Several submaximal exercise tests reliable, valid and acceptable in patients with chronic pain, fibromyalgia or chronic fatigue: a systematic review.

Question: Are submaximal and maximal exercise tests reliable, valid and acceptable in people with chronic pain, fibromyalgia and fatigue disorders? Design: Systematic review of studies of the psychometric properties of exercise tests. Participants: People older than 18 years with chronic pain, fibromyalgia and chronic fatigue disorders. Intervention: Studies of the measurement properties of tests of physical capacity in people with chronic pain, fibromyalgia or chronic fatigue disorders were included. Outcome measures: Studies were required to report: reliability coefficients (intraclass correlation coefficient, alpha reliability coefficient, limits of agreements and Bland-Altman plots); validity coefficients (intraclass correlation coefficient, Spearman's correlation, Kendal T coefficient, Pearson's correlation); or dropout rates. Results: Fourteen studies were eligible: none had low risk of bias, 10 had unclear risk of bias and four had high risk of bias. The included studies evaluated: Åstrand test; modified Åstrand test; Lean body mass-based Åstrand test; submaximal bicycle ergometer test following another protocol other than Åstrand test; 2-km walk test; 5-minute, 6-minute and 10-minute walk tests; shuttle walk test; and modified symptom-limited Bruce treadmill test. None of the studies assessed maximal exercise tests. Where they had been tested, reliability and validity were generally high. Dropout rates were generally acceptable. The 2-km walk test was not recommended in fibromyalgia. Conclusion: Moderate evidence was found for reliability, validity and acceptability of submaximal exercise tests in patients with chronic pain, fibromyalgia or chronic fatigue. There is no evidence about maximal exercise tests in patients with chronic pain, fibromyalgia and chronic fatigue

Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.

BACKGROUND: Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis. METHODS: We investigated in vitro and in vivo effects of metformin in humans. RESULTS: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to nonclassical monocytes. At a functional level, metformin lowered ex vivo production of tumor necrosis factor α, interferon γ, and interleukin 1β but increased phagocytosis activity and reactive oxygen species production. CONCLUSION: Metformin has a range of potentially beneficial effects on cellular metabolism, immune function, and gene transcription involved in innate host responses to M. tuberculosis

Effects of conversion of native cerrado vegetation to pasture on soil hydro-physical properties, evapotranspiration and streamflow on the Amazonian agricultural frontier

Understanding the impacts of land-use change on landscape-hydrological dynamics is one of the main challenges in the Northern Brazilian Cerrado biome, where the Amazon agricultural frontier is located. Motivated by the gap in literature assessing these impacts, we characterized the soil hydro-physical properties and quantified surface water fluxes from catchments under contrasting land-use in this region. We used data from field measurements in two headwater micro-catchments with similar physical characteristics and different land use, i.e. cerrado sensu stricto vegetation and pasture for extensive cattle ranching. We determined hydraulic and physical properties of the soils, applied ground-based remote sensing techniques to estimate evapotranspiration, and monitored streamflow from October 2012 to September 2014. Our results show significant differences in soil hydro-physical properties between the catchments, with greater bulk density and smaller total porosity in the pasture catchment. We found that evapotranspiration is smaller in the pasture (639 ± 31% mm yr-1) than in the cerrado catchment (1,004 ± 24% mm yr-1), and that streamflow from the pasture catchment is greater with runoff coefficients of 0.40 for the pasture and 0.27 for the cerrado catchment. Overall, our results confirm that conversion of cerrado vegetation to pasture causes soil hydro-physical properties deterioration, reduction in evapotranspiration reduction, and increased streamflow

Effectiveness and cost‐effectiveness of the Transmural Trauma Care Model investigated in a multicenter trial with a controlled before‐and‐after design: A study protocol

Objective: The rehabilitation of trauma patients in primary care is challenging, and there are no guidelines for optimal treatment. Also, the organization of care is not well-structured. The Transmural Trauma Care Model (TTCM) has been developed in the Netherlands, aiming to improve patient outcomes by optimizing the organization and the quality of the rehabilitation process in primary care. A recent feasibility study showed that implementation of the TTCM at a Dutch Level 1 trauma center was feasible, patient outcomes were improved, and costs were reduced. This study aims to assess the effectiveness and cost-effectiveness of the TTCM compared to the usual care in a multicenter trial. Methods: A multicenter trial with a controlled before-and-after design will be performed at 10 hospitals in the Netherlands. First, participating hospitals will include 322 patients in the control group, receiving usual care as provided in these specific hospitals. Subsequently, the TTCM will be implemented in all participating hospitals, and hospitals will include an additional 322 patients in the intervention group. The TTCM consists of a multidisciplinary team at the outpatient clinic (trauma surgeon and hospital-based physical therapist), an educated and trained network of primary care trauma physical therapists, and structural communication between them. Co-primary outcomes will investigate generic and disease-specific, health-related quality of life. Secondary outcomes will include pain, patient satisfaction, perceived recovery, and patient-reported physical functioning. For the economic evaluation, societal and healthcare costs will be measured. Measurements will take place at baseline and after 6 weeks, 3, 6, and 9 months. Analyses will be based on the intention-to-treat principle. Missing data will be handled using longitudinal data analyses in the effect analyses and by multivariate imputation in the economic evaluation. Conclusion: This trial with a controlled before-and-after design will give insight into the effectiveness and cost-effectiveness of the TTCM in a multicenter trial

Physical therapy treatment in children with cerebral palsy after single-event multilevel surgery:a qualitative systematic review. A first step towards a clinical guideline for physical therapy after single-event multilevel surgery

Background: The aim of this study was to review available evidence for physical therapy treatment (PTT) after single-event multilevel surgery (SEMLS), and to realize a first step towards an accurate and clinical guideline for developing effective PTT for children with cerebral palsy (CP) after SEMLS. Methods: A qualitative systematic review (PubMed, Medline, Embase, CINAHL, and the Cochrane Library) investigating a program of PTT after SEMLS in children aged 4-18 years with CP classified by Gross Motor Function Classification System level I-III. Results: Six articles meeting the inclusion criteria were selected. The selected studies provide only incomplete descriptions of interventions, and show no consensus regarding PTT after SEMLS. Neither do they show any consensus on the outcome measures or measuring instruments. Conclusions: Based on the results of this literature review in combination with our best practice, we propose a preliminary protocol of PTT after SEMLS

Effectiveness and cost-effectiveness of the Transmural Trauma Care Model investigated in a multicenter trial with a controlled before-and-after design: A study protocol

Objective: The rehabilitation of trauma patients in primary care is challenging, and there are no guidelines for optimal treatment. Also, the organization of care is not well-structured. The Transmural Trauma Care Model (TTCM) has been developed in the Netherlands, aiming to improve patient outcomes by optimizing the organization and the quality of the rehabilitation process in primary care. A recent feasibility study showed that implementation of the TTCM at a Dutch Level 1 trauma center was feasible, patient outcomes were improved, and costs were reduced. This study aims to assess the effectiveness and cost-effectiveness of the TTCM compared to the usual care in a multicenter trial. Methods: A multicenter trial with a controlled before-and-after design will be performed at 10 hospitals in the Netherlands. First, participating hospitals will include 322 patients in the control group, receiving usual care as provided in these specific hospitals. Subsequently, the TTCM will be implemented in all participating hospitals, and hospitals will include an additional 322 patients in the intervention group. The TTCM consists of a multidisciplinary team at the outpatient clinic (trauma surgeon and hospital-based physical therapist), an educated and trained network of primary care trauma physical therapists, and structural communication between them. Co-primary outcomes will investigate generic and disease-specific, health-related quality of life. Secondary outcomes will include pain, patient satisfaction, perceived recovery, and patient-reported physical functioning. For the economic evaluation, societal and healthcare costs will be measured. Measurements will take place at baseline and after 6 weeks, 3, 6, and 9 months. Analyses will be based on the intention-to-treat principle. Missing data will be handled using longitudinal data analyses in the effect analyses and by multivariate imputation in the economic evaluation. Conclusion: This trial with a controlled before-and-after design will give insight into the effectiveness and cost-effectiveness of the TTCM in a multicenter trial

Barriers and facilitators associated with the upscaling of the Transmural Trauma Care Model: a qualitative study

Abstract Background To assess the barriers and facilitators associated with upscaling the Transmural Trauma Care Model (TTCM), a multidisciplinary and patient‐centred transmural rehabilitation care model. Methods Semi-structured interviews were conducted with eight trauma surgeons, eight hospital-based physiotherapists, eight trauma patients, and eight primary care physiotherapists who were part of a trauma rehabilitation network. Audio recordings of the interviews were made and transcribed verbatim. Data were analysed using a framework method based on the “constellation approach”. Identified barriers and facilitators were grouped into categories related to structure, culture, and practice. Results Various barriers and facilitators to upscaling were identified. Under structure, barriers and facilitators belonged to one of five themes: “financial structure”, “communication structure”, “physical structures and resources”, “rules and regulations”, and “organisation of the network”. Under culture, the five themes were “commitment”, “job satisfaction”, “acting as a team”, “quality and efficiency of care”, and “patients’ experience”. Under practice, the two themes were “practical issues at the outpatient clinic” and “knowledge gained”. Conclusion The success of upscaling the TTCM differed across hospitals and settings. The most important prerequisites for successfully upscaling the TTCM were adequate financial support and presence of “key actors” within an organisation who felt a sense of urgency for change and/or expected the intervention to increase their job satisfaction. Trial registration NL8163 The Netherlands National Trial Register, date of registration 16-11-2019

Insulin acutely activates metabolism of primary human monocytes and promotes a proinflammatory phenotype

Increased glycolysis is a metabolic trait of activated innate immune cells and supports functional changes including cytokine production. Insulin drives glycolysis in nonimmune cells, yet its metabolic effects on human innate immune cells remain unexplored. Potential effects of insulin on immune cell metabolism may occur acutely after a postprandial increase in plasma insulin levels or as a consequence of chronically elevated insulin levels as observed in obese insulin-resistant individuals and patients with diabetes. Here, we investigated the effects of acute and chronic exposure to insulin on metabolism and function of primary human monocytes. Insulin acutely activated the PI3K/Akt/mTOR pathway in monocytes and increased both oxygen consumption and glycolytic rates. Functionally, acute exposure to insulin increased LPS-induced IL-6 secretion and reactive oxygen species production. To model chronically elevated insulin levels in patients with diabetes, we exposed monocytes from healthy individuals for 24 h to insulin. Although we did not find any changes in expression of metabolic genes that are regulated by insulin in non-immune cells, chronic exposure to insulin increased LPS-induced TNFα production and enhanced MCP-1-directed migration. Supporting this observation, we identified a positive correlation between plasma insulin levels and macrophage numbers in adipose tissue of overweight individuals. Altogether, insulin acutely activates metabolism of human monocytes and induces a shift toward a more proinflammatory phenotype, which may contribute to chronic inflammation in patients with diabetes.</p

Content validity and measurement properties of the Lower Extremity Functional Scale in patients with fractures of the lower extremities: a systematic review

Background: Fractures of lower extremities are common trauma-related injuries, and have major impact on patients' functional status. A frequently used Patient-Reported Outcome Measure (PROM) to evaluate patients’ functional status with lower extremity fractures is the Lower Extremity Functional Scale (LEFS). However, there is no systematic review regarding content validity and other measurement properties of the LEFS in patients with lower extremity fractures. Methods: A search was performed in PubMed, Embase, Scopus, and Cochrane Library from inception until November 2020. Studies on development of the LEFS and/or the evaluation of one or more measurement properties of the LEFS in patients with lower extremity fractures were included, and independently assessed by two reviewers using COSMIN guidelines. Results: Seven studies were included. Content validity of the LEFS was rated 'inconsistent', supported by very low quality of evidence. Structural validity was rated ‘insufficient’ supported by doubtful methodological quality. Internal consistency, measurement error, and responsiveness were rated 'indeterminate' supported by inadequate to adequate methodological quality. The methodological quality of the construct validity (hypotheses testing) assessment was rated as 'inadequate'. Conclusion: The LEFS has several shortcomings, the lack of sufficient content validity being the most important one as content validity is considered the most crucial measurement property of a PROM according to the COSMIN guidelines. In interpreting the outcomes, one should therefore be aware that not all relevant aspects of physical functioning may be accounted for in the LEFS. Further validation in a well-designed content validity study is needed, including a clearly defined construct and patient involvement during the assessment of different aspects of content validity. Plain English summary: Bone fractures of the lower extremities are a common injury. During rehabilitation it is essential to evaluate how patients experience their physical functioning, in order to monitor the progress and to optimize treatment. To measure physical functioning often questionnaires (also known as Patient Reported Outcome Measures) are used, such as the Lower Extremity Functional Scale (LEFS). However, it is not clear if the LEFS actually measures physical function, and if its other measurement properties are sufficient for using this questionnaire among patients with fractures in the lower extremities. Therefore, we systematically searched and assessed scientific papers on the development of the LEFS (i.e., its ability to measure physical functioning), and papers on the performance of the LEFS with regard to several measurement properties to identify possible factors that may cause measurement errors. Hereby we have assessed the quality of the studies included. Our main finding was that the LEFS may not measure all aspects of physical function. Given the low quality of the papers included in our study, these findings come with considerable uncertainty. As the LEFS was developed more than 20 years ago, it may not represent physical functioning as we currently conceptualize this. Therefore, we recommend to perform a study in which the content of the LEFS will be evaluated by experts in the field as well as patients, and modify the questionnaire as needed