A recent French report suggested that cobalt metal ions released from total hip replacements (THRs) were associated with an increased risk of dilated cardiomyopathy and heart failure. If the association is causal the consequences would be significant given the millions of Orthopaedic procedures in which cobalt-chrome is used annually. We examined whether cobalt-chrome containing THRs were associated with an increased risk of all-cause mortality, heart failure, cancer, and neurodegenerative disorders. Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 375,067 primary THRs with up to 14·5 years follow-up. Implants were grouped as either containing cobalt-chrome or not containing cobalt-chrome. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. There were 132,119 individuals (35·2%) with an implant containing cobalt-chrome. There were 48,106 deaths, 27,406 heart outcomes, 35,823 cancers, and 22,097 neurodegenerative disorders. There was no evidence of an association that patients with cobalt-chrome implants had higher rates of any of the outcomes. For all-cause mortality there was a very small survival advantage for patients having a cobalt-chrome implant (restricted mean survival time 13·8=days, 95% CI=6·8-20·9). Cobalt-chrome containing THRs did not have an increased risk of all-cause mortality, heart failure, cancer, and neurodegenerative disorders into the second decade post-implantation. Our findings will reassure clinicians and patients that primary THR is not associated with systemic implant effects.
Total hip replacement (THR) for end-stage osteoarthritis is a commonly performed cost-effective procedure, which provides patients with significant clinical improvement. Estimating the future demand for joint replacement is important to identify the healthcare resources needed. We estimated the number of primary THRs that will need to be performed up to the year 2060. We used data from The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man on the current volume of primary THR (n=94,936) performed in 2018. We projected future numbers of THR using a static estimated rate from 2018 applied to population growth forecast data from the UK Office for National Statistics up to 2060. By 2060, primary THR volume would increase from 2018 levels by an estimated 37.7% (n=130,766). For both males and females demand for surgery was also higher for patients aged 70 and over, with older patients having the biggest relative increase in volume over time: 70–79 years (144.6% males, 141.2% females); 80–89 years (212.4% males, 185.6% females); 90 years and older (448.0% males, 298.2% females). By 2060 demand for THR is estimated to increase by almost 40%. Demand will be greatest in older patients (70 years+), which will have significant implications for the health service that requires forward planning given morbidity and resource use is higher in this population. There is a backlog of current demand with cancellation of elective surgery due to seasonal flu pressures in 2017 and now Covid-19 in 2020. Orthopaedics already has the largest waiting list of any speciality. These issues will negatively impact the health services ability to deliver timely joint replacement to many patients for a number of years and require urgent planning.
Considerable debate exists regarding which agent(s) should be preferred for venous thromboembolism (VTE) chemical prophylaxis following joint replacement. We assessed the practice of surgeons regarding VTE chemical prophylaxis for primary THR and TKR, pre and post issuing of updated NICE guidance in 2018. A survey, circulated through the British Hip Society and regional trainee networks/collaboratives, was completed by 306 UK surgeons at 187 units. VTE chemical prophylaxis prescribing patterns for surgeons carrying out primary THR (n=258) and TKR (n=253) in low-risk patients were assessed post publication of 2018 NICE recommendations. Prescribing patterns before and after the NICE publication were subsequently explored. Questions were also asked about surgeon equipoise for participation in future RCTs. Following the new guidance, 34% (n=87) used low-molecular weight heparin (LMWH) alone, 33% (n=85) aspirin (commonly preceded by LMWH), and 31% (n=81) direct oral anticoagulants (DOACs: with/without preceding LMWH) for THR. For TKR, 42% (n=105) used aspirin (usually monotherapy), 31% (n=78) LMWH alone, and 27% (n=68) DOAC (with/without preceding LMWH). NICE guidance changed the practice of 34% of hip and 41% of knee surgeons, with significantly increased use of aspirin preceded by LMWH for THR (before=25% vs. after=73%;p<0.001), and aspirin for TKR (before=18% vs. after=84%;p<0.001). Significantly more regimens were NICE guidance compliant after the 2018 update for THR (before=85.7% vs. after=92.6%;p=0.011) and TKR (before=87.0% vs. after=98.8%;p<0.001). Support from surgeons for future RCTs was dependent on the clinical question, ranging from 48% participation in trials (effectiveness of aspirin vs. a DOAC) to 79% (effectiveness of 14 days LMWH vs. 28 days LMWH). Over one-third of surveyed surgeons changed their VTE chemical prophylaxis in response to 2018 NICE recommendations, with more THR and TKR surgeons now compliant with latest NICE guidance. The major change in practice was an increased use of aspirin for VTE chemical prophylaxis. Furthermore, there is an appetite amongst UK surgeons for participating in future RCTs, with a trial comparing standard versus extended duration LMWH likely feasible in current practice.
Few studies have compared aspirin with DOACs (direct oral anticoagulants = direct thrombin inhibitors and factor Xa inhibitors) for venous thromboembolism (VTE) prophylaxis following total hip and knee replacement (THR and TKR). We assessed the efficacy and safety of aspirin compared with DOACs for VTE prophylaxis following THR and TKR using the world's largest joint replacement registry. We studied the National Joint Registry linked to English hospital inpatient episodes for 218,650 THR and TKR patients. Patients receiving aspirin were matched separately to (1) direct thrombin inhibitors, and (2) factor Xa inhibitors using propensity scores. Outcomes assessed at 90 days included VTE, length of stay, and adverse events.Background
Methods
Many worldwide regulatory authorities recommend regular surveillance of metal-on-metal hip arthroplasty patients given high failure rates. However concerns have been raised about whether such regular surveillance, which includes asymptomatic patients, is evidence-based and cost-effective. We determined: (1) the cost of implementing the 2015 MHRA surveillance in “at-risk” Birmingham Hip Resurfacing (BHR) patients, and (2) how many asymptomatic hips with adverse reactions to metal debris (ARMD) would have been missed if patients were not recalled. All BHR patients subject to the 2015 MHRA recall (all females, and males with head sizes 46mm or below, regardless of symptoms) at one specialist centre were invited for review (707 hips). All patients were investigated (Oxford Hip Score, radiographs, blood metal ions, and targeted cross-sectional imaging) and managed accordingly. Surveillance costs were calculated using finance department data, as was the number needed to treat (NNT) to avoid missing one case of asymptomatic ARMD.Introduction
Methods
Total hip replacement (THR) is clinically and cost-effective. The surgical approach influences outcomes, however there is little generalisable and robust evidence to guide practice. We assessed the effect of surgical approach on THR outcomes. 723,904 primary THRs captured in the National Joint Registry, linked to hospital inpatient, mortality and patient reported outcome measures (PROMs) data with up to 13.75 years follow-up were analysed. There were seven surgical approach groups: conventional posterior, lateral, anterior and trans-trochanteric groups and minimally invasive posterior, lateral and anterior. Survival methods were used to compare revision rates and 90-day mortality. Groups were compared using Cox proportional hazards and Flexible Parametric Survival Modelling (FPM). Confounders included age at surgery, sex, risk group (indications additional to osteoarthritis), ASA grade, THR fixation, thromboprophylaxis, anaesthetic, body mass index (BMI), and deprivation. PROMs were analysed with regression modelling or non-parametric methods.Background
Methods
We investigated predictors of poor outcomes following metal-on-metal hip arthroplasty (MoMHA) revision surgery performed for adverse reactions to metal debris (ARMD), to help inform the revision threshold and type of reconstruction. A retrospective cohort study was performed involving 346 MoMHAs revised for histologically confirmed ARMD at two specialist centres (245=hip resurfacing, 101=total hip arthroplasty). Numerous preoperative (blood metal ions and imaging) and intraoperative (findings, and components removed/implanted) factors were used to predict poor outcomes. Poor outcomes were postoperative complications (including re-revisions), 90-day mortality, and poor Oxford Hip Scores (<27/48). Multivariable logistic regression models for predicting poor outcomes were developed using stepwise selection methods.Introduction
Patients and Methods
Smoking, a modifiable factor, may adversely affect post-operative outcomes. Healthcare providers are increasingly denying smokers access to total hip arthroplasty (THA) until they stop smoking. Evidence supporting this is unclear. We assessed the effect of smoking on outcomes following THA. We performed a retrospective observational study involving 60,812 THAs (12.4%=smokers, 31.2%=ex-smokers, 56.4%=non-smokers) from the Clinical Practice Research Datalink. Data were linked with Hospital Episode Statistics and the Office for National Statistics to identify outcomes. The effect of smoking on post-operative outcomes (complications, medications, revision, mortality, PROMs) was assessed using adjusted regression.Introduction
Patients and Methods
Total hip arthroplasty (THA) is indicated in independently mobile patients sustaining displaced intracapsular hip fractures. Studies presently suggest that the anterolateral approach is preferable to the posterior approach due to a perceived reduced risk of reoperations and dislocations. However, these observations come from small studies with short follow-up. We assessed whether surgical approach in THA performed for hip fractures effects outcomes. A retrospective observational study was performed using data collected prospectively by the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. All primary stemmed THAs implanted for hip fractures between 2003–2015 were eligible for inclusion (n=19,432). The two surgical approach groups (posterior versus anterolateral) were propensity-score matched for multiple potential patient and surgical confounding factors (n=14,536, with 7,268/group). Outcomes (implant survival, patient survival, intraoperative complications) were compared between the approach groups using regression analysis.Introduction
Patients and Methods
Intraoperative periprosthetic femoral fractures (IOPFF) lead to reduced implant survival. A deeper understanding of predictors enables surgeons to modify techniques and patient selection to reduce the risk of IOPFF. The aim of this study was to estimate predictors of IOPFF and each anatomical subtype (calcar crack, trochanteric fracture, femoral shaft fracture) during primary THA. This retrospective cohort study included 793823 primary THAs between 2004 and 2016. Relative risks for patient, surgical and implant factors are estimated for any IOPFF fracture and for all anatomical subtypes of IOPFF.Introduction
Methods
The aim of this study was to investigate the local recurrence rate at an extended follow-up in patients following navigated resection of primary pelvic and sacral tumours. This prospective cohort study comprised 23 consecutive patients (nine female, 14 male) who underwent resection of a primary pelvic or sacral tumour, using computer navigation, between 2010 and 2012. The mean age of the patients at the time of presentation was 51 years (10 to 77). The rates of local recurrence and mortality were calculated using the Kaplan–Meier method.Aims
Patients and Methods
Unicompartmental knee arthroplasty (UKA) offers significant advantages over total knee arthroplasty (TKA) but is reported to have higher revision rates in joint registries. In both the New Zealand and the UK national registry the revision rate of cementless UKR is less than cementless. It is not clear whether this is because the cementless is better or because more experienced surgeons, who tend to get better results are using cementless. We aim to use registry data to compare cemented and cementless UKA outcomes, matching for surgical experience and other factors. We performed a retrospective observational study using National Joint Registry (NJR) data on 10,836 propensity matched Oxford UKAs (5418 cemented and 5418 cementless) between 2004 and 2015. Logistic regression was utilized to calculate propensity scores to match the cemented and cementless groups for multiple confounders using a one to one ratio. Standardised mean differences were used before and after matching to assess for any covariate imbalances. The outcomes studied were implant survival, reasons for revision and patient survival. The endpoint for implant survival was revision surgery (any component removal or exchange). Cumulative patient and implant survival rates were determined using the Kaplan-Meier method. Patients not undergoing revision or death were censored on the study end date. The study endpoints implant and patient survival were compared between cemented and cementless groups using Cox regression models with a robust variance estimator.Introduction
Methods
Pseudotumours have recently been reported in non-metal-on-metal total hip replacements (non-MoM THRs), however the magnitude and risk factors for this complication are unknown, as is the outcome of its treatment. 3340 primary THR undergoing revision for pseudotumour between 2008 and 2015 were identified in the National Joint Registry for England and Wales. 7.5% (n=249) of these pseudotumour revisions, had non-MoM bearing surfaces. The risk of revision for pseudotumour in non-MoM hips was 0.032% (249/789,397; 95% CI 0.028%–0.036%). The risk of pseudotumour revision was 2.35 times (95% CI 1.76–3.11) higher in ceramic-on-ceramic compared with hard-on-soft bearings, and 2.80 times (95% CI 1.74–4.36) higher in 36mm metal-on-polyethylene bearings compared to 28mm and 32mm metal-on-polyethylene bearings. The outcome of revision for pseudotumour non-MoM hips was studied in 185 hips. 13.5% (n=25) had re-revisions at a mean of 1.2 years (range 0.1–3.1 years). Infection (32%), dislocation/subluxation (24%), and aseptic loosening (24%) were the commonest indications for re-revision. The 4-year survival rate was 83.8% (95% CI=76.7%–88.9%). Multiple revision indications (Hazard Ratio (HR)=2.78; 95% CI=1.03–7.49) and incomplete revision procedures (HR=5.76; 95% CI=1.28–25.9) increased the risk of re-revision Although the overall risk of revision for pseudotumour in non-MoM THRs is low, the risk is increasing and is significantly higher in ceramic-on-ceramic and large head metal-on-polyethylene THR. These revisions have a high early failure rate.
Outcomes following metal-on-metal hip replacement (MoMHR) revision surgery for adverse reactions to metal debris (ARMD) have been poor, and inferior compared with non-ARMD revisions. Subsequently, surgeons and worldwide authorities widely recommended early revision for ARMD, with a lower surgical threshold adopted. However, the impact of early surgery for ARMD is unknown. We compared the rates of adverse outcomes following MoMHR revision surgery in matched ARMD and non-ARMD patients. We performed a retrospective observational study using data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. All MoMHR patients subsequently undergoing revision surgery for any indication between August 2008 and August 2014 were eligible. ARMD and non-ARMD revisions were matched one-to-one for multiple potential confounding factors using propensity scores. Adverse outcomes following revision surgery (intra-operative complications, mortality, re-revision surgery) were compared between matched groups using regression analysis. In 2,576 matched MoMHR revisions (ARMD=1,288 and non-ARMD=1,288), intra-operative complications were similar between ARMD (2.4%) and non-ARMD (2.5%) revisions (odds ratio=0.97, 95% CI=0.59–1.60; p=0.899). All-cause mortality rates were lower following ARMD revision compared with non-ARMD revision (hazard ratio (HR)=0.43, 95% CI=0.22–0.86; p=0.018). All-cause re-revision rates were lower following ARMD revision compared with non-ARMD revision (HR=0.52, 95% CI=0.36–0.75; p<0.001). Compared with ARMD revision (5-years=94.3%), MoMHR revisions for infection (5-years=81.2%) and dislocation/subluxation (5-years=81.9%) had the lowest implant survival rates. Contrary to previous observations, MoMHRs revised for ARMD have approximately half the risk of re-revision and death compared to non-ARMD revisions. We suspect worldwide regulatory authorities have positively influenced outcomes following ARMD revision by widely recommending that surgeons exercise a lower revision threshold. Our findings suggest the threshold for ARMD revision surgery need not be lowered further. The high risk of failure following MoMHR revision for infection and dislocation is concerning.
Recent studies have demonstrated that implant-specific blood metal ion thresholds exist in unilateral and bilateral metal-on-metal (MoM) hip arthroplasty patients, with these thresholds being most effective for identifying patients at low-risk of adverse reactions to metal debris (ARMD). We investigated whether these new blood metal ion thresholds could effectively identify patients at risk of ARMD in an external cohort of MoM hip arthroplasty patients. We performed a validation study involving 803 MoM hip arthroplasties implanted in 710 patients at three European centres (323=unilateral Birmingham Hip Resurfacing (BHR); 93=bilateral BHR; 294=unilateral Corail-Pinnacle). All patients underwent whole blood metal ion sampling. Patients were divided into those with ARMD (revised for ARMD or ARMD on imaging; n=75), and those without ARMD (n=635). Previously devised implant-specific blood metal ion thresholds (cobalt=2.15μg/l for unilateral BHR; maximum cobalt or chromium=5.5μg/l for bilateral BHR; cobalt=3.57μg/l for unilateral Corail-Pinnacle) were applied to the validation cohort, with receiver operating characteristic curve analysis used to establish the discriminatory characteristics for each respective threshold. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for distinguishing between patients with and without ARMD for each implant-specific threshold were respectively: unilateral BHR=89.4% (95% CI=82.8%-96.0%), 78.9%, 86.7%, 44.1%, 96.9%; bilateral BHR=89.2% (95% CI=81.3%-97.1%), 70.6%, 86.8%, 54.5%, 93.0%; unilateral Corail-Pinnacle=76.9% (95% CI=63.9%-90.0%), 65.0%, 85.4%, 24.5%, 97.1%. The 7μg/l UK MHRA threshold missed significantly more patients with ARMD compared with the implant-specific thresholds (4.9% vs. 2.8%; p=0.0003). This external multi-centre validation study has confirmed that MoM hip arthroplasty patients with blood metal ion levels below newly devised implant-specific thresholds have a low-risk of ARMD. Compared to implant-specific thresholds, the currently proposed fixed MHRA threshold missed more patients with ARMD. We recommend using implant-specific thresholds over fixed thresholds when managing MoM hip arthroplasty patients.
Recent studies have reported on non-metal-on-metal hip arthroplasty (non-MoMHA) patients requiring revision surgery for adverse reactions to metal debris (ARMD). Although the outcomes following revision surgery for ARMD in MoMHA patients are known to generally be poor, little evidence exists regarding outcomes following non-MoMHA revision surgery performed for ARMD. We determined the outcomes following non-MoMHA revision surgery performed for ARMD, and identified predictors of re-revision. We performed a retrospective observational study using data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. All primary non-MoMHA patients who subsequently underwent revision surgery for ARMD between 2008–2014 were included (n=185). Outcome measures following ARMD revision were intraoperative complications, mortality, and re-revision surgery. Predictors of re-revision surgery were identified using Cox regression analysis. Intra-operative complications occurred in 6.0% (n=11) of ARMD revisions. The cumulative 4-year patient survival rate was 98.2% (95% CI=92.9–99.5%). Re-revision surgery was performed in 13.5% (n=25) of hips at a mean time of 1.2 years (range 0.1–3.1 years) following ARMD revision. Infection (32%), dislocation/subluxation (24%), and aseptic loosening (24%) were the commonest re-revision indications. The cumulative 4-year implant survival rate was 83.8% (95% CI=76.7%-88.9%). Significant predictors of re-revision were: multiple revision indications (Hazard Ratio (HR)=2.78; 95% CI=1.03–7.49; p=0.043), incomplete revision procedures (including modular component exchange only) (HR=5.76; 95% CI=1.28–25.9; p=0.022), and ceramic-on-polyethylene revision bearings (HR=3.08; 95% CI=1.01–9.36; p=0.047). Non-MoMHA patients undergoing ARMD revision have a high short-term risk of re-revision. Infection, dislocation/subluxation, and aseptic loosening were the commonest re-revision indications. Furthermore, important and potentially modifiable predictors of future re-revision were identified. Although the poor prognostic factors identified require validation in future studies, our findings may be used to counsel patients about the risks associated with ARMD revision surgery, and guide decisions about the reconstructive procedure.
We investigated whether blood metal ions could effectively identify bilateral metal-on-metal hip patients at risk of adverse reactions to metal debris (ARMD). This single-centre, prospective study involved 235 patients (185 bilateral Birmingham Hip Resurfacings (BHRs) and 50 bilateral Corail-Pinnacles) undergoing whole blood metal ion sampling (mean time=6.8 years from latest implant to sampling). Patients were divided into ARMD (revised or ARMD on imaging; n=40) and non-ARMD groups (n=195). Metal ion parameters (cobalt; chromium; maximum cobalt or chromium; cobalt-chromium ratio) were compared between groups. Optimal metal ion thresholds for identifying ARMD patients were determined using receiver operating characteristic (ROC) analysis, which compares the performance of different tests using the area under the curve (AUC) (higher AUC=more discriminatory).Introduction
Patients and methods
The impact of pseudotumours associated with metal-on-metal hip resurfacings (MoMHRs) within the second decade is unknown. We investigated: (1) the incidence and risk factors for all-cause and pseudotumour revision following MoMHR at 15-years follow-up, and (2) whether risk factors were gender specific. This single-centre prospective cohort study included 1429 MoMHRs (1216 patients; 40% female) implanted between 1999–2009. All patients were contacted in 2010 and 2012 as per national recommendations. Patients with hip problems and/or suboptimal Oxford Hip Scores (<41/48) underwent cross-sectional imaging and blood metal ion sampling. Revisions were performed as indicated with diagnoses confirmed from operative and histopathological findings. Multi-variate Cox proportional hazard models assessed the association of predictor variables on time to all-cause and pseudotumour revision.Introduction
Patients and methods
Blood metal ion sampling can help detect poorly functioning metal-on-metal hip arthroplasties (MoMHA's) requiring revision. Little is known about the variation in these levels following bearing exchange. This study aimed to determine the changes that occur in blood and urine metal ion concentrations following MoMHA revision. A single-centre prospective cohort study was undertaken between 2005 and 2012 of patients with failing large-diameter MoMHA's and high blood metal ions requiring revision to non-metal-on-metal articulations. All patients had normal renal function. Whole blood and urine were collected for metal ion analysis preoperatively and regularly following revision. Twenty-three MoMHAs (21 hip resurfacings and 2 total hip arthroplasties; mean age 56.0 years and 65% female) were revised at a mean time of 7.9 years (range 2.0–14.5 years) from primary surgery. All revisions were performed by the senior author using primary total hip implants (12 ceramic-on-polyethylene bearings, 10 oxinium-on-polyethylene bearings, and 1 metal-on-polyethylene bearing implanted). Mean (range) metal ion concentrations pre-revision were: blood cobalt 13.9µg/l (1.32–74.7µg/l), blood chromium 8.9µg/l (1.29–57.3µg/l), urine cobalt 104.6µg/24 hours (4.35–747.3µg/24 hours), urine chromium 33.2µg/24 hours (4.39–235.4µg/24 hours). After revision the mean metal ion concentrations (percentage of pre-revision values) were: blood cobalt at 2 days=10.7µg/l (77%), 6 days=7.7µg/l (55%), 2 months=3.4µg/l (24%), 1 year=1.0µg/l (7%), 2 years=0.42µg/l (3%); blood chromium at 2 days=8.7µg/l (98%), 6 days=5.5µg/l (62%), 2 months=2.2µg/l (25%), 1 year=1.5µg/l (16%), 2 years=0.97µg/l (11%); urine cobalt at 2 days=31.9µg/24 hours (30%), 6 days=21.5µg/24 hours (21%), 2 months=6.1µg/24 hours (6%), 1 year=0.99µg/24 hours (1%), 2 years=0.61µg/24 hours (1%); urine chromium at 2 days=34.4µg/24 hours (103%), 6 days=15.8µg/24 hours (48%), 2 months=9.3µg/24 hours (28%), 1 year=2.8µg/24 hours (8%), 2 years=1.9µg/24 hours (6%). Following MoM revision cobalt levels decline rapidly in an exponential pattern with a single rate of decay through the 2 year period, reaching reference levels within the first year. Chromium follows a similar pattern but starts lower and takes longer. Renal response to cobalt returns to reference level within days of revision.
High short-term failure rates have been observed with a number of metal-on-metal (MoM) hip designs. Most patients require follow-up with blood metal ions, whichprovide a surrogate marker of in-vivo bearing wear. Given these results are used in clinical decision making it is important values obtained within and between laboratories are reproducible. To assess the intra-laboratory and inter-laboratory variability of blood metal ion concentrations analysed by four accredited laboratories. Whole blood was taken from two participants in this prospective study. The study specimen was obtained from a 42 year-old female with ceramic-on-ceramic hip arthroplasty failure resulting in unintended metal-on-ceramic wear and excessively high systemic metal ion levels. The control specimen was from a 52 year-old healthy male with no metal exposure. The two specimens were serially diluted to produce a total of 25 samples with different metal ion concentrations in two different anticoagulants each. Thus 50 samples were sent blinded in duplicate (total 100) to four accredited laboratories (A, B, C, D) to independently analyse blood metal ion concentrations. Ten commercially available reference specimens spiked with different amounts of metal ions were also obtained with known blood metal ion concentrations (range for cobalt 0.15µg/l-11.30µg/l and chromium 0.80µg/l to 37.00µg/l) and analysed by the four laboratories. The intra-laboratory coefficients of variation for repeat analysis of identical patient specimens were 7.32% (laboratory A), 4.64% (B), 7.50% (C), and 20.0% (D). The inter-laboratory variability for the analysis of all 25 samples was substantial. For the unmixed study specimen the laboratory results ranged from a cobalt of 263.7µg/l (D) to 525.1µg/l (D) and a chromium of 13.3µg/l (D) to 36.9µg/l (A). For the unmixed control specimen the laboratory results ranged from a cobalt of 0.13µg/l (B) to 0.77µg/l (D) and a chromium of 0.13µg/l (D) to 7.1µg/l (A). For one of the mixed specimens the laboratory results ranged from a cobalt of 12.50µg/l (A) to 20.47µg/l (D) and a chromium of 0.73µg/l (D) to 5.60µg/l (A). Similar inter-laboratory variation was observed for the other mixed samples. The true mean (standard deviation) of the 10 commercial samples was 4.48µg/l (4.20) for cobalt and 8.97µg/l (10.98) for chromium. This was similar to the values obtained by all four laboratories: mean (standard deviation) cobalt ranged from 3.54µg/l (3.17) in laboratory A to 4.35µg/l (4.13) in laboratory D, and chromium ranged from 7.76µg/l (9.50) in laboratory B to 9.55µg/l (9.16) in laboratory A. When testing patient samples, large variations existed both between and within four laboratories accredited to perform analysis of blood metal ion concentrations. However, this was not the case when assessing commercially spiked samples which are regularly used to validate laboratory testing. This is of great clinical concern and could lead clinicians to either recommend unnecessary revision or delay surgery, with both having the potential to adversely affect patient outcomes. It is recommended that laboratories use patient samples to assess the accuracy and reproducibility of the analyses performed. This may also assist in explaining the variations observed in this study.
