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Liverpool, United Kingdom

Veal G.J.,Northumbria University | Errington J.,Northumbria University | Hayden J.,Alder Hey Childrens NHS Trust | Hobin D.,Birmingham Childrens Hospital | And 5 more authors.
European Journal of Cancer | Year: 2015

Introduction Administration of the most appropriate dose of chemotherapy to neonates is particularly challenging and frequently not standardised based on any scientific rationale. We report the clinical utility of carboplatin therapeutic drug monitoring in preterm and full-term neonates within the first month of life. Methods Carboplatin therapeutic monitoring was performed to achieve target drug exposures area under the plasma concentration-time curve (AUC values) in nine preterm and full-term neonates diagnosed with retinoblastoma or neuroblastoma treated over an 8 year period. Carboplatin was administered over 3 days with therapeutic drug monitoring utilised to target cumulative AUC values of 5.2-7.8 mg/ml min. Results AUC values achieved were within 15% of target values for the individual courses of treatment in all but one patient (12/13 courses of treatment), with dose modifications of up to 215% required to achieve target AUC values, based on initial mg/kg dosing schedules. Carboplatin clearance determined across three consecutive chemotherapy courses in two patients increased from 3.4 to 7.1 ml/min and from 7.2 to 16.5 ml/min, representing increases of 210-230% over several weeks of treatment. Complete remission was observed in 8/9 patients, with no renal toxicity reported and only one patient experiencing ototoxicity. Conclusion The study highlights the benefits of utilising therapeutic drug monitoring to achieve target carboplatin AUC values in preterm and full-term neonates treated within the first few weeks of life, particularly in view of marked increases in drug clearance observed over consecutive chemotherapy courses. In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform future treatment. © 2015 The Authors.

Elsone L.,Walton Center Foundation Trust | Panicker J.,Walton Center Foundation Trust | Mutch K.,Walton Center Foundation Trust | Boggild M.,Townsville Hospital | And 2 more authors.
Multiple Sclerosis Journal | Year: 2014

Prompt treatment of neuromyelitis optica (NMO) relapses with steroids or plasma exchange (PLEX) often prevents irreversible disability. The objective of this study is to report the use of intravenous immunoglobulins (IVIG) as treatment for acute relapses in NMO. A retrospective review of 10 patients treated with IVIG for acute relapses was conducted. IVIG was used in the majority of cases because of lack of response to steroids with/without PLEX. Improvement was noted in five of 11 (45.5%) events; the remaining had no further worsening. One patient, a 79-year-old woman, had a myocardial infarction seven days after IVIG. IVIG may have a role in treating acute NMO relapses. © The Author(s) 2013.

White H.D.,University of Liverpool | Goenka N.,Countess of Chester NHS Trust | Furlong N.J.,St Helens and Knowsley NHS Trust | Saunders S.,Warrington and Halton Hospitals NHS Trust | And 5 more authors.
Diabetic Medicine | Year: 2014

Aims: The National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of continuous subcutaneous insulin infusion in 2008 (technology appraisal 151). The first UK-wide insulin pump audit took place in 2012 with the aim of determining adherence to the guidance issued in NICE technology appraisal 151. The results of the adult service level audit are reported here. Methods: All centres providing continuous subcutaneous insulin infusion services to adults with diabetes in the UK were invited to participate. Audit metrics were aligned to technology appraisal 151. Data entry took place online using a DiabetesE formatted data collection tool. Results: One hundred and eighty-three centres were identified as delivering adult continuous subcutaneous insulin infusion services in the UK, of which 178 (97.3%) participated in the audit. At the time of the audit, 13 428 adults were using insulin pump therapy, giving an estimated prevalence of use of 6%. Ninety-three per cent of centres did not report any barriers in obtaining funding for patients who fulfilled NICE criteria. The mean number of consultant programmed activities dedicated to continuous subcutaneous insulin infusion services was 0.96 (range 0-8), mean whole-time equivalent diabetes specialist nurses was 0.62 (range 0-3) and mean whole-time equivalent dietitian services was 0.3 (range 0-2), of which 39, 61 and 60%, respectively, were not formally funded. Conclusions: The prevalence of continuous subcutaneous insulin infusion use in the UK falls well below the expectation of NICE (15-20%) and that of other European countries (> 15%) and the USA (40%). This may be attributable, in part, to lack of healthcare professional time needed for identification and training of new pump therapy users. © 2013 Diabetes UK.

Michael B.,Walton Center for Neurology and Neurosurgery Trust | Michael B.,University of Liverpool | Menezes B.F.,Walton Center for Neurology and Neurosurgery Trust | Cunniffe J.,Arrowe Park Hospital | And 6 more authors.
Emergency Medicine Journal | Year: 2010

Introduction: Bacterial meningitis is a medical emergency, the outcome of which is improved by prompt antibiotic treatment. For patients with suspected meningitis and no features of severe disease, the British Infection Society recommends immediate lumbar puncture (LP) before antibiotics, to maximise the chance of a positive cerebrospinal (CSF) culture. In such patients, CT scanning before LP is not needed. Methods: The case notes of adults with meningitis admitted to a large district general hospital over 3 years were reviewed. Patients were classified as Likely Bacterial Meningitis or Likely Viral Meningitis based on their CSF and peripheral blood results using the Meningitest Criteria, with microbiological and virological confirmation. Results: Of 92 patients studied, 24 had Likely Bacterial Meningitis, including 16 with microbiologically confirmed disease (none had PCR tests for bacteria). Sixty-eight had Likely Viral Meningitis, four of whom had viral PCR, including one with herpes simplex virus. No patient had an LP before antibiotics. CSF culture was positive for eight (73%) of the 11 patients who had an LP up to 4 h after starting antibiotics, compared with eight (11%) of 71 patients with a later LP (p<0.001). None of the 34 LPs performed more than 8 h after antibiotics was culture-positive. For 62 (67%) of the 92 patients, the delay was due to a CT scan, although only 20 of these patients had a contraindication to an immediate LP. Conclusions: Too many patients with acute bacterial meningitis are being sent for unnecessary CT scans, causing delays in the LP, and reducing the chances of a positive CSF culture after starting antibiotics. However, even if antibiotics have been started, an LP within 4 h is still likely to be positive. Molecular tests for diagnosis should also be requested.

Murray P.,University of Liverpool | Vasilev K.,University of South Australia | Mora C.F.,University of Liverpool | Ranghini E.,University of Liverpool | And 6 more authors.
Biochemical Society Transactions | Year: 2010

In the future, stem-cell-based therapies could offer new approaches to treat kidney disease and reduce the incidence of ESRD (end-stage renal disease), but, as yet, research in this area is only being conducted in rodents and it is not clear whether or when it could be applied to human patients. Drug therapies, on the other hand, have been very effective at delaying the progression of kidney disease, but, for various reasons, current drug regimes are not suitable for all patients. A greater understanding of the molecular mechanisms that underlie disease progression in chronic kidney disease could help to identify novel drug targets. However, progress in this area is currently hindered due to the lack of appropriate in vitro culture systems for important renal cell types, such as proximal tubule cells and podocytes. This problem could be overcome if it were possible to direct the differentiation of kidney stem cells to renal cell types in vitro. In the present review, we highlight the potential of surface gradients of small chemical functional groups to direct the differentiation of kidney stem cells. ©The Authors.

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