OL-Co-founder of and Chairman of the Executive Committee of the ERAS Society. Founder and shareholder in Encare AB, Advisor to Nutricia, NL; Advanced Medical Nutrition, Can. Speaker's honoraria and travel support from Nutricia, Fresenius-kabi, BBraun, Merck, Medtronic, and Baxter.TW conceived and designed the study. TW, MG, OL, DM, RGM, MR, OS, and PY all contributed to data collection and manuscript writing. All authors provided critical input on the manuscript.Acta thanks Henrik Husted and Stephan Vehmeijer for help with peer review of this study.

Background and purposeMultimodal techniques can aid early rehabilitation and discharge of patients following primary joint replacement. We hypothesized that this not only reduces the economic burden of joint replacement by reducing length of stay, but also helps in reduction of early complications.Patients and methodsWe evaluated 4,500 consecutive unselected total hip replacements and total knee replacements regarding length of hospital stay, mortality, and perioperative complications. The first 3,000 underwent a traditional protocol while the other 1,500 underwent an enhanced recovery protocol involving behavioral, pharmacological, and procedural modifications.ResultsThere was a reduction in 30-day death rate (0.5% to 0.1%, p = 0.02) and 90-day death rate (0.8% to 0.2%, p = 0.01). The median length of stay decreased from 6 days to 3 days (p < 0.001), resulting in a saving of 5,418 bed days. Requirement for blood transfusion was reduced (23% to 9.8%, p < 0.001). There was a trend of a reduced rate of 30-day myocardial infarction (0.8% to 0.5%. p = 0 .2) and stroke (0.5% to 0.2%, p = 0.2). The 60-day deep vein thrombosis figures (0.8% to 0.6%, p = 0.5) and pulmonary embolism figures (1.2% to 1.1%, p = 0.9) were similar. Re-admission rate remained unchanged during the period of the study (4.7% to 4.8%, p = 0.8).InterpretationThis large observational study of unselected consecutive hip and knee arthroplasty patients shows a substantial reduction in death rate, reduced length of stay, and reduced transfusion requirements after the introduction of a multimodal enhanced recovery protocol.

SummaryBackgroundOsteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity.MethodsWe undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11 009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42 938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent.FindingsWe identified five genome-wide significant loci (binomial test p≤5·0×10−8) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08–1·16]; p=7·24×10−11), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight—a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects.InterpretationOur findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.FundingarcOGEN was funded by a special purpose grant from Arthritis Research UK.

Background and purposeEnhanced Recovery (ER) is a well-established multidisciplinary strategy in lower limb arthroplasty and was introduced in our department in May 2008. This retrospective study reviews short-term outcomes in a consecutive unselected series of 3,000 procedures (the “ER” group), and compares them to a numerically comparable cohort that had been operated on previously using a traditional protocol (the “Trad” group).MethodsProspectively collected data on surgical endpoints (length of stay (LOS), return to theater (RTT), re-admission, and 30- and 90-day mortality) and medical complications (stroke, gastrointestinal bleeding, myocardial infarction, and pneumonia within 30 days; deep vein thrombosis and pulmonary embolism within 60 days) were compared.ResultsER included 1,256 THR patients and 1,744 TKR patients (1,369 THRs and 1,631 TKRs in Trad). The median LOS in the ER group was reduced (3 days vs. 6 days; p = 0.01). Blood transfusion rate was also reduced (7.6% vs. 23%; p < 0.001), as was RTT rate (p = 0.05). The 30-day incidence of myocardial infarction declined (0.4% vs. 0.9%; p = 0.03) while that of stroke, gastrointestinal bleeding, pneumonia, deep vein thrombosis, and pulmonary embolism was not statistically significantly different. Mortality at 30 days and at 90 days was 0.1% and 0.5%, respectively, as compared to 0.5% and 0.8% using the traditional protocol (p = 0.03 and p = 0.1, respectively).InterpretationThis is the largest study of ER arthroplasty, and provides safety data on a consecutive unselected series. The program has achieved a statistically significant reduction in LOS and in cardiac ischemic events for our patients, with a near-significant decrease in return to theater and in mortality rates.