Nuffield Orthopaedic Centre

About: Nuffield Orthopaedic Centre is a healthcare organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Arthroplasty. The organization has 2082 authors who have published 2920 publications receiving 145718 citations.

Improved fixation in cementless unicompartmental knee replacement: five-year results of a randomized controlled trial.

Abstract: Background: When used for appropriate indications, unicompartmental knee replacement is associated with fewer complications, faster recovery, and better function than total knee replacement. However, joint registries demonstrate a higher revision rate for unicompartmental knee replacement. Currently, most unicompartmental knee replacements are cemented; common reasons for revision include aseptic loosening and pain. These problems could potentially be addressed by using cementless implants, with coatings designed to improve fixation. The objectives of this study were to compare the quality of fixation as well as clinical outcomes of cemented and cementless unicompartmental knee replacements at five years of follow-up. Methods: A randomized controlled trial was established with sixty-three knees (sixty-two patients) receiving either cemented (thirty-two patients) or cementless Oxford unicompartmental knee replacements (thirty patients). Fixation was assessed with fluoroscopic radiographs aligned to the bone-implant interface at one and five years. Outcome scores, including the Oxford Knee Score, Knee Society objective and functional scores, and Tegner Activity Score, were collected preoperatively and at six months and one, two, and five years postoperatively. At each postoperative time point, these were recorded as absolute scores and change from the preoperative score. Results: Four patients died during the study period. There were no revisions. Mean operative time was nine minutes shorter in the cementless group (p = 0.049). At five years, there was no significant difference in any outcome measure except the Knee Society functional score and the change in the Knee Society functional score, which were significantly better in the cementless group (p = 0.003 for both). There were significantly more tibial radiolucencies in the cemented group (twenty of thirty knees versus two of twenty-seven knees; p < 0.001). There were nine complete radiolucencies in the cemented group and none in the cementless group (p = 0.01). Conclusions: Cementless fixation provides improved fixation at five years compared with cemented fixation in mobilebearing unicompartmental knee replacements, maintaining equivalent or superior clinical outcomes with a shorter operative time and no increase in complications. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Stratification analysis of an osteoarthritis genome screen-suggestive linkage to chromosomes 4, 6, and 16

Abstract: To the Editor: We have previously carried out a two-stage genomewide linkage screen for osteoarthritis (MIM 165720) susceptibility loci, using an affected-sibling-pair approach (Chapman et al. 1999). In stage 1 of this screen, we tested 272 microsatellite markers in 297 families, each of which contained at least one pair of siblings who had undergone hip-, knee-, or hip and knee–replacement surgery for primary osteoarthritis. Loci that demonstrated evidence for linkage at nominal P=.05 were then taken through to stage 2, in which they were tested against a further 184 families. Sixteen markers within nine genomic regions from stage 1 had evidence of linkage, at P=.05. When the data for stages 1 and 2 were combined, the P value decreased for 3 of the 16 loci (D2S202, D11S907, and D11S903) and was constant for a 4th (D11S901). We subsequently concentrated our analysis on the chromosome regions to which these markers map. To test these linkages further, we genotyped additional markers and obtained maximum multipoint LOD scores (MLSs) of 1.2 for chromosome 2 and 3.1 for chromosome 11. Because there is evidence, from epidemiological, twin, and segregation studies, that the genetic contribution to osteoarthritis differs between the sexes and between different joint groups (Lindberg 1986; Cooper et al. 1994; Kaprio et al. 1996; Chitnavis et al. 1997; Felson et al. 1998), we stratified our chromosomes 2 and 11 linkage data according to sex and site of osteoarthritis (hip or knee). This stratification indicated that the suggestion of linkage to chromosome 2 was principally accounted for by affected sibling pairs with hip osteoarthritis (MLS 2.2), whereas the suggestion of linkage to chromosome 11 was restricted to affected female pairs (MLS 2.8). Because this analysis highlighted substantial differences between the strata tested, we have now reanalyzed stage 1 of our genome screen, for the remaining 20 autosomes, to determine whether any regions harbor susceptibility loci that are obscured in the unstratified data set. We stratified our stage 1 data into the same six strata tested in our analysis of chromosomes 2 and 11: affected females only (132 families), affected males only (60 families), hips only (194 families), knees only (34 families), female hip (85 families), and male hip (44 families). (A more detailed breakdown of these families can be found in the study by Chapman et al. [1999].) We did not stratify for female knee or male knee, because the number of families was too small (16 and 4, respectively) to allow reliable inference of linkage. Multipoint linkage analysis was performed on the stratified data by means of the ASPEX program. Ten of the 20 autosomes have one or more multipoint peaks with uncorrected MLS⩾1.0 for one or more of the six strata tested (table 1). The highest MLS is 3.9, for chromosome 4q in the female-hip strata, followed by 2.9, for chromosome 6 in the hip-only strata, and 2.1, for chromosome 16 in the female-hip strata. When we adjust MLS values to correct for the seven models tested (one unstratified analysis and six stratified analyses), by deducting from the original values (Kidd and Ott 1984), chromosome 4 has an MLS value of 3.1, chromosome 6 has an MLS value of 2.1, and chromosome 16 has an MLS value of 1.3. The uncorrected multipoint plots of these three chromosomes are shown in figure 1. Figure 1 Multipoint analysis. A, Chromosome 4, female hip (n=85 families) and female only (n=132 families). B, Chromosome 6, hip only (n=194 families). C, Chromosome 16, female hip (n=85 families) and female only (n=132 families). Table 1 Stratified MLSs The suggestion of linkage on chromosome 4 is centered on 4q12–4q21.2 and is restricted to female pairs with hip disease. Roby et al. (1999) have recently reported linkage of chromosome 4q to severe early-onset hip osteoarthritis in a large pedigree of Dutch origin. This locus maps to the telomeric end of 4q (4q35), placing it >50 cM distal to the linkage that we have observed. It is therefore unlikely that the two linkages have detected the same locus. More than 50 cM of chromosome 6 has an uncorrected MLS⩾2.0 in the hip-only stratum, between markers D6S257 and D6S262. This region of chromosome 6 contains a strong candidate gene for osteoarthritis, COL9A1 (6q12–6q13). This gene maps within the 11-cM interval between D6S257 and D6S286 and encodes the α1 chain of type IX collagen. This collagen is a quantitatively minor cartilage collagen that decorates the type II collagen fibril and that interacts with extrafibrillar macromolecules (Ayad et al. 1994). Two transgenic mouse models have demonstrated that mutations in the equivalent mouse gene can result in an osteoarthritis phenotype. In the first model, a truncated form of the gene resulted in mice with a mild osteochondrodysplasia phenotype and secondary osteoarthritis (Nakata et al. 1993). In the second model, a knockout mouse had no congenital abnormality but developed a severe osteoarthritis that was comparable, in timing and pathology, to human primary osteoarthritis (Fassler et al. 1994). A more detailed analysis of this second model revealed that the synthesis of the α1 polypeptide chain was necessary for type IX collagen assembly (Hagg et al. 1997). Chromosome 16 does not contain any known genes that can be considered as strong candidates for osteoarthritis susceptibility. As more genes are mapped, candidate loci on this chromosome may become apparent. Overall, the stratification of our genome screen has revealed additional chromosomal regions that may harbor susceptibility loci for osteoarthritis. Stratification increases the level of genetic homogeneity and can therefore assist in the mapping of loci for complex traits. Our analysis highlights the potential utility of this approach for osteoarthritis.

A Meta-Analysis on the Use of Gabapentinoids for the Treatment of Acute Postoperative Pain Following Total Knee Arthroplasty

Abstract: Total knee arthroplasty is a painful procedure, with approximately half of patients reporting severe pain during the early postoperative period. Gabapentinoids are used as an adjunct for the management of acute pain in approximately half of enhanced recovery programs. We performed a meta-analysis to assess the effectiveness and safety of gabapentinoids for the treatment of acute postoperative pain following total knee arthroplasty. Randomized controlled trials of patients undergoing elective primary total knee arthroplasty that compared the use of the gabapentinoid class of drugs (gabapentin [Neurontin; Pfizer]) or pregabalin [Lyrica; Pfizer]) with that of placebo were retrieved, with 12 studies meeting inclusion criteria. The primary outcome was pain intensity with activity at 48 hours following the surgical procedure. The secondary outcomes included pain intensity at other time points, opioid consumption, knee function, incidence of chronic pain, and adverse events. No difference in pain score at 12, 24, 48, or 72 hours following the surgical procedure was seen between gabapentin and placebo. Although pregabalin was associated with reduced pain scores at 24 and 48 hours, this corresponded to a reduction of 0.5 point (95% confidence interval, 0 to 1.0 point) at 24 hours and 0.3 point (95% confidence interval, 0 to 0.6 point) at 48 hours on an 11-point numeric rating scale, which was assessed as not clinically important. Overall, no clinically relevant reduction in pain scores was associated with the use of gabapentinoids. Likewise, gabapentinoids were associated with a small, but not clinically important, reduction in cumulative opioid consumption at 48 hours (mean difference, -23.2 mg [95% confidence interval, -40.9 to -5.4 mg]). There was no difference in knee flexion at 48 hours (p = 0.63) or in the incidence of chronic pain at 3 months (p = 0.31) or 6 months (p = 0.54) associated with the use of gabapentinoids. Although gabapentinoids were associated with a significant reduction in the incidence of nausea (risk ratio, 0.7 [95% confidence interval, 0.6 to 0.9]; p < 0.001), pregabalin was also associated with a significant, clinically relevant increase in the risk of sedation (risk ratio, 1.4 [95% confidence interval, 1.1 to 1.9]; p = 0.02). On the basis of this meta-analysis, we found no evidence to support the routine use of gabapentinoids in the management of acute pain following total knee arthroplasty. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Disc herniations in astronauts: What causes them, and what does it tell us about herniation on earth?

Abstract: Purpose Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities.