27 research outputs found
Pravastatin for early-onset pre-eclampsia:a randomised, blinded, placebo-controlled trial
Objective: Women with pre-eclampsia have elevated circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1). Statins can reduce sFlt-1 from cultured cells and improve pregnancy outcome in animals with a pre-eclampsia-like syndrome. We investigated the effect of pravastatin on plasma sFlt-1 levels during pre-eclampsia. Design: Blinded (clinician and participant), proof of principle, placebo-controlled trial. Setting: Fifteen UK maternity units. Population: We used a minimisation algorithm to assign 62 women with early-onset pre-eclampsia (24 +0–31 +6 weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth. Primary outcome: Difference in mean plasma sFlt-1 levels over the first 3 days following randomisation. Results: The difference in the mean maternal plasma sFlt-1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days 1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50–1.40; P = 0.6). The median time from randomisation to childbirth was 9 days [interquartile range (IQR) 5–14 days] for the pravastatin group and 7 days (IQR 4–11 days) for the placebo group. There were three perinatal deaths in the placebo-treated group and no deaths or serious adverse events attributable to pravastatin. Conclusions: We found no evidence that pravastatin lowered maternal plasma sFlt-1 levels once early-onset pre-eclampsia had developed. Pravastatin appears to have no adverse perinatal effects. Tweetable abstract: Pravastatin does not improve maternal plasma sFlt-1 or placental growth factor levels following a diagnosis of early preterm pre-eclampsia #clinicaltrial finds
Statistical analysis plan for the Stroke Oxygen Study (SO2S): a multi-center randomized controlled trial to assess whether routine oxygen supplementation in the first 72 hours after a stroke improves long-term outcome
Genomic investigations of unexplained acute hepatitis in children
Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children
Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials.
Outcome of reduced intensity allografts in patients aged over 45 years with Acute Myeloid Leukaemia: initial results of the MRC AML15 trial
Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials
This analysis, of 2483 patients with acute myeloid leukaemia (AML) aged
60+ years entered into two UK trials, was performed to determine the
baseline parameters related to survival and to develop a risk index. The
Medical Research Council (MRC) AML11 trial (n = 1071) was used to
develop the index; this was validated using data from the Leukaemia Research
fund (LRF) AML14 trial on 1137 intensively (AML14I) and 275 nonintensively
(AML14NI) treated patients. In AML11, cytogenetic group, age,
white blood count, performance status and type of AML (de novo, secondary)
were all highly significantly related to prognosis in multivariate analysis. The
regression coefficients were used to define good, standard and poor risk
groups, with 1-year survival of 53%, 43% and 16% respectively (P < 0Æ0001).
The risk index showed very good discrimination in both AML14I and
AML14NI (both P < 0Æ0001), thereby providing validation, although survival
in all groups was very poor in AML14NI. The risk factors for survival in older
AML patients were similar to those in younger ones and discrimination of
patient groups with relatively good to very poor prognosis was possible.
These risk groups apply to both intensively and non-intensively treated
patients. Randomized trials of intensive versus non-intensive therapy are
needed to determine which types of patient should be given which type of
treatment
Hyperfractionated Accelerated Radiotherapy (HART) with maintenance chemotherapy for metastatic (M1-3) Medulloblastoma--a safety/feasibility study
Background and purpose: To evaluate feasibility and toxicity of Hyperfractionated Accelerated Radiotherapy (HART) 1.24 Gy b.i.d. followed by chemotherapy for M1-3 Medulloblastoma (MB). The aim of HART was to use hyperfractionation to improve therapeutic ratio combined with acceleration to minimise tumour cell repopulation during radiotherapy (RT). Materials and methods: Between February 2002 and May 2008, 34 eligible patients (22 male, 12 female) aged 3-15 years (median 7) with metastatic MB (M1-9; M2-3, M3-22) received HART with a craniospinal radiotherapy (CSRT) dose of 39.68 Gy followed by 22.32 Gy boost to the whole posterior fossa and 9.92 Gy metastatic boosts. The 8th and subsequent patients received vincristine (VCR) 1.5 mg/m(2) weekly x 8 doses over 8 weeks starting during the 1st week of RT. Maintenance chemotherapy comprised 8 six-weekly cycles of VCR 1.5 mg/m(2) weekly x 3, CCNU 75 mg/m(2) and cisplatin 70 mg/m(2). Results: Median duration of HART was 34 days (range 31-38). Grade 3-4 toxicities included mucositis (8), nausea (10), anaemia (5), thromboeytopaenia (2), leucopaenia (24). With 4.5-year median follow-up, 3-year EFS and OS were 59% and 71%, respectively. Of 10 relapses, 1 was outside the central nervous system (CNS), 1 posterior fossa alone and 8 leptomeningeal with 3 also associated with posterior fossa. Conclusion: HART with or without VCR was well tolerated and may have a place in the multi-modality management of high-risk MB. (C) 2014 Elsevier Ireland Ltd. All rights reserved