Decreased Pain and Improved Dynamic Knee Instability Mediate the Beneficial Effect of Wearing a Soft Knee Brace on Activity Limitations in Patients With Knee Osteoarthritis

OBJECTIVE: To evaluate whether improvement of proprioception, pain or dynamic knee instability mediate the effect of wearing a soft knee brace on activity limitations in persons with knee osteoarthritis (OA). METHODS: Exploratory analysis from 44 participants with knee OA and self-reported knee instability in a laboratory trial evaluating the effect of wearing a commercially available soft knee brace. Activity limitations were assessed with the 10-meter walk test and the Get up and Go test. Knee joint proprioception was assessed by an active joint position sense test; pain was assessed with the Numeric Rating Scale (NRS); pressure pain threshold (PPT) was assessed with a hand-held pressure algometer; dynamic knee instability was expressed by the Perturbation Response, i.e. a measure reflecting a deviation in mean knee varus-valgus angle after a controlled mechanical perturbation on a treadmill, with respect to level walking. Mediation analysis was conducted with the product of coefficients approach. Confidence intervals were calculated with a bootstrap procedure. RESULTS: A decrease of pain (NRS) and a decrease of dynamic knee instability mediated the effect of wearing a soft knee brace on reduction of activity limitations (p < 0.05), while changes of proprioception and PPT did not mediate this effect (p > 0.05). CONCLUSION: This study shows that decreased pain and reduced dynamic knee instability are pathways via which wearing a soft knee brace decreased activity limitations in persons with knee OA. This article is protected by copyright. All rights reserved

The immediate effect of a soft knee brace on pain, activity limitations, self-reported knee instability, and self-reported knee confidence in patients with knee osteoarthritis

Background: We aimed to (i) evaluate the immediate effect of a soft knee brace on pain, activity limitations, self-reported knee instability, and self-reported knee confidence, and (ii) to assess the difference in effect between a non-tight and a tight soft brace in patients with knee osteoarthritis (OA). Methods: Forty-four patients with knee OA and self-reported knee instability participated in the single-session, laboratory, experimental study. A within-subject design was used, comparing a soft brace with no brace, and comparing a non-tight with a tight soft brace. The outcome measures were pain, self-reported knee instability and knee confidence during level and perturbed walking on the treadmill and activity limitations (10-m walk test and the get up and go (GUG) test). Linear mixed-effect model analysis for continuous outcomes and logistic generalized estimating equations for categorical outcomes were used to evaluate the effect of wearing a soft brace. Results: Wearing a soft brace significantly reduced pain during level walking (B - 0.60, P = 0.001) and perturbed walking (B - 0.80, P < 0.001), reduced the time to complete the 10-m walk (B - 0.23, P < 0.001) and the GUG tests (B - 0.23, P = 0.004), reduced self-reported knee instability during level walking (OR 0.41, P = 0.002) and perturbed walking (OR 0.36, P < 0.001), and reduced lack of confidence in the knees during level walking (OR 0.45, P < 0.001) and perturbed walking (OR 0.56, P < 0.001), compared with not wearing a soft brace. There was no difference in effects between a non-tight and tight brace, except for the 10-m walk test. Wearing a tight brace significantly reduced the time to complete the 10-m walk test in comparison with wearing a non-tight brace (B - 0.11, P = 0.03). Conclusion: The results of this study indicate that a soft brace is an efficacious intervention targeting pain, activity limitations, self-reported knee instability, and knee confidence in the immediate term in patients with knee OA. Further studies are needed evaluating the mode of action based on exerted pressure, and on the generalization to functioning in daily life. Trial registration: trialregister.nl, NTR6363. Retrospectively registered on 15 May 2017

The immediate effect of a soft knee brace on pain, activity limitations, self-reported knee instability, and self-reported knee confidence in patients with knee osteoarthritis

BACKGROUND: We aimed to (i) evaluate the immediate effect of a soft knee brace on pain, activity limitations, self-reported knee instability, and self-reported knee confidence, and (ii) to assess the difference in effect between a non-tight and a tight soft brace in patients with knee osteoarthritis (OA). METHODS: Forty-four patients with knee OA and self-reported knee instability participated in the single-session, laboratory, experimental study. A within-subject design was used, comparing a soft brace with no brace, and comparing a non-tight with a tight soft brace. The outcome measures were pain, self-reported knee instability and knee confidence during level and perturbed walking on the treadmill and activity limitations (10-m walk test and the get up and go (GUG) test). Linear mixed-effect model analysis for continuous outcomes and logistic generalized estimating equations for categorical outcomes were used to evaluate the effect of wearing a soft brace. RESULTS: Wearing a soft brace significantly reduced pain during level walking (B - 0.60, P = 0.001) and perturbed walking (B - 0.80, P < 0.001), reduced the time to complete the 10-m walk (B - 0.23, P < 0.001) and the GUG tests (B - 0.23, P = 0.004), reduced self-reported knee instability during level walking (OR 0.41, P = 0.002) and perturbed walking (OR 0.36, P < 0.001), and reduced lack of confidence in the knees during level walking (OR 0.45, P < 0.001) and perturbed walking (OR 0.56, P < 0.001), compared with not wearing a soft brace. There was no difference in effects between a non-tight and tight brace, except for the 10-m walk test. Wearing a tight brace significantly reduced the time to complete the 10-m walk test in comparison with wearing a non-tight brace (B - 0.11, P = 0.03). CONCLUSION: The results of this study indicate that a soft brace is an efficacious intervention targeting pain, activity limitations, self-reported knee instability, and knee confidence in the immediate term in patients with knee OA. Further studies are needed evaluating the mode of action based on exerted pressure, and on the generalization to functioning in daily life. TRIAL REGISTRATION: trialregister.nl, NTR6363 . Retrospectively registered on 15 May 2017

The immediate effect of a soft knee brace on dynamic knee instability in persons with knee osteoarthritis

Objectives Wearing a soft knee brace has been shown to reduce self-reported knee instability in persons with knee OA. There is a need to assess whether a soft knee brace has a beneficial effect on objectively assessed dynamic knee instability as well. The aims of the study were to evaluate the effect of a soft knee brace on objectively assessed dynamic knee instability and to assess the difference in effect between a non-tight and a tight soft knee brace in persons with knee OA. Methods Thirty-eight persons with knee OA and self-reported knee instability participated in a laboratory study. A within-subject design was used comparing no brace vs brace and comparing a non-tight vs a tight brace. The primary outcome measure was dynamic knee instability, expressed by the perturbation response (PR). The PR reflects deviation in the mean knee varus-valgus angle during level walking after a controlled mechanical perturbation. Linear mixed-effect model analysis was used to evaluate the effect of a brace on dynamic knee instability. Results Wearing a brace significantly reduced the PR compared with not wearing a brace (B = -0.16, P = 0.01). There was no difference between a non-tight and a tight brace (B = -0.03, P = 0.60). Conclusion This study is the first to report that wearing a soft knee brace reduces objectively assessed dynamic knee instability in persons with knee OA. Wearing a soft brace results in an objective improvement of knee instability beyond subjectively reported improvement. Trial registration Nederlands Trial register (trialregister.nl) NTR6363Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Biomechatronics & Human-Machine Contro

Long‐term follow‐up of 64 children with classical infantile‐onset Pompe disease since 2004: a French real‐life observational study

International audienceBackground: Classical infantile-onset Pompe disease (IOPD) is the most severe form of Pompe disease. Enzyme replacement therapy (ERT) has significantly increased survival but only a few studies have reported long-term outcomes.Methods: We retrospectively analyzed the outcomes of classical IOPD patients diagnosed in France between 2004 and 2020.Results: Sixty-four patients were identified. At diagnosis (median age 4 months) all patients had cardiomyopathy and most had severe hypotonia (57 of 62 patients, 92%). ERT was initiated in 50 (78%) patients and stopped later due to being ineffective in 10 (21%). Thirty-seven (58%) patients died during follow-up, including all untreated and discontinued ERT patients, and 13 additional patients. Mortality was higher during the first 3 years of life and after the age of 12 years. Persistence of cardiomyopathy during follow-up and/or the presence of heart failure were highly associated with an increased risk of death. In contrast, cross-reactive immunologic material (CRIM)-negative status (n = 16, 26%) was unrelated to increased mortality, presumably because immunomodulation protocols prevent the emergence of high antibody titers to ERT. Besides survival, decreased ERT efficacy appeared after the age of 6 years, with a progressive decline in motor and pulmonary functions for most survivors.Conclusions: This study reports the long-term follow-up of one of the largest cohorts of classical IOPD patients and demonstrates high long-term mortality and morbidity rates with a secondary decline in muscular and respiratory functions. This decreased efficacy seems to be multifactorial, highlighting the importance of developing new therapeutic approaches targeting various aspects of pathogenesis

Hepatic PPARα is critical in the metabolic adaptation to sepsis.

Although the role of inflammation to combat infection is known, the contribution of metabolic changes in response to sepsis is poorly understood. Sepsis induces the release of lipid mediators, many of which activate nuclear receptors such as the peroxisome proliferator-activated receptor (PPAR)α, which controls both lipid metabolism and inflammation. We aimed to elucidate the previously unknown role of hepatic PPARα in the response to sepsis. Sepsis was induced by intraperitoneal injection of Escherichia coli in different models of cell-specific Ppara-deficiency and their controls. The systemic and hepatic metabolic response was analyzed using biochemical, transcriptomic and functional assays. PPARα expression was analyzed in livers from elective surgery and critically ill patients and correlated with hepatic gene expression and blood parameters. Both whole body and non-hematopoietic Ppara-deficiency in mice decreased survival upon bacterial infection. Livers of septic Ppara-deficient mice displayed an impaired metabolic shift from glucose to lipid utilization resulting in more severe hypoglycemia, impaired induction of hyperketonemia and increased steatosis due to lower expression of genes involved in fatty acid catabolism and ketogenesis. Hepatocyte-specific deletion of PPARα impaired the metabolic response to sepsis and was sufficient to decrease survival upon bacterial infection. Hepatic PPARA expression was lower in critically ill patients and correlated positively with expression of lipid metabolism genes, but not with systemic inflammatory markers. During sepsis, Ppara-deficiency in hepatocytes is deleterious as it impairs the adaptive metabolic shift from glucose to FA utilization. Metabolic control by PPARα in hepatocytes plays a key role in the host defense against infection. As the main cause of death in critically ill patients, sepsis remains a major health issue lacking efficacious therapies. While current clinical literature suggests an important role for inflammation, metabolic aspects of sepsis have mostly been overlooked. Here, we show that mice with an impaired metabolic response, due to deficiency of the nuclear receptor PPARα in the liver, exhibit enhanced mortality upon bacterial infection despite a similar inflammatory response, suggesting that metabolic interventions may be a viable strategy for improving sepsis outcomes