Background: The risk of venous thromboembolism (VTE) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) is 1.0% to 1.5%, despite uniform thromboprophylaxis. Objectives: To... Show moreBackground: The risk of venous thromboembolism (VTE) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) is 1.0% to 1.5%, despite uniform thromboprophylaxis. Objectives: To develop and validate a prediction model for 90-day VTE risk. Methods: A multinational cohort study was performed. For model development, records were used from the Oxford Royal College of General Practitioners Research and Surveillance Centre linked to Hospital Episode Statistics and Office of National Statistics UK routine data. For external validation, data were used from the Danish Hip and Knee Arthroplasty Registry, the National Patient Registry, and the National Prescription Registry. Binary multivariable logistic regression techniques were used for development. Results: In the UK data set, 64 032 THA/TKA procedures were performed and 1.4% developed VTE. The prediction model consisted of age, body mass index, sex, cystitis within 1 year before surgery, history of phlebitis, history of VTE, presence of varicose veins, presence of asthma, history of transient ischemic attack, history of myocardial infarction, presence of hypertension and THA or TKA. The area under the curve of the model was 0.65 (95% CI, 0.63-0.67). Furthermore, 36 169 procedures were performed in the Danish cohort, of whom 1.0% developed VTE. Here, the area under the curve was 0.64 (95% CI, 0.61-0.67). The calibration slope was 0.92 in the validation study and 1.00 in the development study. Conclusion: This clinical prediction model for 90-day VTE risk following THA and TKA performed well in both development and validation data. This model can be used to estimate an individual’s risk for VTE following THA/TKA. Show less
Boone, I.; Tuerlings, M.; Almeida, R.C. de; Lehmann, J.; Ramos, Y.; Nelissen, R.; ... ; Meulenbelt, I. 2023
Heterogeneous accumulation of senescent cells expressing the senescence-associated secretory phenotype (SASP) affects tissue homeostasis which leads to diseases, such as osteoarthritis (OA). In... Show moreHeterogeneous accumulation of senescent cells expressing the senescence-associated secretory phenotype (SASP) affects tissue homeostasis which leads to diseases, such as osteoarthritis (OA). In this study, we set out to characterize heterogeneity of cellular senescence within aged articular cartilage and explored the presence of corresponding metabolic profiles in blood that could function as representative biomarkers. Hereto, we set out to perform cluster analyses, using a gene-set of 131 senescence genes (N = 57) in a previously established RNA sequencing dataset of aged articular cartilage and a generated metabolic dataset in overlapping blood samples. Using unsupervised hierarchical clustering and pathway analysis, we identified two robust cellular senescent endotypes. Endotype-1 was enriched for cell proliferating pathways, expressing forkhead box protein O4 (FOXO4), RB transcriptional corepressor like 2 (RBL2), and cyclin-dependent kinase inhibitor 1B (CDKN1B); the FOXO mediated cell cycle was identified as possible target for endotype-1 patients. Endotype-2 showed enriched inflammation-associated pathways, expressed by interleukin 6 (IL6), matrix metallopeptidase (MMP)1/3, and vascular endothelial growth factor (VEGF)C and SASP pathways were identified as possible targets for endotype-2 patients. Notably, plasma-based metabolic profiles in overlapping blood samples (N = 21) showed two corresponding metabolic clusters in blood. These non-invasive metabolic profiles could function as biomarkers for patient-tailored targeting of senescence in OA. Show less
AimsThis study aimed to investigate the estimated change in primary and revision arthroplasty rate in the Netherlands and Denmark for hips, knees, and shoulders during the COVID- 19 pandemic in... Show moreAimsThis study aimed to investigate the estimated change in primary and revision arthroplasty rate in the Netherlands and Denmark for hips, knees, and shoulders during the COVID- 19 pandemic in 2020 (COVID-period). Additional points of focus included the comparison of patient characteristics and hospital type (2019 vs COVID-period), and the estimated loss of quality-adjusted life years (QALYs) and impact on waiting lists.MethodsAll hip, knee, and shoulder arthroplasties (2014 to 2020) from the Dutch Arthroplasty Reg-ister, and hip and knee arthroplasties from the Danish Hip and Knee Arthroplasty Registries, were included. The expected number of arthroplasties per month in 2020 was estimated using Poisson regression, taking into account changes in age and sex distribution of the general Dutch/Danish population over time, calculating observed/expected (O/E) ratios. Country-specific proportions of patient characteristics and hospital type were calculated per indication category (osteoarthritis/other elective/acute). Waiting list outcomes including QALYs were estimated by modelling virtual waiting lists including 0%, 5% and 10% extra capacity.ResultsDuring COVID-period, fewer arthroplasties were performed than expected (Netherlands: 20%; Denmark: 5%), with the lowest O/E in April. In the Netherlands, more acute indica-tions were prioritized, resulting in more American Society of Anesthesiologists grade III to IV patients receiving surgery. In both countries, no other patient prioritization was present. Relatively more arthroplasties were performed in private hospitals. There were no clinically relevant differences in revision arthroplasties between pre- COVID and COVID-period. Esti-mated total health loss depending on extra capacity ranged from: 19,800 to 29,400 QALYs (Netherlands): 1,700 to 2,400 QALYs (Denmark). With no extra capacity it will take > 30 years to deplete the waiting lists.ConclusionThe COVID- 19 pandemic had an enormous negative effect on arthroplasty rates, but more in the Netherlands than Denmark. In the Netherlands, hip and shoulder patients with acute indications were prioritized. Private hospitals filled in part of the capacity gap. QALY loss due to postponed arthroplasty surgeries is considerable. Show less
Off-label use is frequently practiced in hip revision arthroplasty, as there may be indications for the application of implants for purposes outside the one the manufacturers intended (i.e. large... Show moreOff-label use is frequently practiced in hip revision arthroplasty, as there may be indications for the application of implants for purposes outside the one the manufacturers intended (i.e. large bone and soft tissue defects, obesity). Patients may also benefit from selective application of mix & match in hip revision, when the exchange of one component only is necessary and the invasiveness of surgery can be reduced. Currently, there are no formal guidelines for these situations. Therefore, within a recent EFORT initiative, evidence- and consensus-based recommendations have been developed for the safe application of off-label use and mix & match in revision hip and knee arthroplasty. Show less
Nemeth, B.; Kaaij, M. van der; Nelissen, R.; Wijnen, J.K. van; Drost, K.; Blauw, G.J. 2022
Background Hip and pelvic fractures do commonly occur among older adults. This pilot study aimed to evaluate the effect of introduction of the WOLK hip airbag on the incidence of hip fractures.... Show moreBackground Hip and pelvic fractures do commonly occur among older adults. This pilot study aimed to evaluate the effect of introduction of the WOLK hip airbag on the incidence of hip fractures. Methods A retrospective study was performed among 969 participants residing within 11 long-term care facilities for older patients, belonging to one large healthcare organization in The Netherlands. The intervention concerned application of 45 WOLK hip-airbags, distributed among selected residents of the long-term care facilities. Inclusion criteria; physically active participants with a pelvic circumference between 90-125 cm able to wear the hip airbag. Exclusion criteria; participants who continuously removed the hip airbag themselves or participants who depended on a wheelchair for mobility. Main outcome measures were the occurrence of falls and hip, pelvic and other fractures. Results The incidence of hip and pelvic fractures declined from 3.3/100 person years to 1.8/100 person years during the study for an Incidence Rate Ratio (IRR) of 0.55 (95% confidence interval (95%CI) 0.34-0.87) in the entire study population. The incidence of other fractures did not decline during the study period (IRR 0.72;95%CI 0.37-1.40). The incidence of falls declined to some extent during the study (IRR 0.88; 95%CI 0.83-0.93). Conclusions After introduction of the WOLK hip airbag a reduction of the incidence of hip and pelvic fractures by almost half was observed in older patients residing in long-term care facilities, even though only 45 hip airbags were distributed among the 969 residents. As selection bias cannot be ruled out in this study, the results of this pilot study warrant replication by a future clinical trial to determine true effectiveness of this intervention. Show less
Tuerlings, M.; Boone, I.; Amirabadi, H.E.; Vis, M.; Suchiman, E.; Linden, E. van der; ... ; Meulenbelt, I. 2022
Given the multi-tissue aspects of osteoarthritis (OA) pathophysiology, translation of OA susceptibility genes towards underlying biological mechanism and eventually drug target discovery requires... Show moreGiven the multi-tissue aspects of osteoarthritis (OA) pathophysiology, translation of OA susceptibility genes towards underlying biological mechanism and eventually drug target discovery requires appropriate human in vitro OA models that incorporate both functional bone and cartilage tissue units. Therefore, a microfluidic chip is developed with an integrated fibrous polycaprolactone matrix in which neo-bone and cartilage are produced, that could serve as a tailored human in vitro disease model of the osteochondral unit of joints. The model enables to evaluate OA-related environmental perturbations to (individual) tissue units by controlling environmental cues, for example by adding biochemical agents. After establishing the co-culture in the system, a layer of cartilaginous matrix is deposited in the chondrogenic compartment, while a bone-like matrix is deposited between the fibers, indicated by both histology and gene expression levels of collagen type 2 and osteopontin, respectively. As proof-of-principle, the bone and cartilaginous tissue are exposed to active thyroid hormone, creating an OA disease model. This results in increased expression levels of hypertrophy markers integrin-binding sialoprotein and alkaline phosphatase in both cartilage and bone, as expected. Altogether, this model could contribute to enhanced translation from OA risk genes towards novel OA therapies. Show less
Gerritsen, M.; Khawar, A.; Scheper, H.; Wal, R. van der; Schoones, J.; Boer, M. de; ... ; Pijls, B. 2021
AimsThe aim of this meta-analysis is to assess the association between exchange of modular parts in debridement, antibiotics, and implant retention (DAIR) procedure and outcomes for hip and knee... Show moreAimsThe aim of this meta-analysis is to assess the association between exchange of modular parts in debridement, antibiotics, and implant retention (DAIR) procedure and outcomes for hip and knee periprosthetic joint infection (PJI).MethodsWe conducted a systematic search on PubMed, Embase, Web of Science, and Cochrane library from inception until May 2021. Random effects meta-analyses and meta-regression was used to estimate, on a study level, the success rate of DAIR related to component exchange. Risk of bias was appraised using the (AQUILA) checklist.ResultsWe included 65 studies comprising 6,630 patients. The pooled overall success after DAIR for PJI was 67% (95% confidence interval (CI) 63% to 70%). This was 70% (95% CI 65% to 75%) for DAIR for hip PJI and 63% (95% CI 58% to 69%) for knee PJI. In studies before 2004 (n = 27), our meta-regression analysis showed a 3.5% increase in success rates for each 10% increase in component exchange in DAIR for hip PJI and a 3.1% increase for each 10% increase in component exchange for knee PJI. When restricted to studies after 2004 (n = 37), this association changed: for DAIR for hip PJI a decrease in successful outcome by 0.5% for each 10% increase in component exchange and for DAIR for knee PJI this was a 0.01% increase in successful outcome for each 10% increase in component exchange.ConclusionThis systematic review and meta-regression found no benefit of modular component exchange on reduction of PJI failure. This limited effect should be weighed against the risks for the patient and cost on a case-by-case basis. The association between exchange of modular components and outcome changed before and after 2004. This suggests the effect seen after 2004 may reflect a more rigorous, evidence-based, approach to the infected implant compared to the years before. Show less
Nemeth, B.; Nelissen, R.; Arya, R.; Cannegieter, S. 2020
Venous thromboembolism (VTE) is a common complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Many guidelines advise on the ideal pharmacological... Show moreVenous thromboembolism (VTE) is a common complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Many guidelines advise on the ideal pharmacological thromboprophylaxis strategy; however, despite its use, approximately 1.5% of patients still develop symptomatic VTE. Considering the large number of THAs and TKAs performed worldwide (2.5 million in total), the impact of VTE following these interventions is enormous. This paper discusses a concept how to further lower rates of VTE and bleeding complications following surgery. By stratifying patients according to their risk, we can optimize the balance between VTE and bleeding for each individual. This way, low-risk patients may be safely withheld from treatment (and avoid unnecessary bleeding complications and costs), whereas high-risk patients should receive adequate therapy (for instance, an increased thromboprophylaxis dosage and duration). An individualized strategy requires a well-functioning VTE prediction model following THA and TKA to help physicians to decide on optimal thromboprophylaxis therapy. Show less
Nemeth, B.; Adrichem, R. van; Nelissen, R.; Cessie, S. le; Cannegieter, S.C. 2019
Background Accelerometer-based navigation is a handheld navigation tool that was introduced to offer a simpler technique compared with more-cumbersome computer-assisted surgery (CAS). Considering... Show moreBackground Accelerometer-based navigation is a handheld navigation tool that was introduced to offer a simpler technique compared with more-cumbersome computer-assisted surgery (CAS). Considering the increasing number of adopters, it seems important to evaluate the potential clinical benefits of this technology compared with conventional TKA.Questions/purposes In this systematic review, we asked: (1) Is accelerometer-based navigation more accurate than conventional TKA? (2) Does accelerometer-based navigation provide better functional outcome than conventional TKA? (3) Does accelerometer-based navigation increase surgical time or decrease the risk of complications or reoperations compared with conventional TKA?Methods This systematic review included all comparative prospective and retrospective studies published in the MEDLINE/PubMed and Cochrane libraries over the last 10 years. Inclusion criteria were all studies in English that compared accelerometer-based navigation with conventional TKA. Eleven studies met these criteria with 621 knees in accelerometer-based navigation group and 677 knees in conventional TKA group. Results related to alignment, objective and subjective functional scores, duration of surgery, complications and reoperations were extracted and compared between accelerometer-based-navigation and conventional TKA. Methodological quality was assessed using Methodological Index for Non-Randomized Studies (MINORS) tool (for nonrandomized control trials) and Cochrane Risk of Bias (for randomized control trials (RCTs). All studies with fair or better quality were included. Four RCTs and six nonrandomized studies comparing accelerometer-based navigation to conventional TKA were found.Results Inconsistent evidence on mechanical axis alignment was found, with five of nine studies slightly favoring the accelerometer-based navigation group, and the other four showing no differences between the groups. Only two of eight studies favored accelerometer-based navigation in terms of tibial component alignment in the coronal plane; the other six found no between-group differences. Similarly, mixed results were found regarding other metrics related to component alignment; a minority of studies favored accelerometer-based navigation by a smallmargin, and most studies found no between-group differences. Only three studies evaluated functional outcome and none of them showed a difference in range of motion or patient-reported outcomes. Most studies, six of seven, found no between-group differences concerning surgical time; one study demonstrated a slight increase in time with accelerometer-based navigation. There were no between-group differences in terms of the risk of complications, which generally were uncommon in both groups, and no reoperations or revisions were reported in either group.Conclusions We found conflicting evidence about whether accelerometer-based navigation reduces the number of coronal-plane outliers or improves alignment to a clinically important degree, and we found no evidence that it improves patient-reported outcomes or reduces the risk of complications or reoperations. Accelerometer-based navigation may increase surgical time. The overall quality of the evidencewas low, which suggested that any observed benefits were over-estimated. Given the absence of higher-quality evidence demonstrating compelling benefits of this accelerometer-based navigation technology, it should not bewidely adopted. Show less
