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Hypertension is the most common avoidable medical indication for postponing anaesthesia and surgery and although care guidelines exist for the medical patient with hypertension, there are no accepted guidelines for pre-operative evaluation and perioperative care of patients with hypertension who undergo non-cardiac surgery. Therefore management of hypertensive surgical patients remains unclear, whether blood pressure (BP) level or BP-related target organ damage at the time of surgery predicts perioperative cardiovascular complications in patients undergoing major surgery, and thus whether deferring surgery in order to improve BP control will lead to a reduction in perioperative cardiac risk. The literature review critically evaluates the current literature on the topics of hypertension and the surgical patient, white coat hypertension and hypertension and obesity. The literature review supports the uncertainty of patient's management prior to non-cardiac elective surgery as there are no published national guidelines as a direct association between pre-operative hypertension and the perioperative cardiac complications are unclear. Although there appears to be a general agreement that patients with mild-to-moderate hypertension can proceed with surgery because such hypertension poses little additional risk of perioperative cardiovascular complications. Severe hypertension and the presence of hypertension-induced end organ damage should be postponed until better BP control is obtained. © 2010, British Association of Anaesthetic and Recovery Nursing. All rights reserved.


Campbell G.,Royal Infirmary | Rollin A.M.,Epsom General Hospital | Smith A.F.,Royal Infirmary
Anaesthesia | Year: 2013

The General Medical Council is the regulatory body charged with maintaining standards in the medical profession in the UK. We analysed cases relating to anaesthetists handled in 2009 using fitness-to-practise data, comparing them with the profession as a whole and examining patterns of referral. Complaints were made about 105 doctors practising in anaesthesia. The 81 anaesthetists who were investigated further were subject to a total of 225 separate allegations, median (IQR [range]) of 2 (1-3) allegations per anaesthetist. Anaesthetists had a lower rate of referral compared with doctors in general (0.095% vs 0.20%, respectively, p = 0.0001). They were less likely than doctors in general to be referred by an individual member of the public (27% vs 64%, respectively, p = 0.0001). As with other specialties, allegations were most commonly made about clinical care, probity and relationships with patients. On the basis of 2009 data, we calculated that a mean (95% CI) of 1 in 120 (1 in 100-145) doctors practising in anaesthesia in the UK will be referred to the General Medical Council every year. We have provided examples of allegations and made recommendations for maintaining good practice in anaesthesia. © 2013 The Association of Anaesthetists of Great Britain and Ireland.


Williams D.P.,University of Oxford | Blakey C.M.,Sheffield Teaching Hospitals NHS Trust | Hadfield S.G.,Epsom General Hospital | Murray D.W.,University of Oxford | And 2 more authors.
Journal of Bone and Joint Surgery - Series B | Year: 2013

The Oxford knee score (OKS) is a validated and widely accepted disease-specific patient-reported outcome measure, but there is limited evidence regarding any long-term trends in the score. We reviewed 5600 individual OKS questionnaires (1547 patients) from a prospectively-collected knee replacement database, to determine the trends in OKS over a ten-year period following total knee replacement. The mean OKS pre-operatively was 19.5 (95% confidence interval (CI) 18.8 to 20.2). The maximum post-operative OKS was observed at two years (mean score 34.4 (95% CI 33.7 to 35.2)), following which a gradual but significant decline was observed through to the ten-year assessment (mean score 30.1 (95% CI 29.1 to 31.1)) (p < 0.001). A similar trend was observed for most of the individual OKS components (p < 0.001). Kneeling ability initially improved in the first year but was then followed by rapid deterioration (p < 0.001). Pain severity exhibited the greatest improvement, although residual pain was reported in over two-thirds of patients post-operatively, and peak improvement in the night pain component did not occur until year four. Post-operative OKS was lower for women (p < 0.001), those aged < 60 years (p < 0.003) and those with a body mass index > 35 kg/m2 (p < 0.014), although similar changes in scores were observed. This information may assist surgeons in advising patients of their expected outcomes, as well as providing a comparative benchmark for evaluating longer-term outcomes following knee replacement. © 2013 British Editorial Society of Bone & Joint Surgery.


Williams D.P.,University of Oxford | Price A.J.,University of Oxford | Beard D.J.,University of Oxford | Hadfield S.G.,Epsom General Hospital | And 3 more authors.
Journal of Bone and Joint Surgery - Series B | Year: 2013

We present a comparison of patient-reported outcomes (PROMs) in relation to patient age, in patients who had received a total (TKR) or unicompartmental knee replacement (UKR). The outcome was evaluated using the Oxford knee score (OKS), EuroQol (EQ-5D) and satisfaction scores. Patients aged 65 to 84 years demonstrated better pre-operative function scores than those aged < 65 years (OKS, p = 0.03; EQ-5D, p = 0.048) and those aged ≥ 85 years (OKS, p = 0.03). Post-operative scores were comparable across age groups, but a linear trend for greater post-operative improvement in OKS and EQ-5D was seen with decreasing age (p < 0.033). The overall mean satisfaction score at six months was 84.9, but those aged < 55 years exhibited a lower mean level of satisfaction (78.3) compared with all other age groups (all p < 0.031). The cumulative overall two-year revision rate was 1.3%. This study demonstrates that good early outcomes, as measured by the OKS and EQ-5D, can be anticipated following knee replacement regardless of the patient's age, although younger patients gain greater improvement. However, the lower satisfaction in those aged < 55 years is a concern, and suggests that outcome is not fully encapsulated by the OKS and EQ-5D evaluation, and raises the question whether the OKS alone is an appropriate measure of pain and function in younger, more active individuals. © 2013 British Editorial Society of Bone & Joint Surgery.


Stone T.W.,University of Glasgow | Forrest C.M.,University of Glasgow | Darlington L.G.,Epsom General Hospital
FEBS Journal | Year: 2012

The oxidative pathway for the metabolism of tryptophan along the kynurenine pathway generates quinolinic acid, an agonist at N-methyl-d-aspartate receptors, as well as kynurenic acid which is an antagonist at glutamate and nicotinic receptors. The pathway has become recognized as a key player in the mechanisms of neuronal damage and neurodegenerative disorders. As a result, manipulation of the pathway, so that the balance between the levels of components of the pathway can be modified, has become an attractive target for the development of pharmacological agents with the potential to treat those disorders. This review summarizes some of the relevant background information on the pathway itself before identifying some of the chemical strategies for its modification, with examples of their successful application in animal models of infection, stroke, traumatic brain damage, cerebral malaria and cerebral trypanosomiasis. Tryptophan is oxidised along the kynurenine pathway to quinolinic acid, an agonist at N-methyl-d-aspartate (NMDA) receptors, and kynurenic acid which is an antagonist. This minireview summarises the potential role of kynurenines in brain disorders as well as chemical strategies for drug development, some of which have been tested in animal models of infection, stroke, cerebral malaria and trypanosomiasis © 2012 The Authors Journal compilation © 2012 FEBS.


Forrest C.M.,University of Glasgow | Khalil O.S.,University of Glasgow | Pisar M.,University of Glasgow | Darlington L.G.,Epsom General Hospital | Stone T.W.,University of Glasgow
Brain Research | Year: 2013

Glutamate receptors sensitive to N-methyl-d-aspartate (NMDA) are important in early brain development, influencing cell proliferation and migration, neuritogenesis, axon guidance and synapse formation. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at these receptors. Rats were treated in late gestation with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]-benzene-sulphonamide (Ro61-8048), an inhibitor of kynurenine-3-monoxygenase which diverts kynurenine metabolism to kynurenic acid. Within 5 h of drug administration, there was a significant decrease in GluN2A expression and increased GluN2B in the embryo brains, with changes in sonic hedgehog at 24 h. When injected dams were allowed to litter normally, the brains of offspring were removed at postnatal day 21 (P21). Recordings of hippocampal field excitatory synaptic potentials (fEPSPs) showed that prenatal exposure to Ro61-8048 increased neuronal excitability and paired-pulse facilitation. Long-term potentiation was also increased, with no change in long-term depression. At this time, levels of GluN2A, GluN2B and postsynaptic density protein PSD-95 were all increased. Among several neurodevelopmental proteins, the expression of sonic hedgehog was increased, but DISC1 and dependence receptors were unaffected, while raised levels of doublecortin and Proliferating Cell Nuclear Antigen (PCNA) suggested increased neurogenesis. The results reveal that inhibiting the kynurenine pathway in utero leads to molecular and functional synaptic changes in the embryos and offspring, indicating that the pathway is active during gestation and plays a significant role in the normal early development of the embryonic and neonatal nervous system. Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved.


Banerjee P.,Epsom General Hospital | McLean C.R.,Epsom General Hospital
Current Reviews in Musculoskeletal Medicine | Year: 2011

Hip pain in adults has traditionally been associated with osteoarthritis in the joint. However, many young patients with hip pain do get referred to orthopaedic surgeons without arthritis. Subtle bony and soft tissues abnormalities can present with hip pain in the active young adult. These abnormalities can lead to premature arthritis. With the improvements in clinical examination for hip impingement, radiological imaging using magnetic resonance arthrography (MRA) and or computed tomograms (CT) Scans, these lesions are being detected early. Though the cause of primary osteoarthritis is unknown, it is suggested that femoro-acetabular impingement (FAI) may be responsible for the progression of the disease in these patients. FAI is a pathological condition leading to abutment between the proximal femur and the acetabular rim. Two different mechanisms are described, although a combination of both is seen in clinical practice. Cam impingement is a result of reduced anterior femoral head neck offset. Pincer lesion is caused by abnormalities on the acetabular side. FAI due to either mechanism can lead to chondral lesions and labral pathology. Patients present with groin pain and investigated with radiographs, CT and MRA. Surgery is the treatment of choice. Open or arthroscopic exploration of the hip is undertaken with bony resection to improve the femoral head neck junction with resection or repair of the damaged labrum. This may involve femoral osteochondroplasty for the cam lesion and acetabular rim resection for pincer lesion. There is no difference in outcome between open and arthroscopic surgery for FAI. © 2011 Springer Science+Business Media, LLC.


Forrest C.M.,University of Glasgow | Khalil O.S.,University of Glasgow | Pisar M.,University of Glasgow | Smith R.A.,University of Glasgow | And 2 more authors.
Molecular Brain | Year: 2012

Background: There is mounting evidence for a neurodevelopmental basis for disorders such as autism and schizophrenia, in which prenatal or early postnatal events may influence brain development and predispose the young to develop these and related disorders. We have now investigated the effect of a prenatal immune challenge on brain development in the offspring. Pregnant rats were treated with the double-stranded RNA polyinosinic:polycytidylic acid (poly(I:C); 10 mg/kg) which mimics immune activation occurring after activation of Toll-like receptors-3 (TLR3) by viral infection. Injections were made in late gestation (embryonic days E14, E16 and E18), after which parturition proceeded naturally and the young were allowed to develop up to the time of weaning at postnatal day 21 (P21). The brains of these animals were then removed to assess the expression of 13 different neurodevelopmental molecules by immunoblotting. Results: Measurement of cytokine levels in the maternal blood 5 hours after an injection of poly(I:C) showed significantly increased levels of monocyte chemoattractant protein-1 (MCP-1), confirming immune activation. In the P21 offspring, significant changes were detected in the expression of GluN1 subunits of NMDA receptors, with no difference in GluN2A or GluN2B subunits or the postsynaptic density protein PSD-95 and no change in the levels of the related small GTPases RhoA or RhoB, or the NMDA receptor modulator EphA4. Among presynaptic molecules, a significant increase in Vesicle Associated Membrane Protein-1 (VAMP-1; synaptobrevin) was seen, with no change in synaptophysin or synaptotagmin. Proliferating Cell Nuclear Antigen (PCNA), as well as the neurogenesis marker doublecortin were unchanged, although Sox-2 levels were increased, suggesting possible changes in the rate of new cell differentiation. Conclusions: The results reveal the induction by prenatal poly(I:C) of selective molecular changes in the brains of P21 offspring, affecting primarily molecules associated with neuronal development and synaptic transmission. These changes may contribute to the behavioural abnormalities that have been reported in adult animals after exposure to poly(I:C) and which resemble symptoms seen in schizophrenia and related disorders. © 2012 Forrest et al.; licensee BioMed Central Ltd.


Watts K.,Epsom General Hospital
Cochrane database of systematic reviews (Online) | Year: 2012

Acute asthma presentation in the emergency setting frequently leads to hospital admission. Currently available treatment options include corticosteroid therapy, beta(2)-agonists and oxygen. Antileukotriene agents are beneficial in chronic asthma as additional therapy to inhaled steroids. Their value when used orally or intravenously in the acute setting requires evaluation. To determine if the addition of a leukotriene receptor antagonist (LTRA) produces a beneficial effect in children and adults with acute asthma who are currently receiving inhaled bronchodilators and systemic corticosteroids. We searched the Cochrane Airways Group's Specialised Register of trials with predefined terms. Searches are current to February 2012. We included randomised trials comparing antileukotrienes and standard acute asthma care versus placebo and standard care in people with acute asthma of any age. We considered any dose and method of delivery of the leukotriene agent. Two authors independently assessed studies for inclusion in the review and extracted data. We then checked data and resolved disagreements by discussion. We contacted study authors where necessary to provide additional information and data. Eight trials, generating 10 treatment-control comparisons, that recruited 1470 adults and 470 children met the entry criteria. These studies were of mixed quality, and there was heterogeneity in the severity of asthma exacerbation.For oral treatment, there was no significant difference in hospital admission between LTRAs and control in three trials on 194 children (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.21 to 3.52). Using a broader composite outcome which measured requirement for additional care there was no significant difference between treatments (RR 0.87; 95% CI 0.60 to 1.28). Results demonstrated some indication of improvement in lung function with a significant difference in forced expiratory volume in one second (FEV(1)) favouring LTRAs in two trials on 641 adults (mean difference (MD) 0.08; 95% CI 0.01 to 0.14). There were insufficient data to assess this outcome in children. The most common adverse event described was headache; however, there was no significant difference between LTRAs and control (RR 0.81; 95% CI 0.22 to 2.99). Due to insufficient numbers, we were unable to conduct a subgroup analysis based on age.The combined results of two trials of intravenous treatment in 772 adults and one trial in 276 children demonstrated a reduction in the risk of hospital admission which was not quite statistically significant (RR 0.78; 95% CI 0.61 to 1.01). There was a statistically significant small difference in FEV(1) in the adult studies (MD 0.12; 95% CI 0.06 to 0.17), but not in the single trial in children (MD 0.01; 95% CI -0.06 to 0.08). Presently, the available evidence does not support routine use of oral LTRAs in acute asthma. Further studies are required to assess whether intravenous treatment can reduce the risk of hospital admission, and what the most appropriate dose regimen is. Additional research is also needed into safety and efficacy of additional doses for those on maintenance therapy, and larger paediatric trials are required to allow subgroup analysis. Prolonged studies would be required to establish other health economic outcomes in admitted patients.


Craik J.D.,Epsom General Hospital | Cobb A.G.,Epsom General Hospital
British Journal of Haematology | Year: 2013

Until recently, both the British Society for Haematology and American College of Chest Physicians recommended platelet monitoring in all surgical patients receiving prophylactic low molecular weight heparin (LMWH) for the early diagnosis of heparin-induced thrombocytopenia (HIT). These guidelines were reversed in 2012 based upon an analysis considering resource expenditure, assay result timeframes, and complications relating to HIT treatment. However, there are no large studies reviewing lower limb arthroplasty patients on an individual basis to determine the incidence of HIT in this patient group. This study investigated 10 797 patients who underwent primary hip or knee arthroplasty with LMWH prophylaxis over a 5 years period. 32·6% of patients (n = 3515) had platelet counts recorded up to 14 d postoperatively with 13 patients (0·37%) developing thrombocytopenia. Platelet counts recovered spontaneously in five patients, and two patients had other identifiable causes. Only one of the remaining six patients developed thrombosis indicating an incidence of HIT-related thrombosis of 0·03%. The potential for identifying HIT with platelet monitoring in patients receiving LMWH prophylaxis is low and therefore routine monitoring for HIT is not justified. © 2013 Blackwell Publishing Ltd.

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