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The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 8 | Pages 1025 - 1030
1 Aug 2009
Ollivere B Darrah C Barker T Nolan J Porteous MJ

The rate and mode of early failure in 463 Birmingham hip resurfacings in a two-centre, multisurgeon series were examined. Of the 463 patients two have died and three were lost to follow-up. The mean radiological and clinical follow-up was for 43 months (6 to 90).

We have revised 13 resurfacings (2.8%) including seven for pain, three for fracture, two for dislocation and another for sepsis. Of these, nine had macroscopic and histological evidence of metallosis. The survival at five years was 95.8% (95% confidence interval (CI) 94.1 to 96.8) for revision for all causes and 96.9% (95% CI 95.5 to 98.3) for metallosis.

The rate of metallosis related revision was 3.1% at five years. Risk factors for metallosis were female gender, a small femoral component, a high abduction angle and obesity. We do not advocate the use of the Birmingham Hip resurfacing procedure in patients with these risk factors.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 12 | Pages 1617 - 1620
1 Dec 2011
Willis-Owen CA Sarraf KM Martin AE Martin DK

Symptomatic and asymptomatic deep-vein thrombosis (DVT) is a common complication of knee replacement, with an incidence of up to 85% in the absence of prophylaxis. National guidelines for thromboprophylaxis in knee replacement are derived from total knee replacement (TKR) data. No guidelines exist specific to unicompartmental knee replacement (UKR). We investigated whether the type of knee arthroplasty (TKR or UKR) was related to the incidence of DVT and discuss the applicability of existing national guidelines for prophylaxis following UKR.

Data were collected prospectively on 3449 knee replacements, including procedure type, tourniquet time, surgeon, patient age, use of drains and gender. These variables were related to the incidence of symptomatic DVT.

The overall DVT rate was 1.6%. The only variable that had an association with DVT was operation type, with TKR having a higher incidence than UKR (2.2% versus 0.3%, p < 0.001). These data show that the incidence of DVT after UKR is both clinically and statistically significantly lower than that after TKR.

TKR and UKR patients have different risk profiles for symptomatic DVT. The risk-benefit ratio for TKR that has been used to produce national guidelines may not be applicable to UKR. Further research is required to establish the most appropriate form of prophylaxis for UKR.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 7 | Pages 919 - 927
1 Jul 2012
Baker PN Petheram T Jameson SS Avery PJ Reed MR Gregg PJ Deehan DJ

Following arthroplasty of the knee, the patient’s perception of improvement in symptoms is fundamental to the assessment of outcome. Better clinical outcome may offset the inferior survival observed for some types of implant. By examining linked National Joint Registry (NJR) and patient-reported outcome measures (PROMs) data, we aimed to compare PROMs collected at a minimum of six months post-operatively for total (TKR: n = 23 393) and unicondylar knee replacements (UKR: n = 505). Improvements in knee-specific (Oxford knee score, OKS) and generic (EuroQol, EQ-5D) scores were compared and adjusted for case-mix differences using multiple regression. Whereas the improvements in the OKS and EQ-5D were significantly greater for TKR than for UKR, once adjustments were made for case-mix differences and pre-operative score, the improvements in the two scores were not significantly different. The adjusted mean differences in the improvement of OKS and EQ-5D were 0.0 (95% confidence interval (CI) -0.9 to 0.9; p = 0.96) and 0.009 (95% CI -0.034 to 0.015; p = 0.37), respectively.

We found no difference in the improvement of either knee-specific or general health outcomes between TKR and UKR in a large cohort of registry patients. With concerns about significantly higher revision rates for UKR observed in worldwide registries, we question the widespread use of an arthroplasty that does not confer a significant benefit in clinical outcome.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 12 | Pages 1660 - 1664
1 Dec 2011
Judge A Arden NK Price A Glyn-Jones S Beard D Carr AJ Dawson J Fitzpatrick R Field RE

We obtained pre-operative and six-month post-operative Oxford hip (OHS) and knee scores (OKS) for 1523 patients who underwent total hip replacement and 1784 patients who underwent total knee replacement. They all also completed a six-month satisfaction question.

Scatter plots showed no relationship between pre-operative Oxford scores and six-month satisfaction scores. Spearman’s rank correlation coefficients were -0.04 (95% confidence interval (CI) -0.09 to 0.01) between OHS and satisfaction and 0.04 (95% CI -0.01 to 0.08) between OKS and satisfaction. A receiver operating characteristic (ROC) curve analysis was used to identify a cut-off point for the pre-operative OHS/OKS that identifies whether or not a patient is satisfied with surgery. We obtained an area under the ROC curve of 0.51 (95% CI 0.45 to 0.56) for hip replacement and 0.56 (95% CI 0.51 to 0.60) for knee replacement, indicating that pre-operative Oxford scores have no predictive accuracy in distinguishing satisfied from dissatisfied patients.

In the NHS widespread attempts are being made to use patient-reported outcome measures (PROMs) data for the purpose of prioritising patients for surgery. Oxford hip and knee scores have no predictive accuracy in relation to post-operative patient satisfaction. This evidence does not support their current use in prioritising access to care.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 4 | Pages 510 - 516
1 Apr 2012
Hickey BA Kempshall PJ Metcalfe AJ Forster MC

As part of the national initiative to reduce waiting times for joint replacement surgery in Wales, the Cardiff and Vale NHS Trust referred 224 patients to the NHS Treatment Centre in Weston-Super-Mare for total knee replacement (TKR). A total of 258 Kinemax TKRs were performed between November 2004 and August 2006. Of these, a total of 199 patients (232 TKRs, 90%) have been followed up for five years. This cohort was compared with 258 consecutive TKRs in 250 patients, performed at Cardiff and Vale Orthopaedic Centre (CAVOC) over a similar time period. The five year cumulative survival rate was 80.6% (95% confidence interval (CI) 74.0 to 86.0) in the Weston-Super-Mare cohort and 95.0% (95% CI 90.2 to 98.2) in the CAVOC cohort with revision for any reason as the endpoint. The relative risk for revision at Weston-Super-Mare compared with CAVOC was 3.88 (p < 0.001). For implants surviving five years, the mean Oxford knee scores (OKS) and mean EuroQol (EQ-5D) scores were similar (OKS: Weston-Super-Mare 29 (2 to 47) vs CAVOC 29.8 (3 to 48), p = 0.61; EQ-5D: Weston-Super-Mare 0.53 (-0.38 to 1.00) vs CAVOC 0.55 (-0.32 to 1.00), p = 0.79). Patients with revised TKRs had significantly lower Oxford knee and EQ-5D scores (p < 0.001).

The results show a higher revision rate for patients operated at Weston-Super-Mare Treatment Centre, with a reduction in functional outcome and quality of life after revision. This further confirms that patients moved from one area to another for joint replacement surgery fare poorly.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 3 | Pages 412 - 418
1 Mar 2012
Judge A Arden NK Kiran A Price A Javaid MK Beard D Murray D Field RE

We obtained information from the Elective Orthopaedic Centre on 1523 patients with baseline and six-month Oxford hip scores (OHS) after undergoing primary hip replacement (THR) and 1784 patients with Oxford knee scores (OKS) for primary knee replacement (TKR) who completed a six-month satisfaction questionnaire.

Receiver operating characteristic curves identified an absolute change in OHS of 14 points or more as the point that discriminates best between patients’ satisfaction levels and an 11-point change for the OKS. Satisfaction is highest (97.6%) in patients with an absolute change in OHS of 14 points or more, compared with lower levels of satisfaction (81.8%) below this threshold. Similarly, an 11-point absolute change in OKS was associated with 95.4% satisfaction compared with 76.5% below this threshold. For the six-month OHS a score of 35 points or more distinguished patients with the highest satisfaction level, and for the six-month OKS 30 points or more identified the highest level of satisfaction. The thresholds varied according to patients’ pre-operative score, where those with severe pre-operative pain/function required a lower six-month score to achieve the highest levels of satisfaction.

Our data suggest that the choice of a six-month follow-up to assess patient-reported outcomes of THR/TKR is acceptable. The thresholds help to differentiate between patients with different levels of satisfaction, but external validation will be required prior to general implementation in clinical practice.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 6 | Pages 746 - 754
1 Jun 2012
Jameson SS Baker PN Mason J Porter ML Deehan DJ Reed MR

Modern metal-on-metal hip resurfacing has been widely performed in the United Kingdom for over a decade. However, the literature reports conflicting views of the benefits: excellent medium- to long-term results with some brands in specific subgroups, but high failure rates and local soft-tissue reactions in others. The National Joint Registry for England and Wales (NJR) has collected data on all hip resurfacings performed since 2003. This retrospective cohort study recorded survival time to revision from a resurfacing procedure, exploring risk factors independently associated with failure. All patients with a primary diagnosis of osteoarthritis who underwent resurfacing between 2003 and 2010 were included in the analyses. Cox’s proportional hazard models were used to analyse the extent to which the risk of revision was related to patient, surgeon and implant covariates.

A total of 27 971 hip resurfacings were performed during the study period, of which 1003 (3.59%) underwent revision surgery. In the final adjusted model, we found that women were at greater risk of revision than men (hazard ratio (HR) = 1.30, p = 0.007), but the risk of revision was independent of age. Of the implant-specific predictors, five brands had a significantly greater risk of revision than the Birmingham Hip Resurfacing (BHR) (ASR: HR = 2.82, p < 0.001, Conserve: HR = 2.03, p < 0.001, Cormet: HR = 1.43, p = 0.001, Durom: HR = 1.67, p < 0.001, Recap: HR = 1.58, p = 0.007). Smaller femoral head components were also significantly more likely to require revision (≤ 44 mm: HR = 2.14, p < 0.001, 45 to 47 mm: HR = 1.48, p = 0.001) than medium or large heads, as were operations performed by low-volume surgeons (HR = 1.36, p <  0.001). Once these influences had been removed, in 4873 male patients < 60 years old undergoing resurfacing with a BHR, the five-year estimated risk of revision was 1.59%.

In summary, after adjustment for a range of covariates we found that there were significant differences in the rate of failure between brands and component sizes. Younger male patients had good five-year implant survival when the BHR was used.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 4 | Pages 433 - 440
1 Apr 2012
Sridhar MS Jarrett CD Xerogeanes JW Labib SA

Given the growing prevalence of obesity around the world and its association with osteoarthritis of the knee, orthopaedic surgeons need to be familiar with the management of the obese patient with degenerative knee pain. The precise mechanism by which obesity leads to osteoarthritis remains unknown, but is likely to be due to a combination of mechanical, humoral and genetic factors.

Weight loss has clear medical benefits for the obese patient and seems to be a logical way of relieving joint pain associated with degenerative arthritis. There are a variety of ways in which this may be done including diet and exercise, and treatment with drugs and bariatric surgery. Whether substantial weight loss can delay or even reverse the symptoms associated with osteoarthritis remains to be seen.

Surgery for osteoarthritis in the obese patient can be technically more challenging and carries a risk of additional complications. Substantial weight loss before undertaking total knee replacement is advisable. More prospective studies that evaluate the effect of significant weight loss on the evolution of symptomatic osteoarthritis of the knee are needed so that orthopaedic surgeons can treat this patient group appropriately.


Bone & Joint Research
Vol. 1, Issue 4 | Pages 56 - 63
1 Apr 2012
Langton DJ Sidaginamale R Lord JK Nargol AVF Joyce TJ

Objectives

An ongoing prospective study to investigate failing metal-on-metal hip prostheses was commenced at our centre in 2008. We report on the results of the analysis of the first consecutive 126 failed mated total hip prostheses from a single manufacturer.

Methods

Analysis was carried out using highly accurate coordinate measuring to calculate volumetric and linear rates of the articular bearing surfaces and also the surfaces of the taper junctions. The relationship between taper wear rates and a number of variables, including bearing diameter and orientation of the acetabular component, was investigated.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 1 | Pages 58 - 63
1 Jan 2009
Hooper G Rothwell A Frampton C

We have examined the outcome of 400 consecutive patients who underwent total knee replacement with the Low Contact Stress mobile-bearing system between 1993 and 1994 and were followed up for a minimum of ten years. All operations were performed by surgeons in Christchurch, New Zealand, who used no other knee prosthesis during the study time.

At ten years after operation 238 patients (244 knees) remained for independent clinical and radiological assessment. There was a significant improvement (p < 0.001) in the postoperative knee scores at one, three, seven and ten years, although a slight deterioration in the score occurred between seven and ten years which did not reach statistical significance. The survival for polyethylene wear or loosening was 97% (95% CI 96 to 98) and survival using reoperation for any cause was 92% (95% CI 90 to 94) at 12 years. Polyethylene wear was more common in the meniscal-bearing component, with five knees requiring revision and a further eight demonstrating early wear. Osteolysis was not seen in the rotating platform component, but was present in three of the meniscal-bearing knees.

There was no association between the radiological alignment at one year and those knees that subsequently required revision. However, there was an association between the overall limb alignment and the Western Ontario McMasters University score (p < 0.001).

The Low Contact Stress mobile-bearing total knee replacement has proved to be a reliable implant at ten years when used in primary knee replacement irrespective of the deformity and diagnosis.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 12 | Pages 1602 - 1609
1 Dec 2011
Malviya A Ramaskandhan JR Bowman R Hashmi M Holland JP Kometa S Lingard E

The aim of this study was to investigate the possible benefit of large-head metal-on-metal bearing on a stem for primary hip replacement compared with a 28 mm diameter conventional metal-on-polyethylene bearing in a prospective randomised controlled trial. We investigated cemented stem behaviour between these two different bearings using Einzel-Bild-Röntgen-Analyse, clinical and patient reported measures (Harris hip score, Western Ontario and McMaster Universities osteoarthritis index, Short Form-36 and satisfaction) and whole blood metal ion levels at two years. A power study indicated that 50 hips were needed in each group to detect subsidence of > 5 mm at two years with a p-value of < 0.05.

Significant improvement (p < 0.001) was found in the mean clinical and patient reported outcomes at two years for both groups. Comparison of outcomes between the groups at two years showed no statistically significant difference for mean stem migration, clinical and patient reported outcomes; except overall patient satisfaction which was higher for metal-on-metal group (p = 0.05). Metal ion levels were raised above the Medicines and Healthcare products Regulatory Agency advised safety level (7 µg per litre) in 20% of the metal-on-metal group and in one patient in metal-on-polyethylene group (who had a metal-on-metal implant on the contralateral side). Two patients in the metal-on-metal group were revised, one for pseudotumour and one for peri-prosthetic fracture.

Use of large modular heads is associated with a risk of raised whole blood metal ion levels despite using a proven bearing from resurfacing. The head-neck junction or excess stem micromotion are possibly the weak links warranting further research.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 476 - 478
1 Apr 2011
Kang S Smith TO De Rover WBS Walton NP

There has been debate about the role of unicompartmental knee replacement in the presence of radiologically identifiable degenerative changes of the patellofemoral joint. We studied 195 knees in 163 patients in whom an Oxford unicompartmental knee replacement had been performed for medial osteoarthritis between January 2004 and July 2007. The mean age of the patients was 66 years (51 to 93). The degree of degenerative change of the patellofemoral joint was assessed using Jones’ criteria. Functional outcome was assessed at a mean of 3.4 years (2 to 7) post-operatively, using the Oxford knee score and the Short-form 12 score.

Degenerative changes of the patellofemoral joint were seen pre-operatively in 125 knees (64%) on the skyline radiographs. There was no statistically significant difference in the Oxford knee or Short-form 12 scores between those patients who had patellofemoral osteoarthritis pre-operatively and those who did not (p = 0.22 and 0.54, respectively).

These results support the opinion expressed at the designer’s hospital that degenerative changes of the patellofemoral joint in isolation should not be considered to be a contraindication to medial Oxford unicompartmental knee replacement.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 4 | Pages 446 - 450
1 Apr 2008
Bailie AG Lewis PL Brumby SA Roy S Paterson RS Campbell DG

The Unispacer knee system is a cobalt-chrome self-centring tibial hemiarthroplasty device for use in the treatment of isolated medial compartment osteoarthritis of the knee. The indications for use are similar to those for high tibial osteotomy, but insertion does not require bone cuts or component fixation, and does not compromise future knee replacement surgery. A prospective study of a consecutive series of 18 patients treated with the Unispacer between June 2003 and August 2004 was carried out to determine the early clinical results of this device. The mean age of the patients was 49 years (40 to 57). A total of eight patients (44%) required revision within two years. In two patients revision to a larger spacer was required, and in six conversion to either a unicompartmental or total knee replacement was needed. At the most recent review 12 patients (66.7%) had a Unispacer remaining in situ. The mean modified visual analogue score for these patients at a mean follow-up of 19 months (12 to 26) was 3.0 (0 to 11.5). The mean pain level was 30% that of the mean pre-operative level of 10. The early clinical results using this device have been disappointing.

This study demonstrates that use of the Unispacer in isolated medial compartment osteoarthritis is associated with a high rate of revision surgery and provides unpredictable relief of pain.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1001 - 1004
1 Aug 2011
Fisher J

Bioengineering reasons for increased wear and failure of metal-on-metal (MoM) bearings in hip prostheses have been described. Low wear occurs in MoM hips when the centre of the femoral head is concentric with the centre of the acetabular component and the implants are correctly positioned. Translational or rotational malpositioning of the components can lead to the contact-patch of the femoral component being displaced to the rim of the acetabular component, resulting in a ten- to 100-fold increase in wear and metal ion levels. This may cause adverse tissue reactions, loosening of components and failure of the prosthesis.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 11 | Pages 1465 - 1470
1 Nov 2011
Jameson SS Charman SC Gregg PJ Reed MR van der Meulen JH

We compared thromboembolic events, major haemorrhage and death after total hip replacement in patients receiving either aspirin or low-molecular-weight heparin (LMWH). We analysed data from the National Joint Registry for England and Wales linked to an administrative database of hospital admissions in the English National Health Service. A total of 108 584 patients operated on between April 2003 and September 2008 were included and followed up for 90 days. Multivariable risk modelling and propensity score matching were used to estimate odds ratios (OR) adjusted for baseline risk factors. An OR <  1 indicates that rates are lower with LMWH than with aspirin. In all, 21.1% of patients were prescribed aspirin and 78.9% LMWH. Without adjustment, we found no statistically significant differences. The rate of pulmonary embolism was 0.68% in both groups and 90-day mortality was 0.65% with aspirin and 0.61% with LMWH (OR 0.93; 95% CI 0.77 to 1.11). With risk adjustment, the difference in mortality increased (OR 0.84; 95% CI 0.69 to 1.01). With propensity score matching the mortality difference increased even further to 0.65% with aspirin and 0.51% with LMWH (OR 0.77; 95% CI 0.61 to 0.98). These results should be considered when the conflicting recommendations of existing guidelines for thromboprophylaxis after hip replacement are being addressed.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 881 - 885
1 Jul 2011
Cobb JP Davda K Ahmad A Harris SJ Masjedi M Hart AJ

Large-head metal-on-metal total hip replacement has a failure rate of almost 8% at five years, three times the revision rate of conventional hip replacement. Unexplained pain remains a feature of this type of arthroplasty.

All designs of the femoral component of large-head metal-on-metal total hip replacements share a unique characteristic: a subtended angle of 120° defining the proportion of a sphere that the head represents. Using MRI, we measured the contact area of the iliopsoas tendon on the femoral head in sagittal reconstruction of 20 hips of patients with symptomatic femoroacetabular impingement. We also measured the articular extent of the femoral head on 40 normal hips and ten with cam-type deformities. Finally, we performed virtual hip resurfacing on normal and cam-type hips, avoiding overhang of the metal rim inferomedially.

The articular surface of the femoral head has a subtended angle of 120° anteriorly and posteriorly, but only 100° medially. Virtual surgery in a normally shaped femoral head showed a 20° skirt of metal protruding medially where iliopsoas articulates.

The excessive extent of the large-diameter femoral components may cause iliopsoas impingement independently of the acetabular component. This may be the cause of postoperative pain with these implants.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 10 | Pages 1327 - 1333
1 Oct 2011
Jameson SS Dowen D James P Serrano-Pedraza I Reed MR Deehan DJ

Arthroscopy of the knee is one of the most commonly performed orthopaedic procedures worldwide. Large-volume outcome data have not previously been available for English NHS patients. Prospectively collected admissions data, routinely collected on every English NHS patient, were analysed to determine the rates of complications within 30 days (including re-operation and re-admission), 90-day symptomatic venous thromboembolism and all-cause mortality. There were 301 701 operations performed between 2005 and 2010 – an annual incidence of 9.9 per 10 000 English population. Of these, 16 552 (6%) underwent ligament reconstruction and 106 793 (35%) underwent meniscal surgery. The 30-day re-admission rate was 0.64% (1662) and 30-day wound complication rate was 0.26% (677). The overall 30-day re-operation rate was 0.40% (1033) and the 90-day pulmonary embolism rate was 0.08% (230), of which six patients died. 90-day mortality was 0.02% (47). Age < 40 years, male gender and ligament reconstruction were significantly associated with an increased rate of 30-day re-admission and unplanned re-operation. In addition, a significant increase in 30-day admission rates were seen with Charlson comorbidity scores of 1 (p = 0.037) and ≥ 2 (p <  0.001) compared with scores of 0, and medium volume units compared with high volume units (p < 0.001).

Complications following arthroscopy of the knee are rare. It is a safe procedure, which in the majority of cases is performed as day case surgery. These data can be used for quality benchmarking, in terms of consent, consultant re-validation and individual unit performance.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 435 - 438
1 Apr 2011
Gilbody J

Aseptic loosening of the acetabular component continues to be the most common indication for revision of total hip replacements in younger patients. Early in the evolution of the cemented hip, arthroplasty surgeons switched from removal to retention of the acetabular subchondral bone plate, theorising that unfavourable mechanical forces were the cause of loosening at the bone-cement interface.

It is now known that the cause of aseptic loosening is probably biological rather than mechanical and removing the subchondral bone plate may enhance biological fixation of cement to bone. With this in mind, perhaps it is time to revive removal of the subchondral bone as a standard part of acetabular preparation.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 1 - 4
1 Jan 2007
Robertsson O

This article considers the establishment, purpose and conduct of knee arthroplasty registers using the Swedish register as an example. The methods of collection of appropriate data, the cost, and the ways in which this information may be used are considered.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 9 | Pages 1169 - 1177
1 Sep 2011
Underwood R Matthies A Cann P Skinner JA Hart AJ

The Articular Surface Replacement (ASR) hip resurfacing arthroplasty has a failure rate of 12.0% at five years, compared with 4.3% for the Birmingham Hip Resurfacing (BHR). We analysed 66 ASR and 64 BHR explanted metal-on-metal hip replacements with the aim of understanding their mechanisms of failure. We measured the linear wear rates of the acetabular and femoral components and analysed the clinical cause of failure, pre-revision blood metal ion levels and orientation of the acetabular component.

There was no significant difference in metal ion levels (chromium, p = 0.82; cobalt, p = 0.40) or head wear rate (p = 0.14) between the two groups. The ASR had a significantly increased rate of wear of the acetabular component (p = 0.03) and a significantly increased occurrence of edge loading (p < 0.005), which can be attributed to differences in design between the ASR and BHR. The effects of differences in design on the in vivo wear rates are discussed: these may provide an explanation as to why the ASR is more sensitive to suboptimal positioning than the BHR.