The MultiKnee Trial

• Getachew, Mestawet ; Lerdal, Anners; Småstuen, Milada Cvancarova; Gay, Caryl; Aamodt, Arild & Tesfaye, Million [Show all 7 contributors for this article] (2022). Worst pain intensity and opioid intake during the early postoperative period were not associated with moderate-severe pain 12 months after total knee arthroplasty - a longitudinal study. Scandinavian Journal of Pain. ISSN 1877-8860. doi: 10.1515/sjpain-2022-0007.
• Olsen, Unni ; Lindberg, Maren Falch; Rose, Christopher James; Denison, Eva Marie-Louise; Gay, Caryl & Aamodt, Arild [Show all 11 contributors for this article] (2022). Factors Correlated with Physical Function 1 Year after Total Knee Arthroplasty in Patients with Knee Osteoarthritis: A Systematic Review and Meta-analysis. JAMA Network Open. ISSN 2574-3805. 5(7), p. 1–15. doi: 10.1001/jamanetworkopen.2022.19636. Full text in Research Archive
• Sellevold, Vibeke Bull; Steindal, Simen Alexander; Lindberg, Maren Falch; Småstuen, Milada Cvancarova; Aamodt, Arild & Lerdal, Anners [Show all 7 contributors for this article] (2022). Many Patients with Persistent Pain One Year After TKA Report Improvement by 5-7 years: A Mixed Methods Study . Clinical Orthopaedics and Related Research. ISSN 0009-921X. 480(11), p. 2075–2088. doi: 10.1097/CORR.0000000000002183.
• Lindberg, Maren Falch; Aamodt, Arild; Badawy, Mona; Bergvad, Ingvild Buset; Borchgrevink, Petter Chr. & Furnes, Ove Nord [Show all 21 contributors for this article] (2021). The effectiveness of exercise therapy and education plus cognitive behavioral therapy, alone or in combination with total knee arthroplasty in patients with knee osteoarthritis – study protocol for the MultiKnee trial. BMC Musculoskeletal Disorders. ISSN 1471-2474. 22:1054, p. 1–14. doi: 10.1186/s12891-021-04924-z. Full text in Research Archive Show summary

  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 ersonalized 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.

• Rognsvåg, Turid; Lindberg, Maren Falch; Lerdal, Anners; Stubberud, Jan Egil; Furnes, Ove Nord & Holm, Inger [Show all 11 contributors for this article] (2021). Development of an internet-delivered cognitive behavioral therapy program for use in combination with exercise therapy and education by patients at increased risk of chronic pain following total knee arthroplasty. BMC Health Services Research. ISSN 1472-6963. 21(1), p. 1–14. doi: 10.1186/s12913-021-07177-7. Full text in Research Archive
• Bragstad, Line Kildal; Lerdal, Anners Vetle; Gay, Caryl L.; Kirkevold, Marit; Lee, Kathryn A. & Lindberg, Maren Falch [Show all 10 contributors for this article] (2020). Psychometric properties of a short version of Lee Fatigue Scale used as a generic PROM in persons with stroke or osteoarthritis: assessment using a Rasch analysis approach. Health and Quality of Life Outcomes. ISSN 1477-7525. 18, p. 1–8. doi: 10.1186/s12955-020-01419-8. Full text in Research Archive
• Rehman, Yasser; Lindberg, Maren Falch; Arnljot, Kristine; Gay, Caryl; Lerdal, Anners & Aamodt, Arild (2020). More severe radiographic osteoarthritis is associated with increased improvements in patients' health state following a total knee arthroplasty. Journal of Arthroplasty. ISSN 0883-5403. 35(11). doi: 10.1016/j.arth.2020.06.025. Full text in Research Archive Show summary

  Background To assess whether preoperative radiological severity of osteoarthritis (OA) is related to the level of improvement in patients’ health state measured 1 year after total knee arthroplasty (TKA). Methods Radiographic severity of OA was graded using the Kellgren-Lawrence (KL) classification. Two independent observers were blinded to patients’ outcome scores. Health-related quality of life was measured using EQ-5D-3L preoperatively and at 12-month follow-up. The 5 dimensions of the EQ-5D were converted into a health state index score. The association between KL grade and improvement in health state score was analyzed using multiple linear regression. Results Among 156 consecutive patients (68% females, mean age 69 years) who underwent primary TKA, 3 knees (2%) were classified as KL grade 2, 115 as KL grade 3 (74%), and 38 as KL grade 4 (24%). Follow-up rate was 77%. There was substantial intra-rater and inter-rater agreement (Cohen’s kappa = 0.80 and 0.79). Most patients (64%) had clinically significant improvement in their health state score 1 year after TKA. However, after adjusting for relevant covariates, patients with severe OA (KL grade 4) were found to have significantly more improvement in their health state score than patients with mild or moderate OA (KL grade 2 or 3, respectively). Separate analysis of the 5 EQ-5D dimensions showed that the KL group differences were most evident in the “usual activities” and “pain/discomfort” dimensions. Conclusion Patients with severe OA have significantly more improvement in their usual activities and pain/discomfort 1 year after TKA than patients with less severe OA.

• Olsen, Unni Solveig Johansen; Lindberg, Maren Falch; Denison, Eva Marie-Louise; Rose, Christopher James; Gay, Caryl & Aamodt, Arild [Show all 11 contributors for this article] (2020). Predictors of chronic pain and level of physical function in total knee arthroplasty: a protocol for a systematic review and meta-analysis. BMJ Open. ISSN 2044-6055. 10, p. 1–9. doi: 10.1136/bmjopen-2020-037674. Full text in Research Archive Show summary

  Abstract Introduction One in five patients undergoing total knee arthroplasty (TKA) experience unchanged or worse pain and physical function 1 year after surgery. Identifying risk factors for unfavourable outcomes is necessary to develop tailored interventions to minimise risk. There is a need to review more current literature with updated methodology that addresses the limitations of earlier systematic reviews and meta-analyses. We present a Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols compliant protocol for a systematic review and meta-analysis of predictors of chronic pain and impaired function after TKA. Methods and analysis This review will include prospective longitudinal observational studies, or randomised trials (including cluster and crossover designs) that report arm-wise predictors of chronic postsurgical pain or impaired physical function at 3 months, 6 months or 12 months. A comprehensive literature search of studies published between 2000 and 2019 will be performed in Medline, Embase, CINAHL, Cochrane Library and PEDro. Blinded assessment with consensus agreement will be applied for inclusion of studies, data extraction and assessment of bias risk (Quality in Prognosis Studies tool). The co-primary outcomes, pain and impaired function, at 12 months after TKA will be analysed separately. Estimates of association between each outcome and any preoperative or intraoperative factor that may predict chronic pain or impaired physical function will be extracted from the included studies, where possible. For randomised studies, results will only be extracted from TKA arms (or the first period of crossover trials). Estimates of association from the primary evidence will be synthesised narratively, and quantitatively using multivariate meta-analysis to provide ‘pooled’ estimates of association. Subgroup and sensitivity analyses will be performed. Certainty of evidence for each predictor will be derived from the Grading of Recommendations Assessment, Development and Evaluation framework. Ethics and dissemination No ethical issues are associated with this project. The results from this review will be published in peer-reviewed journals and presented at international conferences.

• Lindberg, Maren Falch; Schweitz, Turid Undebakke; Aamodt, Arild; Gay, Caryl & Lerdal, Anners (2020). High pre- and postoperative symptom burden in non-responders to total knee arthroplasty. PLOS ONE. ISSN 1932-6203. 15(5)(5), p. 1–14. doi: 10.1371/journal.pone.0233347.
• Enbakom, Mestawet Getachew; Lerdal, Anners; Småstuen, Milada Cvancarova; Gay, Caryl; Aamodt, Arild & Tesfaye, Million [Show all 7 contributors for this article] (2020). High levels of preoperative pain and fatigue are red flags for moderate‐severe pain 12 months after total knee arthroplasty—A longitudinal cohort study. Musculoskeletal Care. ISSN 1478-2189. p. 1–7. doi: 10.1002/msc.1522. Full text in Research Archive Show summary

  Background: Moderate/severe pain after total knee arthroplasty (TKA) is a poor surgical outcome. Many studies have identified preoperative risk factors of painafter TKA, but studies of the joint contributions of co-occurring symptoms arelacking. Methods: Patients undergoing primary TKA (n=202) were enrolled in a longitu-dinal cohort study. Preoperatively, patients completed questionnaires measuring demographics and symptoms (pain, fatigue, sleep problems and depression). Painwas re-assessed 12 months after TKA. Logistic regression analysis was used to compute the probabilities of moderate-severe pain at 12 months based on preoperative symptom levels, and results were combined into a risk matrix. Results: More than one-third (40%) of patients (n=187) reported moderate-severepain after TKA. Among preoperative risk factors included in the logistic regressionanalyses were age, sex, pain, fatigue, sleep problems and depression. Adjusting forpossible confounders, fatigue (p=0.02) and pain (p=0.01) were significant riskfactors for moderate-severe pain at 12-months follow-up and were retained in the final risk matrix. The co-occurrence of high-preoperative fatigue and pain scores resulted in 57% estimated probability of moderate-severe pain at 12 months.Similarly, the co-occurrence of low-preoperative fatigue and pain scores resulted in14% estimated probability of moderate-severe pain 12 months after TKA. Conclusion: The combination of high fatigue and pain scores prior to surgery was akey risk factor for moderate-severe pain 12 months after TKA. Mapping of these factors could be used preoperatively to identify patients who are at risk to expe-rience a poor outcome of TKA.

• Lindberg, Maren Falch; Miaskowski, Christine; Rustøen, Tone; Cooper, Bruce A.; Aamodt, Arild & Lerdal, Anners (2020). Preoperative risk factors associated with chronic pain profiles following total knee arthroplasty. European Journal of Pain. ISSN 1090-3801. p. 1–13. doi: 10.1002/ejp.1703. Full text in Research Archive

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• Rustøen, Tone & Lerdal, Anners (2021). Klinisk forskning innen helsefag. Fagbokforlaget. ISBN 9788245022926. 256 p.

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• Lindberg, Maren Falch; Lerdal, Anners; Kise, Nina Jullum; Ludvigsen, Eirin Sigurdssøn; Rognsvåg, Turid & Bergvad, Ingvild Buset (2022). Maren Falch Lindberg, seniorforsker i MultiKnee.
• Rognsvåg, Turid; Buset Bergvad, Ingvild; Furnes, Ove Nord; Indrekvam, Kari; Lerdal, Anners & Lindberg, Maren Falch [Show all 9 contributors for this article] (2022). Effekt av trening, undervisning og kognitiv adferdsterapi for artrosepasienter med eller uten totalprotese i kne: En randomisert feasibility studie.
• Rognsvåg, Turid; Lindberg, Maren Falch; Lerdal, Anners; Furnes, Ove Nord; stubberud, jan & Holm, Inger [Show all 11 contributors for this article] (2022). Development of an internet-delivered cognitive behavioral therapy program for use in combination with exercise therapy and education by patients at increased risk of chronic pain following total knee arthroplasty .
• Sellevold, Vibeke Bull; Steindal, Simen Alexander; Lindberg, Maren Falch; Småstuen, Milada Cvancarova; Aamodt, Arild & Lerdal, Anners [Show all 7 contributors for this article] (2022). Many patients with persistent pain one year after total knee arthroplasty report improvement by 5-7 years.
• Lindberg, Maren Falch; Miaskowski, Christine; Rustøen, Tone; Cooper, Bruce A; Aamodt, Arild & Lerdal, Anners (2021). Chronic pain profiles and associated risk factors following total knee arthroplasty - a prospective observational study.
• Ludvigsen, Eirin Sigurdssøn; Lindberg, Maren Falch; Bergvad, Ingvild Buset; Aamodt, Arild; Lerdal, Anners & Rognsvåg, Turid (2021). Bakgrunn for MultiKnee studien.
• Rehman, Yasser; Lindberg, Maren Falch; Arnljot, Kristine; Gay, Caryl; Lerdal, Anners & Aamodt, Arild (2021). More Severe Radiographic Osteoarthritis Is Associated With Increased Improvement in Patients’ Health State Following a Total Knee Arthroplasty.
• Schweitz, Turid Undebakke; Lindberg, Maren Falch; Aamodt, Arild; Gay, Caryl & Lerdal, Anners (2021). Preoperative symptoms as risk factors for non-response to total knee arthroplasty.
• Ludvigsen, Eirin Sigurdssøn; Lindberg, Maren Falch; Aamodt, Arild; Lerdal, Anners; Bergvad, Ingvild Buset & Frøyen Lillegård, Julianne Helene (2021). Hva kan jeg forvente dersom jeg bli med i MultiKnee studien?
• Lindberg, Maren Falch (2021). MAGIC and Lovisenberg. Enhancing the evidence ecosystem, for increased value and reduced waste in health care.
• Lindberg, Maren Falch (2021). Fra praksissykepleier til forsker i praksis. In Rustøen, Tone & Lerdal, Anners (Ed.), Klinisk forskning innen helsefag. Fagbokforlaget. ISSN 9788245022926. p. 141–152.
• Lindberg, Maren Falch; Rustøen, Tone; Cooper, Bruce A; Aamodt, Arild & Lerdal, Anners Vetle (2021). Authors’ reply to the comment by Riddle et al. European Journal of Pain. ISSN 1090-3801. doi: 10.1002/ejp.1756.
• Stubberud, Jan (2020). CBT-kurs for fysioterapeuter 2020.
• Lau, Bjørn & Stubberud, Jan (2019). Kognitivt adferdsterapi knyttet til smerte og bruk av e-CBT program - for fysioterapeuter i MultiKnee studien.
• Lindberg, Maren Falch (2019). Which patients do not benefit from total knee replacement? .
• Lindberg, Maren Falch; Rognsvåg, Turid; Badawy, Mona; Borchgrevink, Petter Chr.; Furnes, Ove & Gay, Caryl [Show all 13 contributors for this article] (2019). Optimal behandling av artrosepasienter - en feasibilitystudie (MultiKnee trial).
• Haaland Jahren, Henrik & Lau, Bjørn (2018). CBT-kurs for fysioterapeuter 2018.
• Rognsvåg, Turid; Lindberg, Maren Falch; Borchgrevink, Petter Chr.; Furnes, Ove; Gay, Caryl & Holm, Inger [Show all 13 contributors for this article] (2018). Multi-Knee Trial. En feasibilty-studie av en intervensjon for artrosepasienter med økt risiko for langvarige smerter etter operasjon med kneprotese.
• Lindberg, Maren Falch; Witzøe, Andreas & Rognsvåg, Turid (2018). Ny studie: Vil se på alternativer til operasjon med kneprotese. [Business/trade/industry journal]. Fysioterapeuten.
• Lindberg, Maren Falch; Aamodt, Arild & Lerdal, Anners (2018). A multidisciplinary intervention in total knee arthroplasty - a multicenter randomized controlled trial in patients on waiting list for TKA (The MULTI-KNEE trial).
• Rose, Christopher James; Olsen, Unni ; Lindberg, Maren Falch; Denison, Eva Marie-Louise; Aamodt, Arild & Lerdal, Anners (2020). A new multivariate meta-analysis model for many variates and few studies. arXiv.
• Olsen, Unni Solveig Johansen; Lerdal, Anners; Aamodt, Arild; Brox, Jens Ivar; Furnes, Ove & Denison, Eva Marie-Louise [Show all 8 contributors for this article] (2018). Preoperative and intraoperative predictors of persistent postoperative pain and impaired physical function in total knee arthroplasty - a systematic review of prognostic studies. PROSPERO, International prospective register of systematic reviews.

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