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Abstract Background Exercise is recommended to protect physical health among people with severe mental illness and holds the potential to facilitate long-term recovery. An inclusive exercise community provides an opportunity for life skill training and social connectedness and may reduce the experience of loneliness and internalized stigmatization which together may improve personal recovery. Using a pragmatic randomized design, we aim to examine the effectiveness of a gym-based exercise intervention tailored to young adults in antipsychotic treatment (i.e., Vega Exercise Community) compared to usual care. It is hypothesized that the Vega Exercise Community will be superior to usual care for personal recovery at four months. Methods The trial will be conducted at four sites in Denmark from which 400 participants, aged 18 to 35 years, who are in current treatment with antipsychotic medications for the management of schizophrenia spectrum or affective disorders, will be recruited. Participants will be randomized (2:1) to Vega Exercise Community or usual care. Vega Exercise Community includes three weekly group-based exercise sessions hosted in commercial functional training centers delivered by certified Vega instructors. After four months, participants in Vega Exercise Community will be randomized (1:1) to minimal versus extended support with regards to sustained physical activity. Data will be collected at baseline, four, six and 12 months. The primary outcome is personal recovery assessed by Questionnaire about the Process of Recovery at four months. Behavioral symptoms, health-related quality of life, metabolic health, and program costs will be evaluated to further determine the effectiveness and cost-effectiveness of the Vega Exercise Community. Finally, the quality of life and physical and mental health of the participants’ primary relative will be evaluated. Discussion The results of this trial may have important implications for health, sustained physical activity, and recovery for individuals in treatment with antipsychotics. Given the pragmatic design, positive results may readily be implemented by mental health care professionals to promote exercise as an integrated part of treatment of severe mental illness. Trial registration Clinical Trials.gov (NCT05461885, initial registration June 29th, 2022). WHO Universal Trial Number (UTN): U1111-1271–9928.

Abstract Background Prehabilitation with exercise interventions during neoadjuvant chemotherapy (NACT) is effective in reducing physical and psychosocial chemotherapy-related adverse events in patients with cancer. In preclinical studies, data also support a growth inhibitory effect of aerobic exercise on the tumour microenvironment with possible improved chemotherapy delivery but evidence in human patients is limited. The aim of the study here described is to investigate if supervised exercise with high-intensity aerobic and resistance training during NACT can improve tumour reduction in patients with breast cancer. Methods This parallel two-armed randomized controlled trial is planned to include 120 women aged ≥ 18 years with newly diagnosed breast cancer starting standard NACT at a university hospital in Denmark (a total of 90 participants needed according to the power calculation and allowing 25% (n = 30) dropout). The participants will be randomized to usual care or supervised exercise consisting of high-intensity interval training on a stationary exercise bike and machine-based progressive resistance training offered three times a week for 24 weeks during NACT, and screening-based advice to seek counselling in case of moderate-severe psychological distress (Neo-Train program). The primary outcome is tumour size change (maximum diameter of the largest lesion in millimetre) measured by magnetic resonance imaging prior to surgery. Secondary outcomes include clinical/pathological, physical and patient-reported measures such as relative dose intensity of NACT, hospital admissions, body composition, physical fitness, muscle strength, health-related quality of life, general anxiety, depression, and biological measures such as intratumoural vascularity, tumour infiltrating lymphocytes, circulating tumour DNA and blood chemistry. Outcomes will be measured at baseline (one week before to 1–2 weeks after starting NACT), during NACT (approximately week 7, 13 and 19), pre-surgery (approximately week 21–29), at surgery (approximately week 21–30) and 3 months post-surgery (approximately 33–42 weeks from baseline). Discussion This study will provide novel and important data on the potential benefits of supervised aerobic and resistance exercise concomitant to NACT on tumour response and the tumour microenvironment in patients with breast cancer, with potential importance for survival and risk of recurrence. If effective, our study may help increase focus of exercise as an active part of the neoadjuvant treatment strategy. Trial registration The trial was registered at ClinicalTrials.gov (NCT04623554) on November 10, 2020.

Abstract Background Previous studies have found that lumbar spinal stenosis (LSS) often co-occurs with knee or hip OA and can impact treatment response. However, it is unclear what participant characteristics may be helpful in identifying individuals with these co-occurring conditions. The aim of this cross-sectional study was to explore characteristics associated with comorbid symptoms of lumbar spinal stenosis (LSS) in people with knee or hip osteoarthritis (OA) enrolled in a primary care education and exercise program. Methods Sociodemographic, clinical characteristics, health status measures, and a self-report questionnaire on the presence of LSS symptoms was collected at baseline from the Good Life with osteoArthritis in Denmark primary care program for knee and hip OA. Cross-sectional associations between characteristics and the presence of comorbid LSS symptoms were assessed separately in participants with primary complaint of knee and hip OA, using domain-specific logistic models and a logistic model including all characteristics. Results A total of 6,541 participants with a primary complaint of knee OA and 2,595 participants with a primary complaint of hip OA were included, of which 40% and 50% reported comorbid LSS symptoms, respectively. LSS symptoms were associated with similar characteristics in knee and hip OA. Sick leave was the only sociodemographic variable consistently associated with LSS symptoms. For clinical characteristics, back pain, longer symptom duration and bilateral or comorbid knee or hip symptoms were also consistently associated. Health status measures were not consistently related to LSS symptoms. Conclusion Comorbid LSS symptoms in people with knee or hip OA undergoing a primary care treatment program of group-based education and exercise were common and associated with a similar set of characteristics. These characteristics may help to identify people with co-occurring LSS and knee or hip OA, which can be used to help guide clinical decision-making.

Abstract Background Exercise therapy is safe and effective in people with single conditions, but the feasibility in people with two or more conditions is unclear. Therefore, the aim was to evaluate the feasibility of exercise therapy and self-management in people with multimorbidity prior to a randomised, controlled trial (RCT). Methods This was a mixed-methods feasibility study performed in two general hospitals and one psychiatric hospital. 20 adult patients (8 females; mean age (SD) 67 (6.9)) with at least two long-term conditions and a score of ≥ 3 on Disease Burden Impact Scale for at least one condition (at least moderate limitations of daily activities) and of ≥ 2 for at least one other condition. Patients with unstable health conditions, at risk of serious adverse events (SAE) or with terminal conditions were excluded. Participants received 12 weeks of exercise (18 60-min group-based and 6 home-based sessions) and self-management support (6 90-min group-based sessions) supervised by physiotherapists. Pre-defined progression to RCT criteria were the primary outcomes and included recruitment rate (acceptable 20 participants in 3 months), retention through follow-up (75% retention), compliance (75% complete > 9 of exercise and > 3 self-management sessions), outcome burden (80% do not find outcomes too burdensome), improvement in quality of life (EQ-5D-5L) and function (6-min walk test; ≥ 50% experience clinically relevant improvements) and intervention-related SAEs (No SAEs). Furthermore, a purposeful sample including eleven participants and two facilitators were interviewed about their experiences of participating/facilitating. Qualitative data was analysed using thematic analysis. Results Recruitment rate (20 in 49 days), retention (85%), outcome burden (95%), and SAEs (0 related to intervention) were acceptable, while compliance (70%) and improvements (35% in quality of life, 46% in function) were not (amendment needed before proceeding to RCT). The intervention was found acceptable by both participants and physiotherapists with some barriers among participants relating to managing multiple chronic conditions while caring for others or maintaining a job. Physiotherapists expressed a need for additional training. Conclusions Exercise therapy and self-management are feasible in people with multimorbidity. The subsequent RCT, amending the intervention according to progression criteria and feedback, will determine whether the intervention is superior to usual care alone. Trial registration ClinicalTrials.gov registration: NCT04645732 Open Science Framework https://osf.io/qk6yg/

Abstract Background To our knowledge, there is no intervention which includes personalised exercise therapy and self-management support for people with multimorbidity, although these interventions may be as effective as for people with single chronic conditions. Therefore, we developed a novel intervention, including personalised exercise therapy and self-management support for people with multimorbidity. Methods We followed the Medical Research Council framework and conducted one scoping review, five systematic reviews, two registry-based studies, one qualitative interview study and a mixed-methods feasibility study. Following an iterative approach, together with feedback from people with multimorbidity and relevant stakeholders, we developed the MOBILIZE intervention. Results The intervention included 24 (60 minutes) sessions of personalised exercise therapy and 24 (30 minutes) sessions of self-management support twice a week for 12 weeks, delivered in small groups by specifically trained physiotherapists. The intervention targets physiological, psychosocial, behavioural, and contextual factors to improve health-related quality of life and physical function in people living with multimorbidity. Conclusions We developed a personalised exercise therapy and self-management support programme for people with multimorbidity. The intervention will be tested for its safety and effectiveness in a randomised controlled trial.

Abstract Background The prevalence of low back pain increases with age and has a profound impact on physical and psychosocial health. With increasing age comes increasing comorbidity, and this also has pronounced health consequences. Whilst exercise is beneficial for a range of health conditions, trials of exercise for low back pain management often exclude older adults. It is currently unknown whether an exercise program for older adults with low back pain, tailored for the presence of comorbidities, is acceptable for participants and primary healthcare providers (PHCPs). Therefore, this mixed-methods study will assess the feasibility of an 8-week comorbidity-adapted exercise program for older people with low back pain and comorbid conditions. Methods The 3-phased feasibility study will be performed in a primary healthcare setting. PHCPs will be trained to deliver a comorbidity-adapted exercise program for older people with low back pain and comorbidities. Healthcare-seeking adults > 65 will be screened for eligibility over telephone, with a recruitment target of 24 participants. Eligible participants will attend an initial appointment (diagnostic phase). During this initial appointment, a research assistant will collect patient demographics, self-reported outcome measurement data, and perform a physical and functional examination to determine contraindications and restrictions to an exercise program. During the development phase, PHCPs will adapt the exercise program to the individual and provide patient education. During the intervention phase, there will be two supervised exercise sessions per week, over 8 weeks (total of 16 exercise sessions). Each exercise session will be approximately 60 min in duration. A qualitative evaluation after the last exercise program session will explore the feasibility of the exercise program for participants and PHCPs. Progression criteria will determine the suitability for a fully powered randomised controlled trial. Discussion This mixed-methods feasibility study will assess an exercise program for older adults with low back pain and comorbidities. Once assessed for feasibility, the exercise program may be tested for effectiveness in a larger, fully powered randomised controlled trial. This information will add to the sparse evidence base on appropriate options for managing back pain in older adults. Trial registration Australian and New Zealand Clinical Trials Registry registration number: ACTRN12621000379819p (06/04/2021; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621000379819p ). Trial sponsor Macquarie University, Department of Chiropractic, Faculty of Medicine, Health and Human Sciences, Macquarie University, NSW 2109, Australia.

Abstract Background One in five patients report chronic pain following total knee arthroplasty (TKA) and are considered non-improvers. Psychological interventions such as cognitive behavioral therapy (CBT), combined with exercise therapy and education may contribute to reduced pain an improved function both for patients with OA or after TKA surgery, but the evidence for the effectiveness of such interventions is scarce. This randomized controlled trial with three arms will compare the clinical effectiveness of patient education and exercise therapy combined with internet-delivered CBT (iCBT), evaluated either as a non-surgical treatment choice or in combination with TKA, in comparison to usual treatment with TKA in patients with knee OA who are considered candidates for TKA surgery. Methods The study, conducted in three orthopaedic centers in Norway will include 282 patients between ages 18 and 80, eligible for TKA. Patients will be randomized to receive the exercise therapy + iCBT, either alone or in combination with TKA, or to a control group who will undergo conventional TKA and usual care physiotherapy following surgery. The exercise therapy will include 24 one hour sessions over 12 weeks led by a physiotherapist. The iCBT program will be delivered in ten modules. The physiotherapists will receive theoretical and practical training to advise and mentor the patients during the iCBT program. The primary outcome will be change from baseline to 12 months on the pain sub-scale from the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include the remaining 4 sub-scales from the KOOS (symptoms, function in daily living, function in sports and recreation, and knee-related quality of life), EQ-5D-5L, the Pain Catastrophizing Scale, the 30-s sit-to-stand test, 40-m walking test and ActiGraph activity measures. A cost-utility analysis will be performed using QALYs derived from the EQ-5D-5L and registry data. Discussion This is the first randomized controlled trial to investigate the effectiveness of exercise therapy and iCBT with or without TKA, to optimize outcomes for TKA patients. Findings from this trial will contribute to evidence-based personalized treatment recommendations for a large proportion of OA patients who currently lack an effective treatment option. Trial registration Clinicaltrials.gov : NCT03771430 . Registered: Dec 11, 2018.

Abstract Background Approximately 20% of patients experience chronic pain after total knee arthroplasty (TKA). Due to the growing number of TKA procedures, this will affect an increasing number of people worldwide. Catastrophic thinking, dysfunctional illness perception, poor mental health, anxiety and depression characterize these non-improvers, and indicate that these patients may need individualized treatment using a treatment approach based on the bio-psycho-social health model. The present study developed an internet-delivered cognitive behavioral therapy (iCBT) program to be combined with exercise therapy and education for patients with knee osteoarthritis (OA) at increased risk of chronic pain after TKA. Methods The development process followed the first two phases of the UK Medical Research Council framework for complex interventions. In the development phase, the first prototype of the iCBT program was developed based on literature review, established iCBT programs and multidisciplinary workshops. The feasibility phase consisted of testing the program, interviewing users, condensing the program, and tailoring it to the patient group. A physiotherapist manual was developed and adapted to physiotherapists who will serve as mentors. Results The development process resulted in an iCBT program consisting of 10 modules with educational texts, videos and exercises related to relevant topics such as goalsetting, stress and pain, lifestyle, automatic thoughts, mindfulness, selective attention, worry and rumination. A physiotherapist manual was developed to guide the physiotherapists in supporting the patients through the program and to optimize adherence to the program. Conclusions The iCBT program is tailored to patients at risk of chronic pain following TKA, and may be useful as a supplement to surgery and/or exercise therapy. A multicentre RCT will evaluate the iCBT program in combination with an exercise therapy and education program. This novel intervention may be a valuable contribution to the treatment of OA patients at risk of chronic pain after TKA. Trial registration The RCT is pre-registered at ClinicalTrials.gov: NCT03771430 11/12/2018.

Abstract Background Evidence on prognostic factors associated with progression to total hip replacement (THR) in hip osteoarthritis (OA) is for the most patient- and disease-specific characteristics either conflicting or inconclusive. Therefore, the objectives of this study of participants with hip OA enrolled in a structured program of supervised education and exercise therapy were to describe the rate of THR and to identify prognostic factors for receiving THR within the following 2 years. Methods Participants aged ≥ 45 years with hip OA enrolled in Good Life with osteoArthritis in Denmark (GLA:D®) from July 2014 to March 2017 were included. Potential prognostic factors included demographic and disease-specific baseline characteristics and measures of physical activity and quality of life (QoL). Information on THR was retrieved from The Danish National Patient Registry. A multivariable Cox proportional hazards model was developed. Results Of 3657 included participants, 30% received a THR within 2 years. Of the 100 participants already wait-listed for THR, 60% had the procedure. Of 22 candidate prognostic factors, 14 were statistically significant for receiving THR. Factors associated with a faster rate of THR included being “male” (HR 1.43), having “self-reported radiographic hip OA” (HR 2.32), being “wait-listed for THR” (HR 2.17), and having a higher “pain intensity” (HR 1.01). In contrast, faster “walking speed” (HR 0.64), better “hip-related QoL” (HR 0.98), and having “three or more comorbidities” (HR 0.62) were predictive of a slower rate of THR. Conclusion During the 2-year follow-up period, 30% of the cohort received a THR. Notably, 40% of those wait-listed for THR when entering the program did not receive THR within 2 years. A number of baseline prognostic factors for receiving THR were identified.

Abstract Aim To quantify recruitment, retention and differential retention rates and associated trial, participant and intervention characteristics in randomised controlled trials (RCTs) evaluating the effect of exercise therapy in people with multimorbidity. Data sources MEDLINE, EMBASE, CINAHL and CENTRAL from 1990 to April 20, 2020. Study selection RCTs including people with multimorbidity comparing exercise therapy with a non-exposed comparator group reporting at least one of the following outcomes: physical function, health-related quality of life, depression symptoms, or anxiety symptoms. Data extraction and synthesis Recruitment rates (proportion of people randomised/proportion of people eligible), retention rates (proportion of people providing the outcomes of interest/proportion randomised) and differential retention rates (difference in proportion of people providing the outcomes in the intervention group and comparator group) were calculated. Meta-analysis using a random-effects model was used to estimate pooled proportions. Methodological quality was assessed using Cochrane ´Risk of Bias tool 2.0´ for individual studies, and the GRADE approach was used to assess the overall quality of the evidence. Results Twenty-three RCTs with 3363 people were included. The pooled prevalence for recruitment rate was 75% (95%CI 66 to 84%). The pooled prevalence for retention rate was 90% (95%CI 86 to 94%) at the end of the intervention (12 weeks; interquartile range (IQR) (12 to 12)). Meta-regression analyses showed that increasing age and including a higher proportion of people with hypertension was associated with lower retention rates. Retention rates did not differ between the intervention and comparator groups. The overall quality of the evidence was deemed very low. Conclusion Three in four eligible people with multimorbidity were randomised to RCTs using exercise therapy, of which nine out of 10 provided end of treatment outcomes with no difference seen between the intervention and comparison groups. However, the results must be interpreted with caution due to large differences between the included studies. Trial registration ClinicalTrials.gov CRD42020161329 . Registered on 28 April 2020.

Abstract Background Four out of five patients with hypermobility spectrum disorder (HSD) or hypermobile Ehlers-Danlos syndrome (hEDS) experience shoulder complaints including persistent pain and instability. Evidence suggests that patients with HSD/hEDS who experience knee and back complaints improve with exercise-based therapy. However, no study has focused on exercise-based treatment for the shoulder in this patient group. The potential benefits of strengthening the shoulder muscles, such as increased muscle-tendon stiffness, may be effective for patients with HSD/hEDS who often display decreased strength and increased shoulder laxity/instability. The primary aim is to investigate the short-term effectiveness of a 16-week progressive heavy shoulder strengthening programme and general advice (HEAVY) compared with low-load training and general advice (LIGHT), on self-reported shoulder symptoms, function, and quality of life. Methods A superiority, parallel group, randomised controlled trial will be conducted with 100 patients from primary care with HSD/hEDS and shoulder complaints (persistent pain and/or instability) for more than 3 months. Participants will be randomised to receive HEAVY (full range of motion, high load) or LIGHT (neutral to midrange of motion, low load) strengthening programme three times weekly with exercises targeting scapular and rotator cuff muscles. HEAVY will be supervised twice weekly, and LIGHT three times during the 16 weeks. The primary outcome will be between-group difference in change from baseline to 16-week follow-up in the Western Ontario Shoulder Instability Index (WOSI, 0-2100 better to worse). Secondary outcomes will include a range of self-reported outcomes covering symptoms, function, and quality of life, besides clinical tests for shoulder strength, laxity/instability, and proprioception. Outcome assessors will be blinded to group allocation. Participants will be kept blind to treatment allocation through minimal information about the intervention content and hypotheses. Primary analyses will be performed by a blinded epidemiologist. Discussion If effective, the current heavy shoulder strengthening programme will challenge the general understanding of prescribing low-load exercise interventions for patients with HSD/hEDS and provide a new treatment strategy. The study will address an important and severe condition using transparent, detailed, and high-quality methods to potentially support a future implementation. Trial registration ClinicalTrials.gov NCT03869307 . Registered on 11 March 2019.

Abstract Background A comprehensive overview of treatments of common fractures is missing, although it would be important for shared decision-making in clinical practice. The aim was to determine benefits and harms of surgical compared to non-surgical treatments for traumatic skeletal fractures. Methods We searched Medline, Embase, CINAHL, Web of Science, and CENTRAL until November 2018, for randomized trials of surgical treatment in comparison with or in addition to non-surgical treatment of fractures in adults. For harms, only trials with patient enrollment in 2000 or later were included, while no time restriction was applied to benefits. Two reviewers independently assessed studies for inclusion, extracted data from full-text trials, and performed risk of bias assessment. Outcomes were self-reported pain, function, and quality of life, and serious adverse events (SAEs). Random effects model (Hedges’ g) was used. Results Out of 28375 records screened, we included 61 trials and performed meta-analysis on 12 fracture types in 11 sites: calcaneus, clavicula, femur, humerus, malleolus, metacarpus, metatarsus, radius, rib, scaphoideum, and thoraco-lumbar spine. Seven other fracture types only had one trial available. For distal radius fractures, the standardized mean difference (SMD) was 0.31 (95% CI 0.10 to 0.53, n = 378 participants) for function, favoring surgery, however, with greater risk of SAEs (RR = 3.10 (1.42 to 6.77), n = 436). For displaced intra-articular calcaneus fractures, SMD was 0.64 (0.13 to 1.16) for function (n = 244) and 0.19 (0.01 to 0.36) for quality of life (n = 506) favoring surgery. Surgery was associated with a smaller risk of SAE than non-surgical treatment for displaced midshaft clavicular fractures (RR = 0.62 (0.42 to 0.92), n = 1394). None of the other comparisons showed statistical significance differences and insufficient data existed for most of the common fracture types. Conclusions Of 12 fracture types with more than one trial, only two demonstrated a difference in favor of surgery (distal radius fractures and displaced intra-articular calcaneus fractures), one of which demonstrated a greater risk of harms in the surgical group (distal radius fractures). Our results highlight the current paucity of high-quality randomized trials for common fracture types and a considerable heterogeneity and risk of bias in several of the available trials. Systematic review registration PROSPERO CRD42015020805

Abstract Background People with hypermobility spectrum disorder (HSD) are in great risk of experiencing shoulder symptoms, but evidence for treatment is sparse. Therefore, the objective was to evaluate the feasibility of 16-week shoulder strengthening programme for improving shoulder strength and function in people with HSD and shoulder symptoms for more than 3 months to inform a future randomised controlled trial (RCT). Methods Twelve participants (11 females, 39.3 ± 13.9 years) with HSD and shoulder instability and/or pain for more than 3 months underwent a 16-week heavy shoulder strengthening exercise programme three times weekly using exercises targeting scapular and rotator cuff muscles. Primary outcomes were pre-defined research progression criteria including recruitment rate (acceptable, 6 participants/month), assessment duration (acceptable: < 120 min), participant retention (acceptable: > 80% complete intervention), training adherence (acceptable: > 75% adhere to > 36 training sessions) and adverse events (acceptable: minor events with no participants discontinuing the study), besides participant and physiotherapist feedback. Secondary treatment outcomes were assessed using the Western Ontario Shoulder Instability Index (WOSI, 0–2100 better to worse), self-reported pain, kinesiophobia and fatigue, isometric shoulder strength, besides clinical tests for instability, hypermobility, laxity, and proprioception. Results Recruitment rate was 5.6/month, assessment duration (mean ± SD) 105 ± 9 min, retention 100%, adherence 83%, and four participants experienced short-lasting soreness or pain. Participant feedback was positive, and physiotherapists found the intervention relevant and applicable to the population. The WOSI total score showed an improvement by 51% (mean ± SD, points: baseline 1037 ± 215; Follow up 509 ± 365; mean change (95% CI), − 528 (− 738, − 318)), and participants reported reduced pain, kinesiophobia and fatigue. Shoulder strength measurements improved by 28–31% (mean change (95% CI), Nm/kg: scaption 0.51 (0.23, 0.78); internal rotation 1.32 (0.70, 1.95) and external rotation 0.89 (0.37, 1.40)), and clinical tests indicated decreased shoulder laxity/instability. Conclusions The shoulder strengthening exercise programme was feasible and safe for people with HSD and long-lasting shoulder symptoms. A future RCT, with an improved recruitment strategy, will demonstrate whether the exercise programme is also effective in improving symptoms and muscle-tendon function in this population. Trial registration ClinicalTrials.gov : NCT03547570 . Registered on May 3, 2018.

Abstract Background Total knee arthroplasty (TKA) is considered an effective treatment for pain relief and improved physical performances in end-stage knee osteoarthritis. However, several studies have reported less favorable outcomes after TKA with chronic pain rates of approximately 20%. Exercise might be an effective treatment strategy for chronic pain following TKA, but no randomized controlled trials have evaluated its effect. Therefore, the purpose of this randomized controlled trial is to investigate whether a 12-week neuromuscular exercise (NEuroMuscular EXercise training program for patients with knee or hip osteoarthritis assigned for total joint replacement; NEMEX-TJR) program combined with pain neuroscience education (PNE) provides greater pain relief and improvement in physical performances than PNE alone at 12 months follow-up in a population of patients with chronic pain after primary TKA. Methods For this randomized controlled superiority trial, 120 patients with moderate-to-severe chronic pain after TKA are recruited from Aalborg University Hospital, Denmark. Patients are randomly assigned in a 1:1 ratio to one of two interventions: (a) NEMEX-TJR twice weekly for 12 weeks combined with two sessions of PNE or (b) two sessions of PNE given over 6 weeks. Assessment is performed at baseline before intervention and at 3, 6, and 12 months after initiation of the intervention. Outcome assessors are blinded toward group allocation. The primary outcome is the change in the Knee Injury and Osteoarthritis Outcome Score4 (KOOS4), defined as the mean score for the KOOS subscales pain, symptoms, activities of daily living, and quality of life. Secondary outcomes include all KOOS subscale scores and scores for PainDETECT, the Fear-Avoidance Beliefs Questionnaire, Global Perceived Effect, the Pain Catastrophizing Scale, pain intensities, temporal summation, conditioned pain modulation, and pressure pain thresholds. Physical performances are measured with walking, stair climbing, and chair standing tests as well as tests of muscle strength and power. Discussion The findings will be useful in establishing effective treatment strategies for chronic pain after TKA. The randomized controlled trial involves rigorous scientific methods and uses clinically applicable interventions. The study interventions are conducted in clinical settings, thereby enhancing the possibility of future implementation of the treatments in the health care systems. Trial registration ClinicalTrials.gov identifier: NCT03886259. Registered 22 March 2019. Ethics committee registration: N-20180046.

Abstract Background Clinical guidelines recommend that people with back pain be given information and education about their back pain, advice to remain active and at work, and exercises to improve mobility and physical activity. Guidelines, however, rarely describe how this is best delivered. The aim of this paper is to present the development, theories, and underlying evidence for ‘GLA:D Back’ - a group education and exercise program that translates guideline recommendations into a clinician-delivered program for the promotion of self-management in people with persistent/recurrent back pain. Methods GLA:D Back, which included a rationale and objectives for the program, theory and evidence for the interventions, and program materials, was developed using an iterative process. The content of patient education and exercise programs tested in randomised trials was extracted and a multidisciplinary team of expert researchers and clinicians prioritised common elements hypothesised to improve back pain beliefs and management skills. The program was tested on eight people with persistent back pain in a university clinic and 152 patients from nine primary care physiotherapy and chiropractic clinics. Following feedback from the clinicians and patients involved, the working version of the program was created. Results Educational components included pain mechanisms, pain modulation, active coping strategies, imaging, physical activity, and exercise that emphasised a balance between the sum of demands and the individual’s capacity. These were operationalised in PowerPoint presentations with supporting text to aid clinicians in delivering two one-hour patient education lectures. The exercise program included 16 supervised one-hour sessions over 8 weeks, each comprising a warm-up section and eight types of exercises for general flexibility and strengthening of six different muscle groups at four levels of difficulty. The aims of the exercises were to improve overall back fitness and, at the same time, encourage patients to explore variations in movement by incorporating education content into the exercise sessions. Conclusion From current best evidence about prognostic factors in back pain and effective treatments for back pain, research and clinical experts developed a ready-to-use structured program - GLA:D® Back - to support self-management for people with persistent/recurrent back pain.

Abstract Background Knee osteoarthritis (OA) is a leading cause of global disability. The understanding of the role of psychosocial factors in knee OA outcomes is still evolving particularly in an Asian context. The primary aim of this study is to explore psychosocial factors that prognosticate short and long-term clinical outcomes, productivity, and healthcare utilization in patients with knee OA. Secondary aims are to explore the mediation and directional relationships and the role it plays in predicting the discordance between self-reported measures (SRM), physical-performance measures (PPMs) and objective clinical parameters. Methods A multi-centre prospective cohort study of community ambulant knee OA patients seeking treatment in the tertiary healthcare institutions in Singapore will be conducted. Patients with secondary arthritis, significant cognitive impairment, severe medical comorbidities or previous knee arthroplasty will be excluded. Primary clinical outcome measure is the Knee injury and OA Outcome Score-12 (KOOS-12). Baseline characteristics include sociodemographic status, arthritis status including symptom duration and radiographic severity, comorbidities and functional status through Charlson Comorbidities Index (CCI), Barthel Index (BI) and Parker Mobility Score (PMS). Psychosocial variables include social support, kinesiophobia, negative affect, self-efficacy, injustice, chronic illness shame and the built environment. Clinical outcomes include quality of life, physical performance, global assessment, satisfaction and physical activity levels. Productivity and healthcare utilization will be assessed by a modified OA Cost and Consequences Questionnaire (OCC-Q) and the Work Productivity and Activity Impairment Questionnaire (WPAI). Variables will be collected at baseline, 4, 12 months and yearly thereafter. Regression, mediation and structural equation modelling will be used for analysis. Discussion Results will allow contextualization, identification, and phenotyping of the critical (and potentially modifiable) psychosocial parameters that predict positive clinical outcomes in the OA population to guide optimization and refinement of healthcare and community. This will facilitate: 1. identification of high-risk knee OA subpopulations that will likely experience poor outcomes and 2. formulation of targeted multidisciplinary comprehensive approaches to address these psychosocial factors to optimize non-surgical treatment care, maximize functional outcomes and create more value-based care model for knee OA. Ethics and dissemination The study has been registered under clinicaltrials.gov registry (Identifier: NCT04942236).

Abstract Background The evidence-based interventions of exercise and education have been strongly recommended as part of prominent clinical guidelines for hip and knee osteoarthritis (OA) for more than ten years. Despite the wealth of strong evidence that exists, implementation in practice is sub-optimal. This paper describes the key methodologies used in the co-design, tailoring, and evaluation of the IMPACT project implementation strategies, to confront this problem across multiple levels (micro, meso, macro) in public and private healthcare settings in Ireland. Methods Using a type III hybrid implementation-effectiveness design, a participatory, dynamic and iterative process will be used to tailor and evaluate multi-level implementation strategies using the following stages: 1) Co-design the implementation strategies with key stakeholders using best evidence, a theory-driven implementation framework (Consolidated Framework for Implementation Research), local context and expert consensus; 2) Pilot and evaluate the implementation strategies by training physiotherapists to deliver the evidence-based Good Life with osteoArthritis Denmark (GLA:D®) education and exercise programme using the implementation strategies, and conduct a mixed-methods process evaluation; 3) Adapt the implementation strategies based on implementation process evaluation indicators from stage two. The adapted strategies will be used for scale-up and sustainability in subsequent GLA:D® Ireland training programmes that will be rolled out nationally. Evaluation of effectiveness on patient and cost outcomes will continue up to 12 months post-programme delivery, using an online patient registry and pre-post design. Discussion This implementation science project aims to use participatory health research to address a gap in management of OA across public and private healthcare settings. This research has the potential to change practice and promote a policy of exercise and physical activity referral for chronic musculoskeletal disease that utilises community engagement effectively and enacts change ‘together’, with involvement of researchers, decision-makers, clinicians and patients.

Abstract Background One in five patients experience chronic pain 1 year after total knee arthroplasty (TKA), highlighting the need for enhanced treatment strategies to improve outcomes. This feasibility trial aimed to optimize the content and delivery of a complex intervention tailored to osteoarthritis (OA) patients at risk of poor outcome after TKA and assess the feasibility of initiating a full-scale multicenter randomized controlled trial (RCT). Methods Patients scheduled for TKA were included between August 2019 and June 2020 and block-randomized into one of three groups: (a) 12-week exercise therapy and education (ExE) and 10-module internet-delivered cognitive behavioral therapy (iCBT), (b) TKA followed by ExE and iCBT and (c) TKA and standard postoperative care. Outcomes were (i) recruitment and retention rate, (ii) compliance to the intervention and follow-up, (iii) crossover, and (iv) adverse events, reported by descriptive statistics. Results Fifteen patients were included in the study. Only 1 out of 146 patients screened for eligibility was included during the first 4 months. During the next 3 months, 117 patients were not included since they lived too far from the hospital. To increase the recruitment rate, we made three amendments to the inclusion criteria; (1) at-risk screening of poor TKA outcome was removed as an eligibility criterion, (2) patients across the country could be included in the study and (3) physiotherapists without specific certification were included, receiving thorough information and support. No patients withdrew from the study or crossed over to surgery during the first year. Nine out of 10 patients completed the ExE program and six out of 10 completed the iCBT program. Fourteen out of 15 patients completed the 1-year follow-up. One minor adverse event was registered. Conclusions Except for recruitment and compliance to iCBT, feasibility was demonstrated. The initial recruitment process was challenging, and necessary changes were made to increase the recruitment rate. The findings informed how a definitive RCT should be undertaken to test the effectiveness of the complex intervention. Trial registration The MultiKnee RCT, including the feasibility study, is pre-registered at ClinicalTrials.gov: NCT03771430 11/12/2018.