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Winchester, United Kingdom

Ahmed H.U.,University College London | Hindley R.G.,Hampshire Hospitals NHS Foundation Trust | Dickinson L.,University College London | Freeman A.,University College London | And 7 more authors.
The Lancet Oncology | Year: 2012

Background: Radical whole-gland therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer. We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden. Methods: Men aged 45-80 years were eligible for this prospective development study if they had low-risk to high-risk localised prostate cancer (prostate specific antigen [PSA] ≤15 ng/mL, Gleason score ≤4 + 3, stage ≤T2), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI and have a general anaesthetic. Patients received focal therapy using high-intensity focused ultrasound, delivered to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. Analyses were done on a per-protocol basis. This study is registered with . ClinicalTrials.gov, number . NCT00561314. Findings: 42 men were recruited between June 27, 2007, and June 30, 2010; one man died from an unrelated cause (pneumonia) 3 months after treatment and was excluded from analyses. After treatment, one man was admitted to hospital for acute urinary retention, and another had stricture interventions requiring hospital admission. Nine men (22%, 95% CI 11-38) had self-resolving, mild to moderate, intermittent dysuria (median duration 5·0 days [IQR 2·5-18·5]). Urinary debris occurred in 14 men (34%, 95% CI 20-51), with a median duration of 14·5 days (IQR 6·0-16·5). Urinary tract infection was noted in seven men (17%, 95% CI 7-32). Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 12 months (p=0·060), as were median IIEF-15 scores for intercourse satisfaction (p=0·454), sexual desire (p=0·644), and overall satisfaction (p=0·257). Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile (p=0·042) and orgasmic function (p=0·003). Of 35 men with good baseline function, 31 (89%, 95% CI 73-97) had erections sufficient for penetration 12 months after focal therapy. Median UCLA Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence scores were similar at baseline as and 12 months (p=0·045). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 12 months (p=0·026), but the IPSS-quality of life score showed no difference between baseline and 12 months (p=0·655). All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months. No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months (p=0·113) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate (p=0·045) and median FACT-General scores (p=0·041). No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months (77%, 95% CI 61-89); 36 (92%, 79-98) were free of clinically significant cancer. After retreatment in four men, 39 of 41 (95%, 95% CI 83-99) had no evidence of disease on multiparametric MRI at 12 months. Interpretation: Focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinically significant prostate cancer. Funding: Medical Research Council (UK), Pelican Cancer Foundation, and St Peters Trust. © 2012 Elsevier Ltd.

Dryden M.S.,Hampshire Hospitals NHS Foundation Trust
Current Opinion in Infectious Diseases | Year: 2014

PURPOSE OF REVIEW: Acute bacterial skin and skin structure infection (ABSSSI) is a common and significant indication for antibiotic treatment. The microbial aetiology is becoming more resistant to available antibiotics and the treatment of patients is additionally challenged by extremes of age, obesity, diabetes and other co-morbidities. This review examines recent antimicrobial developments. RECENT FINDINGS: In many parts of the world, multidrug-resistant (MDR) staphylococci are the predominant cause of ABSSSI in both the community and in hospital. Increasing resistance in Gram-negative organisms presents problems in the management of surgical-site infections. Most new antibiotics have been developed to treat MDR Gram-positive bacteria and there are few agents to treat infections caused by MDR Gram-negative pathogens. SUMMARY: A number of novel agents are available clinically, with other agents of related chemical structure under development. There are no entirely new classes of antibiotics. Maintaining the efficacy of antimicrobial treatment require effective antibiotic stewardship, good infection prevention and the development of further new antibiotics. Copyright © 2014 Wolters Kluwer Health / Lippincott Williams & Wilkins.

Ahmed H.U.,University College London | Dickinson L.,University College London | Charman S.,London School of Hygiene and Tropical Medicine | Charman S.,Clinical Effectiveness Unit | And 11 more authors.
European Urology | Year: 2015

Background Although localised prostate cancer is multifocal in most instances, the index lesion might be responsible for disease progression. Objective To determine the early genitourinary functional and cancer control outcomes of index lesion ablation. Design, setting, and participants This was a single-centre prospective development study in which 56 men were treated (July 2009-January 2011). The mean age was 63.9 yr (standard deviation 5.8) and median prostate-specific antigen (PSA) was 7.4 ng/ml (interquartile range [IQR] 5.6-9.5). There were seven (12.5%) low-risk, 47 (83.9%) intermediate-risk, and two (3.6%) high-risk cancers. Intervention Multiparametric magnetic resonance imaging (mpMRI) and prostate biopsies to localise disease, followed by index lesion ablation using high-intensity focused ultrasound. Outcome measurements and statistical analysis Primary outcomes were genitourinary side effects measured using validated questionnaires. Secondary outcomes included absence of clinically significant disease at 12 mo. Results and limitations The composite of leak-free, pad-free continence, and erections sufficient for penetration decreased from a baseline frequency of 40/56 (71.4%) to 33/56 (58.9%) at 12 mo. Pad-free and leak-free, pad-free continence was preserved in 48/52 (92.3%) and 46/50 (92.0%) patients, respectively. Erections sufficient for intercourse were preserved in 30/39 (76.9%) patients. The median PSA nadir decreased to 2.4 ng/ml (IQR 1.6-4.1). At 12 mo, 42/52 (80.8%) patients had histological absence of clinically significant cancer and 85.7% (48/56) had no measurable prostate cancer (biopsy and/or mpMRI). Two (3.6%) patients had clinically significant disease in untreated areas not detected at baseline. The main study limitation is the short follow-up duration. Conclusions Index lesion ablation had low rates of genitourinary side effects and acceptable short-term absence of clinically significant cancer. Comparative effectiveness trials are required to assess cancer control outcomes against radical therapy. Patient summary In this study we looked at whether it is possible to treat the largest and highest-grade tumour in men who have more than one known prostate tumour. We show that the side effects of targeted ablation were low, with acceptable rates of early cancer control. Larger studies with longer follow-up are needed. © 2015 European Association of Urology.

Ross M.,Brisbane Hand and Upper Limb Research Institute | Ross M.,University of Queensland | Hope B.,Brisbane Hand and Upper Limb Research Institute | Stokes A.,Grace Orthopaedic Center | And 4 more authors.
Journal of Shoulder and Elbow Surgery | Year: 2015

Background: The purpose of this study was to review the survivorship, radiologic and clinical outcomes of reverse shoulder arthroplasty (RSA) used for the treatment of 3-part and 4-part proximal humeral fractures in the elderly. Methods: Between 2003 and 2009, 29 shoulders in 28 elderly patients (87% female) with a 3-part or 4-part fractures were managed with RSA in Brisbane, Australia. Clinical and radiologic outcomes of this continuous cohort were retrospectively reviewed at an average follow-up of 54.9months. Average age at surgery was 79years. Survivorship and radiologic outcome assessment for all patients was undertaken. Seven patients died, and 1 was unavailable for clinical review, leaving 21 shoulders in 20 patients available for clinical review. Results: There were no revisions of the reverse prosthesis. Mean average pain was 2.19 of 100 (standard deviation [SD], 6.97). Mean American Shoulder and Elbow Surgeons score was 89.3 (SD, 13.65). Mean normalized Constant score was 88.03 (SD, 11.24). Grade 1 scapular notching was observed radiologically in 4 shoulders. A scapular spur was observed in 7 shoulders. Class 1 heterotopic ossification was seen in 4 shoulders. Nonprogressive lucent lines were seen in 2 shoulders. Nonprogressive radiolucency was observed around the superior screw in 3 shoulders. No loosening of the glenoid baseplate or of the humeral component was observed. There was 1 complication of an axillary nerve palsy, which spontaneously resolved by 12months after surgery. Conclusion: RSA using the shoulder technique described in this series provides good clinical and radiologic outcomes in elderly patients with 3-part and 4-part fractures. © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees.

Sykes L.,Hampshire Hospitals NHS Foundation Trust
The Cochrane database of systematic reviews | Year: 2014

This is an updated version of the original Cochrane review published in 2010, Issue 1. Seizures after stroke are an important clinical problem, and they may be associated with poor outcome. The effects of antiepileptic drugs for the primary and secondary prevention of seizures after stroke remain unclear. We aimed to assess the effects of antiepileptic drugs for the primary and secondary prevention of seizures after stroke. We searched the Specialised Registers of the Cochrane Epilepsy Group (12 August 2013) and the Cochrane Stroke Group (12 August 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 7), and MEDLINE (OVID, 1946 to 12 August 2013). We also checked the reference lists of articles retrieved from these searches. Randomised and quasi-randomised controlled trials in which participants were assigned to treatment or control group (placebo or no drug). Two review authors independently screened all the titles, abstracts, and keywords of publications identified by the searches to assess their eligibility, and both review authors assessed their suitability for inclusion according to prespecified selection criteria. We included only one study for data collection and analysis. We found only one trial that fulfilled the study inclusion criteria of comparison of the effects of an antiepileptic drug with placebo (or no drug) for the primary or secondary prevention of seizures after stroke. This was a prospective randomised, double-blind, placebo-controlled trial comparing valproic acid with placebo for primary prevention of seizures in 72 adults (over 18 years of age) with spontaneous non-aneurysmal, non-traumatic intracerebral haemorrhage; no statistically significant difference in outcome (seizure occurrence at one year) was demonstrated between groups. Currently, there is insufficient evidence to support the routine use of antiepileptic drugs for the primary or secondary prevention of seizures after stroke. Further well-conducted research is needed for this important clinical problem.

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