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Newcastle upon Tyne, United Kingdom

Chappell L.C.,Kings College London | Duckworth S.,Kings College London | Seed P.T.,Kings College London | Griffin M.,Kings College London | And 8 more authors.
Circulation | Year: 2013

BACKGROUND - : Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. METHODS AND RESULTS - : In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks' gestation (and up to 41 weeks' gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks' gestation, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89-0.99) and negative predictive value (0.98; 0.93-0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48-0.61). Area under the receiver operating characteristic curve for low PlGF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58-0.76), in women presenting with suspected preeclampsia (P<0.001 for all comparisons). CONCLUSIONS - : In women presenting before 35 weeks' gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women. © 2013 American Heart Association, Inc.

McElnay P.J.,Newcastle upon Tyne Hospitals NHS Foundation Trust | Choong A.,Imperial College London | Jordan E.,University of Bristol | Song F.,University of East Anglia | Lim E.,Imperial College London
Thorax | Year: 2015

Objective Chemoradiotherapy is often considered the 'standard of care' for patients with N2 disease. The aim was to evaluate survival outcomes of patients with N2 disease in multimodality trials of chemotherapy, radiotherapy and surgery. Methods Systematic review and meta-analyses (random and fixed effects) were performed. Searches of Medline and Embase (1980-2013) were conducted. Abstracts from thoracic scientific meetings were searched. Reference lists of all relevant studies were reviewed. All studies of patients with N2 disease who received induction chemotherapy or chemoradiotherapy and randomised to surgery or radiotherapy were included. No language restrictions were imposed. The main outcome was overall survival. Results 805 publications were identified. 519 and 281 were excluded because they were not primary results from randomised trials (or did not include N2 disease) or did not compare surgery with radiotherapy, respectively. The final six trials consisted of 868 patients. In four trials, patients received induction chemotherapy and in two trials patients received induction chemoradiotherapy. The HR comparing patients randomised to surgery after chemotherapy was 1.01 (95% CI 0.82 to 1.23; p=0.954) whereas for patients randomised to surgery after chemoradiotherapy was 0.87 (0.75 to 1.01; p=0.068). The overall HR of all pooled trials was 0.92 (0.81 to 1.03; p=0.157). Conclusions Surgery should be considered as part of multimodality treatment for patients with resectable lung cancer and ipsilateral mediastinal nodal disease. In trials where patients received surgery as part of trimodality treatment, overall survival was better than chemoradiotherapy alone.

Cromwell D.,London School of Hygiene and Tropical Medicine | Hilton P.,Newcastle upon Tyne Hospitals NHS Foundation Trust
BJU International | Year: 2013

Study Type - Therapy (retrospective cohort) Level of Evidence 3a What's known on the subject? and What does the study add? Many case series of lower urinary tract fistula have been reported, usually reporting the results from individual surgeons using their preferred techniques. Definitions of cure and the case-mix or complexity of reported cases vary widely, and a wide range of outcome results are reported in the literature, with primary closure rates between 53% and 95%. Using the Hospital Episode Statistics database we have demonstrated for the first time the pattern of care provided nationally. A large number of surgeons (490) are currently involved in providing this care in a large number of units (138), with individual workloads varying between 1 and 90 procedures in 10 years; only three undertook >3 operations per year. We have demonstrated an overall operative failure rate (re-operation rate) of 12%, and a high rate of urinary diversion (24%). Cure rates varied between 50 and 100% and were higher in units undertaking >3 operations per year. OBJECTIVES To examine patterns of care among women with urogenital fistula treated in the English National Health Service (NHS) between 2000 and 2009. To assess whether failure of repair was associated with hospital or surgeon workload. PATIENTS AND METHODS We conducted a retrospective cohort study using data from Hospital Episode Statistics on women undergoing vesicovaginal or urethrovaginal fistula repair between January 2000 and December 2009 in English NHS hospitals. The main outcome measure was the number of fistula repairs and the incidence of re-repair; re-repair rates were stratified by age, NHS trust and consultant team volume. RESULTS Between 2000 and 2009, 1194 women underwent surgical repair (n= 905) or ileal conduit (n= 289) for urogenital fistula under the care of 490 consultant teams. A total of 281 teams performed only a single index procedure, and only three consultant teams performed a mean of >3 per year. The rate of unsuccessful repair was 11.9% (108/905). The rate of re-operation at NHS trusts who performed over 30 procedures over the 10-year study period was 7.4% compared with 13.2% at those undertaking fewer (P= 0.02). A similar difference in re-operations between consultant teams performing > or <30 procedures did not reach significance (8.4% v 12.7%, P= 0.13). CONCLUSIONS One in nine women required re-operation after surgical repair of a urogenital fistula. Our results lend weight to the argument for a 'minimum workload' for fistula management; given the number of fistulae occurring in England currently, this would best be provided by a network of supra-regional centres. © 2012 BJU INTERNATIONAL.

Berrington J.E.,Newcastle Neonatal Service | Hearn R.I.,Newcastle Neonatal Service | Bythell M.,Regional Maternity Survey Office | Wright C.,Newcastle upon Tyne Hospitals NHS Foundation Trust | Embleton N.D.,Newcastle Neonatal Service
Journal of Pediatrics | Year: 2012

Objective: To establish how cause of death for live-born preterm infants (24-31 weeks gestation) has changed in a single large UK population over 2 decades. Study design: This was an interrogation of a population-based survey of >680 000 live births (between 1988 and 2008) for deaths in the first postnatal year. We collected cause of death grouped into major etiologies: respiratory, infection, malformation, necrotizing enterocolitis (NEC), and other. Data were analyzed in three 7-year epochs and 2 gestational groups (<27 and 28-31 weeks). Numbers, rates per 1000 live births, and proportional contributions to each epoch were analyzed. Results: A total of 1504 deaths occurred. The infants who died had a median gestational age of 26 weeks (IQR, 25-28 weeks) and a median birth weight of 880 g (IQR, 700-1170 g). The number of deaths decreased with each later epoch (from 671 to 473 and then to 360), as did the proportion of deaths from respiratory causes (64% to 62% and then to 49%). The proportion of deaths occurring after 40 weeks postmenstrual age remained stable across the 3 epochs (8.8%, 8%, and 8%). Deaths from infection and NEC increased with time (from 11% to 13% and then to 21%), as did median time to death (from 2.7 to 3.8 days). Conclusion: Infection and NEC are increasingly prevalent causes of death in preterm infants. Copyright © 2012 Mosby Inc. All rights reserved.

Skinner R.,Newcastle upon Tyne Hospitals NHS Foundation Trust
Pediatric Health | Year: 2010

Chronic renal impairment in children with cancer may be caused by the malignant process itself or result from adverse effects of treatment including cytotoxic drugs, radiotherapy, surgery or supportive treatment. Although severe renal chronic disease is uncommon, occurring in only 0.8% of long-term survivors of childhood cancer, 1.9% of all cases of established renal failure are due to malignancy and 0.8% to drug nephrotoxicity. The relative risk of severe renal chronic disease (compared with siblings) is 8.1, and that of renal failure or the need for dialysis is 8.9. The cytotoxic drugs most likely to cause important chronic nephrotoxicity are ifosfamide and cisplatin, both of which are used widely in many solid tumors and may cause chronic glomerular and/or renal tubular toxicity in 30-60% of treated children. Significant renal toxicity is less frequent with other chemotherapeutic drugs, but may result from treatment with carboplatin, methotrexate and nitrosoureas. Other cytotoxic drugs occasionally cause specific patterns of glomerular or tubular toxicity in children. Partial or unilateral nephrectomy leads to hypertrophy and hyperfiltration of the remaining renal tissue, and may result in microalbuminuria, hypertension and in rare cases, chronic renal impairment. Radiotherapy to a field including renal tissue may cause late onset chronic renal damage, manifest by hematuria, proteinuria, hypertension and anemia, sometimes progressing to chronic renal failure. Chronic nephrotoxicity is also common in survivors of hemopoietic stem cell transplantation, and is often multifactorial with contributions from prior chemotherapy, total body irradiation, immunosuppressive drugs and transplant complications, such as infection or hemorrhage. Patients at risk of renal damage should be monitored regularly with a defined surveillance protocol to enable timely management. General measures often employed to prevent or reduce nephrotoxicity include the use of intravenous hydration during drug administration and avoidance of known risk factors, such as high drug doses. Although numerous potentially nephroprotective drugs have been suggested and investigated, none have yet been introduced into clinical use in children due to the lack of proven efficacy. Improved understanding of the pathogenesis of nephrotoxicity is necessary to reduce the frequency and severity of this potentially serious complication of treatment in children with cancer. © 2010 Future Medicine Ltd.

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