Intra-articular injection of gold micro-particles with hyaluronic acid for painful knee osteoarthritis.

BACKGROUND: Recently, in an open pilot study, we found up to two years, a potential pain-relieving effect of intra-articular gold micro-particles using the patient's synovial fluid for patients with knee osteoarthritis (KOA). During the study the excluded group of patients, due to multisite pain, co-morbidities, and other exclusion criteria., received intra-articular gold micro-particles using hyaluronic acid,. We aimed to identify if pre-treatment characteristics influence the global outcome two years after intra-articular treatment for painful KOA with gold microparticles using hyaluronic acid. METHODS: Using hyaluronic acid as the carrier, 136 patients with KOA received intraarticular injections with 20 mg gold microparticles (72.000 particles, 20-40 µm in diameter). In the analysis, we included the Global Rating of Change Scale, Pain Detect Questionnaire (PDQ), Body Mass Index (BMI), and Kellgren & Lawrence score at the inclusion, Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) sub-scores for pain, stiffness, and function at inclusion and two years. RESULTS: On the Global Rating Change Scale, 69.1% of patients reported a positive effect, 28.7% no effect, and 2.2% worse. PDQ and the three WOMAC subscores all improved at two years of follow-up. PDQ ≥ 13 (P = 0.028), BMI (P = 0.022) and Kellgren & Lawrence grade 4 (P = 0.028) at inclusion reduced the effect with a minor odds ratio compared to the baseline effect of treatment (P = 0.025). WOMAC subscores at inclusion did not influence the outcome (P > 0.5). CONCLUSIONS: Severe osteoarthritis, obesity, and neuropathic pain, reduced the effect of intra-articular gold microparticles for knee OA. TRIAL REGISTRATION: The study followed the principles of the Declaration of Helsinki and was approved by the local ethics committee of the North Denmark Region by 27/07/2016 (N-20,160,045). The regional data protection agency approved the project by 06/07/2016 (2008-58-0028, ID 2016 - 116) and registered in ClinicalTrial.Gov by 04/01/2018 (NCT03389906).

Simulation-based assessment of upper abdominal ultrasound skills.

BACKGROUND: Ultrasound is a safe and effective diagnostic tool used within several specialties. However, the quality of ultrasound scans relies on sufficiently skilled clinician operators. The aim of this study was to explore the validity of automated assessments of upper abdominal ultrasound skills using an ultrasound simulator. METHODS: Twenty five novices and five experts were recruited, all of whom completed an assessment program for the evaluation of upper abdominal ultrasound skills on a virtual reality simulator. The program included five modules that assessed different organ systems using automated simulator metrics. We used Messick's framework to explore the validity evidence of these simulator metrics to determine the contents of a final simulator test. We used the contrasting groups method to establish a pass/fail level for the final simulator test. RESULTS: Thirty seven out of 60 metrics were able to discriminate between novices and experts (p < 0.05). The median simulator score of the final simulator test including the metrics with validity evidence was 26.68% (range: 8.1-40.5%) for novices and 85.1% (range: 56.8-91.9%) for experts. The internal structure was assessed by Cronbach alpha (0.93) and intraclass correlation coefficient (0.89). The pass/fail level was determined to be 50.9%. This pass/fail criterion found no passing novices or failing experts. CONCLUSIONS: This study collected validity evidence for simulation-based assessment of upper abdominal ultrasound examinations, which is the first step toward competency-based training. Future studies may examine how competency-based training in the simulated setting translates into improvements in clinical performances.

nanoGold and µGold inhibit autoimmune inflammation: a review.

The newest data on metallic gold have placed the noble metal central in the fight for the safe treatment of autoimmune inflammation. There are two different ways to use gold for the treatment of inflammation: gold microparticles > 20 µm and gold nanoparticles. The injection of gold microparticles (µGold) is a purely local therapy. µGold particles stay put where injected, and gold ions released from them are relatively few and taken up by cells within a sphere of only a few millimeters in diameter from their origin particles. The macrophage-induced release of gold ions may continue for years. Injection of gold nanoparticles (nanoGold), on the other hand, is spread throughout the whole body, and the bio-released gold ions, therefore, affect multitudes of cells all over the body, as when using gold-containing drugs such as Myocrisin. Since macrophages and other phagocytotic cells take up and transport nanoGold and remove it after a short period, repeated treatment is necessary. This review describes the details of the cellular mechanisms that lead to the bio-release of gold ions in µGold and nanoGold.

Low- versus standard- pneumoperitoneum in patients undergoing robot-assisted radical prostatectomy: a randomised, triple-blinded study.

OBJECTIVE: To investigate the effectiveness and impact of low-pressure pneumoperitoneum (Pnp) on postoperative quality of recovery (QoR) and surgical workspace (SWS) in patients with prostate cancer undergoing robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: A randomised, triple-blinded trial was conducted in a single centre in Denmark from March 2021 to January 2022. A total of 98 patients with prostate cancer undergoing RARP were randomly assigned to either low-pressure Pnp (7 mmHg) or standard-pressure Pnp (12 mmHg). Co-primary outcomes were postoperative QoR measured via the QoR-15 questionnaire on postoperative Day 1 (POD1), POD3, POD14, and POD30, and SWS assessed intraoperatively by a blinded assessor (surgeon) via a validated SWS scale. Data analysis was performed according to the intention-to-treat principle. RESULTS: Patients who underwent RARP at low Pnp pressure demonstrated better postoperative QoR on POD1 (mean difference = 10, 95% confidence interval [CI] 4.4-15.5), but no significant differences were observed in the SWS (mean difference = 0.25, 95% CI -0.02 to 0.54). Patients allocated to low-pressure Pnp experienced statistically higher blood loss than those in the standard-pressure Pnp group (mean difference = 67 mL, P = 0.01). Domain analysis revealed significant improvements in pain (P = 0.001), physical comfort (P = 0.007), and emotional state (P = 0.006) for patients with low-pressure Pnp. This trial was registered at ClinicalTrials.gov, NCT04755452, on 16/02/2021. CONCLUSION: Performing RARP at low Pnp pressure is feasible without compromising the SWS and improves postoperative QoR, including pain, physical comfort, and emotional state, compared to the standard pressure.

Acquisition and usage of robotic surgical data for machine learning analysis.

BACKGROUND: The increasing use of robot-assisted surgery (RAS) has led to the need for new methods of assessing whether new surgeons are qualified to perform RAS, without the resource-demanding process of having expert surgeons do the assessment. Computer-based automation and artificial intelligence (AI) are seen as promising alternatives to expert-based surgical assessment. However, no standard protocols or methods for preparing data and implementing AI are available for clinicians. This may be among the reasons for the impediment to the use of AI in the clinical setting. METHOD: We tested our method on porcine models with both the da Vinci Si and the da Vinci Xi. We sought to capture raw video data from the surgical robots and 3D movement data from the surgeons and prepared the data for the use in AI by a structured guide to acquire and prepare video data using the following steps: 'Capturing image data from the surgical robot', 'Extracting event data', 'Capturing movement data of the surgeon', 'Annotation of image data'. RESULTS: 15 participant (11 novices and 4 experienced) performed 10 different intraabdominal RAS procedures. Using this method we captured 188 videos (94 from the surgical robot, and 94 corresponding movement videos of the surgeons' arms and hands). Event data, movement data, and labels were extracted from the raw material and prepared for use in AI. CONCLUSION: With our described methods, we could collect, prepare, and annotate images, events, and motion data from surgical robotic systems in preparation for its use in AI.

Cost of simulation-based mastery learning for abdominal ultrasound.

BACKGROUND: Ultrasound is an essential diagnostic examination used in several medical specialties. However, the quality of ultrasound examinations is dependent on mastery of certain skills, which may be difficult and costly to attain in the clinical setting. This study aimed to explore mastery learning for trainees practicing general abdominal ultrasound using a virtual reality simulator and to evaluate the associated cost per student achieving the mastery learning level. METHODS: Trainees were instructed to train on a virtual reality ultrasound simulator until the attainment of a mastery learning level was established in a previous study. Automated simulator scores were used to track performances during each round of training, and these scores were recorded to determine learning curves. Finally, the costs of the training were evaluated using a micro-costing procedure. RESULTS: Twenty-one out of the 24 trainees managed to attain the predefined mastery level two times consecutively. The trainees completed their training with a median of 2h38min (range: 1h20min-4h30min) using a median of 7 attempts (range: 3-11 attempts) at the simulator test. The cost of training one trainee to the mastery level was estimated to be USD 638. CONCLUSION: Complete trainees can obtain mastery learning levels in general abdominal ultrasound examinations within 3 hours of training in the simulated setting and at an average cost of USD 638 per trainee. Future studies are needed to explore how the cost of simulation-based training is best balanced against the costs of clinical training.

Patients with non-operated traumatic primary or recurrent anterior shoulder dislocation have equally poor self-reported and measured shoulder function: a cross-sectional study.

BACKGROUND: Patients with non-operated traumatic primary anterior shoulder dislocation (PASD) are assumed to have less shoulder impairment than patients with recurrent anterior shoulder dislocations (RASD). This may impact treatment decision strategy. The aim was to study whether patients with non-operated traumatic PASD have less shoulder impairment than those with RASD. METHODS: In a cross-sectional study baseline data from patients with PASD and RASD in a randomised controlled trial of non-operative shoulder exercise treatment were used. Shoulder function was self-reported (Western Ontario Shoulder Instability (WOSI), Tampa Scale of Kinesiophobia (TSK), General Health (EQ-5D-VAS), Numeric Pain Rating Scale (NPRS)), and measured (Constant-Murley shoulder Score (CMS total), CMS - Range of Motion (CMS-ROM, CMS - strength, proprioception, clinical tests). RESULTS: In total, 56 patients (34 (28 men) with PASD and 22 (21 men) with RASD) (mean age 26 years) participated. WOSI total was 1064 and 1048, and TSK above 37 (indicating high re-injury fear) was present in 33 (97%) and 21 (96%) of the groups with PASD and RASD, with no group difference. CMS total (66.4 and 70.4), CMS-ROM (28.7 and 31.5), CMS-strength (injured shoulder: 7.6 kg and 9.1 kg), proprioception and clinical tests were the same. Furthermore, 26 (76%) with PASD and 13 (59%) with RASD reported not to have received non-operative shoulder treatment. CONCLUSIONS: Non-operated patients with PASD and self-reported shoulder trouble three-six weeks after initial injury do not have less shoulder impairment (self-reportedly or objectively measured) than non-operated patients RASD and self-reported shoulder trouble three-six weeks after their latest shoulder dislocation event.

72 revision surgeries for aseptic failure after hip or knee arthroplasty: a prospective study with an extended diagnostic algorithm.

BACKGROUND: Unrecognized periprosthetic joint infections are a concern in revision surgery for aseptic failure (AF) after total hip (THA) or knee (TKA) arthroplasties. A gold diagnostic standard does not exist. The aim of the current study was to determine the prevalence of unrecognized periprosthetic joint infection (PJI) in a cohort of revision for AF, using an experimental diagnostic algorithm. METHODS: The surgeons' suspicion of AF was based primarily on patient history and clinical evaluation. X-ray imaging was used to reveal mechanical problems. To rule out an infectious aetiology standard blood biochemical tests were ordered in most patients. Evaluation followed the existing practice in the institute. Cases were included if revision surgery was planned for suspected AF. Intraoperatively, five synovial tissue biopsies were obtained routinely. PJI was defined as ≥3 positive cultures with the same microorganism(s). Patients were followed for 1 year postoperatively. Protocol samples included joint fluid, additional synovial tissue biopsies, bone biopsy, swabs from the implant surface, and sonication of retrieved components. Routine and protocol samples were cultured with extended incubation (14 days) and preserved for batchwise 16S rRNA gene amplification. Patients were stratified based on culture results and a clinical status was obtained at study end. RESULTS: A total of 72 revisions were performed on 71 patients (35 THA and 37 TKA). We found five of 72 cases of unrecognized PJI. Extended culture and protocol samples accounted for two of these. One patient diagnosed with AF was treated for a PJI during follow-up. The remaining patients did not change status from AF during follow-up. CONCLUSIONS: We found a low prevalence of unrecognized periprosthetic joint infections in patients with an AF diagnosis. The algorithm strengthens the surgeons' preoperative diagnosis of a non-infective condition. Evaluation for a failing TKA or THA is complex. Distinguishing between AF and PJI pre-operatively was a clinical decision. Our data did not support additional testing in routine revision surgery for AF.

A Randomized, Controlled Trial of Total Knee Replacement.

BACKGROUND: More than 670,000 total knee replacements are performed annually in the United States; however, high-quality evidence to support the effectiveness of the procedure, as compared with nonsurgical interventions, is lacking. METHODS: In this randomized, controlled trial, we enrolled 100 patients with moderate-to-severe knee osteoarthritis who were eligible for unilateral total knee replacement. Patients were randomly assigned to undergo total knee replacement followed by 12 weeks of nonsurgical treatment (total-knee-replacement group) or to receive only the 12 weeks of nonsurgical treatment (nonsurgical-treatment group), which was delivered by physiotherapists and dietitians and consisted of exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the change from baseline to 12 months in the mean score on four Knee Injury and Osteoarthritis Outcome Score subscales, covering pain, symptoms, activities of daily living, and quality of life (KOOS4); scores range from 0 (worst) to 100 (best). RESULTS: A total of 95 patients completed the 12-month follow-up assessment. In the nonsurgical-treatment group, 13 patients (26%) underwent total knee replacement before the 12-month follow-up; in the total-knee-replacement group, 1 patient (2%) received only nonsurgical treatment. In the intention-to-treat analysis, the total-knee-replacement group had greater improvement in the KOOS4 score than did the nonsurgical-treatment group (32.5 vs. 16.0; adjusted mean difference, 15.8 [95% confidence interval, 10.0 to 21.5]). The total-knee-replacement group had a higher number of serious adverse events than did the nonsurgical-treatment group (24 vs. 6, P=0.005). CONCLUSIONS: In patients with knee osteoarthritis who were eligible for unilateral total knee replacement, treatment with total knee replacement followed by nonsurgical treatment resulted in greater pain relief and functional improvement after 12 months than did nonsurgical treatment alone. However, total knee replacement was associated with a higher number of serious adverse events than was nonsurgical treatment, and most patients who were assigned to receive nonsurgical treatment alone did not undergo total knee replacement before the 12-month follow-up. (Funded by the Obel Family Foundation and others; MEDIC ClinicalTrials.gov number, NCT01410409.).

Variation in Prosthetic Joint Infection and treatment strategies during 4.5 years of follow-up after primary joint arthroplasty using administrative data of 41397 patients across Australian, European and United States hospitals.

BACKGROUND: To identify best practices and quality improvement initiatives, we aimed to assess whether the incidence of Periprosthetic Joint Infection (PJI) and treatment strategies differed across patients treated in Australian, European and United States (US) hospitals. METHODS: Routinely collected administrative data for 41397 patients undergoing a primary total hip or knee arthroplasty between July 2007-December 2010 across 22 hospitals were included. Patients were followed for 2 years looking for PJI occurrence, defined as early (within 4 weeks) and late PJI, and surgical treatment during 2.5 years after PJI diagnosis. Logistic and Poisson regression models were used to test for differences in PJI occurrence and treatment strategies across the three geographical regions, adjusted for age, sex, joint and Elixhauser comorbidity groups. RESULTS: PJI occurrence varied from 1.4% in European to 1.7% in Australian patients, which were significantly higher than US patients after adjustment for patient characteristics (OR 1.24 [1.01-1.52] and 1.40 [1.03-1.91] respectively). Early PJIs varied between 0.3% in European to 0.6% in Australian patients, but adjusted rates were similar. Revision following PJI was significantly lower in Australian than in US patients (OR 0.46 [0.25-0.86]) as were the total number of revisions (RR 0.51 [0.36-0.71]) and number of surgical procedures (RR 0.60 [0.44-0.81]) used to treat PJI. CONCLUSION: The overall PJI rate was significantly higher in Australian patients, but fewer procedures were needed to treat these PJIs. Future research should reveal whether this reflects PJIs caught earlier or less severe when diagnosed, and whether this is associated with the longer length of stay after primary arthroplasty in Australian hospitals.

A Pharmacokinetic-Pharmacodynamic Model of Morphine Exposure and Subsequent Morphine Consumption in Postoperative Pain.

PURPOSE: To characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation. METHODS: Dose, formulation and time of morphine administration was available from a published study in 63 patients receiving intravenous, oral immediate release or oral controlled release morphine on request after hip surgery. The PK-PD relationship between predicted exposure of morphine and morphine consumption was modeled using repeated time to event (RTTE) modeling in NONMEM. To validate the RTTE model, a visual predictive check method was developed with simulated morphine consumption given the exposure of preceding morphine administration. RESULTS: The probability of requesting morphine was found to be significantly related to the exposure of morphine as well as night/day. Oral controlled release morphine was more effective than intravenous and oral immediate release formulations at equivalent average concentrations. Maximum effect was obtained for 8 h by oral controlled release doses ≥ 15 mg, where probability of requesting a new dose was reduced to 20% for a typical patient. CONCLUSION: This study demonstrates the first quantitative link between exposure of morphine and subsequent morphine consumption and introduces an efficient visual predictive check approach with simulation of adaptive dosing.

Local and Widespread Hyperalgesia After Isolated Tibial Shaft Fractures Treated with Intramedullary Nailing.

OBJECTIVES: Knee pain is accepted as a common complication to intramedullary nailing of tibial fractures. However, no studies have systematically studied the pain sequel following tibial fractures. The objective of this study was to assess pain and hyperalgesia from 6 weeks to 12 months postoperatively after intramedullary nailing of tibial shaft fracture. METHODS: A total of 39 patients were included in this 12-month follow-up study. After 6 weeks, 3, 6, and 12 months postoperatively the pain intensity was measured on a visual analog scale (VAS) and the pressure pain sensitivity was assessed bilaterally by pain pressure thresholds (PPTs). RESULTS: The mean age at the time of fracture was 42.9 years. Twelve months after surgery, the pain intensity for worst pain during the last 24 hours was 1.8 ± 2.7 cm. The PPTs progressively increased from 6 weeks after surgery to 12 months postoperatively for all PPT sites except for the forearm (P < 0.012). Moreover, the PPTs on the leg were generally reduced on the injured side compared with the non-injured side (P < 0.04). CONCLUSIONS: This study suggests that localized, distal, and bilateral hyperalgesia are common following an isolated tibial shaft fracture treated with intramedullary nailing, although no widespread (extrasegmental) hyperalgesia was detected. Such observations may be important for developing the most adequate rehabilitation procedure following a tibial fracture.

The design of the run Clever randomized trial: running volume, -intensity and running-related injuries.

BACKGROUND: Injury incidence and prevalence in running populations have been investigated and documented in several studies. However, knowledge about injury etiology and prevention is needed. Training errors in running are modifiable risk factors and people engaged in recreational running need evidence-based running schedules to minimize the risk of injury. The existing literature on running volume and running intensity and the development of injuries show conflicting results. This may be related to previously applied study designs, methods used to quantify the performed running and the statistical analysis of the collected data. The aim of the Run Clever trial is to investigate if a focus on running intensity compared with a focus on running volume in a running schedule influences the overall injury risk differently. METHODS/DESIGN: The Run Clever trial is a randomized trial with a 24-week follow-up. Healthy recreational runners between 18 and 65 years and with an average of 1-3 running sessions per week the past 6 months are included. Participants are randomized into two intervention groups: Running schedule-I and Schedule-V. Schedule-I emphasizes a progression in running intensity by increasing the weekly volume of running at a hard pace, while Schedule-V emphasizes a progression in running volume, by increasing the weekly overall volume. Data on the running performed is collected by GPS. Participants who sustain running-related injuries are diagnosed by a diagnostic team of physiotherapists using standardized diagnostic criteria. The members of the diagnostic team are blinded. The study design, procedures and informed consent were approved by the Ethics Committee Northern Denmark Region (N-20140069). DISCUSSION: The Run Clever trial will provide insight into possible differences in injury risk between running schedules emphasizing either running intensity or running volume. The risk of sustaining volume- and intensity-related injuries will be compared in the two intervention groups using a competing risks approach. The trial will hopefully result in a better understanding of the relationship between the running performed and possible differences in running-related injury risk and the injuries developed. TRIAL REGISTRATION: Clinical Trials NCT02349373 - January 23, 2015.

Enhanced function and quality of life following 5 months of exercise therapy for patients with irreparable rotator cuff tears - an intervention study.

BACKGROUND: Rotator cuff rupture is associated with dysfunction, pain and muscular weakness related to the upper extremity. Some evidence exists to support the beneficial effect of exercises but there is lack of evidence of which exercises imply the best effect and how physiotherapy should be administered. Therefore, the purpose of this study was to examine the effect of a neuromuscular exercise program for patients with irreparable rotator cuff rupture. METHODS: Based on sample-size calculations thirty patients with chronic irreparable rotator cuff tears (of at least m. supraspinatus and m. infraspinatus) was consecutively included. Twenty-four patients completed the five months training to restore function with focus on centering the humeral head in the glenoid cavity trough strengthening m. deltoideus anterior and m. teres minor. The primary outcome measure was Oxford Shoulder Score which was completed at baseline, 3 and 5 months follow-up. One-way, repeated-measure ANOVA was used if data was normally distributed. Secondary outcome measures included EQ-5D, range of motion, strength and muscle activity. Paired t-test and Wilcoxon Signed Ranks Test was used to the appropriate outcomes. RESULTS: Improvements was seen for both primary and secondary outcomes from baseline to follow-up. Oxford Shoulder Score improved from 25.6 (SD 8.1) at baseline to 33.8 (SD 8.7) at 3 months (p = 0.004) and 37.2 (SD 8.2) at five months (p < 0.001). Range of motion in abduction significantly increased by 34.4° (95 % CI: 11.6-57.2). Strength measured in flexion 45, flexion 90 and abduction also significantly increased at 5 months by 10.2 (95 % CI: 0.8-19.6), 7.0 (95 % CI: 0.0-14.0) and 12.3 (95 % CI: 3.4-21.3) respectively. The remaining outcomes for range of motion and strengths only showed small and non-significant changes. Furthermore patients reported higher levels of quality of life and reduced level of pain after five months. CONCLUSION: Following a five months exercise protocol patients with irreparable rotator cuff tears showed increased function in their symptomatic shoulder, reduced pain and increased quality of life. This study therefore supports the use of exercise therapy in patients with irreparable rotator cuff rupture. TRIAL REGISTRATION: This study is approved by The National Committee on Health Research Ethics (N-20120040) and registered retrospectively at ClinicalTrials.gov in April 2016 ( NCT02740946 ).

One-year development of QOL following orthopaedic polytrauma: a prospective observational cohort study of 53 patients.

INTRODUCTION: Most studies of polytrauma examined highly mixed patient groups. The objective of the present study was to report the development of patient-reported quality of life (QOL), in a patient group with musculoskeletal polytrauma, excluding patients with major thoracic, abdominal, and brain injuries. MATERIALS AND METHODS: The study design was a 1-year cohort follow-up study. Recordings of injury severity were measured with the ISS and NISS. Patient-reported QOL was measured with the questionnaires Eq5d-5L and SF-36 and compared to age-matched reference populations. Moreover, patients return to work status was measured. Data were collected prospectively at discharge, 3, 6, and 12 months. RESULTS: 53 patients were included. The mean age was 42.3 years, ranging from 17 to 78 years. Twelve months after trauma admission, the mean Eq5d-5L index was 0.601 (95 % CI 0.546-0.657). A progressive increasing Eq5d-5L index and SF-36 PCS was observed between the discharge and the 12-month follow-up (p < 0.001). The development in QOL from 6 to 12 months almost shows identically scores. Throughout the study period, patients reported significant worse QOL compared with the established reference population. 32 % of patients have resumed earlier employment status at 1-year follow-up. CONCLUSIONS: Throughout the 12-month observational period, patients reported worse QOL compared to the age-matched reference population. The development of QOL from 6- to 12-month time points almost showed identically scores with only little improvement. At the end of 1-year follow-up, 32 % of patients had resumed prior employment status.

Decreased QOL and muscle strength are persistent 1 year after intramedullary nailing of a tibial shaft fracture: a prospective 1-year follow-up cohort study.

INTRODUCTION: To evaluate the development in patient-reported quality of life (QOL) and muscle strength in the period from surgery to 12 months postoperatively after intramedullary nailing of a tibial shaft fracture. MATERIALS AND METHODS: The design was a prospective, follow-up cohort study. QOL was measured with the questionnaire Eq5D-5L and compared to norm data from a reference population. Recordings of pain and contralateral muscle strength (isometric maximal voluntary contraction (MVC) for knee flexion and extension were collected at 6 weeks, 3, 6, and 12 months postoperatively. Ipsilateral MVCs were recorded at 6 and 12 months. RESULTS: Forty-nine patients were included. The mean age at the time of fracture was 43.1 years (18-79 years). Twelve months postoperatively, the mean Eq5D-5L index was 0.792 (95 % CI 0.747-0.837). Throughout the 12 months postoperatively, patients reported worse QOL compared to the reference population. Six and 12 months after surgery patients demonstrated decreased muscle strength in the injured leg compared to the non-injured leg for knee extension and flexion (P < 0.001). Twelve months postoperatively, increasing relative difference in muscle strength during knee extension show a fair correlation to worse QOL (R = 0.541, P < 0.001). CONCLUSIONS: Throughout the 12 months postoperatively, patients reported worse QOL compared to the reference population. Muscle strength in the non-injured leg improved over time and was higher after 6 and 12 months compared with the injured leg.

Repeated Time-to-event Analysis of Consecutive Analgesic Events in Postoperative Pain.

BACKGROUND: Reduction in consumption of opioid rescue medication is often used as an endpoint when investigating analgesic efficacy of drugs by adjunct treatment, but appropriate methods are needed to analyze analgesic consumption in time. Repeated time-to-event (RTTE) modeling is proposed as a way to describe analgesic consumption by analyzing the timing of consecutive analgesic events. METHODS: Retrospective data were obtained from 63 patients receiving standard analgesic treatment including morphine on request after surgery following hip fracture. Times of analgesic events up to 96 h after surgery were extracted from hospital medical records. Parametric RTTE analysis was performed with exponential, Weibull, or Gompertz distribution of analgesic events using NONMEM, version 7.2 (ICON Development Solutions, USA). The potential influences of night versus day, sex, and age were investigated on the probability. RESULTS: A Gompertz distribution RTTE model described the data well. The probability of having one or more analgesic events within 24 h was 80% for the first event, 55% for the second event, 31% for the third event, and 18% for fourth or more events for a typical woman of age 80 yr. The probability of analgesic events decreased in time, was reduced to 50% after 3.3 days after surgery, and was significantly lower (32%) during night compared with day. CONCLUSIONS: RTTE modeling described analgesic consumption data well and could account for time-dependent changes in probability of analgesic events. Thus, RTTE modeling of analgesic events is proposed as a valuable tool when investigating new approaches to pain management such as opioid-sparing analgesia.

Tourniquet induced ischemia and changes in metabolism during TKA: a randomized study using microdialysis.

BACKGROUND: Tourniquet use in total knee arthroplasty (TKA) surgery is applied to minimize blood loss thereby creating better overview of the surgical field. This induces ischemia in the skeletal muscle resulting in reperfusion injury. Our aim was to investigate the in vivo metabolic changes in the skeletal muscle during TKA surgery using microdialysis (MD). METHODS: Seventy patients were randomly allocated to tourniquet group (n = 35) or non-tourniquet group (n = 35). Prior to surgery, catheters were inserted in the operated leg and non-operated leg. Interstitial dialysate was collected before and after surgery and at 20 min intervals during a 5 h reperfusion period. Main variables were ischemic metabolites: glucose, pyruvate, lactate and glycerol and L/P ratio. RESULTS: Significant difference in all metabolites was detected between the two groups, caused by tourniquet application. Tourniquet induced ischemia resulted in decreased levels of glucose and pyruvate to 54 and 60 % respectively, compared to baseline. Simultaneously, accumulation of lactate to 116 % and glycerol to 190 % was observed. L/P ratio was elevated indicating ischemia. In the non-tourniquet group the metabolite changes were less profound and normalized within 60 min. CONCLUSIONS: Microdialysis revealed that performing TKA with tourniquet is associated with increased ischemia. This affects all metabolites but the changes are normalized after 5 h.

Successful conservative treatment of patients with MRI-verified meniscal lesions.

PURPOSE: To follow a prospective cohort of consecutive patients with MRI-verified meniscal lesions to identify pre-treatment prognostic factors for long-term results following arthroscopic or conservative treatment. METHODS: In the course of 1 year, 291 patients with knee pain and clinically suspected of meniscal lesion were referred to the regional orthopaedic division and subjected to MRI and clinical examination by an experienced surgeon. Patients with MRI-verified meniscal lesions were treated according to an arthroscopy restrictive strategy meaning that treatment was initiated by conservative treatment. Arthroscopy was only performed if satisfying pain relief was not obtained. The Lysholm score and Knee Injury and Osteoarthritis Outcome Score (KOOS) were obtained at baseline and after 12-24 months. A multiple linear regression model was used to investigate which pre-treatment prognostic factors were associated with improvement in the KOOS subscale pain from baseline to follow-up. RESULTS: An MRI-verified meniscal lesion was found in 185 patients (64%). Among these, 58% were treated successfully by conservative treatment. A high KOOS subscale pain score at baseline was associated with less improvement from baseline to follow-up. Bucket-handle lesions were associated with larger improvement from baseline to follow-up compared to flap-tear lesions. CONCLUSION: MRI findings and clinical status measured by KOOS subscale pain are prognostic for improvement among patients treated for MRI-verified meniscal lesions. Good results were observed for both operative and conservative treatment. The success rate for conservative treatment was 58%. LEVEL OF EVIDENCE: Prospective cohort study, Level II.