Outcome in design-specific comparisons between highly crosslinked and conventional polyethylene in total hip arthroplasty 163,368 hip replacements in the Nordic Arthroplasty Register Association database with 5-11 years of follow-up

Background and purpose - Most registry studies regarding highly crosslinked polyethylene (XLPE) have focused on the overall revision risk. We compared the risk of cup and/or liner revision for specific cup and liner designs made of either XLPE or conventional polyethylene (CPE), regarding revision for any reason and revision due to aseptic loosening and/or osteolysis.Patients and methods - Using the Nordic Arthroplasty Register Association (NARA) database, we identified cup and liner designs where either XLPE or CPE had been used in more than 500 THAs performed for primary hip osteoarthritis. We assessed risk of revision for any reason and for aseptic loosening using Cox regression adjusted for age, sex, femoral head material and size, surgical approach, stem fixation, and presence of hydroxyapatite coating (uncemented cups).Results - The CPE version of the ZCA cup had a risk of revision for any reason similar to that of the XLPE version (p = 0.09), but showed a 6-fold higher risk of revision for aseptic loosening (p < 0.001). The CPE version of the Reflection All Poly cup had an 8-fold elevated risk of revision for any reason (p < 0.001) and a 5-fold increased risk of revision for aseptic loosening (p < 0.001). The Charnley Elite Ogee/Marathon cup and the Trilogy cup did not show such differences.Interpretation Whether XLPE has any advantage over CPE regarding revision risk may depend on the properties of the polyethylene materials being compared, as well as the respective cup designs, fixation type, and follow-up times. Further research is needed to elucidate how cup design factors interact with polyethylene type to affect the risk of revision

Impact of hip arthroplasty registers on orthopaedic practice and perspectives for the future

Total hip arthroplasty (THA) registers are established in several countries to collect data aiming to improve the results after THA. Monitoring of adverse outcomes after THA has focused mainly on revision surgery, but patient-reported outcomes have also been investigated.Several surgery-related factors influencing the survival of the THA have been thoroughly investigated and have changed clinical practice. These factors include surgical approach, specific implants, the size of the components, type of fixation and different bone cements.Register data have been used to examine the risk of venous thromboembolism and bleeding after THA. These investigations have resulted in shorter duration of thromboprophylaxis and a reduced frequency of blood transfusion.Registers may provide specific information to surgeons on the outcome of all THAs that they have performed with a detailed analysis of revisions rates and reasons for the revisions.A number of other stakeholders can use register data to provide benchmarks. The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man supplies data to the Orthopaedic Device Evaluation Panel (ODEP), which provides benchmarks at 3, 5, 7, 10, and 13 years graded from A*, A, B and C.Future perspectives: National registers have to play a major role in documenting the quality of THA in order to describe best practice and report implant outliers. The registers have to be used for research and post-market surveillance and register data may be a source for intelligent decision tools

Total hip arthroplasties in the Dutch Arthroplasty Register (LROI) and the Nordic Arthroplasty Register Association (NARA): comparison of patient and procedure characteristics in 475,685 cases

Background and purpose - Collaborations between arthroplasty registries are important in order to create the possibility of detecting inferior implants early and improve our understanding of differences between nations in terms of indications and outcomes. In this registry study we compared patient and procedure characteristics, and revision rates in the Nordic Arthroplasty Register Association (NARA) database and the Dutch Arthroplasty Register (LROI).Patients and methods - All total hip arthroplasties (THAs) performed in 2010-2016 were included from the LROI (n = 184,862) and the NARA database (n = 290,823), which contains data from Denmark, Norway, Sweden, and Finland. Descriptive statistics and Kaplan-Meier survival analyses based on all reasons for revision and stratified by fixation were performed and compared between countries.Results - In the Netherlands, the proportion of patients aged < 55 years (9%) and male patients (34%) was lower than in Nordic countries (< 55 years 11-13%; males 35-43%); the proportion of osteoarthritis (OA) (87%) was higher compared with Sweden (81%), Norway (77%), and Denmark (81%) but comparable to Finland (86%). Uncemented fixation was used in 62% of patients in the Netherlands, in 70% of patients in Denmark and Finland, and in 28% and 19% in Norway and Sweden, respectively. The 5-year revision rate for THAs for OA was lower in Sweden (2.3%, 95% CI 2.1-2.5) than in the Netherlands (3.0%, CI 2.9-3.1), Norway (3.8%, CI 3.6-4.0), Denmark (4.6%, CI 4.4-4.8), and Finland (4.4%, CI 4.3-4.5). Revision rates in Denmark, Norway, and Finland were higher for all fixation groups.Interpretation - Patient and THA procedure characteristics as well as revision rates evinced some differences between the Netherlands and the Nordic countries. The Netherlands compared best with Denmark in terms of patient and procedure characteristics, but resembled Sweden more in terms of short-term revision risk. Combining data from registries like LROI and the NARA collaboration is feasible and might possibly enable tracking of potential outlier implants

Implant survival of the most common cemented total hip devices from the Nordic Arthroplasty Register Association database

Background and purpose According to previous Nordic Arthroplasty Register Association (NARA) data, the 10-year implant survival of cemented total hip arthroplasties (THAs) is 94% in patients aged 65-74 and 96% in patients aged 75 or more. Here we report a brand-level comparison of cemented THA based on the NARA database, which has not been done previously.Patients and methods We determined the rate of implant survival of the 9 most common cemented THAs in the NARA database. We used Kaplan-Meier analysis with 95% CI to study implant survival at 10 and 15 years, and Cox multiple regression to assess survival and hazard ratios (HRs), with revision for any reason as endpoint and with adjustment for age, sex, diagnosis, and femoral head material.Results Spectron EF THA (89.9% (CI: 89.3-90.5)) and Elite THA (89.8% (CI: 89.0-90.6)) had the lowest 10-year survivorship. Lubinus (95.7% survival, CI: 95.5-95.9), MS 30 (96.6%, CI: 95.8-97.4), and C-stem THA (95.8%, CI: 94.8-96.8) had a 10-year survivorship of at least 95%. Lubinus (revision risk (RR)=0.77, CI: 0.73-0.81), Muller (RR =0.83, CI: 0.70-0.99), MS-30 (RR =0.73, CI: 0.63-0.86), C-stem (RR =0.70, CI: 0.55-0.90), and Exeter Duration THA (RR =0.84, CI: 0.77-0.90) had a lower risk of revision than Charnley THA, the reference implant.Interpretation The Spectron EF THA and the Elite THA had a lower implant survival than the Charnley, Exeter, and Lubinus THAs. Implant survival of the Muller, MS 30, CPT, and C-stem THAs was above the acceptable limit for 10-year survival

Similar early mortality risk after cemented compared with cementless total hip arthroplasty for primary osteoarthritis: data from 188,606 surgeries in the Nordic Arthroplasty Register Association database

Background and purpose - Current literature indicates no difference in 90-day mortality after cemented compared with cementless total hip arthroplasty (THA). However, previous studies are hampered by potential selection bias and suboptimal adjustment for comorbidity confounding. Therefore, we examined the comorbidity-adjusted mortality up to 90 days after cemented compared with cementless THA performed due to osteoarthritis.Patients and methods - Using the Nordic Arthroplasty Register Association database, 2005-2013, we included 108,572 cemented and 80,034 cementless THA due to osteoarthritis. We calculated the Charlson comorbidity index of each patient based on data from national patient registers. The Kaplan-Meier method was used to estimate unadjusted all-cause mortality. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for 14, 30-, and 90-day mortality comparing cemented with cementless THA, adjusting for age, sex, comorbidity, nation, and year of surgery.Results - Cumulative all-cause mortality within 90 days was 0.41% (CI 0.37-0.46) after cemented and 0.26% (CI 0.22-0.30) after cementless THA. The adjusted HR for cemented vs. cementless fixation was 0.97 (CI 0.79-1.2), and similar risk estimates were obtained for mortality within 14 (adjusted HR 0.91 [CI 0.64-1.3]) and 30 days (adjusted HR 0.94 [CI 0.71-1.3]). We found no clinically relevant differences in mortality between cemented and cementless THA in analyses stratified by age, sex, Charlson comorbidity index, or year of surgery.Interpretation - After adjustment for comorbidity as an important confounder, we observed similar early mortality between the 2 fixation techniques

Effects of osteopontin inhibition on radiosensitivity of MDA-MB-231 breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Osteopontin (OPN) is a secreted glycophosphoprotein that is overexpressed in various tumors, and high levels of OPN have been associated with poor prognosis of cancer patients. In patients with head and neck cancer, high OPN plasma levels have been associated with poor prognosis following radiotherapy. Since little is known about the relationship between OPN expression and radiosensitivity, we investigated the cellular and radiation induced effects of OPN siRNA in human MDA-MB-231 breast cancer cells.</p> <p>Methods</p> <p>MDA-MB-231 cells were transfected with OPN-specific siRNAs and irradiated after 24 h. To verify the OPN knockdown, we measured the OPN mRNA and protein levels using qRT-PCR and Western blot analysis. Furthermore, the functional effects of OPN siRNAs were studied by assays to assess clonogenic survival, migration and induction of apoptosis.</p> <p>Results</p> <p>Treatment of MDA-MB-231 cells with OPN siRNAs resulted in an 80% decrease in the OPN mRNA level and in a decrease in extracellular OPN protein level. Transfection reduced clonogenic survival to 42% (p = 0.008), decreased the migration rate to 60% (p = 0.15) and increased apoptosis from 0.3% to 1.7% (p = 0.04). Combination of OPN siRNA and irradiation at 2 Gy resulted in a further reduction of clonogenic survival to 27% (p < 0.001), decreased the migration rate to 40% (p = 0.03) and increased apoptosis to 4% (p < 0.005). Furthermore, OPN knockdown caused a weak radiosensitization with an enhancement factor of 1.5 at 6 Gy (p = 0.09) and a dose modifying factor (DMF₁₀) of 1.1.</p> <p>Conclusion</p> <p>Our results suggest that an OPN knockdown improves radiobiological effects in MDA-MB-231 cells. Therefore, OPN seems to be an attractive target to improve the effectiveness of radiotherapy.</p

Allogeneic blood transfusion and prognosis following total hip replacement: a population-based follow up study

<p>Abstract</p> <p>Background</p> <p>Allogeneic red blood cell transfusion is frequently used in total hip replacement surgery (THR). However, data on the prognosis of transfused patients are sparse. In this study we compared the risk of complications following THR in transfused and non-transfused patients.</p> <p>Methods</p> <p>A population-based follow-up study was performed using data from medical databases in Denmark. We identified 28,087 primary THR procedures performed from 1999 to 2007, from which we computed a propensity score for red blood cell transfusion based on detailed data on patient-, procedure-, and hospital-related characteristics. We were able to match 2,254 transfused with 2,254 non-transfused THR patients using the propensity score.</p> <p>Results</p> <p>Of the 28,087 THR patients, 9,063 (32.3%) received at least one red blood cell transfusion within 8 days of surgery. Transfused patients had higher 90-day mortality compared with matched non-transfused patients: the adjusted OR was 2.2 (95% confidence interval (CI): 1.2-3.8). Blood transfusion was also associated with increased odds of pneumonia (OR 2.1; CI: 1.2-3.8), whereas the associations with cardiovascular or cerebrovascular events (OR 1.4; CI: 0.9-2.2) and venous thromboembolism (OR 1.2; CI: 0.7-2.1) did not reach statistical significance. The adjusted OR of reoperation due to infection was 0.6 (CI: 0.1-2.9).</p> <p>Conclusions</p> <p>Red blood cell transfusion was associated with an adverse prognosis following primary THR, in particular with increased odds of death and pneumonia. Although the odds estimates may partly reflect unmeasured bias due to blood loss, they indicate the need for careful assessment of the risk versus benefit of transfusion even in relation to routine THR procedures.</p

The benefits of collaboration: the Nordic Arthroplasty Register Association

The Nordic Arthroplasty Register Association (NARA) was established in 2007 by arthroplasty register representatives from Sweden, Norway and Denmark with the overall aim to improve the quality of research and thereby enhance the possibility for quality improvement with arthroplasty surgery. Finland joined the NARA collaboration in 2010.NARA minimal hip, knee and shoulder datasets were created with variables that all countries can deliver. They are dynamic datasets, currently with 25 variables for hip arthroplasty, 20 for knee arthroplasty and 20 for shoulder arthroplasty.NARA has published statistical guidelines for the analysis of arthroplasty register data. The association is continuously working on the improvement of statistical methods and the application of new ones.There are 31 published peer-reviewed papers based on the NARA databases and 20 ongoing projects in different phases. Several NARA publications have significantly affected clinical practice. For example, metal-on-metal total hip arthroplasty and resurfacing arthroplasty have been abandoned due to increased revision risk based on i.a. NARA reports. Further, the use of uncemented total hip arthroplasty in elderly patients has decreased significantly, especially in Finland, based on the NARA data.The NARA collaboration has been successful because the countries were able to agree on a common dataset and variable definitions. The collaboration was also successful because the group was able to initiate a number of research projects and provide answers to clinically relevant questions. A number of specific goals, set up in 2007, have been achieved and new one has emerged in the process

Non-surgical treatment of hip osteoarthritis. Hip school, with or without the addition of manual therapy, in comparison to a minimal control intervention: Protocol for a three-armed randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Hip osteoarthritis is a common and chronic condition resulting in pain, functional disability and reduced quality of life. In the early stages of the disease, a combination of non-pharmacological and pharmacological treatment is recommended. There is evidence from several trials that exercise therapy is effective. In addition, single trials suggest that patient education in the form of a hip school is a promising intervention and that manual therapy is superior to exercise.</p> <p>Methods/Design</p> <p>This is a randomized clinical trial. Patients with clinical and radiological hip osteoarthritis, 40-80 years of age, and without indication for hip surgery were randomized into 3 groups. The active intervention groups A and B received six weeks of hip school, taught by a physiotherapist, for a total of 5 sessions. In addition, group B received manual therapy consisting of joint manipulation and soft-tissue therapy twice a week for six weeks. Group C received a self-care information leaflet containing advice on "live as usual" and stretching exercises from the hip school. The primary time point for assessing relative effectiveness is at the end of the six weeks intervention period with follow-ups after three and 12 months.</p> <p>Primary outcome measure is pain measured on an eleven-point numeric rating scale. Secondary outcome measures are the hip dysfunction and osteoarthritis outcome score, patient's global perceived effect, patient specific functional scale, general quality of life and hip range of motion.</p> <p>Discussion</p> <p>To our knowledge this is the first randomized clinical trial comparing a patient education program with or without the addition of manual therapy to a minimal intervention for patients with hip osteoarthritis.</p> <p>Trial registration</p> <p>ClinicalTrials <a href="http://www.clinicaltrials.gov/ct2/show/NCT01039337">NCT01039337</a></p

Parallel molecular routes to cold adaptation in eight genera of New Zealand stick insects.

The acquisition of physiological strategies to tolerate novel thermal conditions allows organisms to exploit new environments. As a result, thermal tolerance is a key determinant of the global distribution of biodiversity, yet the constraints on its evolution are not well understood. Here we investigate parallel evolution of cold tolerance in New Zealand stick insects, an endemic radiation containing three montane-occurring species. Using a phylogeny constructed from 274 orthologous genes, we show that stick insects have independently colonized montane environments at least twice. We compare supercooling point and survival of internal ice formation among ten species from eight genera, and identify both freeze tolerance and freeze avoidance in separate montane lineages. Freeze tolerance is also verified in both lowland and montane populations of a single, geographically widespread, species. Transcriptome sequencing following cold shock identifies a set of structural cuticular genes that are both differentially regulated and under positive sequence selection in each species. However, while cuticular proteins in general are associated with cold shock across the phylogeny, the specific genes at play differ among species. Thus, while processes related to cuticular structure are consistently associated with adaptation for cold, this may not be the consequence of shared ancestral genetic constraints