24 research outputs found
Effectiveness of physiotherapy exercise following total knee replacement: Systematic review and meta-analysis
Background: Rehabilitation, with an emphasis on physiotherapy and exercise, is widely promoted after total knee replacement. However, provision of services varies in content and duration. The aim of this study is to update the review of Minns Lowe and colleagues 2007 using systematic review and meta-analysis to evaluate the effectiveness of post-discharge physiotherapy exercise in patients with primary total knee replacement. Methods: We searched MEDLINE, Embase, PsycInfo, CINAHL and Cochrane CENTRAL to October 4th 2013 for randomised evaluations of physiotherapy exercise in adults with recent primary knee replacement. Outcomes were: patient-reported pain and function, knee range of motion, and functional performance. Authors were contacted for missing data and outcomes. Risk of bias and heterogeneity were assessed. Data was combined using random effects meta-analysis and reported as standardised mean differences (SMD) or mean differences (MD). Results: Searches identified 18 randomised trials including 1,739 patients with total knee replacement. Interventions compared: physiotherapy exercise and no provision; home and outpatient provision; pool and gym-based provision; walking skills and more general physiotherapy; and general physiotherapy exercise with and without additional balance exercises or ergometer cycling. Compared with controls receiving minimal physiotherapy, patients receiving physiotherapy exercise had improved physical function at 3-4 months, SMD -0.37 (95% CI -0.62, -0.12), and pain, SMD -0.45 (95% CI -0.85, -0.06). Benefit up to 6 months was apparent when considering only higher quality studies. There were no differences for outpatient physiotherapy exercise compared with home-based provision in physical function or pain outcomes. There was a short-term benefit favouring home-based physiotherapy exercise for range of motion flexion. There were no differences in outcomes when the comparator was hydrotherapy, or when additional balancing or cycling components were included. In one study, a walking skills intervention was associated with a long-term improvement in walking performance. However, for all these evaluations studies were under-powered individually and in combination. Conclusion: After recent primary total knee replacement, interventions including physiotherapy and exercise show short-term improvements in physical function. However this conclusion is based on meta-analysis of a few small studies and no long-term benefits of physiotherapy exercise interventions were identified. Future research should target improvements to long-term function, pain and performance outcomes in appropriately powered trials
Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK:a systematic review
Pleural Fluid suPAR Levels Predict the Need for Invasive Management in Parapneumonic Effusions
Predicting outcomes of COVID-19 from admission biomarkers:a prospective UK cohort study
INTRODUCTION: COVID-19 has an unpredictable clinical course, so prognostic biomarkers would be invaluable when triaging patients on admission to hospital. Many biomarkers have been suggested using large observational datasets but sample timing is crucial to ensure prognostic relevance. The DISCOVER study prospectively recruited patients with COVID-19 admitted to a UK hospital and analysed a panel of putative prognostic biomarkers on the admission blood sample to identify markers of poor outcome. METHODS: Consecutive patients admitted to hospital with proven or clinicoradiological suspected COVID-19 were consented. Admission bloods were extracted from the clinical laboratory. A panel of biomarkers (interleukin-6 (IL-6), soluble urokinase plasminogen activator receptor (suPAR), Krebs von den Lungen 6, troponin, ferritin, lactate dehydrogenase, B-type natriuretic peptide, procalcitonin) were performed in addition to routinely performed markers (C reactive protein (CRP), neutrophils, lymphocytes, neutrophil:lymphocyte ratio). Age, National Early Warning Score (NEWS2), CURB-65 and radiographic severity score on initial chest radiograph were included as comparators. All biomarkers were tested in logistic regression against a composite outcome of non-invasive ventilation, intensive care admission or death, with area under the curve (AUC) (figures calculated). RESULTS: 187 patients had 28-day outcomes at the time of analysis. CRP (AUC: 0.69, 95% CI: 0.59 to 0.78), lymphocyte count (AUC: 0.62, 95% CI: 0.53 to 0.72) and other routine markers did not predict the primary outcome. IL-6 (AUC: 0.77, 0.65 to 0.88) and suPAR (AUC: 0.81, 0.72 to 0.88) showed some promise, but simple clinical features alone such as NEWS2 score (AUC: 0.70, 0.60 to 0.79) or age (AUC: 0.70, 0.62 to 0.77) performed nearly as well. DISCUSSION: Admission blood biomarkers have only moderate predictive value for predicting COVID-19 outcomes, while simple clinical features such as age and NEWS2 score outperform many biomarkers. IL-6 and suPAR had the best performance, and further studies should focus on the additive value of these biomarkers to routine care
The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147-receptor-mediated signalling:a potential non-infective mechanism of COVID-19 microvascular disease
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a broad range of clinical responses including prominent microvascular damage. The capacity of SARS-CoV-2 to infect vascular cells is still debated. Additionally, the SARS-CoV-2 Spike (S) protein may act as a ligand to induce non-infective cellular stress. We tested this hypothesis in pericytes (PCs), which are reportedly reduced in the heart of patients with severe coronavirus disease-2019 (COVID-19). Here we newly show that the in vitro exposure of primary human cardiac PCs to the SARS-CoV-2 wildtype strain or the α and Ύ variants caused rare infection events. Exposure to the recombinant S protein alone elicited signalling and functional alterations, including: (1) increased migration, (2) reduced ability to support endothelial cell (EC) network formation on Matrigel, (3) secretion of pro-inflammatory molecules typically involved in the cytokine storm, and (4) production of pro-apoptotic factors causing EC death. Next, adopting a blocking strategy against the S protein receptors angiotensin-converting enzyme 2 (ACE2) and CD147, we discovered that the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in PCs. The neutralisation of CD147, either using a blocking antibody or mRNA silencing, reduced ERK1/2 activation, and rescued PC function in the presence of the S protein. Immunoreactive S protein was detected in the peripheral blood of infected patients. In conclusion, our findings suggest that the S protein may prompt PC dysfunction, potentially contributing to microvascular injury. This mechanism may have clinical and therapeutic implications
Patient outcomes after hospitalisation with COVID-19 and implications for follow-up:results from a prospective UK cohort
The longer-term consequences of SARS-CoV-2 infection are uncertain. Consecutive patients hospitalised with COVID-19 were prospectively recruited to this observational study (n=163). At 8â12 weeks postadmission, survivors were invited to a systematic clinical follow-up. Of 131 participants, 110 attended the follow-up clinic. Most (74%) had persistent symptoms (notably breathlessness and excessive fatigue) and limitations in reported physical ability. However, clinically significant abnormalities in chest radiograph, exercise tests, blood tests and spirometry were less frequent (35%), especially in patients not requiring supplementary oxygen during their acute infection (7%). Results suggest that a holistic approach focusing on rehabilitation and general well-being is paramount
Tyrosine 121 moves revealing a ligandable pocket that couples catalysis to ATP-binding in serine racemase
Human serine racemase (hSR) catalyses racemisation of L-serine to D-serine, the latter of which is a co-agonist of the NMDA subtype of glutamate receptors that are important in synaptic plasticity, learning and memory. In a âclosedâ hSR structure containing the allosteric activator ATP, the inhibitor malonate is enclosed between the large and small domains while ATP is distal to the active site, residing at the dimer interface with the Tyr121 hydroxyl group contacting the α-phosphate of ATP. In contrast, in âopenâ hSR structures, Tyr121 sits in the core of the small domain with its hydroxyl contacting the key catalytic residue Ser84. The ability to regulate SR activity by flipping Tyr121 from the core of the small domain to the dimer interface appears to have evolved in animals with a CNS. Multiple X-ray crystallographic enzyme-fragment structures show Tyr121 flipped out of its pocket in the core of the small domain. Data suggest that this ligandable pocket could be targeted by molecules that inhibit enzyme activity
What is the evidence base to guide surgical treatment of infected hip prostheses? systematic review of longitudinal studies in unselected patients
Effectiveness of physiotherapy exercise following total knee replacement: Systematic review and meta-analysis
© 2015 Artz et al. Background: Rehabilitation, with an emphasis on physiotherapy and exercise, is widely promoted after total knee replacement. However, provision of services varies in content and duration. The aim of this study is to update the review of Minns Lowe and colleagues 2007 using systematic review and meta-analysis to evaluate the effectiveness of post-discharge physiotherapy exercise in patients with primary total knee replacement. Methods: We searched MEDLINE, Embase, PsycInfo, CINAHL and Cochrane CENTRAL to October 4th 2013 for randomised evaluations of physiotherapy exercise in adults with recent primary knee replacement. Outcomes were: patient-reported pain and function, knee range of motion, and functional performance. Authors were contacted for missing data and outcomes. Risk of bias and heterogeneity were assessed. Data was combined using random effects meta-analysis and reported as standardised mean differences (SMD) or mean differences (MD). Results: Searches identified 18 randomised trials including 1,739 patients with total knee replacement. Interventions compared: physiotherapy exercise and no provision; home and outpatient provision; pool and gym-based provision; walking skills and more general physiotherapy; and general physiotherapy exercise with and without additional balance exercises or ergometer cycling. Compared with controls receiving minimal physiotherapy, patients receiving physiotherapy exercise had improved physical function at 3-4 months, SMD -0.37 (95% CI -0.62, -0.12), and pain, SMD -0.45 (95% CI -0.85, -0.06). Benefit up to 6 months was apparent when considering only higher quality studies. There were no differences for outpatient physiotherapy exercise compared with home-based provision in physical function or pain outcomes. There was a short-term benefit favouring home-based physiotherapy exercise for range of motion flexion. There were no differences in outcomes when the comparator was hydrotherapy, or when additional balancing or cycling components were included. In one study, a walking skills intervention was associated with a long-term improvement in walking performance. However, for all these evaluations studies were under-powered individually and in combination. Conclusion: After recent primary total knee replacement, interventions including physiotherapy and exercise show short-term improvements in physical function. However this conclusion is based on meta-analysis of a few small studies and no long-term benefits of physiotherapy exercise interventions were identified. Future research should target improvements to long-term function, pain and performance outcomes in appropriately powered trials