Objective: Obesity is a major risk factor for osteoarthritis (OA). Adipose tissues may be linked to OA development through secretion of potential proinflammatory cytokines including neutrophil gelatinase-associated lipocalin (NGAL). Our objective was to assess changes in serum NGAL after a low-calorie diet (LCD) and subsequent glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment. Design: A secondary analysis of a randomized, double-blinded, placebo-controlled trial in adults with overweight (BMI>27 kg/m(2)) and symptomatic, early-to-moderate radiographic knee OA. Prior to randomization, participants underwent an 8-week LCD (week -8 to 0). Participants who lost min. 5% of initial bodyweight were randomized 1:1 to liraglutide 3 mg/d or placebo for 52 weeks. Main outcome was change in serum NGAL from enrollment (week -8) to randomization (week 0). Other outcome was change in serum NGAL from week 0 to week 52 comparing liraglutide and placebo. Results: 168 participants were enrolled to the initial intensive diet intervention; 127 participants, with NGAL samples, were randomized. Following the 8-week diet intervention, NGAL concentrations rose by 93.0 ng/mL (95 % CI: 18.9 to 167.1, P = 0.015), with no correlation to weight loss magnitude. 52 weeks of treatment with either liraglutide or placebo, liraglutide did not cause a greater decrease in serum NGAL (14.9 ng/ml, 95%CI: -92.1 to 121.7 ng/mL, P = 0.78). Conclusion: An intensive 8-week calorie restriction was associated with a rise in serum NGAL. Compared to placebo, 52 weeks of liraglutide did not cause additional changes in NGAL. This indicates a complex pattern of proinflammatory cytokine-release during hypocaloric diet interventions.

ObjectiveDespite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout.MethodsWe conducted a 16‐week randomized nonmasked parallel‐group trial in Denmark, randomly assigning (one‐to‐one) individuals with obesity and gout to a low‐energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale–assessed pain and fatigue.ResultsBetween December 1, 2018, and June 1, 2019, 61 participants were included in the intention‐to‐treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (−15.4 vs −7.7 kg; difference −7.7 kg [95% confidence interval −10.7 to −4.7], P < 0.001). Despite results being potentially in favor of a low‐energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial.ConclusionAn intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

The UNet has become the golden standard method for the segmentation of 2D medical images that any new method must be validated against. In recent years, a number of variations to the seminal UNet have been proposed with promising results in the papers introducing them. However, there is no clear consensus if any of these architectures generalize as well and the UNet currently remains the methodological golden standard. For the segmentation of 3D scans, UNet‐inspired methods are also dominant, but there is a larger variety across applications. By evaluating the architectures in a different dimensionality, embedded in a different method, and for a different task, we aimed to evaluate if any of these UNet alternatives are promising as a new golden standard that generalizes even better than the UNet. The purpose of this study was to compare UNet inspired models for generalized 3D segmentation. To efficiently segment the 3D scans, we employed each UNet variant architecture as the central 2D segmentation core in the multi‐planar UNet 3D segmentation method that previously demonstrated excellent generalization in the MICCAI Segmentation Decathlon. It would strongly support a claim of generalizability, if a promising UNet‐variant consistently outperforms the UNet in this quite different setting. The experimental results show that the multi‐planar‐based UNet2+ (MPUNet2+) method outperforms other variants including the original multi‐planar UNet (MPUNet).

Background Pain and impaired function due to knee OA (KOA) can be reduced with weight loss in obese patients. The role of synovitis in symptom improvement after weight loss is not fully understood. MRI and ultrasound (US) can be used in assessment of inflammation in the KOA. Knee joint synovitis assessed by MRI does not seem to change with weight loss, however, the typical MRI score is semiquantitative, which might be less sensitive to change than a quantitative score. US has a higher resolution than MRI and borders between synovium and surrounding tissues might be clearer allowing for a quantitative score. Changes in US-based synovitis following a weight has not been assessed. Objectives To assess changes in US synovitis in the knee joint after 8 weeks low-calorie weight loss intervention in overweight persons with KOA. Methods prospective cohort study ( NCT02931370 ) including overweight persons (BMI ≥ 27 kg/m 2 ) with KOA. Weight loss was induced by an intensive 8-week diet (1200 kcal/day), participants had symptomatic and radiographically confirmed KOA (KL grade 1-3). At week 0 and 8 all participants filled in the KOOS questionnaire assessing pain, physical function, symptoms, quality of life, and sport/recreation in relation to KOA (0= worst; 100=best). Furthermore, an US examination of the most affected knee was performed assessing the amount of synovial hypertrophy (SH) and effusion in medial and lateral recesses. The US examination was performed in a strictly standardized manner on a high-end US machine. The subsequent image evaluation was done both according to a semiquantitative score from 0 to 3 (0=no SH/effusion and 3=pronounced SH/effusion) and a quantitative scoring system using specific anatomic landmarks to measure the synovial hypertrophy/effusion in millimeter. Statistical analyses were performed on the per protocol population (participants completing diet intervention). Results 135 patients with KOA with a mean age of 60y (SD 9.8), a body weight of 106.0 kg (SD18.5) and mean BMI of 36.4 (SD5.4) completed the weight loss intervention. After the diet intervention mean weight change was -12.8 kg (95%CI -13.3 to -12.4) and the reductions in SH were -0.3mm (95%CI -0.5 to -0.1) (medial recess) and -0.4mm (95%CI -0.6 to -0.1) (lateral recess), and -0.03 (-0.13 to 0.07) (medial recess) and -0.07 (-0.20 to 0.05) using the semi-quantitative system. The mean change in the KOOS subscales range from 15.8 (sport/recreation) to 7.4 (QoL). See Table 1. Table 1. n=135 Baseline Change Mean (SD ) Mean (95%CI ) P Age 60.0 (9.8) - - Females, n (%) 87 (64.4%) - - BMI 36.4 (5.4) -4.4 (-4.5 to -4.3) <.0001 KL-scores; 1 22 (16.3%) - - KL-scores; 2 56 (41.5%) - - KL-scores; 3 57 (42.2%) - - KL-scores; 4 0 (0%) - - Synovial Hypertrophy Medial, mm 3.8 (1.8) -0.3 (-0.5 to -0.1) 0.0198 Lateral, mm 5.3 (2.3) -0.4 (-0.6 to -0.1) 0.0210 Medial, 0-3 1.2 (0.6) -0.03 (-0.13 to 0.07) 0.5584 Lateral, 0-3 1.8 (0.8) -0.07 (-0.20 to 0.05) 0.2311 KOOS, 0-100 Pain 64.1 (16.0) 12 (10.2 to 13.8) <.0001 Function 68.4 (17.3) 14 (12.4 to 15.6) <.0001 Symptoms 68.9 (16.4) 9 (7.2 to 10.8) <.0001 Sports/Recreation 35.9 (24.0) 15.8 (13.2 to 18.3) <.0001 QoL 43.8 (17.5) 7.4 (5.7 to 9.2) <.0001 SD = Standard Deviation; CI = Confidence Interval; BMI = Body Mass Index; KOOS = Knee injury and Osteoarthritis Outcome Score; QoL = Knee-related Quality of Life Conclusion Quantitative measures of SH assessed by US decreased after a significant weight loss over 8-weeks; however, no linear association with weight loss magnitude was seen. A weak correlation between changes in SH in the lateral recess and change in pain was seen. This indicates changes in SH assessed by US examination is associated with a low-calorie diet but seems uncoupled with weight loss magnitude. The weight loss induced changes in synovitis and KOA symptoms seem vaguely related. Disclosure of Interests None declared

Arthritis & RheumatologyVolume 74, Issue S9 Abstracts Abstract Supplement ACR Convergence 2022 First published: 29 September 2022 https://doi.org/10.1002/art.42355AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract For a searchable version of these abstracts, please visit www.acrabstracts.org. Volume74, IssueS9Special Issue: ACR Convergence 2022 Abstract SupplementSeptember 2022 RelatedInformation

Background: Ki-67 is an established prognostic marker in estrogen receptor (ER)+ breast cancer (BC). Different cut-offs for Ki-67 positivity have been proposed including the 20% cut off for the FDA approved adjuvant abemaciclib. Manual assessment of Ki-67 immunohistochemistry (IHC) is, however, challenging and time consuming limiting its implementation in routine practice especially in view of the pathology workforce shortage. Accurate automated systems for Ki-67 scoring are therefore urgently required. Artificial intelligence (AI) is a promising tool for fast integrated Ki-67 analysis. Validation and comparison with pathologists' scoring, as the gold standard, are needed prior to implementation.

Objective: Intra-Articular (IA) injection of polyacrylamide hydrogel (PAAG) is a possible treatment for symptomatic Osteoarthritis (OA) of the knee.This study evaluated the efficacy and safety of a single injection of 6 ml intra-articular PAAG over 26 weeks.Methods: Open-label study in patients with symptomatic and radiographically confirmed knee OA .Primary outcome was change in WOMAC pain after 13 weeks.Secondary outcomes were WOMAC stiffness and function subscales, Patient Global Assessment of disease impact (PGA) and proportion of OMERACT-OARSI responders.Follow-up time points were 4, 13 and 26 weeks.Results: 49 patients (31 females) received PAAG, with 48 patients completing the 13 and 46 the 26 weeks assessments.Mean change in WOMAC pain after 13 weeks was -18.3 points [95% CI-23.4 to -13.3]; P<.0001 and at 26 weeks -20.8 points [95% CI -26.3 to -15.3]; P<0.0001 with similar benefits for WOMAC stiffness, physical function, and PGA.After 13 weeks 64.6% were OMERACT-OARSI responders and this was maintained at 26 weeks..During the 13 weeks, 18 patients reported 23 adverse events, 13 of which were related to PAAG, none severe.Two serious adverse events, atrial fibrillation and gastrointestinal pain, were assessed as 'not related' to PAAG.Conclusions: PAAG can be delivered in a single 6 ml injection and this non-randomized trial in patients with knee OA demonstrated beneficial clinical effects at 13 and 26 weeks.No serious adverse events were seen with PAAG.These encouraging results need to be confirmed in controlled studies.

BACKGROUNDWeight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA).OBJECTIVETo determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA.METHODSThe trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52.RESULTSIn total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively.CONCLUSIONSIn patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.

Purpose: Intra-articular (IA) injection of polyacrylamide hydrogel (PAAG) has been suggested as a possible treatment for symptomatic osteoarthritis (OA). Previously IA PAAG has been investigated using 2 injections of 3 ml separated by a month. The primary objective of this study was to evaluate the efficacy and safety of a single injection of 6 ml intra-articular PAAG on knee symptoms in participants with moderate to severe knee OA. Methods: Patients with symptomatic (WOMAC A1 ≥2/4 Likert) and radiographic (KL grade 2 to 4) knee OA were consented into this prospective, open-label study. A proprietary 2.5% cross-linked PAAG manufactured by Contura International A/S was used. PAAG contains 2.5% polyacrylamide and 97.5% non-pyrogenic water, with a unique molecular structure that allows normal water exchange with the surrounding tissue without losing shape. PAAG is biocompatible, non-absorbable, non-biodegradable, stable, and sterile. PAAG was provided in sterile, pre-filled 1 ml sealed syringes to be injected intra-articularly with a sterile 21G x 2-inch (0.8 x 50 mm) needle. PAAG is classified as a Class IIb device under Council Directive 93/42/EEC on medical devices. Primary outcome was change in WOMAC pain subscale (normalized to 100 points) after 12 weeks. Secondary outcomes were the WOMAC stiffness and function subscale, Patient Global Assessment of disease impact (PGA) and proportion of OMERACT-OARSI responders. Follow-up time points were 4, 12, 26 and 52 weeks. The protocol for this study was approved by the local Health Research Ethics committee (ref.no: H-19031685), the Danish Health authorities, and was registered at www.clinicaltrials.gov (NCT04179552) before any study related activities. All patients gave informed consent prior to participation, and the study was conducted according to the principles of good clinical practice. Results: 49 patients (31 females) received IA PAAG, and 48 and 46 patients completed the 12-week and 52 weeks assessment, respectively. There were statistically and clinically significant reductions in WOMAC pain after 12 weeks (mean change -18.3 points [95% CI: -23.3 to -13.3]; P<.0001) which were sustained at 52 weeks (mean change -20.8 points [95% CI -26.3 to -15.3]; P<0.0001). Similar benefits were found for WOMAC stiffness, physical function, and patient global assessment. After 12 weeks 64.6% of the patients were OMERACT-OARSI responders and this also was maintained at 52 weeks. During the initial 12 weeks, 18 patients reported 23 adverse events; 13 events were related to PAAG treatment (most frequent: arthralgia and joint swelling) and not considered serious. No new PAAG related AEs were observed from 12 to 52 weeks. Three serious adverse events occurred (atrial fibrillation, gastrointestinal pain and cerebrovascular event) all assessed as ‘not related’ to PAAG. Conclusions: PAAG can be delivered in a single injection and this non-randomized trial suggests that the good clinical effects at 12 weeks were maintained at 52 weeks in patients with moderate to severe knee OA. These encouraging Results need to be confirmed in controlled studies.

Background Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the ‘active’ ingredients are unknown. Designing and executing an adequate and ‘blindable placebo’ version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used ‘state-of-art’ exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA. Methods In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients’ global assessment of disease impact, physical performance tests, and presence of knee joint swelling. Discussion This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA. Trial registration www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019.

Objective: To assess if a change in physical activity occurred after a one-year weight loss period on either liraglutide or placebo in patients with knee osteoarthritis (OA) and overweight. Method: This is secondary analysis of a one-year weight loss trial, with participants randomised (1:1) to either liraglutide 3 mg/day or placebo. The main outcome was change in physical activity (min/day) after one year assessed by accelerometer. Physical function was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS), function subscale with 100 indicating no disability and 0 indicating extreme disability. Analyses were done on the modified intention to treat population defined as complete baseline accelerometer data. Results: A total of 135 participants were analysed (66 liraglutide; 69 placebo). Daily physical activity time did not change in either group (liraglutide: 15.8 min/day; placebo: 14.2 min/day; mean difference 1.6 min/day (95%CI -16 to 19; P = 0.90)). The liraglutide group lost -4.1 kg more than placebo (95% CI -6.0 to -2.1; P < 0.0001) and improved in KOOS function 3.8 points more than placebo (95% CI 0.9 to 6.7; P = 0.01). Conclusion: Despite better outcomes on body weight and self-reported physical functioning liraglutide did not induce changes in physical activity over one year in individuals with knee OA.

Background: The optimal type of ventilation in operating theatres for joint arthroplasty has been debated for decades. Recently, the World Health Organization changed its recommendations based on articles that have since been criticized. The economic and environmental impact of ventilation is also currently an important research topic but has not been well investigated. Aim: To compare how large, high-volume, laminar airflow (LAF) and turbulent airflow (TAF) ventilation systems perform during standardized simulated total hip arthroplasty (THA), as they pertain to colony-forming units (cfu), particle counts, and energy consumption. Methods: Two identical operating theatres were used to perform simulated THA. The only difference was that one was equipped with LAF and the other with TAF. Cfu and particles were collected from key points in the operating theatre, and energy was measured for each simulation. Thirty-two simulations were done in total. Findings: LAF had significantly reduced cfu and particle count when compared with TAF, at both 100% and 50% air influx. Furthermore, it was shown that lowering the air influx by 50% in LAF did not significantly affect cfu or particles, although reducing the fresh air influx from 100% to 50% significantly lowered the energy consumption. Most simulations in TAF did not meet the cleanroom requirements. Conclusion: Cfu were significantly lower in LAF at both 100% and 50% air influx. It is possible to reduce fresh air influx in LAF operating theatres by 50%, significantly reducing energy consumption, while still maintaining cfu and particle counts below the ISO clas-sification threshold required for THA surgery. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of The Healthcare Infection Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Objective To compare the efficacy of an exercise and education programme with open-label placebo given as intra-articular injections of inert saline on pain and function in individuals with knee osteoarthritis (OA). Methods In this open-label, randomised controlled trial, we recruited adults aged ≥50 years with symptomatic and radiographically confirmed knee OA in Denmark. Participants were randomised 1:1 to undergo an 8-week exercise and education programme or four intra-articular saline injections over 8 weeks. Primary outcome was change from baseline to week 9 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale (range 0 (worst)–100 (best)). Prespecified equivalence margins of ±8 KOOS pain points were chosen for the demonstration of comparable efficacy. Key secondary outcomes were the KOOS function and quality of life subscales, and patients’ global assessment of disease impact. Results 206 adults were randomly assigned: 102 to exercise and education and 104 to intra-articular saline injections. For the primary outcome, the least squares mean changes in KOOS pain were 10.0 for exercise and education and 7.3 for saline injections (difference 2.7 points, 95% CI −0.6 to 6.0; test for equivalence p=0.0008). All group differences in the key secondary outcomes respected the predefined equivalence margins. Adverse events and serious adverse events were similar in the two groups. Conclusion In individuals with knee OA, an 8-week exercise and education programme provided efficacy for symptomatic and functional improvements equivalent to that of four open-label intra-articular saline injections over 8 weeks. Trial registration number NCT03843931.

ObjectivesThe main study aim was to examine the applicability of a novel method to assess the criterion of values and preferences within the Grading of Recommendation, Assessment, Development and Evaluation evidence to decision framework. The group concept mapping (GCM) approach was applied to identify, organise and prioritise values and preferences in the example of health professionals’ choice of analgesia for patients with acute trauma pain.SettingPrehospital and emergency care centres in the Nordic countries of Denmark, Norway, Sweden, Finland and Iceland.ParticipantsAcute care health professionals with qualifications to administer analgesic agents to patients in emergency and prehospital settings, including advanced ambulance assistants, rescue officers, paramedics, emergency physicians and emergency nurses, participated in an online survey in which statements were generated (n=40) and structured (n=11) and finally analysed and interpreted in a validation meeting (n=4).ResultsUsing GCM, ideas were generated and structured through online participation. Results were interpreted at a validation meeting. In total, 111 unique ideas were identified and organised into seven clusters: drug profile, administration, context, health professionals’ preferences and logistics, safety profile, patient’s medical history and acute clinical situation.ConclusionsBased on GCM, a conceptual model was developed, and values and preferences around choice of analgesia in emergency care were revealed. Health professionals within acute care can apply the conceptual model to support their decision-making when choosing the best available treatment for pain for their patients in emergency care.

OBJECTIVE:To describe spontaneous changes in time spent being physically inactive that is measured continuously by accelerometry during an 8-week weight-loss intervention in overweight/obese individuals with knee osteoarthritis (OA).METHODS:This study was designed as an observational cohort study including individuals from an OA outpatient clinic who were concomitantly overweight/obese and had symptomatic knee OA. Participants completed an 8-week dietary intervention that had been previously shown to induce substantial weight loss. The main outcome was accelerometer-based measurement of daily physical inactivity for 24 hours during the 8-week intervention period that was presented as change in the average daily time spent inactive (sitting, reclined, or sleeping) from 1 week prior to intervention to the last week of the intervention.RESULTS:A total of 124 participants completed the dietary intervention and had valid accelerometer recordings. The mean weight loss was 12.7 kg (95% confidence interval [95% CI] -13.2, -12.1; P < 0.0001) after 8 weeks, which corresponded to a decrease in body mass index of 4.3 kg/m2 (95% CI -4.5, -4.2; P < 0.0001). Significant improvements in OA symptoms (assessed by the Knee Injury and Osteoarthritis Outcome Score [KOOS]) was found across all subscales; an improvement of 12.8 points (95% CI 10.6, 15.0; P < 0.0001) was observed for pain using the KOOS. No statistically significant change occurred in the average daily time spent inactive from baseline to follow-up (mean change 8.8 minutes/day [95% CI -12.1, 29.7]; P = 0.41).CONCLUSION:Physical inactivity remains stable despite a clinically significant weight loss and improvements in knee OA symptoms. Change in inactivity does not seem to occur spontaneously, suggesting that focused efforts to reduce inactive behaviors are needed.

Background and purpose — Total knee arthroplasty (TKA) has increased substantially in Sweden. We quantified the relative risk for TKA in the Swedish population for different BMI categories and age groups to investigate whether the continued increase in TKA is attributable to increased prevalence of obesity and elderly people in the population, and to put forward model predictions for coming needs for TKA. Patients and methods — We used the Swedish Nationwide Health Survey (SNHS) and the Swedish Knee Arthroplasty Register (SKAR) 2009–2015 to calculate the relative risk (RR) of TKA by age (middle-aged 45–64 years and elderly 65–84 years) and BMI (BMI 18.5–24.9 normal weight; BMI 25.0–29.9 overweight; BMI > 30 obese). The RR for TKA was applied to the demographic forecasts for the Swedish population as a forecasting model. Results — Population size increased 5.2% from 2009 to 2015 to 40,000 middle-aged and 250,000 elderly, and the prevalence of obesity increased from 16% to 18% in these 2 age categories. Compared with those of normal weight, the RR for TKA was 2.7 (95% CI 2.5–3.0) higher for the overweight and 7.3 (6.7–8.0) higher for the obese, aged 45–64. The corresponding figures for individuals aged 65–84 were 2.1 (2.0–2.2) and 4.0 (3.8–4.3) higher, respectively. The changes in the prevalence of obesity and an increase in the elderly population accounted for an estimated increase of 1,700 TKAs over the 7 years. Interpretation — The increase in obesity frequency and the rise in the population of middle-aged and elderly may, to some extent, explain the rise in TKA utilization in Sweden.

Background:There is a strong association between gout and obesity. Lowering urate is the cornerstone of gout management [1] and urate levels correlate strongly with central obesity. Previous studies suggest that weight loss has a positive effect on serum urate, however, the studies are sparse and small [2].Objectives:To assess the impact of an initial low-calorie diet-induced weight loss and subsequent randomisation to the body weight-lowering drug liraglutide (a glucagon-like peptide 1 receptor agonist) or placebo on serum urate levels.Methods:In the LOSE-IT trial (NCT02905864), a randomised, double-blinded, placebo-controlled, parallel group, single-centre trial [3], 156 obese individuals with knee osteoarthritis, but without gout, were offered an initial 8-week intensive diet intervention (week -8 to 0) on Cambridge Weight Plan (800-1000 kcal/day) followed by a weight loss maintenance period in which participants were randomised to either liraglutide 3 mg/day or placebo for 52 weeks. We conducted a secondary analysis of blood samples collected at week -8, 0 and 52. The primary outcome measure was change in serum urate. We used paired t-test for the change from week -8 to 0, and for change from week 0 to 52 we used an ANCOVA model adjusted for stratification factors (sex, age category and obesity class), and the level of the outcome at baseline. Data were analysed as observed (i.e. no imputation of missing data).Results:156 individuals were randomised and 155 had blood samples taken at baseline. In the initial intensive diet intervention period (week -8 to 0) they lost a mean of 12.5 kg (95% CI -13.1 to -11.9, n 156). In the following 52 weeks, the liraglutide group lost an additional 4.1 kg (SE 1.2, n 71) whereas the control group was almost unchanged with a weight loss of 0.2 kg (SE 1.2, n 66). Looking at the main outcome of serum urate levels change, the initial intensive diet resulted in a mean decrease of 0.21 mg/dL (95% CI 0.35 to 0.07, n 155) for the entire cohort. In the following year (week 0 to 52) the liraglutide group exhibited a further mean decrease in serum urate of 0.48 mg/dL (SE 0.11, n 69), whereas the placebo group exhibited a slight decrease in mean serum urate of 0.07 mg/dL (SE 0.12, n 65) resulting in a significant between-group difference of -0.40 mg/dL (95% CI -0.69 to -0.12, n 134) – see Figure 1. Four participants in each group experienced serious adverse events; no deaths were observed.Conclusion:This secondary analysis of the LOSE-IT trial suggests that liraglutide provides a potential novel serum urate lowering drug mechanism in obese patient populations, with potential implication for gout treatment.References:[1]Richette P et al. 2016.Ann Rheum Dis2017;76:29–42.[2]Nielsen SM et al.Ann Rheum Dis2017 76(11):1870-1882.[3]Gudbergsen H et al.BMJ2019. 71–2.Disclosure of Interests:Kristian Zobbe: None declared, Sabrina Mai Nielsen: None declared, Robin Christensen: None declared, Anders Overgaard: None declared, henrik gudbergsen Speakers bureau: Pfizer 2016, Marius Henriksen: None declared, Henning Bliddal Grant/research support from: received research grant fra NOVO Nordic, Consultant of: consultant fee fra NOVO Nordic, Lene Dreyer: None declared, Lisa Stamp: None declared, Filip Krag Knop Shareholder of: Minority shareholder in Antag Therapeutics Aps, Grant/research support from: AstraZeneca, Gubra, Novo Nordisk, Sanofi and Zealand Pharma, Consultant of: Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, MSD/Merck, Mundipharma, Novo Nordisk, Sanofi and Zealand Pharma., Speakers bureau: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Sanofi and Zealand Pharma., Lars Erik Kristensen Consultant of: UCB Pharma (Advisory Board), Sannofi (Advisory Board), Abbvie (Advisory Board), Biogen (Advisory Board), Speakers bureau: AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Forward Pharma, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, and UCB Pharma

Hydronic cooling systems are often used in large buildings. In these systems, chilled water is transported from the chillers to Air Handling Units (AHUs) via a water distribution system. The temperature of exhaust air is controlled by the flow of the chilled water in AHUs. Due to a poorly balanced hydronic network, some of the AHUs may experience starvation at high load conditions, meaning that air temperature control is impossible. To overcome this problem, we propose an automatic approach to balancing the hydronic system, such that all AHUs can control their air temperatures. The cost is that all zones of the building are controlled to a slightly higher air temperature, which often can be compensated by higher air flow, to keep the room temperature at the desired value. The balancing algorithm is verified on a Modelica model of an office building.

In hydronic heating systems, a mixing loop is used to control the temperature and pressure. The task of the mixing loop is to provide enough heat power for comfort while minimizing the cost of heating the building. Control strategies for mixing loops are often limited by the fact that they are installed in a wide range of different buildings and locations without being properly tuned. To solve this problem the reinforcement learning method known as Q-learning is investigated. To improve the convergence rate this paper introduces a Gaussian kernel backup method and a generic model for pre-simulation. The method is tested via high-fidelity simulation of different types of residential buildings located in Copenhagen. It is shown that the proposed method performs better than well tuned industrial controllers.