The past and future of peri-operative interventions to reduce arthrogenic quadriceps muscle inhibition after total knee arthroplasty: A narrative review.

Total knee arthroplasty (TKA) improves patient-reported function by alleviating joint pain, however the surgical trauma exacerbates already impaired muscle function, which leads to further muscle weakness and disability after surgery. This early postoperative strength loss indicates a massive neural inhibition and is primarily driven by a deficit in quadriceps muscle activation, a process known as arthrogenic muscle inhibition (AMI). To enhance acute recovery of quadriceps muscle function and long-term rehabilitation of individuals after TKA, AMI must be significantly reduced in the early post-operative period. The aim of this narrative review is to review and discuss previous efforts to mitigate AMI after TKA and to suggest new approaches and interventions for future efficacy evaluation. Several strategies have been explored to reduce the degree of post-operative quadriceps AMI and improve strength recovery after TKA by targeting post-operative swelling and inflammation or changing neural discharge. A challenge of this work is the ability to directly measure AMI and relevant contributing factors. For this review we focused on interventions that aimed to reduce post-operative swelling or improve knee extension strength or quadriceps muscle activation measured by twitch interpolation. For individuals undergoing TKA, the use of anti-inflammatory medications, tranexamic acid, cryotherapy, intra-articular drains, torniquets, and minimally invasive surgical techniques for TKA have limited benefit in attenuating quadriceps AMI early after surgery. However, interventions such as inelastic compression garments, voluntary muscle contractions, and neuro-muscular electrical stimulation show promise in mitigating or circumventing AMI and should continue to be refined and explored.

Effect of aerobic exercise training on the fat fraction of the liver in persons with chronic hepatitis B and hepatic steatosis: Trial protocol for a randomized controlled intervention trial- The FitLiver study.

BACKGROUND: The global prevalence of chronic hepatitis B is more than 300 million people, and in Denmark, 17,000 people are estimated to have chronic hepatitis B. Untreated, chronic hepatitis B can lead to the development of liver cirrhosis and liver cancer. There is no curable therapy. In persons with obesity and chronic hepatitis B infection, the development of hepatic steatosis imposes a double burden on the liver, leading to an increased risk of cirrhosis and liver cancer. In patients without chronic hepatitis B, exercise interventions have shown beneficial effects on hepatic steatosis through improvements in fat fraction of the liver, insulin resistance, fatty acid metabolism, and glucose metabolism, as well as activation of liver-induced regulatory protein secretion (hepatokines) after the exercise intervention. OBJECTIVE: To investigate in persons with chronic hepatitis B and hepatic steatosis: Primary: Whether exercise will decrease the fat fraction of the liver. Secondary: If exercise will affect hepatokine secretion and if it will improve lipid- and glucose metabolism, liver status, markers of inflammation, body composition, and blood pressure. METHODS: A randomized, controlled, clinical intervention trial consisting of 12 weeks of aerobic exercise training or no intervention. Thirty persons with chronic hepatitis B and hepatic steatosis will be randomized 1:1. Before and after the intervention, participants will undergo an MRI scan of the liver, blood sampling, oral glucose tolerance test, fibroscan, VO2max test, DXA scan, blood pressure measurements, and optional liver biopsy. Lastly, a hormone infusion test with somatostatin and glucagon to increase the glucagon/insulin ratio for stimulating secretion of circulating hepatokines will be performed. The training program includes three weekly training sessions of 40 min/session over 12 weeks. DISCUSSION: This trial, investigating high-intensity interval training in persons with chronic hepatitis B and hepatic steatosis, is the first exercise intervention trial performed on this group of patients. If exercise reduces hepatic steatosis and induces other beneficial effects of clinical markers in this group of patients, there might be an indication to recommend exercise as part of treatment. Furthermore, the investigation of the effect of exercise on hepatokine secretion will provide more knowledge on the effects of exercise on the liver. TRIAL REGISTRATION: Danish Capital Regions committee on health research ethics reference: H-21034236 (version 1.4 date: 19-07-2022) and ClinicalTrials.gov: NCT05265026.

Blood flow restriction added to usual care exercise in patients with early weight bearing restrictions after cartilage or meniscus repair in the knee joint: a feasibility study.

PURPOSE: Blood flow restriction - low load strength training (BFR-LLST) is theoretically superior to traditional heavy strength training when rehabilitating patients who cannot heavily load tissues following surgery. The main purpose of this study was to examine the feasibility of BFR-LLST added to usual care exercise early after cartilage or meniscus repair in the knee joint. METHODS: We included 42 patients with cartilage (n = 21) or meniscus repair (n = 21) of the knee joint. They attended 9 weeks of BFR-LLST added to a usual care exercise program at an outpatient rehabilitation center. Outcome measures were assessed at different time points from four (baseline) to 26 weeks postoperatively and included adherence, harms, knee joint and thigh pain, perceived exertion, thigh circumference (muscle size proxy), isometric knee-extension strength, self-reported disability and quality of life. RESULTS: On average, patients with cartilage or meniscus repair completed > 84% of the total BFR-LLST supervised sessions. Thirty-eight patients reported 146 adverse events of which none were considered serious. No decrease in thigh circumference or exacerbation of knee joint or quadriceps muscle pain of the operated leg was found in either group during the intervention period. CONCLUSIONS: BFR-LLST added to usual care exercise initiated early after cartilage or meniscus repair seems feasible and may prevent disuse thigh muscle atrophy during a period of weight bearing restrictions. Harms were reported, but no serious adverse events were found. Our findings are promising but need replication using a RCT-design. TRIAL REGISTRATION: NCT03371901 , preprint (open access):  https://www.medrxiv.org/content/10.1101/2022.03.31.22272398v1.

Supervised exercise therapy compared with no exercise therapy to reverse debilitating effects of androgen deprivation therapy in patients with prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Androgen deprivation therapy (ADT) in patients with prostate cancer can have several debilitating side effects. Supervised exercise is recommended to ameliorate these negative effects. OBJECTIVE: To systematically evaluate the effect of supervised exercise therapy compared to no exercise therapy in patients with prostate cancer undergoing ADT, primarily according to the patient critical outcomes, 'disease-specific quality of life' and 'walking performance' measured at end of treatment. METHODS: We searched PubMed/Medline, Embase, Cochrane Library, Cinahl and Pedro, to identify randomised controlled trials (RCTs), which investigated the effect of supervised exercise therapy compared to no exercise therapy in patients with prostate cancer receiving ADT, last search: June 2021. Two independent reviewers extracted data, and assessed risk of bias using Cochrane Risk of Bias Tool and evaluated the certainty of evidence using the GRADE-method. RESULTS: Eigthteen RCTs (n = 1477) comprised patients with prostate cancer stages T1-T4 were included in the meta-analyses. Compared to no exercise therapy, supervised exercise therapy showed clinically relevant improvements in 'disease-specific quality of life' and 'walking performance'. The standardised mean differences were 0.43 (95% confidence interval (CI): 0.29, 0.58) and -0.41 (95% CI: -0.60, -0.22), respectively. The overall certainty of evidence was moderate due to serious risk of bias. CONCLUSIONS: Evidence of moderate quality shows that supervised exercise therapy probably is superior to no exercise therapy in improving 'disease-specific quality of life' and 'walking performance' in patients with prostate cancer undergoing ADT. The results apply to all patients receiving androgen deprivation therapy regardless of cancer stage. The results support a strong recommendation for supervised exercise therapy for managing side effects in this population. PROTOCOL REGISTRATION: NKR-38-Focused-questions-PICOs-for-updating1.ashx (sst.dk).

Blood-flow restricted exercise following ankle fractures - A feasibility study.

BACKGROUND: The objective was to investigate the feasibility of blood flow restricted exercise (BFRE) as a rehabilitation modality in patients with a unilateral ankle fracture. METHODS: Feasibility study with a prospective cohort design. Inclusion criteria were above 18 years of age and unilateral ankle fractures. EXCLUSION CRITERIA: history of cardiac or embolic diseases, cancer, diabetes, hypertension and family history of cardio or vascular diseases. The predefined feasibility outcome was based on three criteria regarding patients experience with participating in the BFRE protocol and the absence of any serious adverse events. RESULTS: Eight patients were included. Median age was 33 years (range: 23-60). All eight patients reported maximum satisfaction on the two questions regarding patient's perception of the overall experience with BFRE training and the feasibility to introduce BFRE as an intervention. CONCLUSION: Early use of BFRE in patients with unilateral ankle fractures seems feasible in patients without comorbidity.

Exercise Therapy Is Effective at Improving Short- and Long-Term Mobility, Activities of Daily Living, and Balance in Older Patients Following Hip Fracture: A Systematic Review and Meta-Analysis.

BACKGROUND: A systematic review and meta-analysis was performed to evaluate the short- and long-term effects of exercise therapy on physical function, independence, and well-being in older patients following hip fracture and, secondly, whether the effect was modified by trial-level characteristics such as intervention modality, duration, and initiation timepoint. METHOD: Medline, CENTRAL, Embase, CINAHL, and PEDro were searched up to November 2020. Eligibility criteria were randomized controlled trials investigating the effect of exercise therapy on physical function, independence, and well-being in older patients following hip fracture, initiated from time of surgery up to 1 year. RESULTS: Forty-nine studies involving 3 905 participants showed a small-to-moderate effect of exercise therapy at short term (end of intervention) on mobility (standardized mean difference [SMD] 0.49, 95% confidence interval [CI]: 0.22-0.76); activities of daily living (ADL) (SMD 0.31, 95% CI: 0.16-0.46); lower limb muscle strength (SMD 0.36, 95% CI: 0.13-0.60); and balance (SMD 0.34, 95% CI: 0.14-0.54). At long term (closest to 1 year), small-to-moderate effects were found for mobility (SMD 0.74, 95% CI: 0.15-1.34), ADL (SMD 0.42, 95% CI: 0.23-0.61), balance (SMD 0.50, 95% CI: 0.07-0.94), and health-related quality of life (SMD 0.31, 95% CI: 0.03-0.59). Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation ranging from moderate to very low, due to study limitation and inconsistency. CONCLUSION: We found low certainty of evidence for a moderate effect of exercise therapy on mobility in older patients following hip fracture at end of treatment and follow-up. Further, low evidence was found for small-to-moderate short-term effect on ADL, lower limb muscle strength and balance. CLINICAL TRIALS REGISTRATION NUMBER: CRD42020161131.

Disentangling treatment pathways for knee osteoarthritis: a study protocol for the TREATright study including a prospective cohort study, a qualitative study and a cost-effectiveness study.

INTRODUCTION: Knee osteoarthritis (OA) is associated with chronic knee pain and functional disability that negatively affect the ability to carry out normal daily activities. Patients are offered a large variety of non-surgical treatments, often not in accordance with clinical guidelines. This observational study will provide a comprehensive overview of treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon, including timing and order of treatment modalities, predictors of treatment outcomes, cost-effectiveness of treatment pathways and patients' views on different treatment pathways. METHODS AND ANALYSIS: Patients with primary referrals to an orthopaedic surgeon due to knee OA are consecutively invited to participate and fill out a questionnaire prior to their consultation with an orthopaedic surgeon. Follow-up questionnaires will be obtained at 6 and 24 months after inclusion. Based on a prospective cohort study design, including questionnaires and register data, we will (1) describe treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon; (2) describe the characteristics of patients choosing different treatment pathways; (3) develop predictive models for patient-self-determined classifications of good and poor treatment outcomes; (4) evaluate the cost-effectiveness of treatment pathways that live up to clinical guidelines versus pathways that do not; based on a qualitative study design using semistructured individual interviews, we will (5) describe the patients' perspectives on treatment pathways for knee OA. ETHICS AND DISSEMINATION: The study is approved by the Danish regional ethical committee (journal number H-17017295) and the Danish Data Protection Agency (journal number AHH-2017-072). Data will be anonymised and handled in line with the General Data Protection Regulation and the Danish Data Protection Act. The study results will be submitted to international open-access peer-reviewed journals and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT03746184, pre-results.

What is the effect of supervised rehabilitation regime vs. self-management instruction following unicompartmental knee arthroplasty? - a pilot study in two cohorts.

PURPOSE: The optimal rehabilitation strategy after a unicompartmental knee arthroplasty (UKA) is unclear. This study aims to compare the effect of transitioning from a supervised to a self-management rehabilitation regime by pilot study of patient outcomes subsequent to UKA surgery. METHODS: Fifty consecutive patients scheduled to undergo unilateral UKA surgery at our institution between 22nd February 2016 and 18thof January 2017 were prospectively identified via local medical database and included. Performed UKAs were grouped into two cohorts, Supervised Cohort and Self-management Cohort, temporally separated by introduction of new rehabilitation. Self-management Cohort(n = 25) received an extensive inpatient rehabilitation regime along with outpatient referral to rehabilitation center. The Self-management Cohort(n = 25) were only instructed in use of crutches and free ambulation at own accord. Follow-up (F/U) was 1 year from receiving UKA. A range of outcomes were recorded, and between-cohort differences compared: knee joint range of motion, pain and functional limitations, length of stay (LOS), readmission rate, pain during activity and rest, and knee circumference. RESULTS: Complete data was obtained for n = 45 patients. The mean between-cohort difference in ROM (range of motion) from preoperatively to discharge was 15.4 degrees (CI:5.2,25.8, p = 0.004), favoring the supervised regime, with no difference detected in any outcome at 3- or 12 months F/U. Median LOS was 1 day in both cohorts. CONCLUSION: Transition to a simple rehabilitation regime following UKA surgery was associated with decreased ROM at discharge, which was not present at 3-month F/U. We found no other between-cohort differences for any other outcomes at 3- and 12-month F/U including functional limitations, although the study was likely underpowered for these outcomes. We encourage large-scale replication of these findings using randomized designs. LEVEL OF EVIDENCE: Therapeutic level II.

Effectiveness of Adding a Large Dose of Shoulder Strengthening to Current Nonoperative Care for Subacromial Impingement: A Pragmatic, Double-Blind Randomized Controlled Trial (SExSI Trial).

BACKGROUND: A strong recommendation against subacromial decompression surgery was issued in 2019. This leaves nonoperative care as the only treatment option, but recent studies suggest that the dose of strengthening exercise is not sufficient in current nonoperative care. At this point, it is unknown if adding more strengthening to current nonoperative care is of clinical value. PURPOSE: To assess the effectiveness of adding a large dose of shoulder strengthening to current nonoperative care for subacromial impingement compared with usual care alone. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In this double-blinded, pragmatic randomized controlled trial, we randomly allocated 200 consecutive patients referred to orthopaedic shoulder specialist care for long-standing shoulder pain (>3 months), aged 18 to 65 years and diagnosed with subacromial impingement using validated criteria, to the intervention group (IG) or control group (CG). Outcome assessors were blinded, and participants were blinded to the study hypothesis as well as to the treatment method in the other group. The CG received usual nonoperative care; the IG underwent the same plus an add-on intervention designed to at least double the total dose of shoulder strengthening. The primary outcome was the Shoulder Pain and Disability Index (SPADI; 0-100) at 4-month follow-up, with 10 points defined as the minimal clinically important difference. Secondary outcomes included shoulder strength, range of motion, health-related quality of life, and the Patient Acceptable Symptom State (PASS). RESULTS: Intention-to-treat and per-protocol analyses showed no significant or clinically relevant between-group differences for any outcome. From baseline to 4-month follow-up, SPADI scores improved in both groups (intention-to-treat analysis; IG, -22.1 points; CG, -22.7 points; between-group mean difference, 0.6 points [95% CI, -5.5 to 6.6]). At 4 months after randomization, only 54% of the IG and 48% of the CG (P = .4127) reached the PASS. No serious adverse events were reported. CONCLUSION: Adding a large dose of shoulder strengthening to current nonoperative care for patients with subacromial impingement did not result in superior shoulder-specific patient-reported outcomes. Moreover, approximately half of all randomized patients did not achieve the PASS after 4 months of nonoperative care, leaving many of these patients with unacceptable symptoms. This study showed that adding more exercise is not a viable solution to this problem. REGISTRATION: NCT02747251 (ClinicalTrials.gov identifier).

Feasibility and preliminary effect of anabolic steroids in addition to strength training and nutritional supplement in rehabilitation of patients with hip fracture: a randomized controlled pilot trial (HIP-SAP1 trial).

BACKGROUND: Anabolic steroid has been suggested as a supplement during hip fracture rehabilitation and a Cochrane Review recommended further trials. The aim was to determine feasibility and preliminary effect of a 12-week intervention consisting of anabolic steroid in addition to physiotherapy and nutritional supplement on knee-extension strength and function after hip fracture surgery. METHODS: Patients were randomized (1:1) during acute care to: 1. Anabolic steroid (Nandrolone Decanoate) or 2. Placebo (Saline). Both groups received identical physiotherapy (with strength training) and a nutritional supplement. Primary outcome was change in maximal isometric knee-extension strength from the week after surgery to 14 weeks. Secondary outcomes were physical performance, patient reported outcomes and body composition. RESULTS: Seven hundred seventeen patients were screened, and 23 randomised (mean age 73.4 years, 78% women). Target sample size was 48. Main limitations for inclusion were "not home-dwelling" (18%) and "cognitive dysfunction" (16%). Among eligible patients, the main reason for declining participation was "Overwhelmed and stressed by situation" (37%). Adherence to interventions was: Anabolic steroid 87%, exercise 91% and nutrition 61%. Addition of anabolic steroid showed a non-significant between-group difference in knee-extension strength in the fractured leg of 0.11 (95%CI -0.25;0.48) Nm/kg in favor of the anabolic group. Correspondingly, a non-significant between-group difference of 0.16 (95%CI -0.05;0.36) Nm/Kg was seen for the non-fractured leg. No significant between-group differences were identified for the secondary outcomes. Eighteen adverse reactions were identified (anabolic = 10, control = 8). CONCLUSIONS: Early inclusion after hip fracture surgery to this trial seemed non-feasible, primarily due to slow recruitment. Although inconclusive, positive tendencies were seen for the addition of anabolic steroid. TRIAL REGISTRATION: Clinicaltrials.gov NCT03545347 .

Perceived facilitators and barriers among physical therapists and orthopedic surgeons to pre-operative home-based exercise with one exercise-only in patients eligible for knee replacement: A qualitative interview study nested in the QUADX-1 trial.

AIM: Clinical guidelines recommend non-surgical treatment before surgery is considered in patients eligible for knee replacement. Surgical treatment is provided by orthopedic surgeons and exercise therapy is provided by physical therapists. The aim of this study was to identify perceived facilitators and barriers-among orthopedic surgeons and physical therapists-towards coordinated non-surgical and surgical treatment of patients eligible for knee replacement using pre-operative home-based exercise therapy with one exercise. METHODS: This qualitative study is embedded within the QUADX-1 randomized trial that investigates a model of coordinated non-surgical and surgical treatment for patients eligible for knee replacement. Physical therapists and orthopedic surgeons working with patients with knee osteoarthritis in their daily clinical work were interviewed (one focus group and four single interviews) to explore their perceived facilitators and barriers related to pre-operative home-based exercise therapy with one exercise-only in patients eligible for knee replacement. Interviews were analyzed using thematic analysis. RESULTS: From the thematic analysis three main themes emerged: 1) Physical therapists' dilemma with one home-based exercise, 2) Orthopedic surgeons' dilemma with exercise, and 3) Coordinated non-surgical and surgical care. CONCLUSION: We found that the pre-operative exercise intervention created ambivalence in the professional role of both the physical therapists and orthopedic surgeons. The physical therapists were skeptical towards over-simplified exercise therapy. The orthopedic surgeons were skeptical towards the potential lack of (long-term) effect of exercise therapy in patients eligible for knee replacement. The consequence of these barriers and ambivalence in the professional role is important to consider when planning implementation of the model of coordinated non-surgical and surgical treatment. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02931058.

Preliminary effect and feasibility of physiotherapy with strength training and protein-rich nutritional supplement in combination with anabolic steroids in cross-continuum rehabilitation of patients with hip fracture: protocol for a blinded randomized controlled pilot trial (HIP-SAP1 trial).

BACKGROUND: A 2014 Cochrane review evaluating the effect of anabolic steroids after hip fracture concluded that the quality of the studies was insufficient to draw conclusions on the effects and recommended further high-quality trials in the field. Therefore, the aim of this pilot trial is to determine the preliminary effect and feasibility of a 12-week multimodal intervention consisting of physiotherapy (with strength training), protein-rich nutritional supplement and anabolic steroid on knee-extension muscle strength and function 14 weeks after hip fracture surgery. METHODS: We plan to conduct a randomized, placebo-controlled pilot trial with 48 patients operated for acute hip fracture. The patients are randomized (1:1) to either (1) physiotherapy with protein-rich nutritional supplement plus anabolic steroid or (2) physiotherapy with protein-rich nutritional supplement plus placebo. Outcome assessments will be carried out blinded at baseline (3-10 days after surgery) and at 14 weeks after entering the trial. Primary outcome is the change from baseline to follow-up in maximal isometric knee-extension muscle strength in the fractured limb. Secondary outcomes are physical performance test, patient-reported outcomes, and measures of body composition. DISCUSSION: If the trial is found feasible and the results show an indication of anabolic steroid being a relevant addition to further enhance the recovery of muscle strength and function in an enhanced recovery after surgery program, this trial will constitute the basis of a larger confirmatory trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03545347. Preregistered on 4 June 2018.

Pragmatic Home-Based Exercise after Total Hip Arthroplasty - Silkeborg: Protocol for a prospective cohort study (PHETHAS-1).

Introduction: Rehabilitation exercises are offered to patients after total hip arthroplasty (THA); however, the effectiveness and optimal type and dose of exercise remains unknown. The primary objective of this trial is to indicate the preliminary efficacy of home-based rehabilitation using elastic band exercise on performance-based function after THA, based on the relationship between the performed exercise dose and the change in performance-based function (gait speed) from 3 (start of intervention) to 10 weeks (end of intervention) after surgery. The secondary objective is to investigate if a dose-response relationship exists between the performed exercise dose and changes in: hip-related disability, lower-extremity functional performance, and hip muscle strength Methods: In this prospective cohort study, patients scheduled for THA will be consecutively included until 88 have completed the intervention period from 3 to 10 weeks postoperatively. Participants perform the standard rehabilitation program with elastic band exercises. Exercise dose (exposure) will be objectively quantified using a sensor attached to the elastic band. The primary outcome is gait speed measured by the 40-m fast-paced walk test. Secondary outcomes include: patient reported hip disability (Hip disability and Osteoarthritis Outcome Score (HOOS)), hip muscle strength (hand-held dynamometry) and lower extremity function (30-s chair stand test). Discussion: This trial will add knowledge concerning the relationship between performed exercise dose and post-operative outcomes after THA. The protocol paper describes the study design and methods in detail, including the statistical analysis plan. Trial registration: Pre-registered on March 27, 2017 at ClinicalTrails.gov (ID: NCT03109821).

Efficacy of pre-operative quadriceps strength training on knee-extensor strength before and shortly following total knee arthroplasty: protocol for a randomized, dose-response trial (The QUADX-1 trial).

BACKGROUND: Patients with knee osteoarthritis (OA) report knee pain, limitation in physical activities and low quality of life. The two primary treatments for knee OA are non-surgical treatment (e.g., exercise) and surgery (total knee arthroplasty (TKA)); however, national guidelines recommend non-surgical treatment to be tried prior to surgical procedures. Patients with knee OA are characterized by decreased muscle strength, particularly in the knee-extensor muscles. Correspondingly, decreased knee-extensor strength is found to be associated with an increased risk of development, progression and severity of knee OA symptoms. Recent trials suggest a positive effect of pre-operative exercise on pre- and post-operative outcome; however, the most effective pre-operative knee-extensor strength exercise dosage is not known. The purpose of the present trial is to investigate the efficacy of three different exercise dosages of pre-operative, home-based, knee-extensor strength exercise on knee-extensor strength before and shortly after surgery in patients eligible for TKA due to end-stage knee OA. METHODS: In this randomized dose-response trial with a three-arm parallel design, 140 patients with end-stage knee OA (candidates for TKA) are randomized to one of three exercise dosages (two, four or six session/week) of knee-extensor strength exercise (three sets, 12 repetitions at 12 RM, per exercise session) for 12 weeks. The knee-extensor strength exercise is home-based (unsupervised) and performed with an elastic exercise band following an initial exercise instruction. Adherence is objectively quantified using a sensor attached to the exercise band. The primary outcome will be the change in knee-extensor strength. Following the 12-week exercise period, the need for TKA surgery is re-assessed by an orthopedic surgeon. DISCUSSION: Decreased knee-extensor strength is a major challenge in patients with knee OA. Exercise programs focusing on knee-extensor strength are found to be more effective in relieving knee OA pain and symptoms compared to more general exercise programs. However, the optimal exercise dosage for knee-extensor strength deficits in patients with knee OA is inconclusive. Knowledge on the dose-response relationship for knee-extensor strength exercise in patients with knee OA will help guide future non-surgical treatment in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02931058 . Pre-registered on 10 October 2016.

Physical performance following acute high-risk abdominal surgery: a prospective cohort study.

BACKGROUND: Acute high-risk abdominal (AHA) surgery is associated with high mortality, multiple postoperative complications and prolonged hospital stay. Further development of strategies for enhanced recovery programs following AHA surgery is needed. The aim of this study was to describe physical performance and barriers to independent mobilization among patients who received AHA surgery (postoperative days [POD] 1-7). METHODS: Patients undergoing AHA surgery were consecutively enrolled from a university hospital in Denmark. In the first postoperative week, all patients were evaluated daily with regards to physical performance, using the Cumulated Ambulation Score (CAS; 0-6 points) to assess basic mobility and the activPAL monitor to assess the 24-hour physical activity level. We recorded barriers to independent mobilization. RESULTS: Fifty patients undergoing AHA surgery (mean age 61.4 ± 17.2 years) were included. Seven patients died within the first postoperative week, and 15 of 43 (35%) patients were still not independently mobilized (CAS < 6) on POD-7, which was associated with pulmonary complications developing (53% v. 14% in those with CAS = 6, p = 0.012). The patients lay or sat for a median of 23.4 hours daily during the first week after AHA surgery, and the main barriers to independent mobilization were fatigue and abdominal pain. CONCLUSION: Patients who receive AHA surgery have very limited physical performance in the first postoperative week. Barriers to independent mobilization are primarily fatigue and abdominal pain. Further studies investigating strategies for early mobilization and barriers to mobilization in the immediate postoperative period after AHA surgery are needed.

CONTEXTE: La chirurgie abdominale d'urgence à risque élevé est associée à un fort taux de mortalité, à des complications postopératoires multiples et à des hospitalisations prolongées. Il est donc nécessaire d'élaborer de nouvelles stratégies pour améliorer le rétablissement après ce type de chirurgie. La présente étude visait à décrire le fonctionnement physique et les obstacles aux déplacements autonomes chez les patients ayant subi une chirurgie de ce type (jours postopératoires 1 à 7). MÉTHODES: Nous avons recruté successivement les patients subissant une chirurgie abdominale d'urgence à risque élevé dans un hôpital universitaire du Danemark. Durant la première semaine postopératoire, tous les patients ont subi quotidiennement une évaluation visant à vérifier leur fonctionnement physique. Nous nous sommes servis du Cumulated Ambulation Score (CAS; de 0 à 6 points) pour évaluer la mobilité de base et du moniteur activPAL pour évaluer le niveau d'activé physique 24 heures par jour. Nous avons noté les obstacles aux déplacements autonomes. RÉSULTATS: Cinquante patients (âge moyen : 61,4 ans ± 17,2) ont été retenus. Sept sont décédés durant la première semaine postopératoire, et 15 des 43 patients restants (35 %) ne se déplaçaient pas encore de façon autonome (CAS < 6) le septième jour, une situation associée à l'apparition de complications pulmonaires (53 % c. 14 % de ceux qui avaient un CAS de 6, p = 0,012). Les patients étaient couchés ou assis pendant une durée médiane de 23,4 heures par jour durant la première semaine postopératoire, et les principaux obstacles aux déplacements autonomes étaient la fatigue et la douleur abdominale. CONCLUSION: Les patients qui subissent une chirurgie abdominale d'urgence à risque élevé ont un fonctionnement physique très faible durant la première semaine postopératoire. Les obstacles aux déplacements autonomes sont principalement la fatigue et la douleur abdominale. Il faudra d'autres études sur les stratégies de mobilisation précoces et les obstacles aux déplacements peu après une chirurgie abdominale d'urgence à risque élevé.

Effectiveness of acute in-hospital physiotherapy with knee-extension strength training in reducing strength deficits in patients with a hip fracture: A randomised controlled trial.

QUESTION: Is acute in-hospital physiotherapy with additional progressive knee-extension strength training (ST) of the fractured limb more effective in reducing knee-extension strength deficit at follow-up compared to physiotherapy without strength training in patients with a hip fracture? DESIGN: Assessor blinded, randomised controlled trial with intention-to-treat analysis. PARTICIPANTS: 90 patients with a hip fracture admitted to an acute orthopaedic Hip Fracture Unit at a university hospital between October 2013 and May 2015. INTERVENTION: Daily physiotherapy with or without progressive knee-extension strength training (10RM), 3 x 10 repetitions, of the fractured limb using ankle weight cuffs conducted by ward physical therapists during hospital stay. OUTCOME MEASURES: Primary outcome was the change in maximal isometric knee-extension strength in the fractured limb in percentage of the non-fractured limb from inclusion to postoperative day 10 or discharge (follow-up). Secondary outcome was Timed Up and Go test measured early after surgery and at follow-up. RESULTS: In the intention-to-treat analysis of between-group differences, the primary outcome improved 8.1% (95% CI -2.3; 18.4) by additional strength training from baseline to follow-up. In the per-protocol analysis of non-missing data, significant between-group improvements by 10.5% (95% CI 0.3; 20.7) were found in favour of additional ST. No significant between-group differences were found in any secondary outcome. CONCLUSION: Physiotherapy with addition of 5 sessions of ST yielded no additional improvements compared to physiotherapy without strength training in reducing the knee-extension strength deficit at follow-up in patients with a hip fracture. It is debatable whether larger improvements than the observed 8-10% can be expected given that only five exercise sessions, on average, were completed. In fragile patients with a hip fracture in the acute phase, where the ability to participate in functional exercise is compromised, we still consider early strength training a possibility to improve outcomes of clinical importance, given the results of the per-protocol analysis. The present data provides an important basis and call for future investigations including longer term interventions. TRIAL REGISTRATION: Clinicaltrials.gov NCT00848913.

How inflammation underlies physical and organ function in acutely admitted older medical patients.

OBJECTIVES: To investigate whether systemic inflammation in acutely admitted older medical patients (age >65 years) is associated with physical performance and organ dysfunction. Organ dysfunction´s association with physical performance, and whether these associations are mediated by systemic inflammation, was also investigated. METHODS: A cross-sectional study in an Emergency Department. Physical performance was assessed by handgrip strength and de Morton Mobility Index (DEMMI), and organ dysfunction by FI-OutRef, the number of standard blood tests outside the reference range. Systemic inflammation was assessed by suPAR, TNFα, and IL-6. Associations were investigated by regression analyses adjusted for age, sex, cognitive impairment, CRP, and VitalPAC Modified Early Warning Score. RESULTS: A total of 369 patients were evaluated. In adjusted analyses, suPAR and TNFα was associated with both physical performance measures (p<0.001- p=0.004), and IL-6 with handgrip strength (p=0.007). All inflammation biomarkers were associated with FI-OutRef (p<0.001). FI-OutRef was also associated with physical performance (all p<0.001); suPAR being the inflammatory biomarker with the highest impact when adjusting for inflammation. CONCLUSION: Inflammatory biomarkers are potentially feasible for systematic assessment of vulnerability. Moreover, suPAR may be an important mediator between organ dysfunction and physical performance.

Association between routine laboratory tests and long-term mortality among acutely admitted older medical patients: a cohort study.

BACKGROUND: Older people have the highest incidence of acute medical admissions. Old age and acute hospital admissions are associated with a high risk of adverse health outcomes after discharge, such as reduced physical performance, readmissions and mortality. Hospitalisations in this population are often by acute admission and through the emergency department. This, along with the rapidly increasing proportion of older people, warrants the need for clinically feasible tools that can systematically assess vulnerability in older medical patients upon acute hospital admission. These are essential for prioritising treatment during hospitalisation and after discharge. Here we explore whether an abbreviated form of the FI-Lab frailty index, calculated as the number of admission laboratory test results outside of the reference interval (FI-OutRef) was associated with long term mortality among acutely admitted older medical patients. Secondly, we investigate other markers of aging (age, total number of chronic diagnoses, new chronic diagnoses, and new acute admissions) and their associations with long-term mortality. METHODS: A cohort study of acutely admitted medical patients aged 65 or older. Survival time within a 3 years post-discharge follow up period was used as the outcome. The associations between the markers and survival time were investigated by Cox regression analyses. For analyses, all markers were grouped by quartiles. RESULTS: A total of 4,005 patients were included. Among the 3,172 patients without a cancer diagnosis, mortality within 3 years was 39.9%. Univariate and multiple regression analyses for each marker showed that all were significantly associated with post-discharge survival. The changes between the estimates for the FI-OutRef quartiles in the univariate- and the multiple analyses were negligible. Among all the markers investigated, FI-OutRef had the highest hazard ratio of the fourth quartile versus the first quartile: 3.45 (95% CI: 2.83-s4.22, P < 0.001). CONCLUSION: Among acutely admitted older medical patients, FI-OutRef was strongly associated with long-term mortality. This association was independent of age, sex, and number of chronic diagnoses, new chronic diagnoses, and new acute admissions. Hence FI-OutRef could be a biomarker of advancement of aging within the acute care setting.

RAPID KNEE-EXTENSIONS TO INCREASE QUADRICEPS MUSCLE ACTIVITY IN PATIENTS WITH TOTAL KNEE ARTHROPLASTY: A RANDOMIZED CROSS-OVER STUDY.

BACKGROUND: Inhibition of the quadriceps muscle and reduced knee-extension strength is common shortly following total knee arthroplasty (weeks to months), due to reduced voluntary activation of the quadriceps muscle. In healthy subjects, strength training with heavy loads is known to increase agonist muscle activity, especially if the exercise is conducted using rapid muscle contractions. PURPOSE: The purpose of this study was to examine if patients with total knee arthroplasty could perform rapid knee-extensions using a 10 RM load four to eight weeks after surgery, and the degree to which rapid knee-extensions were associated with greater voluntary quadriceps muscle activity during an experimental strength training session, compared to that elicited using slow knee-extensions. STUDY DESIGN: A randomized cross-over study. METHODS: Twenty-four patients (age 66.5) 4-8 weeks post total knee arthroplasty randomly performed one set of five rapid, and one set of five slow knee-extensions with the operated leg, using a load of their 10 repetition maximum, while surface electromyography recordings were obtained from the vastus medialis and lateralis of the quadriceps muscle. RESULTS: Data from 23 of the 24 included patients were analyzed. Muscle activity was significantly higher during rapid knee-extensions (120.2% [10th-90th percentile: 98.3-149.1]) compared to slow knee-extensions (106.0% [88.8-140.8]) for the vastus lateralis (p<0.01), but not for the vastus medialis (120.8% [90.4-134.0]) and (121.8% [93.0-133.0]) (p = 0.17), respectively. Slow and rapid knee-extensions were performed at a median angular velocity of 19.7 degrees/sec (13.7-24.4) and 51.4 degrees/sec (28.9-63.1), respectively. CONCLUSION: Four to eight weeks after their total knee arthroplasty, the patients in the present study were able to conduct rapid knee-extensions according to the experimental protocol with an approximately doubled angular velocity compared to slow knee-extensions. This was associated with increased muscle activity in the vastus lateralis when compared to slow knee-extensions, but not in the vastus medialis. Whether this significant, although relatively small, difference in vastus lateralis muscle activity has any clinical relevance needs further study. LEVEL OF EVIDENCE: 3.

Physical Activity in the Acute Ward Following Hip Fracture Surgery is Associated with Less Fear of Falling.

Early mobilization following hip fracture surgery reduces medical complications and mortality, but may increase the risk of falling. The aim was to objectively measure the physical activity (time spent upright) the first week after hip fracture surgery and relate it to functional performance and fear of falling at discharge. The 24-hr upright time was measured for a median of six days using a thigh-worn accelerometer in 37 patients (mean 80 years ± 8.4) and increased from median 13 (IQR 6-31) min to 46 (11-107) min at day 7. More upright time at discharge was associated with less fear of falling (r = -.48, p = .01, n = 27), which also was associated with fast gait speed (r = -.50, p = .02, n = 23) and a faster Timed Up and Go test time (r = .54, p < .01, n = 22), indicating a need for further studies on motivation and limitations for more physical activity following hip fracture surgery.