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Dundee, United Kingdom

Neil M.J.E.,Ninewells Hospital and Medical School
Current Clinical Pharmacology | Year: 2011

Pain is an unpleasant sensory perception warning of actual or impending tissue damage. Pain serves a vital physiological role, however, severe and uncontrolled pain in the peri-operative setting can adversely affect outcome fromsurgery and lead to chronic pain. Multiple neurochemical and receptor processes are involved in pain perception but the role of pro-inflammatory cytokines and adrenergic pathways has only recently been recognised. Clonidine is an agonist at the alpha2-adrenergic receptor that has been in clinical use for over 40 years. Clonidine was recognised at an early stage as having analgesic properties however its systemic use was frequently limited by side-effects. Recent advances in anaesthetic practice, allowing more targeted drug delivery and a better understanding of the basic physiology of pain have led to a re-evaluation of the role of clonidine in pain management. Experimental and clinical studies have identified a diverse action of clonidine in modifying not only the adrenergic component to pain perception but also an important effect on modifying the neurohumoral response to tissue injury. This has implications for the management of a diverse range of pain problems and potentially offers a method of preventing the transition from acute to chronic pain. Clonidine is likely to play an increasing role in clinical practice in anaesthetics and pain management. © 2011 Bentham Science Publishers. Source

Tsoulas C.,Institute of Continuing Medical Education of Ioannina | Nathwani D.,Ninewells Hospital and Medical School
International Journal of Antimicrobial Agents | Year: 2015

Vancomycin has been considered the standard of care for treatment of Gram-positive skin and soft-tissue infections (SSTIs). Its value has been questioned over the last decade owing to well acknowledged limitations in efficacy and tolerability and the emergence of newer meticillin-resistant Staphylococcus aureus (MRSA)-active antibacterial agents. However, no single agent has shown better results versus vancomycin in SSTI trials. The aim of this review was to identify and summarise data from meta-analyses (MAs) for the treatment of Gram-positive and MRSA SSTIs. A systematic search identified 21 published MAs examining the use of newer antibiotics and vancomycin in SSTIs. In terms of clinical and microbiological efficacy, linezolid (in Gram-positive and MRSA SSTIs) and telavancin (in MRSA SSTIs) were shown to be more effective than vancomycin. The safety of newer antimicrobials in general was comparable with vancomycin, except for telavancin, which was associated with more severe adverse events (AEs), and tigecycline owing to an all-cause mortality imbalance observed in all infections but not confirmed in SSTIs. Specific AEs were related to the use of newer agents, such as nephrotoxicity for telavancin, creatine phosphokinase elevations for daptomycin, and thrombocytopenia with linezolid. Some evidence suggests that daptomycin could be associated with reduced treatment duration, and linezolid with reduced length of intravenous treatment and hospital length of stay compared with vancomycin. Considering the limitations of this type of research and the comparative efficacy results demonstrated in head-to-head randomised controlled trials, data are still not sufficient to support the widespread use of new agents over vancomycin. © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Source

Leese G.P.,Ninewells Hospital and Medical School
Diabetic medicine : a journal of the British Diabetic Association | Year: 2013

To determine whether geography and/or social deprivation influences the occurrence of foot ulcers or amputations in patients with diabetes. A population-based cohort of people with diabetes (n = 15 983) were identified between 2004 and 2006. Community and hospital data on diabetes care, podiatry care and onset of ulceration and amputation was linked using a unique patient identifier, which is used for all patient contacts with health-care professionals. Postcode was used to calculate social deprivation and distances to general practice and hospital care. Over 3 years' follow-up 670 patients with diabetes developed new foot ulcers (42 per 1000) and 99 proceeded to amputation (6 per 1000). The most deprived quintile had a 1.7-fold (95% CI 1.2-2.3) increased risk of developing a foot ulcer. Distance from general practitioner or hospital clinic and lack of attendance at community retinal screening did not predict foot ulceration or amputation. Previous ulcer (OR 15.1, 95% CI 11.6-19.6), insulin use (OR 2.7, 95% CI 2.1-3.5), absent foot pulses (5.9: 4.7-7.5) and impaired monofilament sensation (OR 6.5, 95% CI 5.0-8.4) all predicted foot ulceration. Previous foot ulcer, absent pulses and impaired monofilaments also predicted amputation. Social deprivation is an important factor, especially for the development of foot ulcers. Geographical aspects such as accessibility to the general practitioner or hospital clinic are not associated with foot ulceration or amputation in this large UK cohort study. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK. Source

Powathil G.G.,University of Dundee | Adamson D.J.A.,Ninewells Hospital and Medical School | Chaplain M.A.J.,University of Dundee
PLoS Computational Biology | Year: 2013

In this paper we use a hybrid multiscale mathematical model that incorporates both individual cell behaviour through the cell-cycle and the effects of the changing microenvironment through oxygen dynamics to study the multiple effects of radiation therapy. The oxygenation status of the cells is considered as one of the important prognostic markers for determining radiation therapy, as hypoxic cells are less radiosensitive. Another factor that critically affects radiation sensitivity is cell-cycle regulation. The effects of radiation therapy are included in the model using a modified linear quadratic model for the radiation damage, incorporating the effects of hypoxia and cell-cycle in determining the cell-cycle phase-specific radiosensitivity. Furthermore, after irradiation, an individual cell's cell-cycle dynamics are intrinsically modified through the activation of pathways responsible for repair mechanisms, often resulting in a delay/arrest in the cell-cycle. The model is then used to study various combinations of multiple doses of cell-cycle dependent chemotherapies and radiation therapy, as radiation may work better by the partial synchronisation of cells in the most radiosensitive phase of the cell-cycle. Moreover, using this multi-scale model, we investigate the optimum sequencing and scheduling of these multi-modality treatments, and the impact of internal and external heterogeneity on the spatio-temporal patterning of the distribution of tumour cells and their response to different treatment schedules. © 2013 Powathil et al. Source

Van Hecke O.,University of Dundee | Austin S.K.,Foundation Year | Khan R.A.,Ninewells Hospital and Medical School | Smith B.H.,University of Dundee | Torrance N.,University of Dundee
Pain | Year: 2014

Most patients with neuropathic pain symptoms present and are managed in primary care, with only a minority being referred for specialist clinical assessment and diagnoses. Previous reviews have focused mainly on specific neuropathic pain conditions based in specialist settings. This is the first systematic review of epidemiological studies of neuropathic pain in the general population. Electronic databases were searched from January 1966 to December 2012, and studies were included where the main focus was on neuropathic pain prevalence and/or incidence, either as part of a specific neuropathic pain-related condition or as a global entity in the general population. We excluded studies in which data were extracted from pain or other specialist clinics or focusing on specific population subgroups. Twenty-one articles were identified and underwent quality assessment and data extraction. Included studies differed in 3 main ways: method of data retrieval, case ascertainment tool used, and presentation of prevalence/incidence rates. This heterogeneity precluded any meta-analysis. We categorised comparable incidence and prevalence rates into 2 main subgroups: (1) chronic pain with neuropathic characteristics (range 3-17%), and (2) neuropathic pain associated with a specific condition, including postherpetic neuralgia (3.9-42.0/100,000 person-years [PY]), trigeminal neuralgia (12.6-28.9/100,000 PY), painful diabetic peripheral neuropathy (15.3-72.3/100,000 PY), glossopharyngeal neuralgia (0.2-0.4/100,000 PY). These differences highlight the importance of a standardised approach for identifying neuropathic pain in future epidemiological studies. A best estimate of population prevalence of pain with neuropathic characteristics is likely to lie between 6.9% and 10%. © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Source

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