Arya M.,UCLH NHS Foundation Trust
British Journal of Cancer | Year: 2017
Background:Transrectal prostate biopsy has limited diagnostic accuracy. Prostate Imaging Compared to Transperineal Ultrasound-guided biopsy for significant prostate cancer Risk Evaluation (PICTURE) was a paired-cohort confirmatory study designed to assess diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) in men requiring a repeat biopsy.Methods:All underwent 3 T mpMRI and transperineal template prostate mapping biopsies (TTPM biopsies). Multiparametric MRI was reported using Likert scores and radiologists were blinded to initial biopsies. Men were blinded to mpMRI results. Clinically significant prostate cancer was defined as Gleason ⩾4+3 and/or cancer core length ⩾6 mm.Results:Two hundred and forty-nine had both tests with mean (s.d.) age was 62 (7) years, median (IQR) PSA 6.8 ng ml (4.98–9.50), median (IQR) number of previous biopsies 1 (1–2) and mean (s.d.) gland size 37 ml (15.5). On TTPM biopsies, 103 (41%) had clinically significant prostate cancer. Two hundred and fourteen (86%) had a positive prostate mpMRI using Likert score ⩾3; sensitivity was 97.1% (95% confidence interval (CI): 92–99), specificity 21.9% (15.5–29.5), negative predictive value (NPV) 91.4% (76.9–98.1) and positive predictive value (PPV) 46.7% (35.2–47.8). One hundred and twenty-nine (51.8%) had a positive mpMRI using Likert score ⩾4; sensitivity was 80.6% (71.6–87.7), specificity 68.5% (60.3–75.9), NPV 83.3% (75.4–89.5) and PPV 64.3% (55.4–72.6).Conclusions:In men advised to have a repeat prostate biopsy, prostate mpMRI could be used to safely avoid a repeat biopsy with high sensitivity for clinically significant cancers. However, such a strategy can miss some significant cancers and overdiagnose insignificant cancers depending on the mpMRI score threshold used to define which men should be biopsied.British Journal of Cancer advance online publication, 28 March 2017; doi:10.1038/bjc.2017.57 www.bjcancer.com. © 2017 Cancer Research UK
News Article | November 30, 2016
Significant numbers of patients whose HIV strains developed resistance to older generation drugs are also resistant to modern drugs, finds a new study led by UCL and funded by Wellcome. The research, co-authored by researchers at the London School of Hygiene and Tropical Medicine and published in The Lancet Infectious Diseases, studied 712 HIV patients across the world whose HIV was not controlled by antiretrovirals. The study found that 16% of people who stopped responding to modern first-line treatments had HIV mutations associated with resistance to an older generation of drugs called thymidine analogues. Among patients with a thymidine analogue mutation, 80% were also resistant to tenofovir, the main drug in most modern HIV treatment and prevention strategies. "We were very surprised to see that so many people were resistant to both drugs, as we didn't think this was possible," explains lead author Professor Ravi Gupta (UCL Infection & Immunity), who is also an Honorary Consultant in Infectious Diseases at The Hospital for Tropical Diseases, UCLH NHS Foundation Trust. "Mutations for thymidine analogue resistance were previously thought to be incompatible with mutations for tenofovir resistance, but we now see that HIV can be resistant to both at once. This emphasises the need to check the genetic profile of patient's virus before prescribing first-line treatments, as they may have already developed resistance to other treatments that they did not mention having taken." Resistance to a drug typically occurs when a patient doesn't take their medication regularly enough, and for first-line treatments to work patients generally need to take their medication 85-90% of the time. When treatment is not taken as advised the virus can develop a resistance to the drugs, and the latest study shows that HIV can be resistant to many different drugs simultaneously. "To prevent these multi-resistant strains from developing, we need cheap, reliable systems to assess people before treatment," says Professor Gupta. "Ideally, we need simple resistance testing kits to help screen for drug resistance before giving treatment. This would also help us to monitor HIV drug resistance globally more effectively. However, until such kits are widely available, we could test the amount of virus in the bloodstream before and after giving treatment. Although not as precise as resistance testing, this could help us to detect treatment failure earlier and switch patients to second line drugs." If a patient's virus becomes resistant to first-line drugs, the next stage is expensive second-line treatment with greater side effects. Many rural patients do not have access to such drugs, so it is important to try to preserve the effectiveness of first-line treatments.
Fitzsimons K.J.,Center for Maternal and Child Enquiries |
Modder J.,Center for Maternal and Child Enquiries |
Modder J.,UCLH NHS Foundation Trust
Seminars in Fetal and Neonatal Medicine | Year: 2010
Obesity is associated with an increased risk of pregnancy-related complications that affect both the mother and baby. National clinical care guidelines have been developed by the Centre for Maternal and Child Enquiries, as part of its Confidential Enquiry into Maternal and Child Health (CEMACH) programme. These guidelines are intended to minimise and manage the risks associated with maternal obesity, and they were developed using formal consensus methods based on the Delphi technique. A multidisciplinary group of 25 members participated in the iterative process. Standards of care were based on the best available evidence and expert clinical knowledge and experience. This article describes the process used to develop standards of maternity care for women with obesity, and the resulting recommendations are presented. © 2009 Elsevier Ltd. All rights reserved.
de santis V.,University College London |
Gresoiu M.,University College London |
Corona A.,University of Milan |
Wilson A.P.R.,UCLH NHS Foundation Trust |
Singer M.,University College London
Journal of Antimicrobial Chemotherapy | Year: 2015
Objectives: The optimal duration of antibiotic treatment in patients with bloodstream infections remains contentious, with concerns regarding both undertreatment and the encouragement of antibiotic resistance. In our ICU we traditionally use short-course antibiotic monotherapy as the mainstay of treatment. We sought to document the impact of this strategy on pathogen type, resistance patterns and patient outcomes. A comparison was made against data collected during a similar exercise in 2000. Methods: We retrospectively reviewed data on all patients with community-, hospital- and ICU-acquired bacteraemia over a 6 month period (1 December 2012 to 31 May 2013) in a general medical-surgical ICU in a London university hospital. Causative pathogens, resistance patterns, use and duration of monotherapy or combination therapy, breakthrough and relapse rates, and patient outcomes were assessed. Results: The 2013 cohort comprised 113 episodes in 87 patients. Short-course monotherapy (median course 4-5 days) was used in 65.7% of episodes (73.5% in 2000). As with the 2000 cohort, the incidence of antimicrobial resistance, fungaemia, bacteraemia breakthrough and relapse remained low. Of note, there was a decreasing incidence of ICU-acquired MRSA, MDR Gram-negative bacteraemia and fluconazole-resistant candidaemia. Hospital mortality was 32% (45% in 2000). Conclusions: Our strategy predominantly utilizing short-course antibiotic monotherapy remains effective in achieving good clinical outcomes among patients with bloodstream infections, with low rates of antibiotic resistance and clinical relapse. Prospective trials of short-course monotherapy are warranted to assess clinical efficacy and antimicrobial resistance. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Comparative study of sensitivity, linearity, and resistance to inhibition of digital and nondigital polymerase chain reaction and loop mediated isothermal amplification assays for quantification of human cytomegalovirus
Nixon G.,LCG Group |
Garson J.A.,University College London |
Grant P.,UCLH NHS Foundation Trust |
Nastouli E.,UCLH NHS Foundation Trust |
And 3 more authors.
Analytical Chemistry | Year: 2014
Performing nucleic acid amplification techniques (NAATs) in digital format using limiting dilution provides potential advantages that have recently been demonstrated with digital polymerase chain reaction (dPCR). Key benefits that have been claimed are the ability to quantify nucleic acids without the need of an external calibrator and a greater resistance to inhibitors than real-time quantitative PCR (qPCR). In this study, we evaluated the performance of four NAATs, qPCR, dPCR, real-time quantitative loop mediated isothermal amplification (qLAMP), and digital LAMP (dLAMP), for the detection and quantification of human cytomegalovirus (hCMV). We used various DNA templates and inhibitors to compare the performance of these methods using a conventional real-time thermocycler platform (Bio-Rad CFX96) and a chip based digital platform (Fluidigm Biomark 12.765 Digital Array). dPCR performed well and demonstrated greater resistance to inhibitors than the other methods although this resistance did not apply equally to all inhibitors tested. dLAMP was found to be less sensitive than dPCR, but its quantitative performance was better than qLAMP, the latter being unable to quantify below 1000 copies. dLAMP was also more resistant to inhibitors than qLAMP. Unlike qPCR, both digital methods were able to quantify viral genomes without requiring a calibrator; however, neither can currently compete with the large reaction volumes, and thus the greater absolute sensitivity, of qPCR. With the introduction of digital instrumentation that will enable larger reaction volumes, digital amplification methods such as those evaluated in this study could potentially offer a robust alternative to qPCR for nucleic acid quantification. © 2014 American Chemical Society.
Ahmed H.U.,University College London |
Ahmed H.U.,UCLH NHS Foundation Trust
Urologic Oncology: Seminars and Original Investigations | Year: 2014
The current diagnostic and therapeutic strategy for localized prostate cancer is not working. In fact, it is severely flawed and, as such, fraught with controversy. Our current strategy has arisen from the imprecision of our diagnostic pathway. We do not know where the cancer is, so we subject the prostate to randomly placed needles in the hope of hitting the tumor. This leads to overdiagnosis, underdiagnosis, missclassification of risk and overtreatment and undertreatment. If we do find cancer, we usually subject the entire prostate to radiotherapy or surgery, which damages the surrounding structures-neurovascular bundles, external urinary sphincter, rectum, and bladder neck. Multiparametric magnetic resonance imaging, coupled with an intensive sampling strategy (targeted biopsies), might be able to rule out clinically significant lesions with a negative predictive value in the order of 90% to 95%. Focal therapy certainly leads to less genitourinary and rectal side effects. Current data from more than 3,000 men treated internationally show that incontinence after focal therapy is 0% to 5% (radical therapy can lead to incontinence in 15%-20%) whereas erectile dysfunction occurs in 5% to 10% of men with good baseline function (radical therapy rates vary between 30% and 60%). Early to medium cancer control using biopsies after treatment shows between 80% and 90% of patients have a successful treatment, with 10% to 15% of men requiring redo-treatment with minimal additional morbidity. © 2014 Elsevier Inc.
Godbole G.,UCLH NHS Foundation Trust |
Godbole G.,Middlesex University |
Gant V.,UCLH NHS Foundation Trust
Current Opinion in Pulmonary Medicine | Year: 2013
Purpose of review: Pulmonary infections are particularly common in the immunosuppressed host. This review discusses emerging threats, newer modalities of diagnostic tests and emerging treatment options, and also highlights the increasing problem of antimicrobial resistance. Recent findings: Nosocomial pneumonia is increasingly due to multidrug-resistant Gram-negative organisms in immunosuppressed patients. Viral pneumonias remain a very significant threat, present atypically and carry a high mortality. Aspergillosis remains the most common fungal infection, and infections due to Mucorales are increasing. Multidrug-resistant tuberculosis is on the increase throughout the world. Mixed infections are common and early bronchoscopy with appropriate microbiological tests, including molecular diagnostics, optimise management and reduce mortality. Conclusion: Pulmonary infection remains the most frequent infectious complication in the immunocompromised host. These complex infections are often mixed, have atypical presentations and can be due to multidrug-resistant organisms. Multidisciplinary involvement in specialist centres with appropriate diagnostics, treatment and infection control improves outcome. There is a desperate need for new antimicrobial agents active against Gram-negative pathogens. Copyright © 2013 Lippincott Williams & Wilkins.
Novelli M.,UCLH NHS Foundation Trust
Histopathology | Year: 2015
Our understanding of the genetics and pathology of familial colorectal cancer continues to evolve with both the discovery of underlying genetic defects and the description of entirely new entities. Genetic analysis has demonstrated phenotypic overlap between some of these syndromes, such that their nosology is rapidly becoming based on genetics with clinicopathological features playing a secondary, but important, role. Further clinical characterization of these syndromes has also demonstrated widely differing risks for the development of colorectal cancer and a range of other malignancies with implications for both the affected patient and members of their families. This review aims to outline the clinical, pathological and genetic features of this increasingly complex group of diseases. © 2015 John Wiley & Sons Ltd.
Christie D.,UCLH NHS Foundation Trust |
Channon S.,South Wales Doctoral Programme in Clinical Psychology
Diabetes, Obesity and Metabolism | Year: 2014
Having good intentions to engage in healthy behaviours, to change our lives in a positive direction and make substantial, lasting changes may not always translate into actions or behaviour that is maintained. Motivational Interviewing is a directive person-centred approach designed to explore ambivalence and activate motivation for change [Miller WR, Rollnick S. Motivational Interviewing: Preparing People to Change Addictive Behaviour. London: Guilford Press, 1991]. A key component of a motivational interviewing conversation is to acknowledge that clients have every right to make no change. It uses a guiding communication style which invites people to consider their own situation and find their own solutions to situations that they identify as problematic that are preventing change. Motivational Interviewing was first introduced in adult health addiction services in the early 1980s. It has developed in the physical health specialties, and in the last 20 years or so attention has turned to the potential of Motivational Interviewing in the paediatric setting and the challenges of using it in families with children at differing ages and developmental stages. This article summarizes studies published from 2006 to 2011 of Motivational Interviewing in individuals across the lifespan with type 1 and type 2 diabetes and obesity. © 2013 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
Payne H.,UCLH NHS Foundation Trust |
Cornford P.,University of Liverpool
Urologic Oncology: Seminars and Original Investigations | Year: 2011
Prostate specific antigen (PSA) was introduced as a prostate cancer screening tool more than 20 years ago. However, there is continuing debate regarding its utility in screening for prostate cancer. Mass screening is costly, may result in the diagnosis and treatment of prostate cancers that never become clinically significant, and the evidence of a subsequent reduction in mortality is inconclusive. In addition to its role in screening, PSA is also used to monitor the progression of the disease, both localized and metastatic. Although the evidence is contradictory, PSA is still an important tool for monitoring patient progression following treatment of definitive localized prostate cancer. However, its use in monitoring castrate-resistant prostate cancer (CRPC) is more controversial, particularly in the context of novel targeted treatments, which may have little impact on PSA levels. These issues highlight the urgent need to identify prostate cancer biomarkers that will improve early disease detection, increase accuracy of diagnosis, determine the aggressiveness of disease, and monitor treatment efficacy, particularly in late-stage disease. This review discusses the key issues associated with the use of PSA as an early screening tool for prostate cancer, as a prognostic marker to measure disease progression in both early- and late-stage prostate cancer, and as a surrogate endpoint in clinical trials with new agents. © 2011 Elsevier Inc.