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OBJECTIVES: To investigate the effects of lower limb strength training in addition to neuromuscular exercise and education (ST + NEMEX-EDU) compared to neuromuscular exercise and education alone (NEMEX-EDU) on self-reported physical function in patients with knee osteoarthritis (KOA). DESIGN: Patient-blinded, parallel-group randomized controlled trial (RCT). METHODS: The trial included 90 patients in secondary care with radiographic and symptomatic KOA, ineligible for knee replacement. Both groups exercised twice weekly for 12 weeks. Additional strength training consisted of a single, fatiguing knee extension set (30-60RM) before four sets of leg-press (8-12RM). Primary outcome was the between-group difference on the subscale activities of daily living from the Knee Injury and Osteoarthritis Outcome Score (KOOSADL) at 12 weeks. Secondary outcomes included KOOS symptoms, pain, function in sport and recreation, and quality of life, 40 m walk, stair climb, leg extension power, EuroQol-5D-5L, pain medication usage, and adverse events. RESULTS: There was no statistically significant between-group difference in KOOSADL at 12-weeks; adjusted mean difference -1.15 (-6.78 to 4.48). Except for the stair climb test, which demonstrated an adjusted mean difference of 1.15 (0.09-2.21) in favor of ST + NEMEX-EDU, all other outcomes showed no statistically significant between-group differences. Neither group improved leg extension power. CONCLUSION: The addition of lower-limb strength training, using a low-dose approach, to neuromuscular exercise and education carried no additional benefits on self-reported physical function or on most secondary outcomes. Both groups displayed similar improvements at 12-week follow-up. Hence, the current low-dose strength training approach provided no additional clinical value in this group of KOA patients. Trial identifier (ClinicalTrials.gov): NCT03215602.

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The membrane-type 1 matrix metalloproteinase (MT1-MMP) drives fundamental physiological and pathophysiological processes. Among other substrates, MT1-MMP cleaves components of the extracellular matrix and activates other matrix-cleaving proteases such as MMP-2. Trafficking is a highly effective means to modulate MT1-MMP cell surface expression, and hence regulate its function. Here, we describe the complex interaction of MT1-MMP with tetraspanins, their effects on MT1-MMP intracellular trafficking and proteolytic function. Tetraspanins are credited as membrane organizers that form a network within the membrane to regulate the trafficking of associated proteins. In short, we found MT1-MMP to interact with the tetraspanin-associated EWI-2 protein by a yeast two-hybrid screen. Immunoprecipitation analysis confirmed this interaction and further revealed that MT1-MMP also stably interacts with distinct tetraspanins (CD9, CD37, CD53, CD63, CD81, and CD82) and the tetraspanin-like MAL protein. By using different MT1-MMP truncation constructs and mutants, we observed that all tetraspanins and MAL associated with the hemopexin domain of MT1-MMP. Moreover, this interaction was independent of O-glycosylation of MT1-MMP and exclusively occurred in the endoplasmic reticulum. Here, the respective subcellular compartment was identified by fitting the MT1-MMP interaction pattern to a model for post-translational processing of MT1-MMP. In addition, tetraspanins differentially affected the cell surface localization of MT1-MMP, its capacity to activate pro-MMP-2, and the collagen invasion capacity. Interestingly, the degree of tetraspanin-MT1-MMP association did not correlate with its impact on MT1-MMP function. Tetraspanins thus distinctly affect MT1-MMP subcellular localization and function, and may constitute an effective mechanism to control MT1-MMP-dependent proteolysis at the cell surface.

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BACKGROUND: Bioactive coating of uncemented total knee arthroplasty (TKA) is believed to increase bone ingrowth and enhance early fixation of the TKA. In a prospective randomized study using radiostereometric analysis (RSA) we examined migrations of the tibial implant, in an uncemented TKA with and without bioactive coating. The study was performed according to new RSA guidelines, and focus was put on some important methodological issues. MATERIALS AND METHODS: Twenty-three patients with osteoarthrosis of the knee received an uncemented Duracon TKA either with bioactive (hydroxyapatite or periapatite) coating (+HA) or without bioactive coating (-HA). Patients had RSA examinations postoperatively and at 3, 6 and 12 months. Nine patients were excluded during the study resulting in 14 knees for final analysis. RESULTS: At 12 months follow-up we found no significant differences in migrations between the two groups. However, in general the -HA group migrated more than the +HA group, and we found a significant larger variation in migration pattern in the -HA group. In the +HA group the tibia component stabilized after 6 months, whereas the -HA group showed continuous migration. Subsidence and posterior tilt were the main migration patterns in both groups. CONCLUSIONS: Bioactive coating of TKA seems to enhance early stabilization of the tibia component. Similar results are found in previous studies.

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Due to the ongoing activities to introduce the Disease Related Groups into the German health system, the PSAPOH (Psychosocial Working Group of Pediatric Oncology and Hematology) has initiated a multicenter study to evaluate relevant parameters regarding the amount of psychosocial care in children and adolescents suffering from malignant diseases. This study was performed in 26 German hospitals over three months and evaluated the kind of psychosocial interventions, their duration and frequency and, in addition, their quality. The data collected were evaluated according to the diagnosis, the phase of disease when collecting the data, the psychosocial diagnosis and the grade of risk for psychosocial strain (standard strain [S], multidimensional strain [M] and extreme strain [H]). The results showed no significant differences comparing the amount of psychosocial care within the various kinds of hematological-oncological diseases. But, as expected, a significant and statistically proven increase of the frequency and duration of psychosocial treatment was found according to the stage of the disease and the psychosocial strain. The frequency of treatment is increasing up to 70 % comparing groups with standard strain to groups with extreme strain. Summarizing the amount of psychosocial care within the different phases of disease, a calculation of costs will be possible for each patient.

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We report the results of 114 AGC 2000 porous-coated, cementless total knee arthroplasties (TKA) performed consecutively in 102 patients during the period 1984-1986. After 10 years, 58 TKAs in 52 patients were evaluated with patient assessment, Hospital for Special Surgery knee score, weight-bearing radiographs done under fluoroscopic control, and survivorship analysis. All dropouts within the first 9 years were patients dying with a functioning TKA except 1 revision secondary to a supracondylar fracture after 8.5 years. Of the patients, 53 (92%) were satisfied or very satisfied with their TKA, and 55 (95%) of the knees were rated good or excellent. There was no pain in 53 knees, and the median knee flexion was 110 degrees. Six radiolucencies >1 mm were found beneath parts of the tibial component, and 5 radiolucencies were seen beneath the femoral component. None had progressed compared with the 5-year follow-up, and in all cases trabeculae could be seen reaching the prosthetic component. No migrations had occurred since the 5-year follow-up. No obvious joint space reduction was seen. Osteolysis presenting as an isolated cyst was found in 1 knee in the lateral tibial condyle and was not progressive. Two tibial components had been revised because of aseptic loosening and 1 because of septic loosening, all within the first 3 years. No femoral or patellar components were revised. The cumulative prosthesis survival rate after 10 to 11 years was 97%. When pain and radiographic loosening also were considered, the success rate was 87%. Cementless insertion of a nonmodular, porous-coated TKA resulted in a long-term durable bone-prosthesis interface. The flat-on-flat articulation did not result in catastrophic polyethylene wear or osteolysis within the first 10 years.

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The effect of a total knee arthroplasty (TKA) on maintaining or restoring working ability for patients who preoperatively still were in active employment has not previously been reported. Between February 1989 and December 1990 a total of 926 patients (1024 knees) had the same type of TKA (AGC-2000) implanted at 14 different Danish hospitals. The patients were followed prospectively. Sixty-two patients (6.7% of the total material) were preoperatively registered as being still engaged in active employment. Follow-up after three years included 51 of these patients (with 62 knees). Fifty-eight percent were still working after three years compared to 79% after the first postoperative year. Only eight out of the 21 who quit their job during the follow-up period stated knee-trouble as being the direct cause. The most common reason for stopping work was ordinary age-determined pension. We found no correlation between the amount of occupational knee-load and the relative risk of not being able to continue working. Thus, four out of five patients who are employed preoperatively will generally be able to return to the same job within a year after a TKA.

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We analyzed prospectively the 5-year survival in 926 patients undergoing 1,024 total knee arthroplasties (TKA) in the period February 1989-December 1990. The patients were compared to an age- and sex-matched general population and to 326 patients operated on in the same period with total hip arthroplasty. Cox analysis showed that male sex, rheumatoid arthritis and complications within the first year increased the mortality rate in the TKA group. When this group was compared to the general population, only rheumatoid patients aged 65-74 years had an increased mortality. Generally, the TKA patients had a longer survival than the general population, especially women > 75 years old with arthrosis. The cumulative 5-year patient survival was 89%, both after hip and knee arthroplasty and was 81% in the matched general population.

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Fifty-one primary consecutive cementless AGC 2000 (Anatomically Graduated Components, Biomet, Warsaw, IN) total knee arthroplasties were performed during 1985 through 1990 in 40 patients with rheumatoid arthritis. Forty-one knees (32 patients) were available for clinical and radiologic follow-up analysis after 24 to 76 months (median, 54 months). There was no pain in 33 knees and mild pain in the rest. Median range of motion was 110 degrees (range, 50 degrees-130 degrees). Median knee score was 90 (range, 71-97), and all knees were rated good or excellent. Radiolucencies greater than 1 mm were found under five tibial components, but no obvious migrations were seen. One tibial component was revised due to aseptic loosening. The cumulative success rate after 4 to 5 years was 97% (lower limit of 95% confidence interval, 91.8%). The medium-term results are considered to compare favorably with reported cemented series.

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From 1970 to 1986 a total of 4578 hip fractures were registered in persons > or = 40 years in a Danish urban municipality. During that period, the annual number almost tripled. The statistical analysis revealed an increase in the age-specific incidence for both females and males (p < 0.0001). Furthermore, the number of fractures increased due to demographic aging. The overall incidence for individuals > or = 40 years increased 9-10% annually; from 2.1 to 5.4 per 1.000 females, and from 0.9 to 2.1 per 1.000 males. The female:male ratio was 2.8 without changes over time. If the observed increase in incidence is extrapolated to the next 17 years, a doubling of the annual number of fractures is predicted by the year 2002, whereas an unchanged incidence would result in a 20% increase in number.

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This retrospective study included 1812 hip-fracture patients 40 years of age or older who did not receive prophylactic anticoagulation. Two hundred seventy-three patients (15.1%) died within 90 days after hospitalization. In 180 autopsies, 27 cases of major pulmonary embolism (PE), defined as occluding at least one lobar or several segmental arteries, were found. Based on an autopsy frequency of 72%, a rate of 1.4% major PEs during the first 30 days could be estimated. No major PE was found among patients with femoral neck fractures treated conservatively or by internal fixation or among patients younger than 66 years of age.

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During a 16-year period, 256 second hip fractures were found in 3898 persons 40 years of age and older who had a previous hip fracture. Ninety-two percent of the second fractures were contralateral, and 68% of these were the same type as the first. Thus, 62% of the femoral neck and 72% of the trochanteric fractures were preceded by a contralateral fracture of the same type. The mean interval between fractures was 3.3 years, and there was no significant difference between genders or among fracture types. The risk of the first fracture was 1.6 per 1000 men per year and 3.6 per 1000 women, and for the second fracture 15 per 1000 men per year and 22 per 1000 women. This increase was highly significant for both genders, especially for men.

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Between 1970 and 1985, a total of 3,895 persons > or = 40 years of age were treated for hip fracture in a Danish municipality. The female: male ratio was 2.7. The cumulative survival was estimated and compared with that of the age- and sex-matched general population. The analysis showed that (a) the mortality was increased compared with the expected mortality, especially during the first year (19% for women, 25% for men), but a statistically significant excess mortality could be demonstrated up to 10 years after a hip fracture; (b) the mortality increased with age, even after adjustment for the expected higher mortality of the elderly; and (c) the mortality was higher for men than for women, even after adjustment for the expected higher mortality of males. This difference was already present after the first 2 weeks among patients > or = 70 years of age.

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A one-year prospective study of injuries caused by violence was performed at the two casualty wards and at the Institute of Forensic Medicine in Arhus, and the results were compared with those of a similar study done six years earlier. Whereas the population at risk increased by 4% to just over a quarter of a million, the number of cases increased by 14% to 1874 (p = 0.06) and the number of persons by 17% to 1726 (p = 0.01). The overall incidence increased for females from 3.0 to 3.7 per 1000 (maximum 7.4 per 1000 females 35-39 years old), and for males from 10.6 to 11.1 per 1000 (maximum 33.4 per 1000 males 15-19 years old). Statistically significant increase of age-specific incidence rates was only found among females 35-49 years old, where, however, also the largest frequency of repeated registrations was noted. As in the former investigation, almost three-fourths of male violence took place at bars and discotheques or on the street, usually associated with unknown person(s), whereas one-half of female violence occurred at home with the partner as the most frequent counterpart. Police recorded cases increased from 16 to 22% (p less than 0.05).

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Between April 1987 and April 1988, all assault victims attending the two casualty wards and the Institute of Forensic Medicine in Arhus were registered, and an extensive questionnaire was completed by the casualty ward physician. These data were compared with the data from an analogous study undertaken six years earlier. A total of 1874 patients were victims of personal violence in 1987 compared to 1639 in 1981. The most common cause of injury was one or more blows from a fist and/or kicks (used in approximately 70% of all cases). The present study demonstrated an increasing use of firearms and assaults involving attempts to strangle the victim. Ninety-eight percent of the injuries were classified as no injury or AIS-grade 1-2 in both 1981 and 1987. The number of AIS-grade 2 injuries increased from 1981 to 1987 due to an increased number of facial injuries, but the number of homicides and AIS-grade 4-6 injuries decreased in the interval. Based on the present study, it is concluded that the severity of interpersonal violence did not increase in the Arhus area in the 1980s.

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The cost and time of hospitalization were analysed for 4161 hip fractures in 3898 patients aged 40 years or over treated in a Danish municipality from 1970 to 1985. The mean hospitalization time decreased from 32 to 21 days (P less than 0.0005). This tendency was most pronounced for patients who were treated with osteosynthesis. However, the annual number of fractures increased from 134 to 367. Consequently, the bed use rose 79 per cent. As the number of hip fractures is predicted to increase further, the total number of bed-days required by these patients will probably also continue to increase. In addition, the standard expense per day for a hospitalized orthopaedic patient increased from 372 to 2982 DKK. Thus, the mean expense per patient was 12,000 DKK in 1970 versus 63,000 in 1985, i.e. the total expense increased 1433 per cent. After adjustment for price indexes the increase was 362 per cent. The total cost of acute hospital care of hip fractures in Denmark was estimated to be greater than 0.5 billion DKK in 1985.

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As part of a one-year prospective investigation of all violent accidents in Arhus undertaken in the casualty departments and the Medicolegal Institute, the extent and severity of street violence were analysed and compared with violence in and near pubs. Street violence constituted 26% of all accidents due to violence and involved 1.3 persons per day. 75% were blameless and 68% of these were attacked outside the region where they lived. Violence in the street, in pubs and in the vicinity of pubs was concentrated in the centre of the city, in the evening and night hours, at weekends and involved young men. Street violence and violence in the vicinity of pubs differed from violence in pubs in that significantly more of the victims were blameless (approximately 75%), several persons were the perpetrators (approximately 40%) and blows and kicks were combined (approximately 15%). As assessed by the Abbreviated Injury Scale (AIS), the lesions sustained in street injury did not differ from those of violence in or near pubs: 86% were minor injuries, 11% moderate and none proved fatal. 75% of the victims could be treated completely in the casualty department or by the general practitioner or dentist. Street violence is concentrated to the middle of the city, at weekends and in the evening and night hours and is similar in many ways to violence in and near pubs. The authors consider that exposure to street violence is, to a great extent, connected with participation in night life of the city.

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As part of a one-year prospective investigation of accidents due to violence in Arhus carried out by the casualty departments and the Institute of Forensic Medicine in cooperation with the Arhus Police and the Crisis centre for female victims of violence, the fraction of violence which involved women was analysed. A total of 492 contacts were received from 424 women. The average age was 32 years. The home was the commonest site of violence with the husband as the commonest perpetrator of violence (192). In 98 cases the perpetrator was unknown. The majority had received blunt injuries (blows and/or kicks). The lesions frequently appeared to be limited from a therapeutic viewpoint. In 143 women, however, the lesions were potentially serious. Thirteen women were hospitalized and 60 were referred for treatment in other departments. Violence was commonest in the evening and night hours and there was a tendency to an increase towards the end of the week. The majority (279) stated that the episode was not their fault. The police were contacted in 25% of the cases. A total of 164 requests were made for access to the Crisis Centre by female victims of violence. Of these, 30 women had been seen by a doctor and 23 had previously been hospitalized. Compared with conditions five years previously, a considerable increase in the number of registered violent accidents to women was observed. On the other hand, no definite evidence was found that the nature of the violence to which they had been exposed had altered during the past five years.

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