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Thangaratinam S.,Queen Mary, University of London | Brown K.,Birmingham Womens NHS Foundation Trust | Zamora J.,Hospital Ramon y Cajal IRYCIS | Zamora J.,CIBER ISCIII | And 3 more authors.
The Lancet | Year: 2012

Background: Screening for critical congenital heart defects in newborn babies can aid in early recognition, with the prospect of improved outcome. We assessed the performance of pulse oximetry as a screening method for the detection of critical congenital heart defects in asymptomatic newborn babies. Methods: In this systematic review, we searched Medline (1951-2011), Embase (1974-2011), Cochrane Library (2011), and Scisearch (1974-2011) for relevant citations with no language restriction. We selected studies that assessed the accuracy of pulse oximetry for the detection of critical congenital heart defects in asymptomatic newborn babies. Two reviewers selected studies that met the predefined criteria for population, tests, and outcomes. We calculated sensitivity, specificity, and corresponding 95% CIs for individual studies. A hierarchical receiver operating characteristic curve was fitted to generate summary estimates of sensitivity and specificity with a random effects model. Findings: We screened 552 studies and identified 13 eligible studies with data for 229 421 newborn babies. The overall sensitivity of pulse oximetry for detection of critical congenital heart defects was 76·5% (95% CI 67·7-83·5). The specificity was 99·9% (99·7- 99·9), with a false-positive rate of 0·14% (0·06- 0·33). The false-positive rate for detection of critical congenital heart defects was particularly low when newborn pulse oximetry was done after 24 h from birth than when it was done before 24 h (0·05% [0·02- 0·12] vs 0·50 [0·29-0·86]; p=0·0017). Interpretation: Pulse oximetry is highly specific for detection of critical congenital heart defects with moderate sensitivity, that meets criteria for universal screening.


Rachaneni S.,University of Birmingham | Latthe P.,Birmingham Womens NHS Foundation Trust
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2015

Background Urodynamics is widely used in the investigation of urinary incontinence. The existing evidence questions its add-on value in improving the outcome of surgical treatment for stress urinary incontinence (SUI). Objectives To compare the surgical outcomes in women with SUI or stress-predominant mixed urinary incontinence (MUI) based on urodynamic diagnoses compared with diagnoses based on office evaluation without urodynamics. Search strategy We searched Cochrane, MedLine, Embase, CINAHL, LILACS, metaRegister of Controlled Trials (mRCT) and Google Scholar databases from inception until March 2013. Selection criteria We included randomised controlled trials (RCTs) comparing surgical outcomes in women investigated by urodynamics and women who had office evaluation only. Data collection and analysis Two independent reviewers (S.R. and P.L.) extracted the data and analysed it using review manager (revman) 5.2 software. Main results Of the 388 articles identified, only four RCTs met our criteria. The data from one study are as yet unpublished. In the other three RCTs, the women with SUI or stress-predominant MUI were randomised either to office evaluation and urodynamics (n = 388) or to office evaluation only (n = 387). There was no statistical difference in the risk ratio (RR) of subjective cure in the two groups (RR 1.02, 95%CI 0.90-1.15, P = 0.79, I2 = 45%), objective cure (RR 1.01, 95%CI 0.93-1.11, P = 0.28, I2 = 20%) or complications such as voiding dysfunction (RR 1.54, 95%CI 0.61-3.89, P = 0.27, I2 = 18%) or urinary urgency (RR 0.80, 95%CI 0.28-2.3, P = 0.19, I2 = 40%). Authors' conclusions In women undergoing primary surgery for SUI or stress-predominant MUI without voiding difficulties, urodynamics does not improve outcomes - as long as the women undergo careful office evaluation. © 2014 Royal College of Obstetricians and Gynaecologists.


Singh A.,Birmingham Womens NHS Foundation Trust | Rasiah S.V.,Birmingham Womens NHS Foundation Trust | Ewer A.K.,Birmingham Womens NHS Foundation Trust | Ewer A.K.,University of Birmingham
Archives of Disease in Childhood: Fetal and Neonatal Edition | Year: 2014

Objectives: (i) To evaluate the impact of routine early pulse oximetry screening on the rate of unexpected neonatal unit (NNU) admissions and the need for echocardiography. (ii) To review the outcomes of babies admitted as a result of a positive pulse oximetry screening test. Design: Retrospective review over a 40-month period. Setting: Level 3 NNU. Patients: All babies admitted as a result of positive pulse oximetry screening. Main outcome measures: Indication for admission, clinical diagnosis and management were collated. Results: 3552 babies were admitted during the study period. Of these, 1651 were unexpected admissions and 208/1651 (12.6%) were as a result of positive pulse oximetry screening. 165/208 babies (79%) had a significant clinical condition which required further intervention including 17 with congenital heart defect (CHD) (nine critical), 55 with pneumonia, 30 with sepsis and 12 with pulmonary hypertension. No baby died or collapsed on the postnatal ward during the study period. 61/208 babies (29%) had echocardiography and CHD was detected in 28%. Conclusions: Routine use of pulse oximetry screening identifies babies with CHD and other illnesses, which, if not identified early could potentially lead to postnatal collapse. It does not appear to overload clinical services, resulting in appropriate admission in the majority and a modest increase in the number of echocardiograms performed.


Pradhan A.,University of Cambridge | Jain P.,Manor Hospital | Latthe P.M.,Birmingham Womens NHS Foundation Trust
International Urogynecology Journal and Pelvic Floor Dysfunction | Year: 2012

Introduction and hypothesis: Midurethral slings (MUS) are the gold standard primary procedure for the surgical treatment of stress urinary incontinence (SUI). There is no robust evidence on the success with MUS in the treatment of recurrent SUI. Our objective was to evaluate the effectiveness and complications of MUS in women with recurrent SUI by systematic review and meta-analysis of the literature. Methods: A systematic literature search was carried out (up to August 2011) using relevant search terms in MEDLINE, EMBASE, CENTRAL and Google Scholar. Relevant randomised controlled trials (RCT) and prospective studies were selected and then analysed by two independent reviewers. Meta-analysis of cure stated in prospective cohort studies was performed with a random effects model using Stata 8. Results: There was 1 randomised trial and 11 good quality prospective studies included in this systematic review. The overall subjective cure rate per meta-analysis of prospective cohort studies following MUS for recurrent SUI after any previous surgery was found to be 78.5 % [95 % confidence interval (CI) 69-88] at the follow-up of 29.72±29.49 months. The subjective cure rate following MUS after previous failed MUS was 73.3 % (95 % CI 55-97) at the follow-up of 15.7± 7.7 months. Conclusions: The studies report good cure rates of SUI after MUS surgery following previous incontinence surgery (62-100 %). There seems to be a lower cure rate with trans-obturator compared to the retropubic tape for recurrent SUI after previous surgery. © The International Urogynecological Association 2012.


Togneri F.S.,Birmingham Womens Nhs Foundation Trust
European Journal of Human Genetics | Year: 2016

Urothelial bladder cancers (UBCs) have heterogeneous clinical characteristics that are mirrored in their diverse genomic profiles. Genomic profiling of UBCs has the potential to benefit routine clinical practice by providing prognostic utility above and beyond conventional clinicopathological factors, and allowing for prediction and surveillance of treatment responses. Urinary DNAs representative of the tumour genome provide a promising resource as a liquid biopsy for non-invasive genomic profiling of UBCs. We compared the genomic profiles of urinary cellular DNA and cell-free DNA (cfDNA) from the urine with matched diagnostic formalin-fixed paraffin-embedded tumour DNAs for 23 well-characterised UBC patients. Our data show urinary DNAs to be highly representative of patient tumours, allowing for detection of recurrent clinically actionable genomic aberrations. Furthermore, a greater aberrant load (indicative of tumour genome) was observed in cfDNA over cellular DNA (P<0.001), resulting in a higher analytical sensitivity for detection of clinically actionable genomic aberrations (P<0.04) when using cfDNA. Thus, cfDNA extracted from the urine of UBC patients has a higher tumour genome burden and allows greater detection of key genomic biomarkers (90%) than cellular DNA from urine (61%) and provides a promising resource for robust whole-genome tumour profiling of UBC with potential to influence clinical decisions without invasive patient interventions.European Journal of Human Genetics advance online publication, 13 January 2016; doi:10.1038/ejhg.2015.281. © 2016 Macmillan Publishers Limited


Verghese T.,Birmingham Womens NHS Foundation Trust | Latthe P.,Birmingham Womens NHS Foundation Trust
International Journal of Urology | Year: 2014

The therapeutic options for management of stress urinary incontinence can be conservative, pharmacological or surgical. The treatment of patients with stress urinary incontinence should be tailored to the individual to optimize care. A multitude of surgical techniques have emerged to treat this condition in recent years. The objective of the present review was to present an overview of current practice in the management of stress urinary incontinence while considering the evidence supporting the clinical effectiveness of these procedures. © 2013 The Japanese Urological Association.


Mason J.,Birmingham Womens NHS Foundation Trust | Griffiths M.,Birmingham Womens NHS Foundation Trust
Expert Review of Molecular Diagnostics | Year: 2012

The diagnosis of leukemia relies upon a multiparametric approach involving a number of different pathology disciplines. Molecular methods are increasingly employed to help refine diagnosis, establish prognosis and determine the most appropriate treatment, including rational therapies targeting the underlying genetic lesion. This review aims to highlight some of the molecular techniques commonly used in the diagnosis of leukemia using relevant examples. The focus is on procedures in current use and technologies showing promise in the research setting that are likely to enter clinical use in the near future. The list is not exhaustive, and this article concentrates on diagnosis of leukemia; techniques used to monitor response to therapy and molecular residual disease are mentioned but have not been covered extensively. © 2012 Expert Reviews Ltd.


Jain P.,Birmingham Womens NHS Foundation Trust | Jirschele K.,Saint Joseph Hospital | Botros S.M.,University of Chicago | Latthe P.M.,Birmingham Womens NHS Foundation Trust
International Urogynecology Journal and Pelvic Floor Dysfunction | Year: 2011

Introduction and hypothesis Mixed urinary incontinence (MUI) is a coexistence of stress (SUI) and urgency urinary incontinence (UUI). There is conflicting evidence on the effectiveness of midurethral slings (MUS) in this condition. The objective of this study is to evaluate the effectiveness of MUS in women with MUI by systematic review of the literature. Methods Systematic literature search was carried (June 2010) using relevant search terms in Medline, EMBASE, CENTRAL and Google Scholar. Relevant randomised controlled trials (RCT) and prospective studies were selected and then analysed by two independent reviewers. Meta-analysis was performed with random effects model using STATA 8. Results There were six randomised trials and seven prospective studies with average to good quality included in this systematic review. There was heterogeneity in outcomes reported. The overall subjective cure from seven prospective nonrandomised studies that included patients with symptomatic± urodynamically proven MUI was found to be 56.4% (95% confidence interval 45.7-69.6%) at 34.9±22.9 months follow-up. The overall cure of urgency and UUI component was 30-85%at a follow-up of few months up to 5 years.Most of the studies described that this cure does not persist over the time. The cure rate of SUI following MUS varies from85%to 97%. On meta-analysis of five RCTs which included women with MUI symptoms, the odds of overall subjective cure with TVT versus transobturator tapes are similar at 6-33 months follow-up (OR, 0.9; 95% CI, 0.63-1.27). This was true when a subgroup analysis was performed on women with MUI who were negative for DO on UDS (OR, 1.21; 95% CI, 0.7-2.08) Conclusions There is evidence of persistent and good cure of stress component following MUS in women with MUI. The cure of the urge component is variable but less than stress component. Methodologically sound RCTs of retropubic and transobturator tapes with long-term follow-up are needed specifically for women with urodynamically proven and symptomatic mixed incontinence. © The International Urogynecological Association 2011.


Bradshaw E.H.,Birmingham Womens NHS Foundation Trust
Pharmacogenomics | Year: 2015

Third Annual Open Meeting of the UK Pharmacogenetics and Stratified Medicine Network 14 January 2015, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK The third Annual Open Meeting of the UK Pharmacogenetics and Stratified Medicine Network was held on 14 January 2015 in association with the Wellcome Trust on the Wellcome Trust Genome Campus at Hinxton, Cambridge, UK. In the morning, speakers from Cancer Research UK, the Medical Research Council, Genomics England, Innovate UK (formerly TSB) and the Department of Health described the current major projects they are funding. In the afternoon, speakers from various universities around the United Kingdom presented data on pharmacogenetics and stratified medicine research covering diverse disease areas including cancers, warfarin dosing, Gaucher disease and rheumatoid arthritis. © 2015 Future Medicine Ltd.


Burton C.,Birmingham Womens NHS Foundation Trust | Sajja A.,Birmingham Womens NHS Foundation Trust | Latthe P.M.,Birmingham Womens NHS Foundation Trust
Neurourology and Urodynamics | Year: 2012

Aim To evaluate the effectiveness of posterior percutaneous tibial nerve stimulation (PTNS) in treating overactive bladder (OAB) symptoms by systematic review of the literature. Methods Systematic literature search was carried out (up to April 2011) using relevant search terms in Medline, EMBASE, CINAHL, CENTRAL, National Library for Health, MetaRegister of controlled trials, LILACS, and Google Scholar. Relevant randomized controlled trials (RCTs) and prospective studies were selected and then analyzed by two-independent reviewers. Meta-analysis was performed with random effects model using STATA 8 for non-randomized prospective studies and with Review Manager 5.1 for RCTs. Results The studies report variable initial success rates (37-82%) for treating OAB symptoms with PTNS. Four randomized trials compared PTNS with Sham treatment showing a significant difference favoring PTNS [RR 7.02 95% confidence interval (CI) 1.69-29.17]. Two randomized trials compared PTNS with antimuscarinic medication with no significant difference in the change in bladder diary parameters between the treatments. Ten prospective non-randomized studies were included. The definitions of success were varied. The pooled subjective success rate was 61.4% (95% CI 57.5-71.8) and objective success rate was 60.6% (95% CI 49.2-74.7). Conclusion There is evidence of significant improvement in OAB symptoms using PTNS which is comparable to the effect of antimuscarinics but with a better side effect profile. The studies included in the review only considered short-term outcomes after initial treatment. In order to recommend PTNS as a practical treatment option, long-term data and health economic analysis are needed. Neurourol. Urodynam. 31:1206-1216, 2012. © 2012 Wiley Periodicals, Inc.

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