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Institution

Leicester Royal Infirmary

HealthcareLeicester, United Kingdom
About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.


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Journal ArticleDOI
TL;DR: The data show that IV TXA reduces the risk of maternal death due to bleeding and was more evident in women given treatment between one and three hours after giving birth with no apparent reduction when given after three hours.
Abstract: BACKGROUND: Postpartum haemorrhage (PPH) - heaving bleeding within the first 24 hours after giving birth - is one of the main causes of death of women after childbirth. Antifibrinolytics, primarily tranexamic acid (TXA), have been shown to reduce bleeding in surgery and safely reduces mortality in trauma patients with bleeding without increasing the risk of adverse events.An earlier Cochrane review on treatments for primary PPH covered all the various available treatments - that review has now been split by types of treatment. This new review concentrates only on the use of antifibrinolytic drugs for treating primary PPH. OBJECTIVES: To determine the effectiveness and safety of antifibrinolytic drugs for treating primary PPH. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (28 May 2017) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), including cluster-randomised trials of antifibrinolytic drugs (aprotinin, TXA, epsilon-aminocaproic acid (EACA) and aminomethylbenzoic acid, administered by whatever route) for primary PPH in women.Participants in the trials were women after birth following a pregnancy of at least 24 weeks' gestation with a diagnosis of PPH, regardless of mode of birth (vaginal or caesarean section) or other aspects of third stage management.We have not included quasi-randomised trials, or cross-over studies. Studies reported as abstracts have not been included if there was insufficient information to allow assessment of risk of bias.In this review we only identified studies looking at TXA. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each study using an agreed form. We entered data into Review Manager software and checked for accuracy.For key review outcomes, we rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach. MAIN RESULTS: Three trials (20,412 women) met our inclusion criteria. Two trials (20,212 women) compared intravenous (IV) TXA with placebo or standard care and were conducted in acute hospital settings (labour ward, emergency department) (in high-, middle- and low-income countries).One other trial (involving 200 women) was conducted in Iran and compared IV TXA with rectal misoprostol, but did not report on any of this review's primary or GRADE outcomes. There were no trials that assessed EACA, aprotinin or aminomethylbenzoic acid.Standard care plus IV TXA for the treatment of primary PPH compared with placebo or standard care aloneTwo trials (20,212 women) assessed the effect of TXA for the treatment of primary PPH compared with placebo or standard care alone. The larger of these (The WOMAN trial) contributed over 99% of the data and was assessed as being at low risk of bias. The quality of the evidence varied for different outcomes, Overall, evidence was mainly graded as moderate to high quality.The data show that IV TXA reduces the risk of maternal death due to bleeding (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.65 to 1.00; two trials, 20,172 women; quality of evidence: moderate). The quality of evidence was rated as moderate due to imprecision of effect estimate. The effect was more evident in women given treatment between one and three hours after giving birth with no apparent reduction when given after three hours ( three hours = RR 1.07, 95% 0.76 to 1.51; test for subgroup differences: Chi² = 4.90, df = 2 (P = 0.09), I² = 59.2%). There was no heterogeneity in the effect by mode of birth (test for subgroup differences: Chi² = 0.01, df = 1 (P = 0.91), I² = 0%). There were fewer deaths from all causes in women receiving TXA, although the 95% CI for the effect estimate crosses the line of no effect (RR 0.88, 95% CI 0.74 to 1.05; two trials, 20,172 women, quality of evidence: moderate). Results from one trial with 151 women suggest that blood loss of ≥ 500 mL after randomisation may be reduced (RR 0.50, 95% CI 0.27 to 0.93; one trial, 151 women; quality of evidence: low). TXA did not reduce the risk of serious maternal morbidity (RR 0.99, 95% CI 0.83 to 1.19; one trial, 20,015 women; quality of evidence: high), hysterectomy to control bleeding (RR 0.95, 95% CI 0.81 to 1.12; one trial, 20,017 women; quality of evidence: high) receipt of blood transfusion (any) (RR 1.00, 95% CI 0.97 to 1.03; two trials, 20,167 women; quality of evidence: moderate) or maternal vascular occlusive events (any), although results were imprecise for this latter outcome (RR 0.88, 95% CI 0.54 to 1.43; one trial, 20,018 women; quality of evidence: moderate). There was an increase in the use of brace sutures in the TXA group (RR 1.19, 95% CI 1.01, 1.41) and a reduction in the need for laparotomy for bleeding (RR 0.64, 95% CI 0.49, 0.85). AUTHORS' CONCLUSIONS: TXA when administered intravenously reduces mortality due to bleeding in women with primary PPH, irrespective of mode of birth, and without increasing the risk of thromboembolic events. Taken together with the reliable evidence of the effect of TXA in trauma patients, the evidence suggests that TXA is effective if given as early as possible.Facilities for IV administration may not be available in non-hospital settings therefore, alternative routes to IV administration need to be investigated.

71 citations

Journal ArticleDOI
TL;DR: In unselected rheumatoid arthritis patients both airflow obstruction and bronchial reactivity are significantly increased compared with controls.
Abstract: OBJECTIVES--To investigate the prevalence of airways obstruction and bronchial reactivity to inhaled methacholine in rheumatoid arthritis patients and unselected controls. The control population consisted of patients attending the rheumatology department for minor degenerative joint problems. METHODS--One hundred patients with rheumatoid arthritis (RA) [72 (72%) women, 28 (28%) men; mean (SD) age 58 (10) years] and fifty controls [30 (60%) women, 20 (40%) men; mean (SD) age 56 (9) years] were studied. Detailed medical, smoking and drug histories were taken; skin prick tests were performed to assess atopy and chest and hand radiographs were performed. Spirometry, flow volume loops and gas transfer factor measurement were performed to detect airflow obstruction and methacholine inhalation tests were carried out to assess bronchial reactivity. RESULTS--There was no significant difference between rheumatoid arthritis patients and the controls in age, sex, smoking status and atopy on skin prick testing (p < 0.05). A significantly higher number of patients with RA had a history of wheeze compared with the controls (18% v 4%, p < 0.05). FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower in the rheumatoid arthritis group (p < 0.05). A significantly higher number of patients with RA compared with controls showed bronchial reactivity to inhaled methacholine [55 (55%) v 8 (16%), p < 0.05]. FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower among the patients with RA achieving PD20 FEV1 to inhaled methacholine (p < 0.05). CONCLUSION--In unselected rheumatoid arthritis patients both airflow obstruction and bronchial reactivity are significantly increased compared with controls.

71 citations

Journal ArticleDOI
TL;DR: In healthy individuals, the source of cell‐free plasma DNA is predominantly apoptotic, whereas, increased plasma DNA integrity is seen in cancer patients, so it is important to carefully isolate absolutely “cell‐free” plasma DNA, and recommend the use of a microcentrifuge spin, prior to DNA extraction.
Abstract: In healthy individuals, the source of cell-free plasma DNA is predominantly apoptotic, whereas, increased plasma DNA integrity is seen in cancer patients. Therefore, it is important to carefully isolate absolutely "cell-free" plasma DNA. Plasma DNA from 30 healthy females was analyzed using 4 PCR amplicons of increasing size, comparing standard blood processing with additional centrifugation steps prior to DNA extraction. Cellular DNA contamination, indicated by positive amplicons >300 bp was eliminated only after the extra centrifugation step. This highlights the importance of careful processing in preparation of cell-free plasma DNA as a tool for cancer detection and we recommend the use of a microcentrifuge spin, prior to DNA extraction.

71 citations

Journal ArticleDOI
TL;DR: The bulk of the literature concerning endocannabinoids is based upon anandamide related studies; therefore, in this review, the metabolism of an andamide and its role in reproduction are focused on.

71 citations

Journal ArticleDOI
01 Apr 2013-Leukemia
TL;DR: Two hundred eighty-five patients with PML-RARα-positive acute promyelocytic leukaemia were randomised to Ara-C-containing ‘Medical Research Council (MRC) Chemotherapy’+ ATRA (All-trans-retinoic acid) or anthracycline+ATRA (modified ‘Spanish’) therapy, finding both approaches deliver similar results with minor differences in quality of life.
Abstract: Two hundred eighty-five patients, median age 42, with PML-RARα-positive acute promyelocytic leukaemia were randomised to Ara-C-containing ‘Medical Research Council (MRC) Chemotherapy’+ATRA (All-trans-retinoic acid) or anthracycline+ATRA (modified ‘Spanish’) therapy. MRC treatment comprised four courses with ATRA in courses 1–2. Spanish treatment comprised four anthracycline-based courses with ATRA in courses 1–3. In course 3 patients were randomised to gemtuzumab ozogamicin (GO) or not. The Spanish arm received 24-month maintenance. Patients were sequentially molecularly monitored. Quality of life was assessed at baseline, 3, 6, 9, 12, 24 months. Remission rates were similar in both arms (93%): cumulative incidence of haematological relapse (CIHR) was 6% at 5 years; 5 patients relapsed molecularly. Survival post relapse was 80%. There were more deaths in remission in the MRC arm (4% vs 10%: P=0.2). The overall 5-year relapse-free and overall survival was similar between arms (81% vs 82% and 84% vs 83%, respectively). More supportive care and hospitalisation (81.8 vs 63 days, P 10 × 109/l) was not prognostic overall, or within treatment arms. Both approaches deliver similar results with minor differences in quality of life. MRC treatment required more hospitalisation. This suggests that additional chemotherapy, Ara-C in particular, is not required.

71 citations


Authors

Showing all 5314 results

NameH-indexPapersCitations
George Davey Smith2242540248373
Nilesh J. Samani149779113545
Peter M. Rothwell13477967382
John F. Thompson132142095894
James A. Russell124102487929
Paul Bebbington11958346341
John P. Neoptolemos11264852928
Richard C. Trembath10736841128
Andrew J. Wardlaw9231133721
Melanie J. Davies8981436939
Philip Quirke8937834071
Kenneth J. O'Byrne8762939193
David R. Jones8770740501
Keith R. Abrams8635530980
Martin J. S. Dyer8537324909
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20234
202219
2021168
2020120
2019110
2018121