Mortality and re-revision following single-stage and two-stage revision surgery for the management of infected primary hip arthroplasty in England and Wales.

We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty. Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies. In total, 535 primary hip arthroplasties were revised with single-stage procedure (1,525 person-years) and 1,605 with two-stage procedure (5,885 person-years). All-cause re-revision was higher following single-stage revision, especially in the first three months (HR at 3 months = 1.98 (95% confidence interval (CI) 1.14 to 3.43), p = 0.009). The risks were comparable thereafter. Re-revision for PJI was higher in the first three postoperative months for single-stage revision and waned with time (HR at 3 months = 1.81 (95% CI 1.22 to 2.68), p = 0.003; HR at 6 months = 1.25 (95% CI 0.71 to 2.21), p = 0.441; HR at 12 months = 0.94 (95% CI 0.54 to 1.63), p = 0.819). Patients initially managed with a single-stage revision received fewer revision operations (mean 1.3 (SD 0.7) vs 2.2 (SD 0.6), p < 0.001). Mortality rates were comparable between these two procedures (29/10,000 person-years vs 33/10,000). The risk of unplanned re-revision was lower following two-stage revision, but only in the early postoperative period. The lower overall number of revision procedures associated with a single-stage revision strategy and the equivalent mortality rates to two-stage revision are reassuring. With appropriate counselling, single-stage revision is a viable option for the treatment of hip PJI.

Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial.

OBJECTIVES: To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures. DESIGN: Pragmatic, parallel group, open label, randomised controlled trial. SETTING: High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018. PARTICIPANTS: 140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision). INTERVENTIONS: A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure. MAIN OUTCOME MEASURES: The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups. RESULTS: The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval -8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of £11 167 (95% confidence interval £638 to £21 696) at a £20 000 per quality adjusted life years threshold (£1.0; $1.1; €1.4). CONCLUSIONS: At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN10956306.

Mortality and re-revision following single-stage and two-stage revision surgery for the management of infected primary knee arthroplasty in England and Wales : evidence from the National Joint Registry.

AIMS: We compared the risks of re-revision and mortality between two-stage revision surgery and single-stage revision surgery among patients with infected primary knee arthroplasty. METHODS: Patients with a periprosthetic joint infection (PJI) of their primary knee arthroplasty, initially revised with a single-stage or a two-stage procedure in England and Wales between 2003 and 2014, were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HR) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies. RESULTS: A total of 489 primary knee arthroplasties were revised with single-stage procedure (1,390 person-years) and 2,377 with two-stage procedure (8,349 person-years). The adjusted incidence rates of all-cause re-revision and for infection were comparable between these strategies (HR overall five years, 1.15 (95% confidence interval (CI) 0.87 to 1.52), p = 0.308; HR overall five years, 0.99 (95% CI 0.70 to 1.39), p = 0.949, respectively). Patients initially managed with single-stage revision received fewer revision procedures overall than after two-stage revision (1.2 vs 2.2, p < 0.001). Mortality was lower for single-stage revision between six and 18 months postoperative (HR at six months, 0.51 (95% CI 0.25 to 1.00), p = 0.049 HR at 18 months, 0.33 (95% CI 0.12 to 0.99), p = 0.048) and comparable at other timepoints. CONCLUSION: The risk of re-revision was similar between single- and two-stage revision for infected primary knee arthroplasty. Single-stage group required fewer revisions overall, with lower or comparable mortality at specific postoperative periods. The single-stage revision is a safe and effective strategy to treat infected knee arthroplasties. There is potential for increased use to reduce the burden of knee PJI for patients, and for the healthcare system.Cite this article: Bone Joint Res 2022;11(10):690-699.

The STAR care pathway for patients with pain at 3 months after total knee replacement: a multicentre, pragmatic, randomised, controlled trial.

BACKGROUND: Approximately 20% of people experience chronic pain after total knee replacement, but effective treatments are not available. We aimed to evaluate the clinical effectiveness and cost-effectiveness of a new care pathway for chronic pain after total knee replacement. METHODS: We did an unmasked, parallel group, pragmatic, superiority, randomised, controlled trial at eight UK National Health Service (NHS) hospitals. People with chronic pain at 3 months after total knee replacement surgery were randomly assigned (2:1) to the Support and Treatment After Replacement (STAR) care pathway plus usual care, or to usual care alone. The STAR intervention aimed to identify underlying causes of chronic pain and enable onward referrals for targeted treatment through a 3-month post-surgery assessment with an extended scope practitioner and telephone follow-up over 12 months. Co-primary outcomes were self-reported pain severity and pain interference in the replaced knee, assessed with the Brief Pain Inventory (BPI) pain severity and interference scales at 12 months (scored 0-10, best to worst) and analysed on an as-randomised basis. Resource use, collected from electronic hospital records and participants, was valued with UK reference costs. Quality-adjusted life-years (QALYs) were calculated from EQ-5D-5L responses. This trial is registered with ISRCTN, ISRCTN92545361. FINDINGS: Between Sept 6, 2016, and May 31, 2019, 363 participants were randomly assigned to receive the intervention plus usual care (n=242) or to receive usual care alone (n=121). Participants had a median age of 67 years (IQR 61 to 73), 217 (60%) of 363 were female, and 335 (92%) were White. 313 (86%) patients provided follow-up data at 12 months after randomisation (213 assigned to the intervention plus usual care and 100 assigned to usual care alone). At 12 months, the mean between-group difference in the BPI severity score was -0·65 (95% CI -1·17 to -0·13; p=0·014) and the mean between-group difference in the BPI interference score was -0·68 (-1·29 to -0·08; p=0·026), both favouring the intervention. From an NHS and personal social services perspective, the intervention was cost-effective (greater improvement with lower cost), with an incremental net monetary benefit of £1256 (95% CI 164 to 2348) at £20 000 per QALY threshold. One adverse reaction of participant distress was reported in the intervention group. INTERPRETATION: STAR is a clinically effective and cost-effective intervention to improve pain outcomes over 1 year for people with chronic pain at 3 months after total knee replacement surgery. FUNDING: National Institute for Health Research.

Common elective orthopaedic procedures and their clinical effectiveness: umbrella review of level 1 evidence.

OBJECTIVE: To determine the clinical effectiveness of common elective orthopaedic procedures compared with no treatment, placebo, or non-operative care and assess the impact on clinical guidelines. DESIGN: Umbrella review of meta-analyses of randomised controlled trials or other study designs in the absence of meta-analyses of randomised controlled trials. DATA SOURCES: Ten of the most common elective orthopaedic procedures-arthroscopic anterior cruciate ligament reconstruction, arthroscopic meniscal repair of the knee, arthroscopic partial meniscectomy of the knee, arthroscopic rotator cuff repair, arthroscopic subacromial decompression, carpal tunnel decompression, lumbar spine decompression, lumbar spine fusion, total hip replacement, and total knee replacement-were studied. Medline, Embase, Cochrane Library, and bibliographies were searched until September 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Meta-analyses of randomised controlled trials (or in the absence of meta-analysis other study designs) that compared the clinical effectiveness of any of the 10 orthopaedic procedures with no treatment, placebo, or non-operative care. DATA EXTRACTION AND SYNTHESIS: Summary data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews instrument. The Jadad decision algorithm was used to ascertain which meta-analysis represented the best evidence. The National Institute for Health and Care Excellence Evidence search was used to check whether recommendations for each procedure reflected the body of evidence. MAIN OUTCOME MEASURES: Quality and quantity of evidence behind common elective orthopaedic interventions and comparisons with the strength of recommendations in relevant national clinical guidelines. RESULTS: Randomised controlled trial evidence supports the superiority of carpal tunnel decompression and total knee replacement over non-operative care. No randomised controlled trials specifically compared total hip replacement or meniscal repair with non-operative care. Trial evidence for the other six procedures showed no benefit over non-operative care. CONCLUSIONS: Although they may be effective overall or in certain subgroups, no strong, high quality evidence base shows that many commonly performed elective orthopaedic procedures are more effective than non-operative alternatives. Despite the lack of strong evidence, some of these procedures are still recommended by national guidelines in certain situations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018115917.

Choice between implants in knee replacement: protocol for a Bayesian network meta-analysis, analysis of joint registries and economic decision model to determine the effectiveness and cost-effectiveness of knee implants for NHS patients-The KNee Implant Prostheses Study (KNIPS).

INTRODUCTION: Knee replacements are highly successful for many people, but if a knee replacement fails, revision surgery is generally required. Surgeons and patients may choose from a range of implant components and combinations that make up knee replacement constructs, all with potential implications for how long a knee replacement will last. To inform surgeon and patient decisions, a comprehensive synthesis of data from randomised controlled trials is needed to evaluate the effects of different knee replacement implants on overall construct survival. Due to limited follow-up in trials, joint registry analyses are also needed to assess the long-term survival of constructs. Finally, economic modelling can identify cost-effective knee replacement constructs for different patient groups. METHODS AND ANALYSIS: In this protocol, we describe systematic reviews and network meta-analyses to synthesise evidence on the effectiveness of knee replacement constructs used in total and unicompartmental knee replacement and analyses of two national joint registries to assess long-term outcomes. Knee replacement constructs are defined by bearing materials and mobility, constraint, fixation and patella resurfacing. For men and women in different age groups, we will compare the lifetime cost-effectiveness of knee replacement constructs. ETHICS AND DISSEMINATION: Systematic reviews are secondary analyses of published data with no ethical approval required. We will design a common joint registry analysis plan and provide registry representatives with information for submission to research or ethics committees. The project has been assessed by the National Health Service (NHS) REC committee and does not require ethical review.Study findings will be disseminated to clinicians, researchers and administrators through open access articles, presentations and websites. Specific UK-based groups will be informed of results including National Institute for Health Research and National Institute for Health and Care Excellence, as well as international orthopaedic associations and charities. Effective dissemination to patients will be guided by our patient-public involvement group and include written lay summaries and infographics. PROSPERO REGISTRATION NUMBER: CRD42019134059 and CRD42019138015.

Patients Receiving a Primary Unicompartmental Knee Replacement Have a Higher Risk of Revision but a Lower Risk of Mortality Than Predicted Had They Received a Total Knee Replacement: Data From the National Joint Registry for England, Wales, Northern Ireland, and the Isle of Man.

BACKGROUND: To determine unicompartmental (UKR) and total knee replacement (TKR) revision rates, compare UKR revision rates with what they would have been had they received TKR instead, and assess subsequent re-revision and 90-day mortality rates. METHODS: Using National Joint Registry data, we estimated UKR and TKR revision and mortality rates. Flexible parametric survival modeling (FPM) was used to model failure in TKR and make estimates for UKR. Kaplan-Meier estimates were used to compare cumulative re-revision for revised UKRs and TKRs. RESULTS: Ten-year UKR revision rates were 2.5 times higher than expected from TKR, equivalent to 70 excess revisions/1000 cases within 10 years (5861 excess revisions in this cohort). Revision rates were 2.5 times higher for the highest quartile volume UKR surgeons compared to the same quartile for TKR and 3.9 times higher for the lowest quartiles respectively. Re-revision rates of revised TKRs (10 years = 17.5%, 95% confidence interval [CI] 16.4-18.7) were similar to revised UKRs (15.2%, 95% CI 13.4-17.1) and higher than revision rates following primary TKR (3.3%, 95% CI 3.1-3.5). Ninety-day mortality rates were lower after UKR compared with TKR (0.08% vs 0.33%) and lower than predicted had UKR patients received a TKR (0.18%), equivalent to 1 fewer death per 1000 cases. CONCLUSION: UKR revision rates were substantially higher than TKR even when demographics and caseload differences were accounted for; however, fewer deaths occur after UKR. This should be considered when forming treatment guidelines and commissioning services. Re-revision rates were similar between revised UKRs and TKRs, but considerably higher than for primary TKR, therefore UKR cannot be considered an intermediate procedure.

Outcomes following primary total hip arthroplasty with pre-existing spinal fusion surgery.

AIMS: There is inconsistent evidence on whether prior spinal fusion surgery adversely impacts outcomes following total hip arthroplasty (THA). We conducted a systematic review and meta-analysis to assess the association between pre-existing spinal fusion surgery and the rate of complications following primary THA. METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Library up to October 2019 for randomized controlled trials (RCTs) and observational studies comparing outcomes of dislocation, revision, or reasons for revision in patients following primary THA with or without pre-existing spinal fusion surgery. Furthermore, we compared short (two or less levels) or long (three or more levels) spinal fusions to no fusion. Summary measures of association were relative risks (RRs) (with 95% confidence intervals (CIs)). RESULTS: We identified ten articles corresponding to nine unique observational studies comprising of 1,992,366 primary THAs. No RCTs were identified. There were 32,945 cases of spinal fusion and 1,752,362 non-cases. Comparing prior spinal fusion versus no spinal fusion in primary THA, RRs (95% CI) for dislocation was 2.23 (1.81 to 2.74; seven studies), revision 2.14 (1.63 to 2.83; five studies), periprosthetic joint infection 1.71 (1.53 to 1.92; four studies), periprosthetic fracture 1.52 (1.28 to 1.81; three studies), aseptic loosening 1.76 (1.54 to 2.01; three studies), and any complications 2.82 (1.37 to 5.80; three studies) were identified. Both short and long spinal fusions, when compared with no fusion, were associated dislocation, revision, or reasons for revision. CONCLUSIONS: Patients with prior spinal fusion are at risk of adverse events following primary THA. Measures that reduce the risk of these complications should be considered in this high-risk population when undergoing primary THA. These patients should also be counselled appropriately around their risks of undergoing THA. Cite this article: Bone Joint J 2020;102-B(6):664-670.

Incidence, temporal trends and potential risk factors for prosthetic joint infection after primary total shoulder and elbow replacement: Systematic review and meta-analysis.

OBJECTIVES: We conducted a systematic meta-analysis to evaluate the incidence, temporal trends and potential risk factors for prosthetic joint infection (PJI) following primary total shoulder replacement (TSR) and elbow replacement (TER). METHODS: Longitudinal studies reporting infection outcomes following primary TSR or TER were sought from MEDLINE, Embase and Cochrane Library up to June 2019. Incidence rates and relative risks (with 95% CIs) were calculated. RESULTS: The search identified 105 eligible articles (108 non-overlapping studies). There were 631,854 TSRs (1,751 PJIs) and 17,485 TERs (525 PJIs). The pooled PJI incidence following TSR was 0.61% (0.34-0.93) over a follow-up period of 1.1 years. The corresponding incidence following TER was 2.53% (1.99-3.12) over a follow-up period of 3.3 years. Shoulder and elbow PJI incidence declined from the 1990s to 2010 and beyond. Males, younger age (<75 years), previous shoulder surgery, reverse TSR, rotator cuff arthropathy and inpatient TSR increased shoulder PJI risk. For TER, high body mass index, psychiatric illness, and previous elbow surgery increased PJI risk. CONCLUSIONS: Shoulder and elbow PJI may be on a temporal decline. Caution should be taken for patients at high PJI risk following primary TSR such as younger males and patients with a previous shoulder surgery.

One- and two-stage surgical revision of infected elbow prostheses following total joint replacement: a systematic review.

BACKGROUND: Prosthetic joint infection (PJI) is a challenging complication of total elbow replacement (TER). Potential surgical treatments include one- or two-stage revision; however, the best treatment for elbow PJI is not clearly defined. We conducted a systematic review in accordance with PRISMA guidelines to compare the clinical effectiveness of one- and two-stage revision surgery for elbow PJI using re-infection (recurrent and new infections) rates; mortality; clinical measures of function, pain, and satisfaction; and non-infection related adverse events. METHODS: MEDLINE, Embase, Web of Science, and The Cochrane Library were searched up to June 2019 to identify observational cohort studies and randomised controlled trials (RCTs) that had recruited patients with elbow PJI following TER and treated with one- or two-stage revision. Of 96 retrieved articles, 2 one-stage and 6 two-stage revision studies were eligible. No RCT was identified. Arcsine transformation was used in estimating rates with 95% confidence intervals (CIs). RESULTS: Staphylococcus aureus was the most common causative organism for PJI of the elbow (24 of 71 elbow PJIs). The re-infection rate (95% CI) for one-stage (7 elbows) ranged from 0.0% (0.0-79.3) to 16.7% (3.0-56.4) and that for two-stage revision (87 elbows) from 0.0% (0.0-49.0) to 20.0% (3.6-62.4). Non-infection related adverse event rate for one-stage (based on a single study) was 16.7% (3.0-56.4) and that for two-stage ranged from 11.8% (4.7-26.6) to 20.0% (3.6-62.4). There were no mortality events recorded following one- or two-stage revision surgery and postoperative clinical measures of function, pain, and satisfaction could not be effectively compared because of limited data. CONCLUSIONS: No strong conclusions can be drawn because of limited data. The one-stage revision may be potentially at least as clinically effective as two-stage revision, but further data is needed. There are clear gaps in the existing literature and studies are urgently warranted to assess the clinical effectiveness of one- and two-stage revision strategies for PJI following TER. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2018: CRD42018118002 .

Risk factors associated with revision for prosthetic joint infection following knee replacement: an observational cohort study from England and Wales.

BACKGROUND: Prosthetic joint infection is a devastating complication of knee replacement. The risk of developing a prosthetic joint infection is affected by patient, surgical, and health-care system factors. Existing evidence is limited by heterogeneity in populations studied, short follow-up, inadequate power, and does not differentiate early prosthetic joint infection, most likely related to the intervention, from late infection, more likely to occur due to haematogenous bacterial spread. We aimed to assess the overall and time-specific associations of these factors with the risk of revision due to prosthetic joint infection following primary knee replacement. METHODS: In this cohort study, we analysed primary knee replacements done between 2003 and 2013 in England and Wales and the procedures subsequently revised for prosthetic joint infection between 2003 and 2014. Data were obtained from the National Joint Registry linked to the Hospital Episode Statistics data in England and the Patient Episode Database for Wales. Each primary replacement was followed for a minimum of 12 months until the end of the observation period (Dec 31, 2014) or until the date of revision for prosthetic joint infection, revision for another indication, or death (whichever occurred first). We analysed the data using Poisson and piecewise exponential multilevel models to assess the associations between patient, surgical, and health-care system factors and risk of revision for prosthetic joint infection. FINDINGS: Of 679 010 primary knee replacements done between 2003 and 2013 in England and Wales, 3659 were subsequently revised for an indication of prosthetic joint infection between 2003 and 2014, after a median follow-up of 4·6 years (IQR 2·6-6·9). Male sex (rate ratio [RR] for male vs female patients 1·8 [95% CI 1·7-2·0]), younger age (RR for age ≥80 years vs <60 years 0·5 [0·4-0·6]), higher American Society of Anaesthesiologists [ASA] grade (RR for ASA grade 3-5 vs 1, 1·8 [1·6-2·1]), elevated body-mass index (BMI; RR for BMI ≥30 kg/m2vs <25 kg/m2 1·5 [1·3-1·6]), chronic pulmonary disease (RR 1·2 [1·1-1·3]), diabetes (RR 1·4 [1·2-1·5]), liver disease (RR 2·2 [1·6-2·9]), connective tissue and rheumatic diseases (RR 1·5 [1·3-1·7]), peripheral vascular disease (RR 1·4 [1·1-1·7]), surgery for trauma (RR 1·9 [1·4-2·6]), previous septic arthritis (RR 4·9 [2·7-7·6]) or inflammatory arthropathy (RR 1·4 [1·2-1·7]), operation under general anaesthesia (RR 1·1 [1·0-1·2]), requirement for tibial bone graft (RR 2·0 [1·3-2·7]), use of posterior stabilised fixed bearing prostheses (RR for posterior stabilised fixed bearing prostheses vs unconstrained fixed bearing prostheses 1·4 [1·3-1·5]) or constrained condylar prostheses (3·5 [2·5-4·7]) were associated with a higher risk of revision for prosthetic joint infection. However, uncemented total, patellofemoral, or unicondylar knee replacement (RR for uncemented vs cemented total knee replacement 0·7 [95% CI 0·6-0·8], RR for patellofemoral vs cemented total knee replacement 0·3 [0·2-0·5], and RR for unicondylar vs cemented total knee replacement 0·5 [0·5-0·6]) were associated with lower risk of revision for prosthetic joint infection. Most of these factors had time-specific effects, depending on the time period post-surgery. INTERPRETATION: We have identified several risk factors for revision for prosthetic joint infection following knee replacement. Some of these factors are modifiable, and the use of targeted interventions or strategies could lead to a reduced risk of revision for prosthetic joint infection. Non-modifiable factors and the time-specific nature of the effects we have observed will allow clinicians to appropriately counsel patients preoperatively and tailor follow-up regimens. FUNDING: National Institute for Health Research.

One- and two-stage surgical revision of infected shoulder prostheses following arthroplasty surgery: A systematic review and meta-analysis.

Periprosthetic joint infection (PJI) is a catastrophic complication of shoulder arthroplasty. Commonly used surgical treatments include one- or two-stage revision, but their effectiveness in controlling infection is uncertain. We aimed to compare re-infection (recurrent and new infections) rates; clinical measures of function and pain; and noninfection complication rates of one- and two-stage revision surgery for shoulder PJI using a systematic review and meta-analysis. We searched MEDLINE, Embase, Web of Science, and The Cochrane Library to February 2018. Longitudinal studies conducted in patients with shoulder PJI treated exclusively by one- or two-stage revision were eligible. No clinical trials were identified. Re-infection rates were meta-analysed using random-effect models after arcsine transformation. The re-infection rate (95% CI) in pooled analysis of eight one-stage studies (147 participants) was 5.3% (1.4-10.6). The corresponding rate for 27 two-stage studies (351 participants) was 11.5% (6.0-18.1). Postoperative clinical measures of function and pain were not significantly different between the two revision strategies. The pooled noninfection complication rate (95% CI) for one-stage and two-stage revision was 12.1% (6.1-19.5) and 18.9% (8.4-31.9) respectively. New evidence suggests one-stage revision is at least equally as effective as the two-stage in controlling infection, maintaining joint function, and improving complications in shoulder PJI.

Risk factors for dislocation after primary total hip replacement: meta-analysis of 125 studies involving approximately five million hip replacements.

BACKGROUND: Dislocation following total hip replacement (THR) is associated with repeated hospitalisations and substantial costs to the health system. Factors influencing dislocation following primary THR are not well understood. We aimed to assess the associations of patient-, surgery-, implant- and hospital-related factors with dislocation risk following primary THR. METHODS: We did a systematic review and meta-analysis of all longitudinal studies reporting these associations. We searched MEDLINE, Embase, Web of Science, and Cochrane Library to March 8, 2019. Summary measures of association were calculated using relative risks (RRs) (with 95% confidence intervals, CIs). The review is registered on PROSPERO, number CRD42019121378. FINDINGS: We identified 149 articles based on 125 unique studies with data on 4 633 935 primary THRs and 35 264 dislocations. The incidence rates of dislocation ranged from 0·12% to 16·13%, with an overall pooled rate of 2·10% (1·83-2·38) over a weighted mean follow-up duration of 6 years. Using median year of data collection, there was a significant decline in dislocation rates from 1971 to 2015. Comparing males vs females, age ≥70 vs <70 years, and high vs low income, RRs (95% CIs) for dislocation were 0·97 (0·88-1·08), 1·27 (1·02-1·57), and 0·79 (0·74-0·85) respectively. White ethnicity, drug use disorder, and social deprivation were each associated with an increased dislocation risk. Comparing body mass index (BMI) ≥30 vs. <30 kg/m2, the RR (95% CI) for dislocation was 1·38 (1·03-1·85). Medical and surgical history-related factors associated with dislocation risk included neurological disorder, psychiatric disease, comorbidity indices, previous surgery including spinal fusion, and surgical indications including avascular necrosis, rheumatoid arthritis, inflammatory arthritis, and osteonecrosis. Surgical factors such as the anterolateral, direct anterior, or lateral approach and posterior with short external rotator and capsule repair were each associated with reduced dislocation risk. At the implant level, larger femoral head diameters, elevated acetabular liners, dual mobility cups, cemented fixations and standard femoral neck lengths reduced the risk of dislocation. Hospital-related factors such as experienced surgeons and high surgeon procedure volume each reduced the risk of dislocation. INTERPRETATION: Dislocation following primary THR is on a temporal decline. Surgical approaches that reduce dislocation risk can be used by clinicians when performing primary THR. Alternative bearings such as dual mobility can be used in individuals at high risk of dislocation. Modifiable risk factors such as high BMI and comorbidities may be amenable to optimisation prior to surgery. FUNDING: National Institute for Health Research.

Exome-chip meta-analysis identifies association between variation in ANKRD26 and platelet aggregation.

Previous genome-wide association studies (GWAS) have identified several variants associated with platelet function phenotypes; however, the proportion of variance explained by the identified variants is mostly small. Rare coding variants, particularly those with high potential for impact on protein structure/function, may have substantial impact on phenotype but are difficult to detect by GWAS. The main purpose of this study was to identify low frequency or rare variants associated with platelet function using genotype data from the Illumina HumanExome Bead Chip. Three family-based cohorts of European ancestry, including ~4,000 total subjects, comprised the discovery cohort and two independent cohorts, one of European and one of African American ancestry, were used for replication. Optical aggregometry in platelet-rich plasma was performed in all the discovery cohorts in response to adenosine diphosphate (ADP), epinephrine, and collagen. Meta-analyses were performed using both gene-based and single nucleotide variant association methods. The gene-based meta-analysis identified a significant association (P = 7.13 × 10-7) between rare genetic variants in ANKRD26 and ADP-induced platelet aggregation. One of the ANKRD26 SNVs - rs191015656, encoding a threonine to isoleucine substitution predicted to alter protein structure/function, was replicated in Europeans. Aggregation increases of ~20-50% were observed in heterozygotes in all cohorts. Novel genetic signals in ABCG1 and HCP5 were also associated with platelet aggregation to ADP in meta-analyses, although only results for HCP5 could be replicated. The SNV in HCP5 intersects epigenetic signatures in CD41+ megakaryocytes suggesting a new functional role in platelet biology for HCP5. This is the first study to use gene-based association methods from SNV array genotypes to identify rare variants related to platelet function. The molecular mechanisms and pathophysiological relevance for the identified genetic associations requires further study.

Risk factors for dislocation after primary total hip replacement: a systematic review and meta-analysis of 125 studies involving approximately five million hip replacements.

BACKGROUND: Dislocation following total hip replacement is associated with repeated admissions to hospital and substantial costs to the health system. Factors influencing dislocation following primary total hip replacement are not well understood. We aimed to assess the association of various factors with dislocation risk following primary total hip replacement. METHODS: We did a systematic review and meta-analysis of longitudinal studies reporting associations of patient-related, surgery-related, implant-related, and hospital-related factors with dislocation risk after primary total hip replacement. We searched MEDLINE, Embase, Web of Science, and the Cochrane Library for all relevant articles published up to March 8, 2019. Summary measures of association were calculated with relative risks (RRs) and 95% CIs. This study is registered on PROSPERO, number CRD42019121378. FINDINGS: We identified 149 articles based on 125 unique studies with data on 4 633 935 primary total hip replacements and 35 264 dislocations. The incidence of dislocation ranged from 0·12% to 16·13%, with an overall pooled incidence of 2·10% (95% CI 1·83-2·38) over a weighted mean follow-up duration of 6 years. Based on the median year of data collection, a significant decline in dislocation rates was observed from 1971 to 2015. The risk of dislocation did not differ significantly between male versus female patients (RR 0·97; 95% CI 0·88-1·08), was higher in those aged 70 years and older than in those younger than 70 years (1·27; 1·02-1·57), and was lower in those from high versus low income groups (0·79; 0·74-0·85). White ethnicity (only when compared with Asian ethnicity), drug use disorder, and social deprivation were significantly associated with increased dislocation risk. The risk of dislocation was higher in patients with body-mass index (BMI) of 30 kg/m2 or higher than in those with BMI lower than 30 kg/m2 (RR 1·38; 95% CI 1·03-1·85). Medical factors and those related to surgical history that were significantly associated with increased dislocation risk included neurological disorder, psychiatric disease, comorbidity indices, previous surgery including spinal fusion, and surgical indications including avascular necrosis, rheumatoid arthritis, inflammatory arthritis, and osteonecrosis. Surgical factors such as the anterolateral, direct anterior, or lateral approach, and posterior approach with short external rotator and capsule repair were significantly associated with reduced dislocation risk. At the implant level, larger femoral head diameters, elevated acetabular liners, dual mobility cups, cemented fixations, and standard femoral neck lengths significantly reduced the risk of dislocation. Hospital-related factors such as experienced surgeons and high surgeon procedure volume significantly reduced the risk of dislocation. INTERPRETATION: Dislocation following primary total hip replacement has declined over time. Surgical approaches that reduce dislocation risk can be used by clinicians during primary total hip replacement, and alternative bearings such as dual mobility can be used in individuals at high risk of dislocation. Modifiable risk factors such as high BMI and comorbidities might also be amenable to optimisation before surgery. FUNDING: National Institute for Health Research.

Systematic review of risk prediction scores for venous thromboembolism following joint replacement.

BACKGROUND: Venous thromboembolism (VTE) is an important cause of morbidity and a preventable cause of deaths following lower limb joint replacement. Risk prediction scores that help to predict individual VTE risk following lower limb joint replacement may inform the development of preventive strategies and guide treatment decisions. We aimed to systematically review the evidence on the development and/or validation of risk prediction scores for VTE following lower limb joint replacement. METHODS: Population-based studies that have developed and/or validated a risk prediction score for VTE following hip or knee replacement and randomised controlled trials (RCTs) that have evaluated the clinical impact of a score were searched for in MEDLINE, Embase, Web of Science, and The Cochrane Library to April 2018. RESULTS: Five observational cohort studies describing five risk scores were included. No RCTs were identified. The number of component variables in a single risk score ranged from 5 to 26. Three risk scores comprised 5-8 component variables. None of the studies reported calibration or discrimination statistics. Two risk scores were externally validated in single-institution cohorts and were reported to perform well. One study evaluated the general surgery Caprini risk score in primary hip and knee replacement patients and did not find it useful for VTE risk stratification. CONCLUSIONS: Few VTE risk prediction scores in lower limb joint replacement exist and these have methodological issues, have been inadequately reported, not been sufficiently validated, and their impact on patient outcomes and decision making is unknown. Research is urgently warranted in the field. Systematic review registration: PROSPERO 2018: CRD42018088712.

Risk factors associated with revision for prosthetic joint infection after hip replacement: a prospective observational cohort study.

BACKGROUND: The risk of prosthetic joint infection (PJI) is influenced by patient, surgical, and health-care factors. Existing evidence is based on short-term follow-up. It does not differentiate between factors associated with early onset caused by the primary intervention from those associated with later onset more likely to result from haematogenous spread. We aimed to assess the overall and time-specific associations of these factors with the risk of revision due to PJI after primary total hip replacement. METHODS: We did a prospective observational cohort study analysing 623 253 primary hip procedures performed between April 1, 2003, and Dec 31, 2013, in England and Wales and recorded the number of procedures revised because of PJI. We investigated the associations between risk factors and risk of revision for PJI across the overall follow-up period using Poisson multilevel models. We reinvestigated the associations by post-operative time periods (0-3 months, 3-6 months, 6-12 months, 12-24 months, >24 months) using piece-wise exponential multilevel models with period-specific effects. Data were obtained from the National Joint Registry linked to the Hospital Episode Statistics data. FINDINGS: 2705 primary procedures were subsequently revised for an indication of PJI between 2003 and 2014, after a median (IQR) follow up of 4·6 years (2·6-7·0). Among the factors associated with an increased revision due to PJI there were male sex (1462 [1·2‰] of 1 237 170 male-years vs 1243 [0·7‰] of 1 849 691 female-years; rate ratio [RR] 1·7 [95% CI 1·6-1·8]), younger age (739 [1·1‰] of 688 000 person-years <60 years vs 242 [0·6‰] of 387 049 person-years ≥80 years; 0·7 [0·6-0·8]), elevated body-mass index (BMI; 941 [1·8‰] 517 278 person-years with a BMI ≥30 kg/m2vs 272 [0·9‰] of 297 686 person-years with a BMI <25 kg/m2; 1·9 [1·7-2·2]), diabetes (245 [1·4‰] 178 381 person-years with diabetes vs 2120 [1·0‰] of 2 209 507 person-years without diabetes; 1·4 [1·2-1·5]), dementia (5 [10·1‰] of 497 person-years with dementia at 3 months vs 311 [2·6‰] of 120 850 person-years without dementia; 3·8 [1·2-7·8]), previous septic arthritis (22 [7·2‰] of 3055 person-years with previous infection vs 2683 [0·9‰] of 3 083 806 person-years without previous infection; 6·7 [4·2-9·8]), fractured neck of femur (66 [1·5‰] of 43 378 person-years operated for a fractured neck of femur vs 2639 [0·9‰] of 3 043 483 person-years without a fractured neck of femur; 1·8 [1·4-2·3]); and use of the lateral surgical approach (1334 [1·0‰] of 1 399 287 person-years for lateral vs 1242 [0·8 ‰] of 1 565 913 person-years for posterior; 1·3 [1·2-1·4]). Use of ceramic rather than metal bearings was associated with a decreased risk of revision for PJI (94 [0·4‰] of 239 512 person-years with ceramic-on-ceramic bearings vs 602 [0·5‰] of 1 114 239 peron-years with metal-on-polyethylene bearings at ≥24 months; RR 0·6 [0·4-0·7]; and 82 [0·4‰] of 190 884 person-years with ceramic-on-polyethyene bearings vs metal-on-polyethylene bearings at ≥24 months; 0·7 [0·5-0·9]). Most of these factors had time-specific effects. The risk of revision for PJI was marginally or not influenced by the grade of the operating surgeon, the absence of a consultant surgeon during surgey, and the volume of procedures performed by hospital or surgeon. INTERPRETATION: Several modifiable and non-modifiable factors are associated with the risk of revision for PJI after primary hip replacement. Identification of modifiable factors, use of targeted interventions, and beneficial modulation of some of these factors could be effective in reducing the incidence of PJI. It is important for clinicians to consider non-modifiable factors and factors that exhibit time-specific effects on the risk of PJI to counsel patients appropriately preoperatively. FUNDING: National Institute for Health Research.

Mortality After Total Knee Arthroplasty: A Systematic Review of Incidence, Temporal Trends, and Risk Factors.

BACKGROUND: The capacity for total knee arthroplasty to improve pain, quality of life, and functional outcomes is widely recognized. Postoperative mortality is rare but of paramount importance, and needs to be accurately quantified and conveyed to patients in order to support decision-making prior to surgery. The purpose of this study was to determine a contemporary estimate of the risk of mortality following total knee arthroplasty, including the identification of temporal trends, common causes, and modifiable and nonmodifiable risk factors. METHODS: We performed a systematic review with searches of MEDLINE, AMED, CAB Abstracts, and Embase. Studies in any language published from 2006 to 2016 reporting 30 or 90-day mortality following total knee arthroplasty were included, supplemented by contact with authors. Meta-analysis and meta-regression were performed for quantitative data. RESULTS: Thirty-seven studies with mortality data from 15 different countries following over 1.75 million total knee arthroplasties formed the basis of this review. The pooled Poisson-normal random-effects meta-analysis estimates of 30 and 90-day mortality were 0.20% (95% confidence interval [CI], 0.17% to 0.24%) and 0.39% (95% CI, 0.32% to 0.49%). Both estimates have fallen over the 10-year study period (p < 0.001). Meta-regression using the median year of surgery as a moderator showed that 30 and 90-day mortality following total knee arthroplasty fell to 0.10% (95% CI, 0.07% to 0.14%) and 0.19% (95% CI, 0.15% to 0.23%), respectively, in 2015. The leading cause of death was cardiovascular disease. CONCLUSIONS: There is an ongoing worldwide temporal decline in mortality following total knee arthroplasty. Improved patient selection and perioperative care and a healthy-population effect may account for this observation. Efforts to further reduce mortality should be targeted primarily at reducing cardiovascular events following total knee arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies.

One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6-20.7) and 32.3 (95% CI 27.3-38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58-5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip.

Post-operative patient-related risk factors for chronic pain after total knee replacement: a systematic review.

OBJECTIVE: To identify postoperative patient-related risk factors for chronic pain after total knee replacement (TKR). DESIGN: The systematic review protocol was registered on the International Prospective Register of Systematic Reviews (CRD42016041374). MEDLINE, Embase and PsycINFO were searched from inception to October 2016 with no language restrictions. Key articles were also tracked in the Institute for Scientific Information (ISI) Web of Science. Cohort studies evaluating the association between patient-related factors in the first 3 months postoperatively and pain at 6 months or longer after primary TKR surgery were included. Screening, data extraction and assessment of methodological quality were undertaken by two reviewers. The primary outcome was pain severity in the replaced knee measured with a patient-reported outcome measure at 6 months or longer after TKR. Secondary outcomes included adverse events and other aspects of pain recommended by the core outcome set for chronic pain after TKR. RESULTS: After removal of duplicates, 16 430 articles were screened, of which 805 were considered potentially relevant. After detailed evaluation of full-text articles, 14 studies with data from 1168 participants were included. Postoperative patient-related factors included acute pain (eight studies), function (five studies) and psychosocial factors (four studies). The included studies had diverse methods for assessment of potential risk factors and outcomes, and therefore narrative synthesis was conducted. For all postoperative factors, there was insufficient evidence to draw firm conclusions about the association with chronic pain after TKR. Selection bias was a potential risk for all studies, as none were reported to be conducted at multiple centres. CONCLUSION: This systematic review found insufficient evidence to draw firm conclusions about the association between any postoperative patient-related factors and chronic pain after TKR. Further high-quality research is required to provide a robust evidence base on postoperative risk factors, and inform the development and evaluation of targeted interventions to optimise patients' outcomes after TKR.