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Crumpsall, United Kingdom

Ajdukiewicz K.M.B.,Monsall Unit | Cartwright K.E.,Royal Infirmary | Zijlstra E.E.,Erasmus Medical Center | French N.,London School of Hygiene and Tropical Medicine | Whitty C.J.M.,London School of Hygiene and Tropical Medicine
The Lancet Infectious Diseases

Background: Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Mortality exceeds 50%, even with appropriate antibiotic therapy, and is not improved with corticosteroids. Glycerol adjuvant therapy reduces long-term morbidity in bacterial meningitis in children, and its use is being promoted. We aimed to assess the effectiveness of glycerol as an adjuvant therapy for adults with bacterial meningitis in Africa. Methods: The study was done in two phases. First, in an open-label dose-finding study, 45 adult patients with symptoms, signs, and cerebrospinal fluid findings consistent with bacterial meningitis received either 50 mL, 75 mL, or 100 mL of glycerol four times a day for 4 days. We then did a randomised, double-blind, placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and cerebrospinal fluid findings suggestive of bacterial meningitis were randomly assigned in blocks of 12 by use of a random number list produced by an independent statistician to receive either glycerol or an equivalent volume of sugar solution. Glycerol and placebo were indistinguishable by colour or taste. The primary outcome was mortality at 40 days, with secondary outcomes including disability and mortality restricted to pneumococcal disease. All patients were analysed for the primary outcome excluding those who were lost to follow-up. This trial is registered at controlled-trials.com, number ISRCTN70121840. Findings: 75 mL glycerol four times a day was the highest tolerated dose, and was used for the main study. 265 patients were assigned treatment: 137 glycerol and 128 placebo. The trial was stopped early on the advice of the data and safety monitoring board after a planned interim analysis. By day 40, 61 (49%) of 125 patients in the placebo group and 86 (63%) of 136 in the glycerol group had died (adjusted odds ratio 2·4, 95% CI 1·3-4·2, p=0·003). There was no benefit from glycerol for death and disability by day 40, and glycerol did not improve death and disability by day 40 or death at day 40 in patients with proven bacterial disease or pneumococcal disease. Two serious adverse events occurred that were possibly due to the study drug. Interpretation: Oral glycerol therapy cannot be recommended as an adjuvant therapy in adults with bacterial meningitis in resource-poor settings with a high HIV prevalence. Funding: Meningitis Research Foundation. © 2011 Elsevier Ltd. Source

Alvarez-Uria G.,Monsall Unit | Alvarez-Uria G.,Autonomous University of Barcelona | Day J.N.,Monsall Unit | Day J.N.,University of Oxford | And 3 more authors.
Digestive Diseases and Sciences

Background: Bone marrow suppression is a well-recognized toxicity of the treatment of hepatitis C virus (HCV). Reduction of the peginterferon dose because of neutropenia is common in clinical practice. However, reduction of peginterferon dose during the first weeks of HCV treatment is associated with failure to achieve sustained virological response. Aims: The objective of this study is to investigate whether the fall of neutrophil count during hepatitis C treatment is associated with achieving sustained virological response. Methods: We performed an observational study of patients who completed peginterferon and ribavirin treatment in an Infectious Diseases Department in Manchester, UK. Results: Of the 74 patients included in the analysis, 78% had genotype 2 or 3 hepatitis C and 15% had liver cirrhosis. Sustained virological response was achieved in 78% of patients. On univariate analysis, factors related to achieving sustained virological response were younger age, genotype 2 or 3, baseline neutrophil count, and fall of neutrophil count during treatment. Multivariate analysis showed baseline neutrophil count >3.5 × 10 3 cells/mm3 [odds ratio (OR) 5.7; 95% confidence interval (CI) 1.24-26.3] and a reduction of neutrophil count >60% (OR 4.5; 95% CI 1.03-19.9) to be independently associated with achieving sustained virological response. Neutropenia was not associated with an increased risk of infections. Conclusions: In this observational study, higher baseline neutrophil count and fall of neutrophil count during the treatment of hepatitis C was associated with achieving sustained virological response. These findings could have important implications for the monitoring and management of HCV treatment with peginterferon if they are confirmed in other studies. © 2009 Springer Science+Business Media, LLC. Source

Price V.A.,University of Liverpool | Smith R.A.S.,University of Liverpool | Douthwaite S.,Monsall Unit | Thomas S.,University of Liverpool | And 7 more authors.
Journal of Travel Medicine

Background. Our aim was to document how often travel histories were taken and the quality of their content. Methods. Patients admitted over 2 months to acute medical units of two hospitals in the Northwest of England with a history of fever, rash, diarrhea, vomiting, jaundice, or presenting as "unwell post-travel" were identified. The initial medical clerking was assessed. Results. A total of 132 relevant admissions were identified. A travel history was documented in only 26 patients (19.7%). Of the 16 patients who had traveled, there was no documentation of pretravel advice or of sexual/other activities abroad in 15 (93.8%) and 12 (75.0%) patients, respectively. Conclusions. There needs to be better awareness and education about travel-related illness and the importance of taking an adequate travel history. © 2011 International Society of Travel Medicine. Source

Wingfield T.,Monsall Unit | Herbert A.,North Manchester General Hospital | Ustianowski A.P.,Monsall Unit
Clinical Medicine, Journal of the Royal College of Physicians of London

More HIV-positive patients are living longer and presenting to non-infection specialties with non-HIV-related issues (eg diabetes, heart disease). National recommendations advise routinely offering HIV testing to all new registrants to primary care and all general medical admissions where community prevalence exceeds 2:1000.1,2 It is, therefore, imperative that all physicians are educated and competent in HIV infection, counselling and testing. This study aimed to establish regional medical registrars' opinions on teaching provision, and confidence in, HIV medicine. The results indicated a lack of confidence in HIV medicine and, in those without postgraduate rotations in HIV medicine or infectious diseases, a perception that HIV and infection-related teaching provision is inadequate. © Royal College of Physicians, 2012. All rights reserved. Source

Hogan C.,Monsall Unit | Denning D.W.,University of Manchester
Seminars in Respiratory and Critical Care Medicine

While allergic bronchopulmonary aspergillosis (ABPA) is well recognized as a fungal complication of asthma, severe asthma with fungal sensitization (SAFS) is not. In ABPA the total immunoglobulin E (IgE) is usually >1,000 IU/mL, whereas in SAFS it is <1,000 IU/mL, and either skin prick tests or fungus-specific IgE tests are positive. ABPA may present with any severity of asthma, and occasionally with no asthma or cystic fibrosis, the other common underlying disease. SAFS is a problem in patients with poorly controlled asthma and occasionally presents in the intensive care unit (ICU). Production of mucous plugs and coughing paroxysms is more common in ABPA. Certain underlying genetic defects seem to underpin these remarkable phenotypic differences. From a management perspective both ABPA and SAFS respond to both high doses of corticosteroids and oral antifungal agents, with ∼60% response rate in both ABPA and SAFS with itraconazole. In 50% of patients itraconazole boosts inhaled corticosteroid exposure, sometimes leading to cushingoid features. Second-line therapy data are scant, but we have shown that 70 to 80% of patients who tolerate either voriconazole or posaconazole also respond. Other useful therapies include nebulized hypertonic saline to aid expectoration of thick sputum and long-term azithromycin for its anti-inflammatory effect on the airways. Omaluzimab is useful in some patients with SAFS and occasionally in ABPA. Complications of ABPA include bronchiectasis, typically central in distribution, and chronic pulmonary aspergillosis. Most patients with ABPA and SAFS can be stabilized for long periods with inhaled corticosteroids and itraconazole or another antifungal agent. Novel immunotherapies are on the horizon. Copyright © 2011 by Thieme Medical Publishers, Inc. Source

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