Self-Reported Neurotoxic Symptoms in Hip Arthroplasty Patients With Highly Elevated Blood Cobalt: A Case-Control Study

OBJECTIVES: This study aimed to investigate the prevalence of self-reported neurotoxicity and cognitive defects in hip replacement patients with markedly raised blood cobalt. METHODS: Case group comprised 53 patients with metal-on-metal (MoM) implants and a history of blood Co ≥20 μg/L for a median of 3 years (interquartile range, 2-5 years). The control group comprised 53 patients with ceramic-on-ceramic prostheses and blood Co <1 μg/L. Median age was 67 years (interquartile range, 60-74 years). The participants completed the Neurotoxic Symptom Checklist-60, Diabetic Neuropathy Score, Douleur Neuropathique-10, and Systemic Symptom Checklist, and underwent the Mini-Mental State Examination. RESULTS: The MoM and ceramic-on-ceramic groups were compared, the results were as follows: Neurotoxic Symptom Checklist-60 (median): cognitive defects (2.0 versus 1.9; P = 0.002), chest complaints (1.3 versus 1.3; P = 0.042), balance disturbances (1.3 versus 1.0; P < 0.001), sleep disturbances (2.7 versus 2.0; P = 0.004), mood disorders (2.0 versus 1.5; P = 0.001), sensorimotor disorders (1.6 versus 1.2; P < 0.001), physical complaints (2.0 versus 1.4; P = 0.009), fatigue (2.0 versus 1.6; P = 0.001), and total score (108 versus 90; P < 0.001); abnormal Diabetic Neuropathy Score/Douleur Neuropathique-10 (%): 60.3/13.2 versus 24.5/1.9 (P < 0.001/P = 0.028). Systemic Symptom Checklist (in percent): feeling cold (37.7 versus 17; P = 0.01), weight gain (18.9 versus 1.9; P = 0.008), metallic taste (26.4 versus 3.8; P = 0.002), worsening eyesight (37.7 versus 15.1; P = 0.008) and hearing (24.5 versus 7.5; 0.032), ankle swelling (32.1 versus 7.5; P = 0.002), shortness of breath on exertion (9.4 versus 5.7; P = 0.015), and generalized rash (28.3 versus 7.5; P = 0.01); and Mini-Mental State Examination (median): 29 versus 30 (P = 0.017). Patients in the MoM group were aware of their high cobalt levels and displayed a higher tendency to overreport symptoms (P < 0.001), which could have contributed to the higher scores. CONCLUSIONS: Frequency of reporting a number of symptoms was markedly higher in MoM patients, but clinically significant neurotoxicity was not observed (possibly due to the short exposure to elevated cobalt). Patients with repeated blood Co ≥20 μg/L measurements should be questioned about possible systemic health complaints at follow-up

Are all metal-on-metal hip revision operations contributing to the National Joint Registry implant survival curves? : a study comparing the London Implant Retrieval Centre and National Joint Registry datasets

AIMS: The National Joint Registry for England, Wales and Northern Ireland (NJR) has extended its scope to report on hospital, surgeon and implant performance. Data linkage of the NJR to the London Implant Retrieval Centre (LIRC) has previously evaluated data quality for hip primary procedures, but did not assess revision records. METHODS: We analysed metal-on-metal hip revision procedures performed between 2003 and 2013. A total of 69 929 revision procedures from the NJR and 929 revised pairs of components from the LIRC were included. RESULTS: We were able to link 716 (77.1%) revision procedures on the NJR to the LIRC. This meant that 213 (22.9%) revision procedures at the LIRC could not be identified on the NJR. We found that 349 (37.6%) explants at the LIRC completed the full linkage process to both NJR primary and revision databases. Data completion was excellent (> 99.9%) for revision procedures reported to the NJR. DISCUSSION: This study has shown that only approximately one third of retrieved components at the LIRC, contributed to survival curves on the NJR. We recommend prospective registry-retrieval linkage as a tool to feedback missing and erroneous data to the NJR and improve data quality. TAKE HOME MESSAGE: Prospective Registry - retrieval linkage is a simple tool to evaluate and improve data quality on the NJR. Cite this article: Bone Joint J 2016;98-B:33-9

Pseudotumors in association with well-functioning metal-on-metal hip prostheses: a case-control study using three-dimensional computed tomography and magnetic resonance imaging.

Many papers have been published recently on the subject of pseudotumors surrounding metal-on-metal hip resurfacing and replacement prostheses. These pseudotumors are sterile, inflammatory lesions within the periprosthetic tissues and have been variously termed masses, cysts, bursae, collections, or aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL). The prevalence of pseudotumors in patients with a well-functioning metal-on-metal hip prosthesis is not well known. The purpose of this study was to quantify the prevalence of pseudotumors adjacent to well-functioning and painful metal-on-metal hip prostheses, to characterize these lesions with use of magnetic resonance imaging, and to assess the relationship between their presence and acetabular cup position with use of three-dimensional computed tomography

A comparison of the diagnostic accuracy of MARS MRI and ultrasound of the painful metal-on-metal hip arthroplasty

Background and purpose — Metal artifact reduction sequence (MARS) MRI and ultrasound scanning (USS) can both be used to detect pseudotumors, abductor muscle atrophy, and tendinous pathology in patients with painful metal-on-metal (MOM) hip arthroplasty. We wanted to determine the diagnostic test characteristics of USS using MARS MRI as a reference for detection of pseudotumors and muscle atrophy. Patients and methods — We performed a prospective cohort study to compare MARS MRI and USS findings in 19 consecutive patients with unilateral MOM hips. Protocolized USS was performed by consultant musculoskeletal radiologists who were blinded regarding clinical details. Reports were independently compared with MARS MRI, the imaging gold standard, to calculate predictive values. Results — The prevalence of pseudotumors on MARS MRI was 68% (95% CI: 43–87) and on USS it was 53% (CI: 29–76). The sensitivity of USS in detecting pseudotumors was 69% (CI 39–91) and the specificity was 83% (CI: 36–97). The sensitivity of detection of abductor muscle atrophy was 47% (CI: 24–71). In addition, joint effusion was detected in 10 cases by USS and none were seen by MARS MRI

Which factors influence the rate of failure following metal-on-metal hip arthroplasty revision surgery performed for adverse reactions to metal debris? AN ANALYSIS FROM THE NATIONAL JOINT REGISTRY FOR ENGLAND AND WALES

Aims To determine the outcomes following revision surgery of metal-on-metal hip arthroplasties (MoMHA) performed for adverse reactions to metal debris (ARMD), and to identify factors predictive of re-revision. Patients and Methods We performed a retrospective observational study using National Joint Registry (NJR) data on 2535 MoMHAs undergoing revision surgery for ARMD between 2008 and 2014. The outcomes studied following revision were intra-operative complications, mortality and rerevision surgery. Predictors of re-revision were identified using competing-risk regression modelling. Results Intra-operative complications occurred in 40 revisions (1.6%). The cumulative five-year patient survival rate was 95.9% (95% confidence intervals (CI) 92.3 to 97.8). Re-revision surgery was performed in 192 hips (7.6%). The cumulative five-year implant survival rate was 89.5% (95% CI 87.3 to 91.3). Predictors of re-revision were high body mass index at revision (subhazard ratio (SHR) 1.06 per kg/m2 increase, 95% CI 1.02 to 1.09), modular component only revisions (head and liner with or without taper adapter; SHR 2.01, 95% CI 1.19 to 3.38), ceramic-on-ceramic revision bearings (SHR 1.86, 95% CI 1.23 to 2.80), and acetabular bone grafting (SHR 2.10, 95% CI 1.43 to 3.07). These four factors remained predictive of re-revision when the missing data were imputed. Conclusion The short-term risk of re-revision following MoMHA revision surgery performed for ARMD was comparable with that reported in the NJR following all-cause non-MoMHA revision surgery. However, the factors predictive of re-revision included those which could be modified by the surgeon, suggesting that rates of failure following ARMD revision may be reduced further

Adverse reactions to metal debris occur with all types of hip replacement not just metal-on-metal hips: a retrospective observational study of 3340 revisions for adverse reactions to metal debris from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Adverse reactions to metal debris (ARMD) have resulted in the high short-term failure rates observed with metal-on-metal hip replacements. ARMD has recently been reported in non-metal-on-metal total hip replacements (non-MoM THRs) in a number of small cohort studies. However the true magnitude of this complication in non-MoM THRs remains unknown. We used a nationwide database to determine the risk of ARMD revision in all non-MoM THRs, and compared patient and surgical factors associated with ARMD revision between non-MoM and MoM hips. METHODS: 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 hip replacements undergoing revision surgery for ARMD were included (n = 3,340). ARMD revision risk in non-MoM THRs was compared between different commonly implanted bearing surfaces and femoral head sizes (Chi-squared test). Differences in patient and surgical factors between non-MoM hips and MoM hips revised for ARMD were also analysed (Chi-squared test and unpaired t-test). RESULTS: Of all ARMD revisions, 7.5% (n = 249) had non-MoM bearing surfaces. The relative risk of ARMD revision was 2.35 times (95% CI 1.76-3.11) higher in ceramic-on-ceramic bearings compared with hard-on-soft bearings (0.055 vs. 0.024%; p < 0.001), and 2.80 times (95% CI 1.74-4.36) higher in 36 mm metal-on-polyethylene bearings compared to 28 mm and 32 mm metal-on-polyethylene bearings (0.058 vs. 0.021%; p < 0.001). ARMD revisions were performed earlier in non-MoM hips compared to MoM hips (mean 3.6-years vs. 5.6-years; p < 0.0001). Non-MoM hips had more abnormal findings at revision (63.1 vs. 35.7%; p < 0.001), and more intra-operative adverse events (6.4 vs. 1.6%; p < 0.001) compared to MoM hips. CONCLUSIONS: Although the overall risk of ARMD revision surgery in non-MoM THRs appears low, this risk is increasing, and is significantly higher in ceramic-on-ceramic THRs and 36 mm metal-on-polyethylene THRs. ARMD may therefore represent a significant clinical problem in non-MoM THRs

Ceramic on ceramic bearing fractures in total hip arthroplasty : an analysis of data from the national joint registry

Aims: Ceramic-on-ceramic (CoC) bearings in total hip arthroplasty (THA) are commonly used but concerns exist regarding ceramic fracture. This study aims to report the risk of revision for fracture of modern CoC bearings and identify factors that might influence this risk, using data from the National Joint Registry (NJR). Patients and Methods: We analysed data on 111,681 primary CoC THA’s and 182 linked revisions for bearing fracture recorded in NJR. We used implant codes to identify ceramic bearing composition and generated Kaplan-Meier estimates for implant survivorship. Logistic regression analyses were performed for implant size and patient specific variables to determine any associated risks for revision. Results: 99.8% of bearings were CeramTec Biolox® products. Revisions for fracture were linked to 7 of 79,442 (0.009%) Biolox® Delta heads, 38 of 31,982 (0.119%) Biolox® Forte heads, 101 of 80,170 (0.126%) Biolox® Delta liners and 35 of 31,258 (0.112%) Biolox® Forte liners. Regression analysis of implant size revealed smaller heads had significantly higher odds of fracture (χ2=68.0, p<0.0001). The highest fracture risk were observed in the 28mm Biolox® Forte subgroup (0.382%). There were no fractures in the 40mm head group for either ceramic type. Liner thickness was not predictive of fracture (p=0.67). BMI was independently associated with revision for both head fractures (OR 1.09 per unit increase, p=0.031) and liner fractures (OR 1.06 per unit increase, p=0.006). Conclusions: We report the largest study of CoC bearing fractures to date. The risk of revision for CoC bearing fracture is very low, however previous studies have underestimated this risk. There is good evidence that the latest generation of ceramic has greatly reduced the odds of head fracture but not of liner fracture. Small head size and high patient BMI are associated with an increased risk of ceramic bearing fracture

Submicroscopic Gametocytes and the Transmission of Antifolate-Resistant Plasmodium falciparum in Western Kenya

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up. CONCLUSIONS/SIGNIFICANCE: In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites