Patients with knee osteoarthritis can be divided into subgroups based on tibiofemoral joint kinematics of gait - an exploratory and dynamic radiostereometric study.

OBJECTIVE: Patients with advanced knee osteoarthritis (KOA) frequently alter their gait patterns in an attempt to alleviate symptoms. Understanding the underlying pathomechanics and identifying KOA phenotypes are essential to improve treatments. We investigated kinematics in patients with KOA to identify subgroups of homogeneous knee joint kinematics. METHOD: A total of 66 patients with symptomatic KOA scheduled for total knee arthroplasty and 15 age-matched healthy volunteers with asymptomatic, non-arthritic knees were included. We used k-means clustering to divide patients into subgroups based on dynamic radiostereometry-assessed tibiofemoral joint kinematics. Clinical characteristics such as knee ligament lesions and KOA scores were graded by magnetic resonance imaging and radiographs, respectively. RESULTS: We identified four clusters that were supported by clinical characteristics. The flexion group (n = 20) consisted primarily of patients with medial KOA. The abduction group (n = 17) consisted primarily of patients with lateral KOA. The anterior draw group (n = 10) was composed of patients with medial KOA, some degree of anterior cruciate ligament lesion and the highest KOA score. The external rotation group (n = 19) primarily included patients with medial collateral and posterior cruciate ligament lesions. CONCLUSION: Based on tibiofemoral gait patterns, patients with advanced KOA can be divided into four subgroups with specific clinical characteristics and different KOA-affected compartments. The findings add to our understanding of how knee kinematics may affect the patient's development of different types of KOA. This may inspire improved and more patient-specific treatment strategies in the future.

Signal and noise in circRNA translation.

Within recent years, circular RNAs (circRNAs) have been an attractive new field of research in RNA biology and disease. Consequently, numerous studies have been published towards the disclosure of circRNA biogenesis and function. Initially, circRNAs were described as a subclass of cytoplasmic non-coding RNA, however, a few recent observations have proposed that circRNAs may instead be templates for protein production. The extent to which this is the case is currently debated, and therefore using rigorous data analysis and proper experimental setups is instrumental to settle the current controversies. Here, the conventional experiments used for detecting circRNA translation are outlined, and guidelines to distinguish signal from the inherent noise are discussed. While these guidelines are specific for circRNA translation, most also apply to other aspects of non-canonical translation.

COMPLETE - a school-based intervention project to increase completion of upper secondary school in Norway: study protocol for a cluster randomized controlled trial.

BACKGROUND: Drop out from upper secondary school represents a risk for the future health and wellbeing of young people. Strengthening of psychosocial aspects of the learning environment may be an effective strategy to promote completion of upper secondary school. This paper is a study protocol of a school based cluster randomized controlled trial (RCT) evaluating two school-based interventions, namely the Dream School Program (DSP) and the Mental Health Support Team (MHST). The interventions aim to improve psychosocial learning environments and subsequently school achievements and decrease drop-out and absence. METHODS/DESIGN: The COMPLETE RCT is aimed at youth in upper secondary school, grade 1 (age 15-16 years), and examines the effect of the combination of the DSP and the MHST; and the DSP only, compared with a comparison group on the following primary outcomes: student completion, presence, average grade, and self-reported mental health. Seventeen upper secondary schools from four counties in Norway were randomized to one of the three arms: 1) DSP and MHST; 2) DSP; and 3) comparison (offered DSP intervention in 2018/2019). The study will evaluate the interventions based on information from two cohorts of students (cohort 1 (C1) and cohort 2 (C2)). For C1, data was collected at baseline (August 2016), and at first follow-up seven months later. Second follow-up will be collected 19 months after baseline. For C2, data was collected at baseline (August 2017), and first and second follow-up will be collected similarly to that of C2 seven and 19 months respectively after baseline. Process evaluations based on focus groups, interviews and observation will be conducted twice (first completed spring 2017). DISCUSSION: The COMPLETE trial is a large study that can provide useful knowledge about what interventions might effectively improve completion of upper secondary school. Its thorough process evaluation will provide critical information about barriers and points of improvement for optimizing intervention implementation. Findings can guide school development in the perspective of improving psychosocial learning environments and subsequent completion of upper secondary schooling. TRIAL REGISTRATION: The trial was retrospectively registered in the ClinicalTrials.gov register on December 22.2017: NCT03382080 .

Incidence and related factors for intraoperative failed spinal anaesthesia for lower limb arthroplasty.

BACKGROUND: Spinal anaesthesia is the preferred choice for total hip- and knee arthroplasty (THA/TKA), due to the claimed superior outcome profile, relative simple technique and without the need for advanced airway support. However, choosing and informing about spinal anaesthesia should also include the risk for intraoperative failed spinal anaesthesia with associated pain, discomfort and suboptimal settings for airway management. Small-scale studies suggest incidences from 1 to 17%; however, no multi-institutional large data exists on failed spinal incidence and related factors during THA/TKA, hindering evidence-based information and potential anaesthesia stratification. METHODS: In a sub-analysis, data from a prospective study on spinal anaesthesia for THA/TKA were examined for incidence of intraoperative conversion to general anaesthesia. Potential perioperative factors (age, gender, American Society of Anaesthesiologist (ASA) score, height, weight, BMI, procedure, bupivacaine dosage and duration of time from spinal administration until end of surgery) were analysed with logistic regression for relation to failed spinal anaesthesia. RESULTS: In all, 1451 patients were included for analysis, whereof 57 (3.9%) had failed spinal anaesthesia. Spinal failure patients were significantly younger (61 vs. 67 years, P = 0.003), and operation time longer in the failed spinal group vs no-failure, respectively (133 vs. 89 min, P < 0.001). No significant differences were found with regard to bupivacaine volume, gender, ASA-score, height, weight, BMI or THA vs. TKA. CONCLUSION: Failed spinal anaesthesia for THA and TKA is a relatively frequent occurrence and identification of risk patients is not feasible. These results should be considered when choosing anaesthesia and included in the information to patients.

Circular RNAs in cancer: opportunities and challenges in the field.

Circular RNA (circRNA) is a novel member of the noncoding cancer genome with distinct properties and diverse cellular functions, which is being explored at a steadily increasing pace. The list of endogenous circRNAs involved in cancer continues to grow; however, the functional relevance of the vast majority is yet to be discovered. In general, circRNAs are exceptionally stable molecules and some have been shown to function as efficient microRNA sponges with gene-regulatory potential. Many circRNAs are highly conserved and have tissue-specific expression patterns, which often do not correlate well with host gene expression. Here we review the current knowledge on circRNAs in relation to their implications in tumorigenesis as well as their potential as diagnostic and prognostic biomarkers and as possible therapeutic targets in future personalized medicine. Finally, we discuss future directions for circRNA cancer research and current caveats, which must be addressed to facilitate the translation of basic circRNA research into clinical use.

Effects of litter provision during early rearing and environmental enrichment during the production phase on feather pecking and feather damage in laying hens.

Feather pecking is a multi-factorial behavioral disorder and a serious welfare issue in the poultry industry. Several studies report early life experience with litter to be a major determinant in the development of feather pecking. The current study aimed to test the large-scale on-farm efficiency of a simple and cheap husbandry procedure applied during the rearing period with the ultimate goal of reducing the incidence of feather pecking and plumage damage during the production stage in laying hens. Five laying hen-rearing farmers from across Norway participated in the study. These farmers were asked to create divisions within their hen rearing houses and to separate their chicks into 2 groups: one reared with access to a paper substrate from the first d of age, the other a control group without access to paper substrate during rearing. All flocks were visited at the production farms at 30 wk of age and observed for pecking behavior and feather damage. Birds in the control group had higher odds of having more feather damage compared to the birds from the treatment group. In addition, flocks provided with environmental enrichment at the production farms had a reduced incidence of feather pecking, irrespective of the treatment. These results indicate that husbandry procedures during both rearing and production stages have the potential to alleviate feather pecking and increase laying hen welfare.

Growth potential of exponential- and stationary-phase Salmonella Typhimurium during sausage fermentation.

Raw meat for sausage production can be contaminated with Salmonella. For technical reasons, meat is often frozen prior to mincing but it is unknown how growth of Salmonella in meat prior to freezing affects its growth potential during sausage fermentation. We investigated survival of exponential- and stationary-phase Salmonella Typhimurium (DT12 and DTU292) during freezing at -18°C and their subsequent growth potential during 72h sausage fermentation at 25°C. After 0, 7 and >35d of frozen storage, sausage batters were prepared with NaCl (3%) and NaNO2 (0, 100ppm) and fermented with and without starter culture. With no starter culture, both strains grew in both growth phases. In general, a functional starter culture abolished S. Typhimurium growth independent of growth phase and we concluded that ensuring correct fermentation is important for sausage safety. However, despite efficient fermentation, sporadic growth of exponential-phase cells of S. Typhimurium was observed drawing attention to the handling and storage of sausage meat.

Evaluation of a cross contamination model describing transfer of Salmonella spp. and Listeria monocytogenes during grinding of pork and beef.

In a previous study, a model was developed to describe the transfer and survival of Salmonella during grinding of pork (Møller, C.O.A., Nauta, M.J., Christensen, B.B., Dalgaard, P., Hansen, T.B., 2012. Modelling transfer of Salmonella typhimurium DT104 during simulation of grinding of pork. Journal of Applied Microbiology 112 (1), 90-98). The robustness of this model is now evaluated by studying its performance for predicting the transfer and survival of Salmonella spp. and Listeria monocytogenes during grinding of different types of meat (pork and beef), using two different grinders, different sizes and different numbers of pieces of meats to be ground. A total of 19 grinding trials were collected. Acceptable Simulation Zone (ASZ), visual inspection of the data, Quantitative Microbiological Risk Assessment (QMRA), as well as the Total Transfer Potential (TTP) were used as approaches to evaluate model performance and to access the quality of the cross contamination model predictions. Using the ASZ approach and considering that 70% of the observed counts have to be inside a defined acceptable zone of ±0.5 log10CFU per portion, it was found that the cross contamination parameters suggested by Møller et al. (2012) were not able to describe all 19 trials. However, for each of the collected grinding trials, the transfer event was well described when fitted to the model structure proposed by Møller et al. (2012). Parameter estimates obtained by fitting observed trials performed at different conditions, such as size and number of pieces of meat to be ground, may not be applied to describe cross contamination of unlike processing. Nevertheless, the risk estimates, as well as the TTP, revealed that the risk of disease may be reduced when the grinding of meat is performed in a grinder made of stainless steel (for all surfaces in contact with the meat), using a well-sharpened knife and holding at room temperatures lower than 4°C.

Association between hospital procedure volume and risk of revision after total hip arthroplasty: a population-based study within the Nordic Arthroplasty Register Association database.

OBJECTIVE: Outcome after total hip arthroplasty (THA) depends on several factors related to the patient, the surgeon and the implant. It has been suggested that the annual number of procedures per hospital affects the prognosis. We aimed to examine if hospital procedure volume was associated with the risk of revision after primary THA in the Nordic countries from 1995 to 2011. DESIGN: The Nordic Arthroplasty Register Association database provided information about primary THA, revision and annual hospital volume. Hospitals were divided into five volume groups (1-50, 51-100, 101-200, 201-300, >300). The outcome of interest was risk of revision 1, 2, 5, 10 and 15 years after primary THA. Multivariable regression was used to assess the relative risk (RR) of revision. RESULTS: 417,687 THAs were included. For the 263,176 cemented THAs no differences were seen 1 year after primary procedure. At 2, 5, 10 and 15 years the four largest hospital volume groups had a reduced risk of revision compared to group 1-50. After 10 years RR was for volume group 51-100 0.79 (CI 0.65-0.95), group 101-200 0.76 (CI 0.61-0.95), group 201-300 0.74 (CI 0.57-0.96) and group >300 0.57 (CI 0.46-0.71). For the uncemented THAs an association between hospital volume and risk of revision were only present for hospitals producing 201-300 THAs per year, beginning at years 2 through 5 and in all subsequent time intervals to 15 years. CONCLUSION: Hospital procedure volume was associated with a long term risk of revision after primary cemented THA. Hospitals operating 50 procedures or less per year had an increased risk of revision after 2, 5, 10 and 15 years follow up.

Chronic pre-operative opioid use and acute pain after fast-track total knee arthroplasty.

BACKGROUND: Pre-operative opioid use has been suggested to increase post-operative pain and opioid consumption after total knee arthroplasty (TKA), but previous studies are either retrospective or inhomogeneous with regard to surgical procedures or control of analgesic regimes, or with few opioid-treated patients, hindering firm conclusions. METHODS: In a prospective observational study, we investigated the effect of > 4 weeks pre-operative opioid use [none vs. low dose (< 30 mg morphine equivalents (eq.)) vs. high dose (> 30 mg morphine eq.] in patients scheduled for primary, unilateral TKA. All patients had well-defined multimodal opioid-sparring perioperative analgesic therapy, and continued any pre-operative opioid medication. The primary outcome was differences between groups in pain at rest and during walk for the first 6 post-operative days. RESULTS: Among 123 patients included, 115 were available for final analysis (93% follow-up rate). Post-operative pain during walk was significantly increased in both opioid-treated groups vs. non-opioid-treated patients (P < 0.009). Secondary analysis of combining all pre-operatively opioid-treated patients vs. opioid-free patients, showed significantly increased pain at rest and walk and increased post-operative opioid requirement - excluding pre-operative dosage - during the first post-operative week in opioid-treated patients (P = 0.001 and P = 0.007, respectively). CONCLUSION: Pre-operative opioid use increases the risk for post-operative pain at rest and walk, and increased opioid consumption after TKA.

Exercise-based cardiac rehabilitation after heart valve surgery: cost analysis of healthcare use and sick leave.

BACKGROUND: Owing to a lack of evidence, patients undergoing heart valve surgery have been offered exercise-based cardiac rehabilitation (CR) since 2009 based on recommendations for patients with ischaemic heart disease in Denmark. The aim of this study was to investigate the impact of CR on the costs of healthcare use and sick leave among heart valve surgery patients over 12 months post surgery. METHODS: We conducted a nationwide survey on the CR participation of all patients having undergone valve surgery between 1 January 2011 and 30 June 2011 (n=667). Among the responders (n=500, 75%), the resource use categories of primary and secondary healthcare, prescription medication and sick leave were analysed for CR participants (n=277) and non-participants (n=223) over 12 months. A difference-in-difference analysis was undertaken. All estimates were presented as the means per patient (95% CI) based on non-parametric bootstrapping of SEs. RESULTS: Total costs during the 12 months following surgery were €16 065 per patient (95% CI 13 730 to 18 399) in the CR group and €15 182 (12 695 to 17 670) in the non-CR group. CR led to 5.6 (2.9 to 8.3, p<0.01) more outpatient visits per patient. No statistically significant differences in other cost categories or total costs €1330 (-4427 to 7086, p=0.65) were found between the groups. CONCLUSIONS: CR, as provided in Denmark, can be considered cost neutral. CR is associated with more outpatient visits, but CR participation potentially offsets more expensive outpatient visits. Further studies should investigate the benefits of CR to heart valve surgery patients as part of a formal cost-utility analysis.

High readmission rate after heart valve surgery: A nationwide cohort study.

BACKGROUND: After heart valve surgery, knowledge on long-term self-reported health status and readmission is lacking. Thus, the optimal strategy for out-patient management after surgery remains unclear. METHODS: Using a nationwide survey with linkage to Danish registers with one year follow-up, we included all adults 6-12 months after heart valve surgery irrespective of valve procedure, during Jan-June 2011 (n = 867). Participants completed a questionnaire regarding health-status (n = 742), and answers were compared with age- and sex-matched healthy controls. Readmission rates and mortality were investigated. RESULTS: After valve surgery, the self-reported health was lower (Short Form-36 (SF-36) Physical Component Scale (PCS): 44.5 vs. 50.6 and Mental Component Scale (MCS): 51.9 vs. 55.0, p < 0.0001) and more were physically sedentary compared with healthy controls (11.1% vs. 15.2%). Clinical signs of anxiety and depression were present in 13.6% and 13.8%, respectively (Hospital Anxiety and Depression Scale score ≥ 8). Twelve months following discharge, 483 persons (56%) were readmitted. Readmission was associated with lower self-reported health (SF-36 PCS: 46.5 vs. 43.9, and MCS 52.2 vs. 50.7). Higher age (hazard ratio (95% CI): 1.3 (1.0-1.6)), male sex (1.2 (1.0-1.5)), mitral valve surgery (1.3 (1.0-1.6)), and infective endocarditis after surgery (1.8 (1.1-3.0), p: 0.01) predicted readmission, whereas higher age (2.3 (1.0-5.4)), higher comorbidity score (3.2 (1.8-6.0)), and infective endocarditis after surgery (3.2 (1.2-8.9)) predicted mortality. CONCLUSIONS: 6-12 months after heart valve surgery the readmission rate is high and the self-reported health status is low. Readmission is associated with low self-reported health. Therefore, targeted follow-up strategies post-surgery are needed.

Early morbidity after aseptic revision hip arthroplasty in Denmark: a two-year nationwide study.

Data on early morbidity and complications after revision total hip replacement (THR) are limited. The aim of this nationwide study was to describe and quantify early morbidity after aseptic revision THR and relate the morbidity to the extent of the revision surgical procedure. We analysed all aseptic revision THRs from 1st October 2009 to 30th September 2011 using the Danish National Patient Registry, with additional information from the Danish Hip Arthroplasty Registry. There were 1553 procedures (1490 patients) performed in 40 centres and we divided them into total revisions, acetabular component revisions, femoral stem revisions and partial revisions. The mean age of the patients was 70.4 years (25 to 98) and the median hospital stay was five days (interquartile range 3 to 7). Within 90 days of surgery, the readmission rate was 18.3%, mortality rate 1.4%, re-operation rate 6.1%, dislocation rate 7.0% and infection rate 3.0%. There were no differences in these outcomes between high- and low-volume centres. Of all readmissions, 255 (63.9%) were due to 'surgical' complications versus 144 (36.1%) 'medical' complications. Importantly, we found no differences in early morbidity across the surgical subgroups, despite major differences in the extent and complexity of operations. However, dislocations and the resulting morbidity represent the major challenge for improvement in aseptic revision THR.

Observational study of child restraining practice on Norwegian high-speed roads: restraint misuse poses a major threat to child passenger safety.

OBJECTIVE: Restraint misuse and other occupant safety errors are the major cause of fatal and, severe injuries among child passengers in motor vehicle collisions. The main objectives of the present, study were to provide estimates of restraining practice among children younger than 16 years, traveling on Norwegian high-speed roads, and to uncover the high-risk groups associated with, restraint misuse and other safety errors. METHODS: A cross-sectional observational study was performed in conjunction with regular traffic, control posts on high-speed roads. The seating and restraining of child occupants younger than 16, years were observed, the interior environment of the vehicles was examined, and a structured, interview of the driver was conducted according to a specific protocol. RESULTS: In total, 1260 child occupants aged 0-15 years were included in the study. Misuse of restraints, was observed in 38% of cases, with this being severe or critical in 24%. The presence of restraint, misuse varied significantly with age (p<0.001), with the frequency being highest among child, occupants in the age group 4-7 years. The most common error in this group was improperly routed, seat belts. The highest frequency of severe and critical errors was observed among child occupants in, the age group 0-3 years. The most common errors were loose or improperly routed harness straps and, incorrect installations of the child restraint system. Moreover, 24% of the children were seated in, vehicles with heavy, unsecured objects in the passenger compartment and/or the trunk that were, likely to move into the compartment upon impact and cause injury. No totally unrestrained children, were observed. CONCLUSIONS: This study provides a detailed description of the characteristics of restraint misuse and, the occupant's exposure to unsecured objects. Future education and awareness campaigns should, focus on children aged <8 years. The main challenges are to ensure correct routing and tightness of, harness straps and seat belts, correct installation of child restraints, and avoidance of premature, graduation from child restraints to seat belts only. Information campaigns should also advocate the use, of chest clips and address the potential risks of hard, heavy objects in the passenger compartment and, the importance of the placement and strapping of heavy objects in the trunk.

Patients with metal-on-metal articulation in trapeziometacarpal total joint arthroplasty may have elevated serum chrome and cobalt.

Serum chrome and cobalt was measured in 50 patients with trapeziometacarpal total joint replacement with metal-on-metal articulation and compared with serum chrome and cobalt values in 23 patients with trapeziometacarpal total joint replacement with metal-on-polyethylene articulation. In 10 of 50 (20%) patients with metal-on-metal articulation, slightly elevated serum chrome or cobalt values were found compared with only one in 23 (4%) patients with metal-on-polyethylene articulation. All metal values were lower than accepted 'normal values' for metal-on-metal hip arthroplasty and so considered not to be a general health risk. However, the mean disabilities of the arm, shoulder and hand (DASH) score was 24 in patients with elevated serum chrome or cobalt compared with 10 in patients with normal metal values (p < 0.05) suggesting a local clinical effect of the elevated serum chrome or cobalt values. We recommend that patients with trapeziometacarpal total joint replacement with metal-on-metal articulation are followed with DASH score and radiological examination every 3-5 years and serum chrome and cobalt should be analysed in symptomatic cases to learn more about possible local complications leading to, or arising from, metal debris.

Effect of natural microbiota on growth of Salmonella spp. in fresh pork--a predictive microbiology approach.

This study was undertaken to model and predict growth of Salmonella and the dominating natural microbiota, and their interaction in ground pork. Growth of Salmonella in sterile ground pork at constant temperatures between 4 °C and 38 °C was quantified and used for developing predictive models for lag time, max. specific growth rate and max. population density. Data from literature were used to develop growth models for the natural pork microbiota. Challenge tests at temperatures from 9.4 to 24.1 °C and with Salmonella inoculated in ground pork were used for evaluation of interaction models. The existing Jameson-effect and Lotka-Volterra species interaction models and a new expanded Jameson-effect model were evaluated. F-test indicated lack-of-fit for the classical Jameson-effect model at all of the tested temperatures and at 14.1-20.2 °C this was caused by continued growth of Salmonella after the natural microbiota had reached their max. population density. The new expanded Jameson-effect model and the Lotka-Volterra model performed better and appropriately described the continued but reduced growth of Salmonella after the natural microbiota had reached their max. population density. The expanded Jameson-effect model is a new and simple species interaction model, which performed as well as the more complex Lotka-Volterra model.

Bone mineral density of the trapezium in osteoarthritic trapeziometacarpal joints.

The aim of this study was to test the precision and reliability of measurements of the bone mineral density (BMD) of the trapezium in patients with osteoarthritic trapeziometacarpal joints using dual-energy X-ray absorptiometry scans and to assess whether there is an acceptable correlation between the BMD of the trapezium and that of the distal radius, for which normative data exist. We included 66 patients (52 women, 14 men) diagnosed with Eaton-Glickel stage II-IV osteoarthritis and a mean age of 59 years (range 40-77) in a prospective study. We found good intra- and inter-observer agreement of BMD measurements. Reliability was also good in repeated measurements. There was an indication of an increase in BMD with progression in the Eaton-Glickel stage. There was only a moderate correlation between the BMD of the trapezium and that of the radius.

Computed tomography improves intra-observer reliability, but not the inter-observer reliability of the Eaton-Glickel classification.

This study aimed to evaluate whether computed tomography improves the intra- and inter-observer reliability of the Eaton-Glickel classification of trapeziometacarpal joint osteoarthritis. The osteoarthritis of the trapeziometacarpal joint was evaluated with conventional radiographs and computed tomography by two hand surgeons, two registrars and one radiologist in 50 hands of 43 patients (12 male and 31 female) who had a median age of 60 years (46-80). Using plain radiographs, we found a mean intra-observer reliability of 0.54 (0.51-0.74), and the intra-observer reliability was improved to 0.76 (0.64-0.86) using computed tomography. Using plain radiographs, the mean inter-observer reliability was poor at 0.17 (0.04-0.51) and did not improve using computed tomography with a mean inter-observer reliability of 0.22 (0.02-0.38). In particular, the agreement in the distinction between Eaton-Glickel stage III and IV and the evaluation of the degenerative changes in the scaphotrapezio joint was low using computed tomography-scans. The detection of bone cysts on computed tomography was more precise than on plain radiographs.

Local anaesthesia versus intravenous regional anaesthesia in endoscopic carpal tunnel release: a randomized controlled trial.

We carried out a prospective randomized trial in 38 patients to compare intravenous regional anaesthesia with local anaesthesia in endoscopic carpal tunnel release using the Agee single-portal technique. There was no significant difference in reported pain during surgery. Immediately after surgery, patients in the local anaesthesia group reported significantly less pain in the hand and at the tourniquet. Two hours after surgery, patients in the local anaesthesia group reported significantly less hand pain. Moreover, significantly fewer patients in the local anaesthetic group required additional analgesics during the first 2 hours after operation. We conclude that local anaesthesia reduces post-operative pain in endoscopic carpal tunnel release compared with intravenous regional anaesthesia.