed as adhesive capsulitis when his/her range of motion is decreased more than
281
30˚ on 2 planes based on normal range of motion (forward flexion 180˚, extension 50˚,
282
abduction 180˚, external rotation 90˚, internal rotation 90˚). Primary adhesive capsulitis
283
is caused by global capsular inflammation and fibrosis, which results in a global
284
limitation of range of motion. Recent studies have, however, argued that an
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anterosuperior or anteroinferior capsular tightening is another characteristic [6] and
286
included a limitation of external rotation in the diagnostic criteria of adhesive capsulitis;
287
external rotation to less than one half of normal [28] or less than 20° of external rotation
288
[13,41]. Considering these changes, it would be more ideal to use a diagnostic criteria
289
that would include the limitation of external rotation in the future studies on adhesive
290
capsulitis.
291
Longer pain duration will most probably push the number of injections up, which can be
292
another reason for advocating early injection. We conducted an additional statistical
293
analysis to explore the relationship between pain duration and the number of injections.
294
The result showed a trend of longer pain leading to increased number of injections.
295
However, factors (dominant arm, gender, and VAS 1) other than pain duration should be
296
considered before drawing any conclusions based merely on injection counts. Further
297
study that considers other factors (e.g. socioeconomic status or personal preference for
298
injection et al) not included in this study will be needed to clarify the correlation
299
between pain duration and number of injections.
300
The greatest limitation of this study lies in the fact that it is a retrospective study.
301
Nonetheless, it has a low drop-out rate (9.6% in total) and includes at least 4 rounds of
302
follow-ups (at month 1, 2, 3, and 12) after IACI to monitor any patients that have
303
received other treatments in a great effort to reduce bias. Second, we excluded patients
304
with diabetes or thyroid dysfunction. However, adhesive capsulitis is often associated
305
with diabetes or thyroid dysfunction [42,43]; the presence of these diseases may be an
306
important prognostic factor for adhesive capsulitis. Therefore, it would be necessary to
307
have further research that would include these patients. Third, this study included
308
patients with pain duration ranging from 3 to 12 months. However, the duration of pain
309
was determined entirely based on the patient’s memory, possibly leading to a recall bias.
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Conclusion
312
This 1-year follow-up retrospective study reveals that an early IACI shows greater
313
improvement in pain and function than late IACI. If pain persists despite non-invasive
314
and conservative treatments, an early injection may be considered to shorten its natural
315
history.
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Acknowledgment
317
The authors thank Aeree Park, MA, for the English translation of the Korean manuscript.
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controlled trial. Am J Sports Med 2013;41:1133-1139. 40.
418 419
ed: Chicago, IL: AMA; 2012, 461-476. 41.
420 421
Rondinelli RD. AMA Guides to the Evaluation of Permanent Impairment. Sixth
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Ando A, Sugaya H, Hagiwara Y, et al. Identification of prognostic factors for the nonoperative treatment of stiff shoulder. Int Orthop 2013;37:859-864.
42.
Balci N, Balci MK, Tuzuner S. Shoulder adhesive capsulitis and shoulder range of motion in type II diabetes mellitus: association with diabetic complications. J
423
Diabetes Complications 1999;13:135-140.
425
43.
Wohlgethan JR. Frozen shoulder in hyperthyroidism. Arthritis Rheum 1987;30:936-939.
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M AN U
424
SC
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Figure 1. Flow diagram indicating progress of patients through the study.
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IACI, intra-articular corticosteroid injection
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Figure 2. The multiple linear regression graph showing the difference of internal
430
rotation and extension between month 0 and 12 (IRE ∆(0-12)), pain duration, and the
431
groups according to the injection number. Dotted line represents the single-injection
432
group (injection number 1, IRE ∆(0-12) = 31.36 + (-1.40) x pain duration). Solid line
433
represents the double- or triple-injection group (injection number 2 or 3, IRE ∆(0-12) =
434
41.98 + (-2.67) x pain duration). IRE ∆(0-12) is greater when the pain duration is
435
shorter, though the decrease in the IRE ∆(0-12) differs depending on the number of the
436
injection.
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18
ACCEPTED MANUSCRIPT Table 1. Changes of outcome measurements after intra-articular corticosteroid injection Month 1
Month 12
∆(0-1)
∆(0-12)
VAS score
7.6±1.0
3.2±1.4
1.9±1.3
4.4±1.8
5.7±1.7
SPADI score
59.5±5.6
30.6±11.0
24.1±9.9
28.9±12.5
35.5±11.4
Flexion, degree
144.9±18.7
153.4±18.2
166.4±13.5
Abduction, degree
72.4±14.7
115.7±33.8
148.9±33.8
ER, degree
32.4±10.8
40.5±8.0
73.5±15.8
IRE, cm
51.7±7.4
42.2±7.7
31.6±8.3
M AN U
∆(a-b) means difference of month a to b.
-8.5±14.3
-21.5±21.7
-43.3±34.0
-76.5±32.7
-8.1±11.1
-41.1±21.4
9.5±8.2
20.0±11.0
SC
Values are expressed as mean ± standard deviation.
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Month 0
VAS=visual analogue scale; SPADI=Shoulder Pain and Disability Index; ER=external
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rotation; IRE= internal rotation and extension.
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Table 2. Results of simple linear regressions. Gender
Beta
SE
P
Beta
SE
P
Beta
SE
∆(0-1)
-.33
.03
<.001
.01
.02
.759
-.35
.21
∆(0-12)
-.24
.03
<.001
-.01
.02
.681
.36
∆(0-1)
-1.84
.21
<.001
.01
.11
.963
-2.64
∆(0-12)
-1.68
.19
<.001
.05
.10
.632
∆(1-0)
-.63
.26
.016
.09
.13
.490
∆(12-0)
-1.35
.39
.001
.29
∆(1-0)
-5.16
.56
<.001
.11
∆(12-0)
-4.74
.54
<.001
∆(1-0)
-1.67
.18
∆(12-0)
-4.82
.29
∆(0-1)
-1.26
∆(0-12)
-2.06
Abduction
.24
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ER
Beta
SE
P
Beta
SE
P
.089
-
-
-
.72
.20
<.001
.067
-1.21
.17
<.001
.37
.19
.047
1.45
.069
-
-
-
1.27
1.40
.368
-3.40
1.31
.010
-7.10
1.19
<.001
-.16
1.27
.902
-.43
1.67
.797
-
-
-
2.47
1.60
.124
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M AN U
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Flexion
Arm dominance
P
VAS
SPADI
Injection number
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Age
EP
Pain duration
.20
.147
-.91
2.51
.718
-3.66
2.37
.124
3.97
2.42
.102
.31
.732
-5.50
3.93
.162
-
-
-
-1.24
3.81
.745
.30
.416
-7.46
3.77
.049
-20.91
3.41
<.001
4.87
3.66
.184
<.001
-.12
.10
.256
-2.24
1.28
.081
-
-
-
.99
1.24
.425
<.001
-.08
.20
.699
-1.77
2.48
.477
-16.69
2.17
<.001
2.87
2.39
.231
.13
<.001
-.10
.08
.173
-.86
.95
.369
-
-
-
-1.10
.92
.232
.17
<.001
-.06
.10
.570
-3.07
1.27
.016
-6.57
1.16
<.001
-.54
1.24
.664
IRE
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∆(a-b) means difference of month a to b.
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VAS=visual analogue scale; SPADI=Shoulder Pain and Disability Index; ER= external rotation; IRE= internal rotation and extension.
ACCEPTED MANUSCRIPT Table 3. Short-term effects by multiple linear regressions. Response variables VAS ∆(0-1)
Effects Intercept *
Pain duration
B
SE
t
P
7.22
.29
24.56
<.001
-.30
.03
-90.3
<.001
-.15
.48
-.30
.763
Dominant Non-dominant
0
Pain duration x arm dominance Dominant
-.07
Non-dominant SPADI ∆(0-1)
Intercept
44.10
Pain duration Intercept
*
Intercept *
Pain duration ER ∆(1-0)
Intercept Pain duration*
IRE ∆(0-1)
Intercept
.
.06
-1.30
.196
.
.
.
1.81
24.41
<.001
.21
-8.91
<.001
13.64
2.28
5.99
<.001
-.63
.26
-2.42
.016
85.78
4.86
17.66
<.001
-5.16
.56
-9.30
<.001
21.86
1.59
13.72
<.001
-1.67
.18
-9.18
<.001
19.84
1.18
16.87
<.001
-1.26
.13
-9.35
<.001
TE D
Pain duration*
.
-1.84
M AN U
Pain duration Abduction ∆(1-0)
.
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*
Flexion ∆(1-0)
0
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Arm dominance
* The effects were statistically significant (P <.05).
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∆(a-b) means difference of month a to b.
VAS=visual analogue scale; SPADI=Shoulder Pain and Disability Index; ER=external
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rotation; IRE=internal rotation and extension.
ACCEPTED MANUSCRIPT Table 4. Long-term effects by multiple linear regressions. Response variables VAS ∆(0-12)
Effects Intercept
Pain duration
*
B
SE
t
P
7.18
.50
14.34
<.001
-.19
.05
-3.77
<.001
.23
.55
.41
.681
1 2 or 3
0
.
.
.
.50
.17
.864
.06
-.80
.426
.04
.07
.68
.496
0
.
.
.
51.26
2.99
17.15
<.001
-2.09
.31
-6.75
<.001
-4.16
3.72
-1.12
.265
0
.
.
.
-2.31
3.49
-.66
.508
.40
1.68
.093
.78
.44
1.78
.076
0
.
.
.
Intercept
32.60
3.41
9.57
<.001
Pain duration*
-1.35
.39
-3.47
.001
120.71
8.67
13.92
<.001
-5.81
.90
-6.48
<.001
-13.04
10.80
-1.21
.228
0
.
.
.
-5.80
10.11
-.57
.567
Arm dominance Dominant
.07
Non-dominant
0
Dominant
-.05
Non-dominant
0
2 or 3 Intercept
Pain duration
*
Injection number 1
Gender
TE D
2 or 3
M AN U
Pain duration x injection number 1
SC
Pain duration x arm dominance
SPADI ∆(0-12)
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Injection number
Male
Female
0
Pain duration x gender
EP
Male
Female
.67 0
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Pain duration x injection number 1
2 or 3
Flexion ∆(12-0)
Abduction ∆(12-0)
Intercept
Pain duration
*
Injection number 1 2 or 3 Gender Male
ACCEPTED MANUSCRIPT Female
0
Pain duration x gender Male
1.51
Female
1.15
1.31
.190
2.56
1.27
2.02
.045
0
.
.
.
4.63
17.63
<.001
.47
-10.64
<.001
5.79
-.63
.528
.
.
.
.73
.68
1.07
.284
0
.
.
.
41.98
2.68
15.69
<.001
-2.67
.28
-9.65
<.001
-10.62
3.33
-3.19
.002
0
.
.
.
4.22
3.12
1.35
.177
.35
-.31
.760
1.27
.39
3.25
.001
0
.
.
.
0
1 2 or 3 ER ∆(12-0)
Intercept
81.57
Pain duration*
-4.97
Injection number 1
-3.66 0
Pain duration x injection number 2 or 3 IRE ∆(0-12)
Intercept
Pain duration
*
Injection number 1* 2 or 3 Gender
M AN U
1
SC
2 or 3
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Pain duration x injection number
TE D
Male
Female
0
Pain duration x gender Male
Female
-.11 0
EP
Pain duration x injection number 1*
AC C
2 or 3
* The effects were statistically significant (P <.05). ∆(a-b) means difference of month a to b. VAS=visual analogue scale; SPADI=Shoulder Pain and Disability Index; ER=external rotation; IRE=internal rotation and extension.
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