Complete mid-portion rupture of the rat achilles tendon leads to remote and time-mismatched changes in uninjured regions.

PURPOSE: To examine healing adaptations over 17 weeks post Achilles tendon (AT) rupture in the injured region (IR) compared to an uninjured region (UIR) of the AT. METHODS: Twenty-four rats were subjected to a complete right-sided AT rupture, while the left side served as a control. ATs were harvested at 1, 2, 8 and 17 weeks post-rupture and stained with antibodies specific to Collagen type I (Col I) and II (Col II) as well as Alcian Blue and Picrosirius Red staining techniques. Histopathological changes, proteoglycan content, collagen alignment and immunoexpression were assessed. RESULTS: Both regions examined, IR and UIR, exhibited over weeks 1-17 similar healing adaptations of increasing collagen alignment, decreasing Col I immunoexpression, as well as increasing proteoglycan content and Col II occurrence. Increased proteoglycan content was found already at week 2 in the UIR, while it first increased at week 8 in the IR. The area positive to Col II was increased compared to controls at week 8 in the UIR, whereas it first raised at week 17 in the IR. Collagen disorganization successively declined to reach control levels at week 17 in the UIR, but was still higher in the IR. CONCLUSION: This study demonstrated that uninjured areas of the AT remote from the rupture site also undergo pronounced remodeling, although with time-span differences relative to injured AT portions. These changes including the pathologic heterotopic mineralization and chondrogenic differentiation observed in both regions may have implications in the choice of rehabilitation regimes in order to prevent secondary rupture.

Postoperative Thromboprophylaxis With New Oral Anticoagulants is Superior to LMWH in Hip Arthroplasty Surgery: Findings from the Swedish Registry.

BACKGROUND: Although the use of thromboprophylaxis is well established, there is no consensus on the preferred thromboprophylaxis regimen after THA; large, population-based studies offer an opportunity to examine this problem in a robust way that can complement results from randomized trials. QUESTIONS/PURPOSES: Using data from a large national registry, we asked: (1) Is there any difference between low-molecular weight heparin (LMWH) and new oral anticoagulants in preventing symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), after THA? (2) Are there any differences in safety parameters, such as bleeding, reoperations and mortality, between LMWH and new oral anticoagulants? METHODS: Between 2008 and 2012, 78,066 THAs were performed in Sweden. This study evaluated 32,663 (42%) of them, selected through the merger of several national registries. These patients underwent unilateral THA due to primary osteoarthritis. They had not experienced any venous thromboembolic events 5 years before the index operation and were not prescribed potent antithrombotic agents, of any type, in the 6 months before the index operation. Additionally, their postoperative thromboprophylaxis was confirmed in a national registry by purchase of prescribed medications. We divided the cohort into two groups: those patients who received new oral anticoagulants (5752, 18%) and those who received LMWH (26,881, 82%) as postoperative thromboprophylaxis. Our primary endpoints were the frequencies of symptomatic DVT and symptomatic PE within 3 months of surgery. Our secondary comparison was a between-group comparison of bleeding (by way of diagnostic coding), reoperation, and mortality within 3 months of surgery. Odds ratios (OR) are presented with 95% confidence intervals (CIs) as pooled results for the two groups after adjustment for duration of thromboprophylaxis (short or extended for at least 28 days), year of the index operation, Elixhauser comorbidity index, sex, age and previous treatment with platelet aggregation inhibitors. RESULTS: The risk of symptomatic DVT was lower in the group that received new oral anticoagulants than the group that received LMWH (0.3% versus 0.6%, OR, 0.47; 95% CI, 0.27-0.76; p = 0.026). The risk of symptomatic PE was lower in the group that received new oral anticoagulants than the group that received LMWH (0.1% versus 0.4%, OR, 0.36; 95% CI, 0.16-0.69; p = 0.005). There was no difference in the risk of bleeding (by way of diagnostic coding) (OR, 1.03; 95% CI, 0.82-1.28; p = 0.688), reoperation (OR, 1.02; 95% CI, 0.71-1.44; p = 0.860) or mortality (OR, 0.83; 95% CI, 0.31-1.88; p = 0.883) between groups. CONCLUSIONS: New oral anticoagulants were associated with a lower risk of symptomatic DVT and symptomatic PE in this large, registry study, and we observed no differences in the risk of bleeding, reoperation, or death between the groups. Although we were able to control for a number of potential confounding variables, we cannot ascertain the indications that drove the prescription decisions in this setting, and there were important between-group differences in terms of duration of thromboprophylaxis (new oral anticoagulants generally were used for a longer period of time after surgery). Future studies, preferably large randomized trials with pragmatic inclusion criteria, to analyze symptomatic DVT, symptomatic PE and death are needed to confirm or refute our findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer's disease.

See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.Subjects with mild cognitive impairment associated with cortical amyloid-ß have a greatly increased risk of progressing to Alzheimer's disease. We hypothesized that neuroinflammation occurs early in Alzheimer's disease and would be present in most amyloid-positive mild cognitive impairment cases. 11C-Pittsburgh compound B and 11C-(R)-PK11195 positron emission tomography was used to determine the amyloid load and detect the extent of neuroinflammation (microglial activation) in 42 mild cognitive impairment cases. Twelve age-matched healthy control subjects had 11C-Pittsburgh compound B and 10 healthy control subjects had 11C-(R)-PK11195 positron emission tomography for comparison. Amyloid-positivity was defined as 11C-Pittsburgh compound B target-to-cerebellar ratio above 1.5 within a composite cortical volume of interest. Supervised cluster analysis was used to generate parametric maps of 11C-(R)-PK11195 binding potential. Levels of 11C-(R)-PK11195 binding potential were measured in a selection of cortical volumes of interest and at a voxel level. Twenty-six (62%) of 42 mild cognitive impairment cases showed a raised cortical amyloid load compared to healthy controls. Twenty-two (85%) of the 26 amyloid-positive mild cognitive impairment cases showed clusters of increased cortical microglial activation accompanying the amyloid. There was a positive correlation between levels of amyloid load and 11C-(R)-PK11195 binding potentials at a voxel level within subregions of frontal, parietal and temporal cortices. 11C-(R)-PK11195 positron emission tomography reveals increased inflammation in a majority of amyloid positive mild cognitive impairment cases, its cortical distribution overlapping that of amyloid deposition.

Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty: pooled analysis of two phase 3 randomized trials.

BACKGROUND: Two phase 3 trials compared 28-35 days of treatment with oral dabigatran 220 mg or 150 mg (RE-NOVATE) or 220 mg (RE-NOVATE II) once daily with subcutaneous enoxaparin 40 mg once daily for prevention of venous thromboembolism (VTE) after elective total hip arthroplasty. METHODS: This prespecified pooled analysis compared the outcomes for the dabigatran 220 mg dose with enoxaparin, which included 4,374 patients. Total VTE (venographic and symptomatic) plus all-cause mortality (primary efficacy), major VTE (proximal deep vein thrombosis [DVT] or non-fatal pulmonary embolism) plus VTE-related death, and bleeding events were evaluated. Efficacy analysis was based on the modified intention-to-treat (ITT) population and safety analysis was based on all treated patients. The common risk difference (RD) for dabigatran versus enoxaparin was estimated using a fixed effects model. RESULTS: Total VTE and all-cause mortality occurred in 6.8 % (114/1,672) and 7.7 % (129/1,682) (RD:-0.8 %, 95 % confidence interval [CI] -2.6 to 0.9) for dabigatran and enoxaparin, respectively. Major VTE plus VTE-related mortality occurred in 2.7 % (46/1,714) and 4.0 % (69/1,711) (RD: -1.4 %, 95 % CI -2.6 to -0.2) of patients receiving dabigatran 220 mg and enoxaparin, respectively. Major bleeding occurred in 1.7 % (37/2,156) and 1.3 % (27/2,157) (RD: 0.5 %, 95 % CI -0.2 to 1.2), for dabigatran and enoxaparin respectively. CONCLUSIONS: Extended prophylaxis with oral dabigatran 220 mg once daily was as effective as enoxaparin 40 mg once daily in reducing the risk of total VTE and all-cause mortality after total hip arthroplasty, with a similar bleeding profile. The clinically relevant outcome of major VTE and VTE-related death was significantly reduced with dabigatran versus enoxaparin. TRIAL REGISTRATION: NCT00657150 and NCT00168818.

Nucleostemin- and Oct 3/4-positive stem/progenitor cells exhibit disparate anatomical and temporal expression during rat Achilles tendon healing.

BACKGROUND: The recent discovery of residing tendon stem/progenitor cells has triggered a growing interest in stem cells as a useful tool in tendon repair. Our knowledge of their involvement in naturally healing tendons is, however, sparse. The aim of this study was to identify and determine stem/progenitor cells in relation to different healing phases and regions in a rat model of Achilles tendon rupture. METHODS: Surgery was performed to create a mid-tendon rupture on the right Achilles tendon of 24 rats, whereas the left tendon was used as a control. Tendons were harvested at one, two, eight and 17 weeks post-rupture and stained with antibodies specific to stem/progenitor cells (Octamer-binding transcription factor 3/4 (Oct 3/4) and nucleostemin), migrating cells (Dynamin 2 (Dyn 2)) and leukocytes (CD45). A histological examination was performed on sections stained with Alcian blue. RESULTS: At one and two weeks post-rupture, a large number of stem/progenitor cells were discovered throughout the tendon. Most of these cells were nucleostemin positive, whereas only a few Oct 3/4-positive cells were found, mainly situated inside the injury region (I region). At eight and 17 weeks, the increment in stem/progenitor cells had diminished to equal that in the control tendons. At all time points, Oct 3/4-positive cells were also found in the connective tissue surrounding the tendon and at the muscle-tendon junction in both ruptured and control tendons and were often seen at the same location as the migration marker, Dyn 2. CONCLUSIONS: The whole length of the Achilles tendon is infiltrated by stem/progenitor cells at early time points after a mid-tendon rupture. However, different stem/progenitor cell populations exhibit varying anatomical and temporal expressions during Achilles tendon healing, suggesting distinct reparative implications. Oct 3/4 may thus act as a more local, migrating stem/progenitor cell involved in injury-site-specific regenerative effects, as compared to the more general proliferative role of nucleostemin-positive stem/progenitor cells.

Mental health nurses responding to suffering in the 21st century occidental world: accompanying people in their search for meaning.

Much of contemporary health and mental health practice pays little attention to suffering, and when it does, invariably suffering is conflated with pain. Within such views, the health care practitioner ought to be concerned with removing or stopping the suffering as, for many parts of the occidental world at least, suffering is regarded as antagonistic to the pursuit of happiness. However, it has been recognized since ancient times that the experience of suffering can give rise to growth. This view sees suffering as an inevitable aspect of the human condition and experience; as something that might need to be endured, minimized, relieved, explored for meaning and maybe even learned from. The former conceptualization of suffering leaves little, if any, room for the sufferer to be to be proud of his suffering and to consider it ennobling rather than degrading, and such views are highly congruent with the increased pathologizing of 'everyday life' and with that, the inexorable proliferation of pharmacological 'treatment'. Accordingly, we assert that there is a clear need for Psychiatric/Mental Health nurses to re-think their views of suffering and consider how they might help the person discover meaning in the experience; how they might accompany the individual on his/her suffering journey. We therefore identify a range of approaches and interventions that Psychiatric/Mental Health nurses can use when attempting to help those experiencing mental health-related suffering.

Ilizarov external fixation or locked intramedullary nailing in diaphyseal tibial fractures: a randomized, prospective study of 58 consecutive patients.

PURPOSE: The aim of this study was to compare the Ilizarov circular fixator (IL) and locked intramedullary nailing (IM). PATIENTS AND METHODS: Patients with isolated tibia shaft fractures were randomly allocated to either the IL (n = 31) or IM (n = 27) method. Conventional radiographs, postoperative pain assessment, self-appraisal scores and complications were evaluated. At the clinical 1-year follow-up, the patients were also evaluated by an independent observer. RESULTS: The minority of patients had open fractures, two and nine patients in the IM and IL groups, respectively. Eight patients in the IM group and four in the IL group sustained major complications (p = 0.107). In the IM group, two patients developed compartment syndrome, one deep infection, one hardware failure, one delayed union, one pseudarthrosis and two had a malunion. In the IL group, two patients developed pseudarthrosis and two had a malunion. Superficial pin-site infections were observed in 16 patients in the IL group. The fractures had healed radiographically at 12 weeks in both groups. At the 1-year follow-up, there were differences in pain (VAS) and satisfaction (VAS) scores in favor of IL treatment (VAS, p = 0.03 and p = 0.02, respectively). There were no differences between the groups with regard to range of motion (ROM) in the knee and ankle joints. The registration of local tenderness and pain revealed that there were 19 patients with anterior knee pain in the IM group and one in the IL group at the 1-year follow-up (p < 0.001). CONCLUSION: The IL is a safe and reliable alternative to IM for the treatment of tibial shaft fractures, with a low complication rate and good clinical outcome. Both treatments were well tolerated, but at the 1-year follow-up the patients in the IM group had more pain and were less satisfied. Finally, there was a high frequency of anterior knee pain in the IM group.

Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism.

The last decade has seen the evaluation of several new oral anticoagulants that directly target thrombin or activated factor X (FXa). All demonstrate a rapid onset of action, a low potential for food and drug interactions, and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. Those agents at the most advanced stages of clinical development are a direct thrombin inhibitor, dabigatran, and direct FXa inhibitors, rivaroxaban and apixaban. Dabigatran and rivaroxaban are approved in more than 70 countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty, and apixaban is being considered for approval by regulatory agencies for this indication. Dabigatran was shown in a large phase III trial to be more effective and safer than warfarin for the prevention of stroke or systemic embolism in patients with atrial fibrillation and has recently been approved for this indication. Edoxaban, an oral FXa inhibitor, is also being evaluated in phase III clinical trials. This review summarizes the pharmacology, clinical trial results, and future role of the new oral anticoagulants in clinical practice.

Treatment of distal tibial fractures with the Ilizarov external fixator--a prospective observational study in 39 consecutive patients.

BACKGROUND: The management of displaced distal tibial fractures is still controversial. The different internal fixation techniques are often burdened by relatively high complication rates. Minimally invasive techniques with ring fixators have been introduced as an alternative allowing immediate reduction and stabilization, avoiding a staged protocol. The aim of this prospective study was to analyze the clinical and radiographic outcome the Ilizarov technique in patients with distal metaphyseal tibial fractures, with or without intra-articular involvement. METHODS: Thirty-nine consecutive patients with isolated fractures treated with the Ilizarov technique were followed prospectively for one year. Depending on the type of fracture, 4 or 5 rings were used, in some cases with additional foot extension. Unrestricted weight-bearing was allowed in all cases. Pre- and post-operatively conventional radiographs, post-operative pain assessment and complications were evaluated. The function was evaluated clinically and with self-appraisal protocols: EQ-5D, NHP and FAOS. RESULTS: No patient developed compartment syndrome or deep venous thrombosis. Pin infections were frequent, but they were mostly superficial and were treated with antibiotics and/or the removal of isolated pins. Two patients required debridement. One of them had a deep infection and developed a residual deformity which was corrected and healed after re-operation. Another patient had a severe residual deformity. The fixator was removed after a median period of 16 weeks (range 11-30). The radiological results were poor in 5 patients but the overall self-appraisal showed satisfactory results in 36 patients. CONCLUSIONS: The Ilizarov method allowed early definitive treatment with a low complication rate and a good clinical outcome.

The Ilizarov external fixator--a useful alternative for the treatment of proximal tibial fractures. A prospective observational study of 30 consecutive patients.

BACKGROUND: In dislocated proximal tibial fractures, the most frequently used treatment is ORIF with screws and plates. Minimally-invasive techniques using external fixation are an alternative. The aim of this study was to analyse the clinical and radiological results using the Ilizarov technique in both uni- and bicondylar tibial fractures. METHODS: Thirty consecutive patients with isolated fractures of the proximal tibia were treated with the Ilizarov technique, 11 Schatzker I-IV with 2-3 rings and 19 Schatzker V-VI with 3-4 tibial rings and a femoral, hinged, two-ring extension. Unrestricted weight-bearing was allowed. Pre and post-operatively, conventional radiographs, computerized tomography scans, post-operative pain assessments and complications were evaluated. The knee function was evaluated with the EQ-5D, NHP and KOOS scores, as well as self-appraisal. RESULTS: All the fractures healed. Twenty-five patients achieved a range of motion better than 10-100º. The type I-IV fractures had a shorter operating time and hospital stay, as well as better knee flexion, and the self-appraisal indicated that they tolerated the treatment better. Pin infections occurred in 4% of the pin sites, but only two patients required debridement. Two patients developed compartment syndrome and underwent fasciotomy. No patient complained of functional knee instability. Two patients underwent a total knee arthroplasty because of residual pain. The overall result was judged as satisfactory in twenty-seven patients. CONCLUSIONS: The Ilizarov method produces a good clinical outcome and is a valuable treatment alternative in proximal tibial fractures of all types.

Detection of slow-cycling and stem/progenitor cells in different regions of rat Achilles tendon: response to treadmill exercise.

PURPOSE: Tendons generally exhibit poor healing capacity, probably due to slow cell regeneration potential and low vascularization. The potential to regenerate may partly be due to activation of stem/progenitor cells localized in the tendon or its vicinity. In the present study, we attempted to determine where in the rat Achilles tendon stem/progenitor cells reside and to investigate the effect of exercise on cell proliferation in the in vivo situation. METHOD: We used bromodeoxyuridine (BrdU) labelling to investigate proliferation and label-retaining cells (i.e. slow-cycling cells) in non-exercised and exercised rats, in combination with immunostaining of the stem cell marker nucleostemin. Rat Achilles tendons were harvested 14, 28, 56 and 105 days after BrdU administration. RESULTS: We found the proportion of stem/progenitor cells to be twice as high in the distal tendon (DT) compared with the mid/proximal tendon (MPT) and that paratenon/endotenon regions appear to host a pool of existing stem/progenitor cells. Exercise increased the BrdU-stained cell population after 14 days only (DT region p = 0.032, MPT p = 0.065), indicating effect mainly on more differentiated cells, since the nucleostemin-positive cells (i.e. stem/progenitor cells) remained unaffected in the intact Achilles tendon. CONCLUSION: Stem/progenitor cells exist in several areas of the rat Achilles tendon which implies a possible stem cell regeneration pool of different origins. The distal region has twice the amount of stem/progenitor cells compared with the mid/proximal region, indicating a potentially higher stem cell activity in this tissue. Daily moderate exercise (treadmill running) mainly improves in vivo cell proliferation in rapidly proliferating cells, whereas the stem/progenitor pool remains constant.

Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses.

Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses.

Type of anaesthesia and the safety and efficacy of thromboprophylaxis with enoxaparin or dabigatran etexilate in major orthopaedic surgery: pooled analysis of three randomized controlled trials.

BACKGROUND: There has been a shift towards greater use of neuraxial over general anaesthesia for patients undergoing total hip or knee arthroplasty. Furthermore, suggestions that peripheral nerve block may reduce adverse effects have recently been put forward. Although older studies showed a reduction in venous thromboembolism (VTE) with neuraxial compared with general anaesthesia, this difference has not been confirmed in studies using effective current thromboprophylaxis. We used a large data set to investigate the pattern of anaesthesia usage, and whether anaesthesia type affects efficacy and bleeding outcomes of thromboprophylaxis overall, within each treatment group, or for the novel oral anticoagulant dabigatran etexilate versus enoxaparin. METHODS: Three previously reported trials compared 220 mg and 150 mg dabigatran etexilate once daily with enoxaparin after knee or hip arthroplasty. A pooled analysis was performed in patients receiving general or neuraxial anaesthesia, or the combination of either with peripheral nerve block (n = 8062). Outcome measures were major VTE plus VTE-related mortality, major bleeding and major plus clinically relevant bleeding events. RESULTS: General, neuraxial and combination anaesthesia were used in 29%, 52% and 19% of patients, respectively. Differences in efficacy and safety between anaesthesia subgroups were small and not significant, except for a slightly higher rate of major VTE and VTE-related mortality with general versus neuraxial anaesthesia (odds ratio: 1.40; 95% confidence interval: 1.03-1.90; p = 0.035) in the overall population. There were no significant effects of anaesthesia type on efficacy or safety of dabigatran etexilate versus enoxaparin. CONCLUSIONS: Anaesthesia type did not greatly affect efficacy and safety outcomes in the pooled population of all three treatment groups. The efficacy and safety of dabigatran etexilate was comparable with enoxaparin, regardless of type of anaesthesia. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00168805, NCT00168818, NCT00152971.

Variability in leg muscle power and hop performance after anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this prospective study was to describe the variability in leg muscle power and hop performance up to 2 years among patients following ACL reconstruction and specifically to illustrate the effects of various criteria for an acceptable level of muscle function. METHODS: Eighty-two patients (56 men and 26 women)with a mean age of 28 years, who underwent ACL reconstruction using either hamstring tendons (n = 46) or a patellar tendon (n = 36), were assessed pre-operatively and 3, 6, 12 and 24 months post-surgery with a battery of three lower extremity muscle power tests and a battery of three hop tests. RESULTS: Leg symmetry index (LSI) values at group level ranged between 73 and 100% at all follow-ups. When the tests were evaluated individually, patients reached an average LSI of ≥ 90% at 24 months. The success rate at 24 months for the muscle power test battery, that is,patients with an LSI of ≥ 90% in all three tests, was 48 and 44% for the hop test battery. The success rate at 24 months for both test batteries on all six muscle function tests was 22%. The criterion of an LSI of ≥ 80% resulted in 53% of the patients having an acceptable level on all six tests,while with a criterion of an LSI of ≥ 100%, none of the patients reached an acceptable level. CONCLUSION: At group level and in single muscle function tests, the muscle function outcome 1 and 2 years after ACL reconstruction is satisfactory in the present study and on a par with the results presented in the literature. However,when using more demanding criteria for a successful muscle function outcome, using batteries of tests or increasing the acceptable LSI level from ≥ 90% to ≥ 95%or ≥ 100%, the results are considered to be poor. It is suggested that this should be taken into consideration when presenting results after ACL rehabilitation, deciding on the criteria for a safe return to sports, or designing rehabilitation programmes after ACL reconstruction. LEVEL OF EVIDENCE: Prognostic prospective cohort study, Level I.

Thromboprophylaxis in patients older than 75 years or with moderate renal impairment undergoing knee or hip replacement surgery [corrected].

PURPOSE: Prospective, double-blind studies in orthopaedic patients have been conducted using the direct thrombin inhibitor dabigatran etexilate (hereafter referred to as dabigatran), with two doses investigated and approved for adults (220 mg and 150 mg once daily) to prevent venous thromboembolism (VTE). The European Medicines Agency decided that in major joint orthopaedic surgery, the lower dose should be used in elderly patients (aged over 75 years) and those with reduced renal function (creatinine clearance between 30 and 50 ml/min). Our objective was to understand the efficacy and bleeding data for the lower dose in this subpopulation. METHODS: We extracted and analysed data from the elderly or from moderately renally impaired patients (n 632 of = 5,539) from the orthopaedic clinical development programme of dabigatran. RESULTS: Dabigatran 150 mg once daily was as effective as the standard European enoxaparin regimen, with numerically fewer major bleeding events. Rates of major VTE were 4.3% vs 6.4% of patients, respectively. Major bleeding events occurred in four (1.3%) vs 11 (3.3%), which shows a trend towards lower bleeding with dabigatran 150 mg [odds ratio (OR) 0.40; 95% confidence interval (CI) 0.13-1.25; p = 0.110]. Mean volume of blood loss was 395 vs 417 ml, and transfused units were 2.4 vs 2.5, respectively. Other safety parameters, including the incidence of wound infections and complications, were similar for 150 mg once daily dabigatran and enoxaparin. CONCLUSION: For patients at higher risk of bleeding, dabigatran 150 mg once daily is as effective as enoxaparin following major orthopaedic surgery and is associated with a favourable bleeding rate.

The Meaning of Social Support in Nature-Based Services for Young Adults with Mental Health Problems.

In previous studies, social context and social support have been found to be important in nature-based services. However, no studies have previously focused on the meaning of different dimensions of social support in these contexts. The aim of this study is therefore to uncover dimensions of social support in relation to mental health among young adults with mental health problems participating in nature-based services in Norway. This study applies data from a survey of 93 young adults participating in nature-based services; in addition, qualitative interview data from 20 interviews are also used. The data are analysed using qualitative content analysis, descriptive statistics, and correlation analysis. The results indicate that participants in nature-based services experience emotional, esteem, informational, and instrumental support in addition to social integration and opportunities for nurturance in these services. The service leader, other participants, and the animals are important contributors to these dimensions of social support. Nature-based services may be a helpful intervention for young adults with mental health problems. The unique context of these services, including nature and animals, adds special qualities to mental health and social work practices.

Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty.

BACKGROUND: This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty. METHODS: In this randomized, double-blind study, we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily, beginning after surgery, or 40 mg of enoxaparin subcutaneously once daily, beginning the evening before surgery, plus a placebo tablet or injection. The primary efficacy outcome was the composite of deep-vein thrombosis (either symptomatic or detected by bilateral venography if the patient was asymptomatic), nonfatal pulmonary embolism, or death from any cause at 36 days (range, 30 to 42). The main secondary efficacy outcome was major venous thromboembolism (proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death from venous thromboembolism). The primary safety outcome was major bleeding. RESULTS: A total of 3153 patients were included in the superiority analysis (after 1388 exclusions), and 4433 were included in the safety analysis (after 108 exclusions). The primary efficacy outcome occurred in 18 of 1595 patients (1.1%) in the rivaroxaban group and in 58 of 1558 patients (3.7%) in the enoxaparin group (absolute risk reduction, 2.6%; 95% confidence interval [CI], 1.5 to 3.7; P<0.001). Major venous thromboembolism occurred in 4 of 1686 patients (0.2%) in the rivaroxaban group and in 33 of 1678 patients (2.0%) in the enoxaparin group (absolute risk reduction, 1.7%; 95% CI, 1.0 to 2.5; P<0.001). Major bleeding occurred in 6 of 2209 patients (0.3%) in the rivaroxaban group and in 2 of 2224 patients (0.1%) in the enoxaparin group (P=0.18). CONCLUSIONS: A once-daily, 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily, 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty. The two drugs had similar safety profiles. (ClinicalTrials.gov number, NCT00329628.)

Selective frontal neurodegeneration of the inferior fronto-occipital fasciculus in progressive supranuclear palsy (PSP) demonstrated by diffusion tensor tractography.

BACKGROUND: The clinical presentation in progressive supranuclear palsy (PSP), an atypical parkinsonian disorder, includes varying degrees of frontal dysexecutive symptoms. Using diffusion tensor imaging (DTI) and tractography (DTT), we investigated whether diffusion changes and atrophy of the inferior fronto-occipital fasciculus (IFO) occurs in PSP and if these changes correlate with disease stage and clinical phenotype. The corticospinal tract (CST), which is often involved in PSP, was investigated for comparison. METHODS: DTI of the whole brain was performed with a 3 T MR scanner using a single shot-EPI sequence with diffusion encoding in 48 directions. Scans were obtained in patients with PSP (n = 13) and healthy age-matched controls (n = 12). DTT of the IFO and CST was performed with the PRIDE fibre tracking tool (Philips Medical System). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated and correlated with disease stage and clinical phenotype. RESULTS: In patients with PSP, significantly decreased FA and increased ADC was found in the frontal part of IFO compared with the medial and occipital parts of IFO, as well as compared to controls. Four of the thirteen patients with PSP showed a marked decrease in the number of tracked voxels in the frontal part of IFO. These findings were most pronounced in patients with severe frontal cognitive symptoms, such as dysexecutive problems, apathy and personality change. There was a strong correlation (r2 = -0.84; p < 0,001) between disease stage and FA and ADC values in the CST. CONCLUSIONS: DTT for identification of neuronal tracts with subsequent measurement of FA and ADC is a useful diagnostic tool for demonstrating patterns of neuronal tract involvement in neurodegenerative disease. In selected tracts, FA and ADC values might act as surrogate markers for disease stage.

Will early reconstruction prevent abnormal kinematics after ACL injury? Two-year follow-up using dynamic radiostereometry in 14 patients operated with hamstring autografts.

PURPOSE: Previous studies have reported that Anterior Cruciate Ligament (ACL) reconstruction does not restore normal tibial rotation in patients with chronic instability and repeated episodes of giving way. We hypothesised that early ACL reconstruction, using quadruple hamstring autografts, before the pivoting episodes had occurred, would protect the knee joint from developing abnormal kinematics with increased external tibial rotation during flexion. METHODS: Fourteen consecutive patients (8 men, 6 women) with a median age of 24 years (18-43), with a complete, isolated unilateral ACL rupture and an intact contralateral knee, were studied. The operations were performed by one experienced surgeon, using quadruple hamstring autografts. We used dynamic radiostereometry (RSA) with tantalum markers inserted in both the injured and the intact contralateral knee to study the pattern of knee motion during active and weight-bearing knee extension. The patients were evaluated pre-operatively and followed for 2 years after the ACL reconstruction. The anterior-posterior laxity was measured using the KT-1000. RESULTS: Before surgical repair of the ACL, the internal/external tibial rotation or abduction/adduction did not differ significantly between the injured and intact knees (P = 0.27-0.91). Separate studies of the anterior-posterior translation of the medial and lateral femoral flexion facet centres (MFC and LFC) relative to a fixed tibia did not reveal any significant differences between the injured and intact knees (P = 0.21-0.59). Pre-operatively, the KT-1000 laxity measurements showed a side-to-side difference of 2.5 (1.0-5.5) mm. At 2 years, the laxity side-to-side difference was 0.5 (0-3.0) mm (P = 0.001), and there were still no significant differences between the injured and intact knees in terms of internal/external tibial rotation and abduction/adduction (P = 0.13-0.60). Nor did the anterior-posterior translation of the flexion facet centres differs (P = 0.27-0.97). CONCLUSION: During the first 6-8 weeks after the ACL injury, before pivoting episodes had occurred, the kinematics of the injured knee were normal and did not differ from those of the intact contralateral knee. Reconstruction of the ACL within 10 weeks after injury using quadruple hamstring autografts resulted in unchanged knee kinematics for 2 years and no difference compared with the intact contralateral knee. Surgical repair during the early phase after the injury appears to protect the knee from developing abnormal knee motion after an ACL rupture. LEVEL OF EVIDENCE: III.

Major functional deficits persist 2 years after acute Achilles tendon rupture.

PURPOSE: The purpose of this prospective randomized controlled study was to evaluate the long-term results after an acute Achilles tendon rupture in patients treated surgically or non-surgically. The focus was to evaluate whether any improvements occurred between the one and 2-year evaluation. METHOD: Eighty-one patients (67 men, 14 women) with a mean (SD) age of 42 (9.1) were included in this study. Forty-two patients were treated surgically, and 39 treated non-surgically otherwise the treatment was identical for the two groups. All patients were evaluated using the Achilles tendon Total Rupture Score (ATRS), the Physical Activity Scale (PAS) and validated functional tests one and 2 years after injury. RESULTS: There were significant functional deficits on the injured side compared with the contralateral side 2 years after Achilles tendon rupture, regardless of treatment. Only minor improvements, even though statistically significant, occurred between the 1- and 2-year evaluations. The physical activity level remained significantly reduced as compared with prior to injury, but the ATRS mean was relatively high in both groups (89 and 90). CONCLUSION: This long-term follow-up indicates that the majority of patients with an Achilles tendon rupture have not fully recovered (in regards to symptoms, physical activity level and function) 2 years after injury regardless of surgical or non-surgical treatment. Furthermore, only minor improvements occur between the 1- and 2-year evaluations. This indicates that to enhance the final outcome the focus should be on improvements in treatment within the first year. The patients appear to have adjusted to their impairments since the patient-reported outcome is relatively high in spite of functional deficits and lower activity level compared with pre-injury. LEVEL OF EVIDENCE: Prospective randomized study, Level I.