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Introduction: Up to >50% of individuals with symptomatic knee osteoarthritis (KOA) also report insomnia. Research suggests that the insomnia-pain link is bi-directional and complex with other factors like anxiety and mood being relevant. Network analysis allows to estimate these dynamic system interactions and to illustrate them graphically. This is an advantage over traditional statistical models (e.g. regression models) which investigate aspects of systems in isolation1. However, network analysis has not yet been utilized in the field of KOA and insomnia. Methods: We will use baseline data from a randomized controlled trial to estimate a cross-sectional network model connecting insomnia and pain in patients with KOA. The network structure will be estimated using Gaussian Graphical models with LASSO-regularization2. Established measures for sleep, pain, depression, anxiety, physical activity, pain catastrophizing and fatigue will be included. We will further analyse global network density and node centrality1. Results: The results will provide us a better understanding of how the network connecting pain and insomnia is built and which factors are most influential. Discussion: Our study will be the first that uses network analysis to understand the connection between KOA pain and insomnia. This will provide relevant clinical insights and interest other researchers in this exciting area of research. Process evaluation: Network analyses are new to me and there are not many examples in the field of chronic pain. It took me some time to understand the basics but the more I read the more excited I get about the opportunities these methods offer. [ABSTRACT FROM AUTHOR]

Introduction: Insomnia is a common sleep disorder in people with knee osteoarthritis (KOA), adversely affecting daily function and general health1. It represents a barrier for effective conservative management. Clinical guidelines for KOA recommend integrating comorbidity-specific interventions as a part of patient-centred care2. However, insomnia is rarely addressed in the often joint-targeted KOA treatment. Methods: A two-arm randomized controlled trial (RCT) will be conducted on 128 patients with KOA and insomnia in a community setting. Subjects will randomly be allocated to the intervention group (cognitive behavioral therapy for insomnia (CBT-I) additional to best-practice KOA-care (education and exercise therapy)) or to the control group (best-practice KOA-care). The physiotherapist-led programme for both treatment arms will contain 18 sessions within 14 weeks, 30 minutes each. The primary outcome is pain intensity. Pain interference, sleep-related outcomes and physical activity/function are secondary outcomes. The tertiary outcomes are inflammation and healthcare utilisation. Blinded assessment will be conducted at baseline, post-intervention, and at 3 months, 6 months, and 12 months follow-up. Results: The results will give insights into the clinical and cost-effectiveness of CBT-I combined with best-practice physiotherapy. Discussion: This will be the first RCT integrating CBT-I in best-practice KOA-care in KOA patients with established insomnia whereby inflammation and sleep will be objectively assessed. This could help to improve the outcomes of a large proportion of KOA patients. Process evaluation: Being involved as a therapist in the trial and in the meanwhile developing my skills as a researcher, seems challenging. Is it all about getting the balance right? [ABSTRACT FROM AUTHOR]

Abstract: Chronic musculoskeletal pain and sleep problems/disorders exhibit a recognized bidirectional relationship; yet, systematic investigations of this claim, particularly in a prospective context, are lacking. This systematic review with meta-analysis aimed to synthesize the literature on the prospective associations between sleep problems/disorders and chronic musculoskeletal pain. A comprehensive search across 6 databases identified prospective longitudinal cohort studies in adults examining the relationship between sleep problems/disorders and chronic musculoskeletal pain. Random-effects meta-analyses, using the Hartung-Knapp adjustment for 95% confidence intervals (CIs), were conducted, and all results were presented as odds ratios (ORs). Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Including 16 articles from 11 study populations (116,746 participants), meta-analyses indicated that sleep problems at baseline may heighten the risk of chronic musculoskeletal pain in both short term (OR 1.64, 95% CI 1.01-2.65) and long term (OR 1.39, 95% CI 1.21-1.59). The evidence for different sleep problem categories was very uncertain. Chronic musculoskeletal pain at baseline may increase the risk of short-term sleep problems (OR 1.56, 95% CI 1.02-2.38), but long-term evidence was very uncertain. The impact of only local or only widespread pain on short-term sleep problems was very uncertain, whereas widespread pain may elevate the risk of long-term sleep problems (OR 2.0, 95% CI 1.81-2.21). In conclusion, this systematic review with meta-analysis suggests that sleep problems are associated with an increased risk of chronic musculoskeletal pain, but the bidirectional nature of this relationship requires further investigation., (Copyright © 2024 International Association for the Study of Pain.)

Objective: Knee osteoarthritis (KOA) is a common musculoskeletal problem worldwide and its key symptom is pain. Guidelines recommend incorporating comorbidity-specific therapies into patient-centered care. Patients diagnosed with KOA frequently have insomnia, which is associated with higher-pain severity. For this reason, this study protocol outlines the methodology of a randomized controlled trial (RCT) investigating the effectiveness of cognitive behavioral therapy for insomnia (CBTi) combined with best-practice KOA care (BPC) compared to best-practice KOA care and lifestyle education., Methods: A 2-arm RCT in patients with KOA and insomnia is conducted, in which a total of 128 patients are randomly allocated to an intervention or control group. The experimental intervention consists of 12 sessions of physical therapist-led BPC with an additional 6 sessions of CBTi. The control intervention also receives BPC, which is supplemented with 6 general lifestyle information sessions. The primary outcome is the between-group difference in change in pain severity at 6 months after intervention. Secondary outcomes are pain-related outcomes, sleep-related outcomes, symptoms of anxiety and depression, level of physical activity and function, perceived global improvement, biomarkers of inflammation, and health-related quality of life. Assessments are conducted at baseline, immediately after intervention, and 3, 6, and 12 months after intervention. Furthermore, a cost-utility analysis for the proposed intervention will be performed alongside the RCT., Impact: This is the first RCT investigating the clinical and cost-effectiveness of a physical therapist-led intervention integrating CBTi into BPC in patients with KOA and insomnia. The results of this trial will add to the growing body of evidence on the effectiveness of individualized and comorbidity-specific KOA care, which can inform clinical decision-making and assist policymakers and other relevant stakeholders in optimizing the care pathway for patients with KOA., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In patients with neck pain, it is unclear whether pain inhibition and facilitation endogenous pain mechanisms are altered. This systematic review and meta-analysis aimed to improve their understanding by assessing conditioned pain modulation (CPM) and temporal summation of pain (TSP) in patients with neck pain associated with whiplash-associated disorders (WAD) or of a nonspecific neck pain (NSNP) nature compared to pain-free controls. Very low certainty evidence suggests: impaired CPM when assessed remotely in chronic WAD patients (n = 7, 230 patients and 204 controls, standardized mean differences (SMD) = -.47 [-.89 to -.04]; P = .04) but not locally (n = 6, 155 patients and 150 controls; SMD = -.34 [-.68 to .01]; P = .05), impaired CPM in chronic NSNP patients when assessed locally (n = 5, 223 patients and 162 controls; SMD = -.55 [-1.04 to -.06]; P = .04) but not remotely (n = 3, 72 patients and 66 controls; SMD = -.33 [-.92 to .25]; P = .13), TSP not facilitated in either chronic WAD (local TSP: n = 4, 90 patients and 87 controls; SMD = .68 [-.62 to 1.99]) (remote TSP: n = 8, 254 patients and 214 controls; SMD = .18 [-.12 to .48]) or chronic NSNP (local TSP: n = 2, 139 patients and 92 controls; SMD = .21 [-1.00 to 1.41]), (remote TSP: n = 3; 91 patients and 352 controls; SMD = .60 [-1.33 to 2.52]). The evidence is very uncertain whether CPM is impaired and TSP facilitated in patients with WAD and NSNP. PERSPECTIVE: This review and meta-analysis present the current evidence on CPM and TSP in patients with WAD and NSNP. Standardization of measurement methodology is needed to draw clear conclusions. Subsequently, future studies should investigate the clinical relevance of these measurements as prognostic variables or predictors of treatment success., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Chronic pain is the most prevalent disease worldwide, leading to substantial disability and socioeconomic burden. Therefore, it can be regarded as a public health disease and major challenge to scientists, clinicians and affected individuals. Behavioral lifestyle factors, such as, physical (in)activity, stress, poor sleep and an unhealthy diet are increasingly recognized as perpetuating factors for chronic pain. Yet, current management options for patients with chronic pain often do not address lifestyle factors in a personalized multimodal fashion. This state-of-the-art clinical perspective aims to address this gap by discussing how clinicians can simultaneously incorporate various lifestyle factors into a personalized multimodal lifestyle intervention for individuals with chronic pain. To do so the available evidence on (multimodal) lifestyle interventions targeting physical (in)activity, stress, sleep and nutritional factors, specifically, was reviewed and synthetized from a clinical point of view. First, advise is provided on how to design a personalized multimodal lifestyle approach for a specific patient. Subsequently, best-evidence recommendations on how to integrate physical (in)activity, stress, sleep and nutritional factors as treatment targets into a personalized multimodal lifestyle approach are outlined. Evidence supporting such a personalized multimodal lifestyle approach is growing, but further studies are needed.

Osteoarthritis (OA) is a leading cause of disability worldwide and clinical pain is the major symptom of OA. This clinical OA-related pain is firmly associated with symptoms of insomnia, which are reported in up to 81% of people with OA. Since understanding the association between both symptoms is critical for their appropriate management, this narrative review synthesizes the existing evidence in people with OA on i) the mechanisms underlying the association between insomnia symptoms and clinical OA-related pain, and ii) the effectiveness of conservative non-pharmacological treatments on insomnia symptoms and clinical OA-related pain. The evidence available identifies depressive symptoms, pain catastrophizing and pain self-efficacy as mechanisms partially explaining the cross-sectional association between insomnia symptoms and pain in people with OA. Furthermore, in comparison to treatments without a specific insomnia intervention, the ones including an insomnia intervention appear more effective for improving insomnia symptoms, but not for reducing clinical OA-related pain. However, at a within-person level, treatment-related positive effects on insomnia symptoms are associated with a long-term pain reduction. Future longitudinal prospective studies offering fundamental insights into neurobiological and psychosocial mechanisms explaining the association between insomnia symptoms and clinical OA-related pain will enable the development of effective treatments targeting both symptoms., Competing Interests: Declaration of competing interest None to declare in relation to this review., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Approximately 23% of patients develop hip pain after total hip arthroplasty (THA). In this systematic review, we aimed to identify risk factors associated with postoperative pain after THA to optimize preoperative surgical planning., Methods: Six literature databases were searched for articles published from January 1995 to August 2020. Controlled trials and observational studies that reported measurements of postoperative pain with assessments of preoperative modifiable and non-modifiable risk factors were included. Three researchers performed a literature review independently., Results: Fifty-four studies were included in the study for analysis. The most consistent association between worse pain outcomes and the female sex is poor preoperative pain or function, and more severe medical or psychiatric comorbidities. The correlation was less strong between worse pain outcomes and preoperative high body mass index value, low radiographic grade arthritis, and low socioeconomic status. A weak correlation was found between age and worse pain outcomes., Conclusions: Preoperative risk factors that were consistently predictive of greater/server postoperative pain after THA were identified, despite the varying quality of studies that prohibited the arrival of concrete conclusions. Modifiable factors should be optimized preoperatively, whereas non-modifiable factors may be valuable to patient education, shared decision-making, and individualized pain management., (© 2023. The Author(s).)

OBJECTIVE: To evaluate if there was an additional benefit of combining manual therapy (MT) and exercise therapy over exercise therapy alone on pain and function in patients with hip or knee osteoarthritis. DESIGN: Intervention systematic review LITERATURE SEARCH: We (1) searched 4 databases from inception to June 20, 2021; (2) hand searched a reference list of included trials and relevant systematic reviews; and (3) contacted 2 researchers in the field. STUDY SELECTION CRITERIA: We included randomized controlled trials that compared MT and exercise therapy to similar exercise therapy programs alone in patients with hip or knee osteoarthritis. DATA SYNTHESIS: The data were combined using random-effects meta-analyses where appropriate. The certainty of evidence for each outcome was judged using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. RESULTS: We included 19 trials. There was very low to moderate certainty of evidence that MT added benefit in the short term for pain, and combined pain, function, and stiffness (WOMAC global scale), but not for performance-based function and self-reported function. In the medium term, there was low- to very-low-certainty evidence that MT added benefit for performance-based function and WOMAC global score, but not for pain. There was high-certainty evidence that MT provided no added benefit in the long term for pain and function. CONCLUSION: There was very low to moderate certainty of evidence supporting MT as an adjunct to exercise therapy for pain and WOMAC global scale, but not function in patients with knee or hip osteoarthritis in the short term. There was high certainty of evidence of no benefit for additional MT over exercise therapy alone in the long term. J Orthop Sports Phys Ther 2022;52(10):675-684. Epub: 27 July 2022. doi:10.2519/jospt.2022.11062 .

The orthopedic surgical specialty is strongly tied to partnerships with industry that have fostered innovation and greatly enhanced patient care. A substantial number of orthopedic surgeons currently receive some form of industry support. These relationships are highly scrutinized because they present the possibility of both personal and financial conflicts of interest (COI). The authors examined orthopedic patients' awareness of existing regulation and perceptions of financial COI by performing a prospective survey-based study of patients seen in an academic orthopedic department. Data were collected during 1 year, in a cross-section of hospital-based and community clinical settings. The authors collected 513 surveys during a 1-year period between 4 clinical locations. Of all respondents, 55% were unconcerned regarding gifts or direct compensation their physicians received from industry, and only 16% were very or extremely concerned regarding these benefits. Patients' opinions regarding possible influence of benefits were similarly ambivalent, with 54% of patients minimally or not at all concerned regarding the potential influence of industry gifts or compensation. Seventy-six percent of patients had never heard of the Sunshine Act, and only 3% indicated that they were aware of the legislation and its intention. The income of the respondents and their level of education were positively correlated with increased concern about handling of COI, as well as knowledge regarding the Sunshine Act. These data suggest that orthopedic surgery patients are widely unconcerned regarding physician COI, but specific subsets of patients may be more likely to have concerns regarding these relationships. [ Orthopedics . 2021;44(5):e682-e686.].

Purpose: Knowledge regarding patients' clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19., Methods: Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models., Results: We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66-85 years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46-65 years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25-2.42, p = 0.001; 66-85 years: aOR 1.93, 95% CI 1.36-2.74, p < 0.001; > 85 years: aOR 2.38, 95% CI 1.49-3.81, p < 0.001 vs. individuals aged 26-45 years], male sex (aOR 1.23, 95% CI 1.01-1.50, p = 0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09-1.72, p = 0.007), and diabetes (aOR 1.33, 95% CI 1.04-1.69, p = 0.023) were associated with complicated stages of COVID-19 at diagnosis., Conclusion: The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required.

Introduction: We report the youngest documented patient (38 years old) to develop an acute popliteal artery thrombus following primary total knee arthroplasty (TKA)., Patient Concerns: The patient presented for an elective TKA secondary to posttraumatic arthritis. Past medical history included a tibial plateau fracture, two knee arthroscopies and an elevated body mass index (37.53). A right TKA was performed with no intraoperative complications. Two hours postoperatively, the right foot was poikilothermic and lacking dorsalis pedal pulse., Diagnosis: Popliteal artery thrombus confirmed by angiogram and venous duplex., Interventions: Immediate vascular surgery consult and subsequent embolectomy., Outcomes: At 1 year postoperatively, the patient is doing well with no further complications., Conclusion: Due to the lack of significant past medical history putting this patient at risk, future research should focus on prior trauma, age, and BMI as risk factors, specifically in patients undergoing TKA.

Pharmacological treatment for peripheral neuropathic pain has only modest effects and is often limited by serious adverse responses. Alternative treatment approaches including physiotherapy management have thus gained interest in the management of people with peripheral neuropathies. This narrative review summarises the current literature on the efficacy and safety of physiotherapy to reduce pain and disability in people with radicular pain and chemotherapy-induced peripheral neuropathy, 2 common peripheral neuropathies. For chemotherapy-induced peripheral neuropathy, the current evidence based on 8 randomised controlled trials suggests that exercise may reduce symptoms in patients with established neuropathy, but there is a lack of evidence for its preventative effect in patients who do not yet have symptoms. For radicular pain, most of the 21 trials investigated interventions targeted at improving motor control or reducing neural mechanosensitivity. The results were equivocal, with some indication that neural tissue management may show some benefits in reducing pain. Adverse events to physiotherapy seemed rare; however, these were not consistently reported across all studies. Although it is encouraging to see that the evidence base for physiotherapy in the treatment of peripheral neuropathic pain is growing steadily, the mixed quality of available studies currently prevents firm treatment recommendations. Based on promising preliminary data, suggestions are made on potential directions to move the field forward., Competing Interests: The authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Background: Initial or between session improvements in pain and/or function are often considered to be predictive of ultimate outcomes in musculoskeletal problems., Objective: To determine the long-term prognostic value of within and between session improvements to pain and function., Design: Systematic review of relevant literature., Method: A search was made of multiple databases (Pubmed/Medline, Cochrane, Cinahl, and AMed) using relevant search terms. Titles, abstracts, and then full texts were filtered to find articles that met the strict inclusion/exclusion criteria. Searching, data extraction, and quality assessment, using GRADE, were done independently by two authors. Disagreements were resolved by consensus., Results: Only 13 articles met the criteria for inclusion. For the effect of pain location or pain intensity changes in the first treatment session on medium or long-term pain, disability, return-to-work, or global outcomes nine outcomes were available. Findings were mostly inconclusive (5) or negative (3). There was only one study evaluating between session improvements with ambiguous results. There were no studies evaluating the prognostic value of early improvements in function., Conclusions: There is no conclusive evidence to support the concept that early changes in pain location or pain intensity offer a good longer-term prognosis on a variety of outcomes; and no evidence relating to early improvements in function. The idea that patients who appear to improve in the first treatment session will do well longer term is not supported by the literature., Competing Interests: Declaration of competing interest None declared., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study assessed the effects of age, word frequency, and background noise on the time course of lexical activation during spoken word recognition. Participants (41 young adults and 39 older adults) performed a visual world word recognition task while we monitored their gaze position. On each trial, four phonologically unrelated pictures appeared on the screen. A target word was presented auditorily following a carrier phrase ("Click on the &#95;&#95;&#95;&#95;&#95;&#95;&#95;&#95;"), at which point participants were instructed to use the mouse to click on the picture that corresponded to the target word. High- and low-frequency words were presented in quiet to half of the participants. The other half heard the words in a low level of noise in which the words were still readily identifiable. Results showed that, even in the absence of phonological competitors in the visual array, high-frequency words were fixated more quickly than low-frequency words by both listener groups. Young adults were generally faster to fixate on targets compared to older adults, but the pattern of interactions among noise, word frequency, and listener age showed that older adults' lexical activation largely matches that of young adults in a modest amount of noise.

Microbes harbor many traits that are dispensable or even unfavorable under industrial and laboratory settings. The elimination of such traits could improve the host's efficiency, genetic stability, and robustness, thereby increasing the predictability and boosting its performance as a microbial cell factory. We engineered solvent-tolerant Pseudomonas taiwanensis VLB120 to yield streamlined chassis strains with higher growth rates and biomass yields, enhanced solvent tolerance, and improved process performance. In total, the genome was reduced by up to 10%. This was achieved by the elimination of genes that enable the cell to swim and form biofilms and by the deletion of the megaplasmid pSTY and large proviral segments. The resulting strain GRC1 had a 15% higher growth rate and biomass yield than the wildtype. However, this strain lacks the pSTY-encoded efflux pump TtgGHI, rendering it solvent-sensitive. Through reintegration of ttgGHI by chromosomal insertion without (GRC2) and with (GRC3) the corresponding regulator genes, the solvent-tolerant phenotype was enhanced. The generated P. taiwanensis GRC strains enlarge the repertoire of streamlined chassis with enhanced key performance indicators, making them attractive hosts for biotechnological applications. The different solvent tolerance levels of GRC1, GRC2, and GRC3 enable the selection of a fitting host platform in relation to the desired process requirements in a chassis à la carte principle. This was demonstrated in a metabolic engineering approach for the production of phenol from glycerol. The streamlined producer GRC1Δ5-TPL38 outperformed the equivalent nonstreamlined producer VLB120Δ5-TPL38 concerning phenol titer, rate, and yield, thereby highlighting the added value of the streamlined chassis.

Background: Centralization and directional preference are common management and prognostic factors in spinal symptoms., Objective: To update the previous systematic review., Design: Systematic review to synthesis multiple aspects of centralization and directional preference., Method: Contemporary search was made of multiple databases using relevant search terms. Abstracts and titles were filtered by two authors; relevant articles were independently reviewed by two authors for content, data extraction, and quality., Results: Forty-three additional relevant articles were found. The quality of the studies, using PEDro for randomized controlled trials, was moderate or high in six out of ten RCTs; moderate or high in six out of 12 cohort studies. Prevalence of centralization was 40%, the same as the previous review. Directional preference without Centralization was 26%; thus Centralization and directional preference combined was 66%, which was very similar to the previous review. Neither clinical response was recorded in about a third of patients. Centralization and directional preference were confirmed as key positive prognostic factors, certainly in patients with low back pain, but limited evidence for patients with neck pain. There was no evidence that these might be important treatment effect modifiers. One study evaluated reliability, and found generally poor levels, despite training., Conclusions: Centralization and directional preference are worthwhile indicators of prognosis, and should be routinely examined for even in patients with chronic low back pain. But they do not occur in all patients with spinal problems, and there was no evidence that they were treatment effect modifiers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)