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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_7 | Pages 71 - 71
1 Jul 2022
Santini A Jamal J Wong P Lane B Wood A Bou-Gharios G Frostick S Roebuck M
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Abstract

Introduction

Risk factors for osteoarthritis include raised BMI and female gender. Whether these two factors influenced synovial gene expression was investigated using a triangulation and modelling strategy which generated 12 datasets of gene expression in synovial tissue from three knee pathologies with matching BMI groups, obese and overweight, and gender distributions.

Methodology

Intra-operative synovial biopsies were immersed in RNAlater at 4oC before storage at -80oC. Total RNA was extracted using RNAeasy with gDNA removal. Following RT- PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Linear models were prepared in limma with gender and BMI factors incorporated sequentially for each pathology comparison, generating 12 models of probes differentially expressed at FDR p<0.05 and Bayes number, B>0. Data analysis of differently expressed genes utilized Ingenuity Pathway Analysis and Cytoscape with Cluego and Cytohubba plug-ins.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_7 | Pages 68 - 68
1 Jul 2022
Jamal J Wong P Lane B Wood A Bou-Gharios G Santini A Frostick S Roebuck M
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Abstract

Introduction

It is increasingly evident that synovium may play a larger role in the aetiology of osteoarthritis. We compared gene expression in whole tissue synovial biopsies from end-stage knee osteoarthritis and knee trauma patients with that of their paired explant cultures to determine how accurately cultured cells represent holistic synovial function.

Methodology

Synovial tissue biopsies were taken from 16 arthroplasty patients and 8 tibial plateau fracture patients with no osteoarthritis. Pairs of whole tissue fragments were either immediately immersed in RNAlater Stabilisation Solution at 4o C before transfer to -80o C storage until RNA extraction; or weighed, minced and cultured at 500mg tissues/5ml media in a humidified incubator at 37oC, 5% CO2. After sub-culturing total RNA was extracted using RNAeasy Plus Mini Kit with gDNA removal. Following RT-PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_7 | Pages 69 - 69
1 Jul 2022
Roebuck M Jamal J Wong P Lane B Wood A Bou-Gharios G Frostick S Santini A
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Abstract

Introduction

Articular cartilage degradation is a defining feature of osteoarthritis. Synovium is a reactive tissue with synovial villae, neoangiogenesis and intimal hyperplasia common to many joint pathologies. The consequences of cartilage debris in osteoarthritis impacting the synovial intima is not well understood. We analysed the immunohistology of synovium from 16 patients with osteoarthritis and 17 patients undergoing knee surgery for non-arthritic pathologies. This data was integrated with imaging and functional scores to correlate synovitis in osteoarthritis.

Methodology

Formalin-fixed paraffin embedded synovial biopsy sections were cut in serial sequence and processed for routine staining (H&E or CD3, CD68, CD20, Vimentin, vWF and PCNA IHC) using standardised Dako monoclonal mouse anti-human antibodies. Digital images scanned at x20 were evaluated for fragments of cartilage and aggregates of inflammatory cells. Clinical data (gender, BMI, KL grade, WOMAC & SF-12 scores) was aligned with histopathological data.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_7 | Pages 70 - 70
1 Jul 2022
Wong P Jamal J Santini A Lane B Wood A Bou-Gharios G Frostick S Roebuck M
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Abstract

Introduction

Synovitis impacts osteoarthritis symptomatology and progression. The transcription factors controlling synovial gene expression have not been described. This study analyses gene expression in synovium samples from 16 patients with osteoarthritis with 9 undergoing arthroscopic and 8 knee trauma surgery for non-arthritic pathologies.

Methodology

Intra-operative synovial biopsies were immersed in RNAlater at 4oC before storage at -80oC. Total RNA was extracted using RNAeasy. After purification, RT-PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Linear models were prepared in limma with gender and BMI factors incorporated sequentially for each pathology comparison, generating 12 models of probes differentially expressed at FDR p<0.05 and Bayes number, B>0. Data analysis of differently expressed genes utilized Ingenuity Pathway Analysis and Cytoscape with Cluego and Cytohubba plug-ins.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 56 - 56
1 Jul 2014
Alizadehkhaiyat O Hawkes D Howard A Frostick S
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Summary Statement

Bio-impedance analysis (BIA) provides a convenient method for the estimation of whole body and segmental measurement of skeletal muscle mass (SMM). BIA-measured SMM parameters may be effectively used for the normalisation of muscle strength and removing body-size dependence.

Introduction

Despite an increasing interest in using bio-impedance analysis (BIA) for the estimation of segmental skeletal muscle mass (SMM); existing data is sparse. On the other hand, there is a need for better understanding of the influence of SMM on gender-related differences in muscle strength. Using BIA technique, this study aimed to measure the SMM, determine its correlation with muscle strength, and examine its relation with gender-related differences in muscle strength.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 269 - 269
1 Jul 2014
Alizadehkhaiyat O Kemp G Frostick S
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Summary Statement

Applying appropriate upper limb regional-specific and joint-specific tools along with suitable psychologic tools provides an effective assessment of supportive, interventional, and treatment strategies in TE.

Background

Tennis elbow (TE) is a painful pathologic condition with its origin in the common wrist extensor muscles at the lateral epicondyle. As the second most frequently diagnosed musculoskeletal disorder in the neck and upper limb in a primary care setting, with an annual incidence of 4 to 7 cases per 1000 patients in general practice (with a peak at 35 to 54 yrs of age), TE has considerable socioeconomic costs. As pain relief and improvement in functional performance are the 2 common aims of all treatment strategies, the importance of using appropriate tools for the assessment of pain and functional disability in TE is evident. In view of the high prevalence of TE, uncertainties about its treatment, and its substantial socioeconomic consequences, using more specific, patient-centred assessment tools is essential for providing more useful information on the level of pain and functional disability in TE. The Study aimed to: 1) compare pain and functional disability in tennis elbow (TE) patients with healthy controls; and 2) evaluate the relationship between the 2 major psychologic factors (anxiety and depression) and TE.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 273 - 273
1 Jul 2014
Alizadehkhaiyat O Vishwanathan K Frostick S
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Summary Statement

Discovery system produced effective functional improvement in both primary and revision total elbow replacement. The incidence of major complications was in an acceptable range.

Introduction

The search for the ideal elbow prosthesis continues as instability and loosening remain the prime reasons for total elbow replacement (TER) failure. The Discovery Elbow System (Biomet) is one of the latest generations of linked prosthesis and has been used in UK since 2003. We report outcome of TER using this system.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 61 - 61
1 Dec 2013
Mandhari AA Kyriakos A Alizadehkhaiyat O Frostick S
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Objective:

Evaluation of the early results of the implementation of reverse shoulder arthroplasty prosthesis “Comprehensive Reverse” in primary and revision shoulder arthroplasties.

Material and Methods:

September 2010–December 2012, 48 patients (32 women, 16 men) underwent reverse shoulder arthroplasty using Comprehensive Reverse system. Average age of 69.88. A total of 46 patients were followed. In 22 patients the operation was performed for revision. Patients were pre-and postoperatively evaluated using Oxford, Constant, SF-12 scores, radiographs, pain and range of motion. Mean follow-up 13 months.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 73 - 73
1 Dec 2013
Alizadehkhaiyat O Hawkes D Frostick S
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Introduction

Rehabilitation after shoulder arthroplasty is a fundamental in enabling patients achieve a good functional outcome. Therapists must consider the underlying diagnosis, operative technique employed and rotator cuff integrity, amongst other factors, in order to select the most appropriate exercise regime. There is an absence of comprehensive studies in the literature with regard to shoulder rotational exercises. Therefore, this study aimed to describe the shoulder girdle muscle activation strategies during eight commonly cited rotational shoulder exercises.

Method

Thirty healthy subjects with no history of shoulder problems participated in the study. EMG was recorded from 16 shoulder girdle muscles (surface electrodes: anterior, middle and posterior deltoid, upper, middle and lower trapezius, upper and lower latissimus dorsi, upper and lower pectoralis major; fine wire electrodes: supraspinatus, infraspinatus, subscapularis and rhomboid major) using a telemetry based EMG system. Five external and three internal rotation exercises were included (table 1). Signal acquisition and processing were in accordance with standardised guidelines. Amplitude normalisation was to external and internal rotation maximum voluntary contraction as appropriate. Mean EMG amplitudes between exercises were compared using repeated measures ANOVA. Data for muscle groups was calculated by averaging the activation of the component muscles.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 310 - 310
1 Dec 2013
Frostick S Roebuck M Davidson J Santini A Peter V Banks J Williams A Wang H Thachil J Jackson R
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Introduction:

Wear debris from articulating joint implants is inevitable. Small debris particles are phagocytosed by macrophages. Larger particles initiate the fusion of many macrophages into multi-nucleated giant cells for particle encasement. Macrophages are recruited into inflamed tissues from the circulating monocyte population. Approximately 10% of white blood cells are monocytes which after release from the bone marrow circulate for 2–3 days, before being recruited into tissues as inflammatory macrophages or undergoing apoptosis. Circulating MRP8/14 (S100A8/A9) is a measure of monocyte recruitment, part of the monocyte-endothelial docking complex, and shed during monocyte transmigration across the endothelium. The higher the S100A8/A9 the more monocytes being recruited giving an indirect measure of debris production.

Methods:

2114 blood samples were collected from arthroplasty patients with hip or knee osteoarthritis (primary, post-traumatic and secondary), 589 before their primary arthroplasty, 1187 patients > 1 year post-arthroplasty, 101 patients before revision for aseptic loosening and 237 patients >1 year post-revision. Plasma S100A8/A9 was measured using BMA Biomedicals Elisa kit, normal levels in health adults are 0.5–3 mg/ml. Joint specific scores, WOMAC knee or Oxford Hip adjusted to percent of maximum, together with SF-12 were completed.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 311 - 311
1 Dec 2013
Frostick S Williams A Wang H Davidson J Santini A Thachil J Banks J Jackson R Roebuck M
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Introduction:

The risk factors for degenerative joint disease are well established: increasing age, obesity, joint abnormalities, trauma and overuse, together with female gender, ethnic and genetic factors. That obesity is a significant risk factor for developing osteoarthritis in non-weight-bearing as well as weight-bearing and joints was one of the first indications that the risk was nor purely that of aberrant biomechanical loading. Low grade chronic systemic inflammation is a component of each of ageing and obesity, atherosclerosis and diabetes, culminating in Metabolic Syndrome. In our study of 1684 patients with joint degeneration 85% were overweight or obese and 65% older than 65 years with 62% being both, 73% of patients were taking medications for serious, ‘non-orthopaedic’ health problems such as cardiovascular or respiratory disease, obesity or NIDDM. Monocytes are a major component of chronic inflammation, approximately 10% of white blood cells are monocytes which circulate for 2–3 days, before being recruited into tissues as inflammatory macrophages or undergoing apoptosis. Circulating S100A8/A9 (MRP8/14) is a measure of monocyte recruitment being shed during monocyte transmigration across the endothelium. The higher the S100A8/A9 the more monocytes being recruited giving an indirect measure of chronic inflammatory status.

Methods:

2154 blood samples were collected from arthroplasty patients (first or second joint replacement), 1135 Female and 1019 Male, age 29–93 years, body mass index (BMI) 18–56, with hip or knee osteoarthritis (primary, post-traumatic and secondary), 589 before a primary arthroplasty, 1187 patients >1 year post-arthroplasty, 101 patients before revision for aseptic loosening and 237 patients >1 year post-revision. All study patients received metal on UHMWPE implants. Plasma S100A8/A9 was measured using BMA Biomedicals Elisa kit, normal levels in healthy adults are 0.5–3 mg/ml. The data were analysed using SPSS, p values were calculated using Spearman's test.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 1 - 1
1 Mar 2013
Al Mandhari A Alizadehkhaiyat O Chrysanthou C Frostick S
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Background

The procedures of total elbow and shoulder replacements increased 6% to 13% annually from 1993 to 2007 with revision-related burden increasing from 4.5% to 7%. The revisions of the shoulder and elbow prostheses due to aseptic loosening, periprosthetic fractures, infections have led to the use of standard or custom-made implants due to significant bone loss. This study reports our experience in the management of complicated primary and revisions of total shoulder and elbow replacements with significant humeral bone loss and in metabolic diseases of the elbow and shoulder treated with bone resection using The Mosaic Humeral Replacement System.

Patients and Materials

A total of 20 patients underwent total elbow or shoulder arthroplasty using the Mosaic Humeral Replacement System (Biomet, UK). The Mosaic system was used in 8 shoulder arthroplasties (Group A) and in 12 elbow arthroplasties (Group B). The underlying pathologis in Group A included 2 malunited proximal humerus fracture, 1 humeral osteomyelitis, 1 shoulder chondrosarcoma, 1 aggressive Gigantic Cell Tumor with prosthetic fracture, 2 metastatic lytic lesion, and 1 failed fixation of non-union proximal humerus. Figure 1 shows Mosaic implant after complex fracture of proximal humerus. Reasons for Mosaic arthroplasty in Group B included 3 humeral component revisions due to periprosthetic fracture, 1 prosthesis breaking-up with fractures, 1 revision of loose Souter Strathclyde prosthesis, 1 loose prosthesis due to infection, 1 highly comminuted elbow fracture, 1 aseptic loosening of humeral component of total elbow replacement, 3 revision of total elbow replacement due loosening and 1 pathological distal humerus fracture due to metastasis. Figure 2&3 shows pre- and post-operative Mosaic implant following complex periprosthetic fracture of distal humerus.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 124 - 124
1 Mar 2013
Alizadehkhaiyat O Kyriakos A Singer MS Frostick S Al Mandhari A
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Background

The Copeland shoulder resurfacing arthroplasty (CSRA) (Figure1) is a cementless, pegged humeral head surface replacement which has been in clinical use since 1986. The indications for CSRA are more or less the same as conventional stemmed arthroplasty. This procedure can be considered for all patients who require shoulder replacement due to GHJ arthritis resulted from primary or secondary OA, RA, and other variations of inflammatory arthritis. It is also suggested as the first choice option for relatively young patients with post-traumatic arthritis, avascular necrosis (AVN), and instability arthropathy. This observational study reports functional and radiological outcome in CSRA during 4 years follow-up.

Methods

109 consecutive patients with primary osteoarthritis (45.9%), rheumatoid arthritis (39.4%), rotator cuff arthropathy (9.2%), and avascular necrosis (5.5%) underwent CSRA. Patients including 68 females (63%) and 41 males (37%) underwent this procedure (63 right-sided and 46 left-sided including 9 bilateral shoulders). The outcome assessment included pain and satisfaction, Oxford Shoulder Score (OSS), Constant Score (CS), and SF-12. Imaging was reviewed for glenoid morphology (Walch classification) (Figure2) and humeral head migration. The average follow-up period was 4 years, (range: 1 to 10 years).


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 2 - 2
1 Mar 2013
Alizadehkhaiyat O Vishwanathan K Frostick S Al Mandhari A
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Background

The quest for the perfectly designed elbow prosthesis continues as instability and loosening remain the foremost reasons for the failure of total elbow replacement (TER). The Discovery® Elbow System (Biomet, UK) (Figure 1), which has been used in UK since 2003, is one of the latest generations of linked prosthesis. This system was designed to decrease polyethylene-bushing wear, improve anatomic stem design, restore elbow joint biomechanics, and produce a hinge that could be easily revised. This report describes the short term outcome of TER using the Discovery® Elbow System.

Patients and Methods

A total of 60 TERs including 48 primary and 12 revisions were performed between 2003 and 2008. Patients included 21 males (37%) and 36 females (63%) with a mean age of 63 years. The indications for primary TER were advanced rheumatoid arthritis (n=19), osteoarthritis (n=16), post traumatic osteoarthritis (n=9), acute fractures (n=3), and haemophilic arthropathy (n=1). The outcome was assessed using pain score, Liverpool Elbow Score (LES), and range of movement during a mean follow-up of 26 months. Associated complications were documented. Radiological assessment included evaluation for loosening, instability and periprosthetic fractures.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 3 - 3
1 Mar 2013
Alizadehkhaiyat O Kyriakos A Williams A Frostick S Al Mandhari A
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BACKGROUND

Reverse total shoulder arthroplasty (RTSA) provides an alternative to standard total shoulder arthroplasty in the treatment of selected complex shoulder problems including failed shoulder replacements. The purpose of this report is to present outcome of RTSA using Comprehensive Reverse System (CRS) as either primary or revision treatment choice.

PATIENTS AND MATERIALS

Between September 2010 and April 2012, 54 patients (36 females, 18 males) with the mean age of 68.4 (±10) underwent RTSA-CRS. In 27 patients RTSA-CRS was performed as a revision due to failed previous arthroplasty. Primary underlying conditions included AVN (2), massive irreparable rotator cuff tear (2), primary osteoarthritis (7), post-traumatic osteoarthritis (2), rheumatoid arthritis (6), and rotator cuff arthropathy (8). It was not possible to complete the operation in 6 patients (4 revisions group 2 AVN cases) due to substantial glenoid erosion. Preoperative CT scan was performed in 50% of patients to assess the bony stock of the glenoid. In some patients ultrasound and MRI were performed to acquire additional information. A total of 46 patients were followed-up by means of antroposterior and axial plain X-rays, pain and satisfaction level (VAS/0–10), stiffness, Constant Score, Oxford Shoulder Score, SF-12 (Physical and mental Subscales), and range of movement for a mean duration of 6.5 months (±4.2).


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XL | Pages 64 - 64
1 Sep 2012
Hawkes D Alizadehkhaiyat O Fisher A Kemp G Roebuck M Frostick S
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Introduction

Shoulder motion results from a complex interaction between the interconnected segments of the shoulder girdle. Coordination is necessary for normal shoulder function and is achieved by synchronous and coordinated muscle activity. During rotational movements, the humeral head translates on the glenoid fossa in the anterior-posterior plane. Tension developed by the rotator cuff muscles compresses the humeral head into the glenoid fossa. This acts to limit the degree of humeral head translation and establishes a stable GH fulcrum about which the arm can be moved. Previous studies have been limited by the use of contrived movement protocols and muscular coordination has not been previously considered with regard to shoulder rotation movements. This study reports the activation profile and coordination of 13 muscles and 4 muscle groups during a dynamic rotational movement task based on activities of daily living.

Methods

Eleven healthy male volunteers were included in the study. Electromyography (EMG) was recorded from 13 muscles (10 surface and 3 fine-wire intramuscular electrodes) using a wireless EMG system. EMG was recorded during a movement task in which the shoulder was consecutively rotated internally (phase 1) and externally (phase 2) with a weight in the hand. Muscle group data was calculated by ensemble averaging the activity of the individual component muscles. Mean signal amplitude and Pearson correlation coefficient (PCC) analysed muscle activation and coordination, respectively.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 84 - 84
1 Feb 2012
Tan C Guisasola I Machani B Kemp G Sinopidis C Brownson P Frostick S
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The aim of this study was to evaluate prospectively the outcome following arthroscopic Bankart repair using two types of suture anchors, absorbable and non-absorbable. Patients with a diagnosis of recurrent traumatic anterior instability of the shoulder, seen between April 2000 and June 2003 in a single unit, were considered for inclusion in the study. Patients were assessed pre-operatively and post-operatively using a subjective patient related outcome measurement tool (Oxford instability score), a visual analogue scale for pain and instability (VAS Pain and VAS instability) and a quality of life questionnaire (SF-12). The incidence of recurrent instability and the level of sporting ability were recorded. Patients were randomised to undergo surgical repair with either non-absorbable or absorbable anchors.

130 patients were included in the study. 6 patients were lost to follow-up and 124 patients (95%) completed the study. Both types of anchors were highly effective. There were no differences in the rate of recurrence or any of the scores between the two. Four patients in the non-absorbable group and 3 in the absorbable group experienced further episodes of dislocation after a traumatic event. The rate of redislocation in the whole series was therefore, 5.6%. In addition, 4 patients, all of them in the absorbable group (4%) described ongoing symptoms of instability but no true dislocations. 85% of the patients have returned to their previous level of sporting activity.

There are no differences in the outcome of Arthroscopic Bankart repair using either absorbable or non-absorbable anchors. Both are highly effective, showing a redislocation rate of 5.6%.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 262 - 262
1 May 2009
Tan CK Guisasola I Sinopidis C Brownson P Frostick S
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Aim: The aim of this study was to evaluate prospectively the mid-term outcome following arthroscopic Bankart repair using two types of suture anchor, the G II (Mitek) non-absorbable and the Panalok (Mitek) absorbable anchor.

Method: Patients with a diagnosis of recurrent traumatic anterior instability of the shoulder seen between April 2000 and June 2003 in a single unit were considered for inclusion in the study. Patients were assessed preoperatively and postoperatively using a subjective patient related outcome measurement tool (Oxford instability score), visual analogue scales for pain and instability and a quality of life questionnaire (SF-12). Patients were randomised to undergo surgical repair with either non-absorbable or absorbable anchors. Length of follow-up was 3.3–6.5 (mean 5.0) years. The incidence of recurrent instability and the level of sporting ability were recorded.

Results: 130 patients were included in the study. 25 patients were lost to follow-up, 105 patients (81%) completed the study. 5 patients in absorbable group and 4 patients in non-absorbable group experienced further dislocation (8.5%). Both types of anchor were highly effective. There were no differences in the rate of recurrence or any of the scores between the two.

Conclusions: There are no differences in the outcome of arthroscopic Bankart repair using either absorbable or non-absorbable anchors. Both are highly effective, showing a redislocation rate of 8.5%.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 258 - 258
1 May 2009
Tan CK Singh S Brownson P Frostick S
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Aim: To compare 2 rehabilitation regimes after arthroscopic interval release: immediate mobilization versus immediate mobilization and external rotation night splint for ten days.

Methods: 30 patients aged 40–67 years with primary frozen shoulder were included in the study. The surgical procedure consisted of release of the coracohumeral ligament, rotator interval and the posterior capsule with electrocautery, followed by gentle manipulation. Patients were randomised into 2 rehabilitation groups: immediate mobilization (IM) or immediate mobilization with external rotation night splint (ERS) used for 10 days post-operatively. Patients were assessed pre & post operatively and using the visual analogue score for pain, Constant and Oxford scoring systems.

Results: There were 15 patients in the IM group and 15 in ERS group. In the IM group the Constant score improved from 35±10 (mean±SD) pre-operatively to 63±14 at 1 month and 75±11 at 6 months, and in the ERS group the Constant score improved from 33±9 pre-operatively to 59±14 at 1 month and 75±7 at 6 months. The Oxford score in the IM group improved from 35±9 pre-operatively to 25±8 at 1 month and 18±9 at 6 months, and in the ERS group from 38±9 pre-operatively to 27±8 at 1 month and 18±8 at 6 months (all changes P< 0.001 cf pre-operative, but NS from 1 to 6 months). Improvements in VAS were significant in both groups (P< 0.02) at 6 months but not at 1 month. There was no significant difference between the two groups in terms of Oxford or Constant scores or VAS at 1 and 6 months.

Conclusion: Arthroscopic interval release is successful in restoring range of motion in patients with idiopathic frozen shoulder. Both groups showed significant improvement during the study period with most improvement in terms of range of movement occurring in the first month. There was no significant difference in outcome between the two groups studied.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 74 - 74
1 Mar 2009
Kurth A Dahl O van Dijk C Eriksson B Frostick S Rosencher N Schnee J Christiansen A Büller H
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BACKGROUND: Oral DVT prophylaxis not requiring monitoring is an advantage in orthopaedic patients. Dabigatran etexilate is an oral direct thrombin inhibitor undergoing evaluation for the prevention of venous thromboembolic events (VTE) following orthopaedic surgery.

METHODS: In a phase III, multicenter, non-inferiority, double-blind study, patients undergoing total knee replacement were randomized to 3 treatments. The patients received 8±2 days of oral dabigatran etexilate, 150 or 220 mg once daily starting with a half dose (i.e.75 or 110 mg) 1–4 hours after surgery, or subcutaneous enoxaparin 40 mg once daily starting 12 hours prior to surgery. The primary efficacy outcome was the composite of total VTE and all causes of mortality during the treatment period. All efficacy and safety outcome events were adjudicated by blinded independent committees.

RESULTS: Efficacy could be evaluated for 1541 (75%) treated and operated patients. Total VTE and death occurred in 40.5%, 36.4% and 37.7% of patients assigned to dabigatran etexilate 150 or 220mg once daily or enoxaparin, respectively. Proximal DVT and/ or PE occurred in 3.8%, 2.6% and 3.5% of patients receiving dabigatran 150 or 220mg or enoxaparin, respectively. Three deaths occurred during the treatment period, one in each of the treatment groups. Safety was evaluated for all 2076 patients receiving study treatment. The rate of major bleeding was 1.3%, 1.5% and 1.3% of patients receiving dabigatran 150 or 220mg or enoxaparin. Elevated LFTs (ALT > 3xULN) occurred in 3.7%, 2.8% and 4.0% of the patients treated with 150 and 220 mg dabigatran or enoxaparin during the study. A temporary rise in LFTs was observed during the follow-up period in 0.5% of the patients who had received dabigatran and in 0.4% of the patients who had received enoxaparin.

CONCLUSIONS: Non-inferiority for the primary efficacy endpoint was met for both doses of dabigatran etexilate compared to enoxaparin. There was no difference in bleeding rates between the treatment groups. Oral administration of dabigatran etexilate once daily, given early in the postoperative period, was effective and safe for the prevention of total VTE in patients undergoing total knee replacement surgery.