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O'Connor D.,Birmingham Childrens Hospital | Sibson K.,Great Ormond Street Hospital for Children | Caswell M.,Alder Hey Childrens Hospital | Connor P.,Childrens Hospital for Wales | And 7 more authors.
British Journal of Haematology | Year: 2011

Summary: Clofarabine is a second-generation purine nucleoside analogue, which has shown promising activity in relapsed and refractory paediatric acute lymphoblastic leukaemia (ALL). This report summarizes the early United Kingdom experience of clofarabine for the treatment of paediatric ALL in 23 patients, outside of the context of a clinical trial. Our results demonstrated that clofarabine-based chemotherapy regimes were effective and well-tolerated in this heavily pre-treated group, with an overall response rate of 67% when used in combination regimes. Responses were seen in both B and T cell disease and in patients with adverse cytogenetics. © 2011 Blackwell Publishing Ltd. Source

Wolf A.,Bristol Royal Childrens Hospital | McKay A.,University of Liverpool | Spowart C.,University of Liverpool | Granville H.,University of Liverpool | And 4 more authors.
Health Technology Assessment | Year: 2014

Background Children in paediatric intensive care units (PICUs) require analgesia and sedation but both undersedation and oversedation can be harmful.Objective Evaluation of intravenous (i.v.) clonidine as an alternative to i.v. midazolam.Design Multicentre, double-blind, randomised equivalence trial.Setting Ten UK PICUs.Participants Children (30 days to 15 years inclusive) weighing ≤ 50 kg, expected to require ventilation on PICU for > 12 hours.Interventions Clonidine (3 µg/kg loading then 0–3 µg/kg/hour) versus midazolam (200 µg/kg loading then 0–200 µg/kg/hour). Maintenance infusion rates adjusted according to behavioural assessment (COMFORT score). Both groups also received morphine.Main outcome measures Primary end point Adequate sedation defined by COMFORT score of 17–26 for ≥ 80% of the time with a ± 0.15 margin of equivalence. Secondary end points  Percentage of time spent adequately sedated, increase in sedation/analgesia, recovery after sedation, side effects and safety data.Results The study planned to recruit 1000 children. In total, 129 children were randomised, of whom 120 (93%) contributed data for the primary outcome. The proportion of children who were adequately sedated for ≥ 80% of the time was 21 of 61 (34.4%) – clonidine, and 18 of 59 (30.5%) – midazolam. The difference in proportions for clonidine–midazolam was 0.04 [95% confidence interval (CI) –0.13 to 0.21], and, with the 95% CI including values outside the range of equivalence (–0.15 to 0.15), equivalence was not demonstrated; however, the study was underpowered. Non-inferiority of clonidine to midazolam was established, with the only values outside the equivalence range favouring clonidine. Times to reach maximum sedation and analgesia were comparable hazard ratios: 0.99 (95% CI 0.53 to 1.82) and 1.18 (95% CI 0.49 to 2.86), respectively. Percentage time spent adequately sedated was similar [medians clonidine 73.8% vs. midazolam 72.8%: difference in medians 0.66 (95% CI –5.25 to 7.24)]. Treatment failure was 12 of 64 (18.8%) on clonidine and 7 of 61 (11.5%) on midazolam [risk ratio (RR) 1.63, 95% CI 0.69 to 3.88]. Proportions with withdrawal symptoms [28/60 (46.7%) vs. 30/58 (52.6%)] were similar (RR 0.89, 95% CI 0.62 to 1.28), but a greater proportion required clinical intervention in those receiving midazolam [11/60 (18.3%) vs. 16/58 (27.6%) (RR 0.66, 95% CI 0.34 to 1.31)]. Post treatment, one child on clonidine experienced mild rebound hypertension, not requiring intervention. A higher incidence of inotropic support during the first 12 hours was required for those on clonidine [clonidine 5/45 (11.1%) vs. midazolam 3/52 (5.8%)] (RR 1.93 95% CI 0.49 to 7.61).Conclusions Clonidine is an alternative to midazolam. Our trial-based economic evaluation suggests that clonidine is likely to be a cost-effective sedative agent in the PICU in comparison with midazolam (probability of cost-effectiveness exceeds 50%). Rebound hypertension did not appear to be a significant problem with clonidine but, owing to its effects on heart rate, specific cardiovascular attention needs to be taken during the loading and early infusion phase. Neither drug in combination with morphine provided ideal sedation, suggesting that in unparalysed patients a third background agent is necessary. The disappointing recruitment rates reflect a reluctance of parents to provide consent when established on a sedation regimen, and reluctance of clinicians to allow sedation to be studied in unstable critically ill children. Future studies will require less exacting protocols allowing enhanced recruitment. © 2014, HTA/HTA TAR. All right reserved. Source

Shalaby M.S.,Bristol Royal Childrens Hospital | Shalaby M.S.,Ain Shams University
Archives of Disease in Childhood | Year: 2015

During the last decade, there has been a significant increase in the number of magnetic toys available for children. Two or more magnets separate from each other along the gastrointestinal course can attract each other across bowel walls, resulting in pressure necrosis, bowel perforations and fistulas formation. This has led to an increasing number of case reports describing serious complications from ingesting more than one magnet. We report the ingestion of a large number of magnets from one toy (>60 pieces). Our patient presented with generalised peritonitis and shock. During emergency laparotomy, she was found to have gross abdominal contamination with multiple bowel perforations and fistulae. This report emphasises the danger of such toys and how important that parents, physicians and manufacturers are aware of such fatal hazards that can arise from 'unsupervised' ingestion of these 'nice-looking' toys. Source

Stoica S.,Bristol Royal Childrens Hospital | Goldsmith K.,Medical Research Council | Demiris N.,Medical Research Council | Punjabi P.,Hammersmith Hospital | And 3 more authors.
Heart | Year: 2010

Objective: To characterise contemporary results of aortic valve replacement in relation to type of prosthesis and subsequent competing hazards. Methods: 5470 procedures in 5433 consecutive patients with aortic valve replacement ± coronary artery bypass grafting (CABG) were studied. Microsimulation of survival and valve-related outcomes was performed based on meta-analysis and patient data inputs, with separate models for age, gender and CABG. Survival was validated against the UK Heart Valve Registry. Results: Patient survival at 1, 5 and 10 years was 90%, 78% and 57%, respectively. The crossover points at which bioprostheses and mechanical prostheses conferred similar life expectancy (LE) was 59 years for men and women (no significant difference between prosthesis types between the ages of 56 and 69 for men, and 58 an 63 for women). The improvement in event-free LE for mechanical valves was greater at younger ages with a crossover point of 66 years for men and 67 years for women. Long-term survival was independently influenced by age, male gender and concomitant CABG, but not by type of prosthesis. In bioprostheses the most common long-term occurrence was structural deterioration. For men aged 55, 65 and 75 at initial operation it had a lifetime incidence of 50%, 30% and 13%, respectively. The simulation output showed excellent agreement with registry data. Conclusion: Bioprostheses can be implanted selectively in patients as young as 56 without significant adverse effects on life expectancy, although event-free life expectancy remains significantly lower with bioprostheses up to age of implant of 63. Source

Shalaby M.S.,Bristol Royal Childrens Hospital | Shalaby M.S.,Ain Shams University | El Hay S.A.,Ain Shams University
Annals of Pediatric Surgery | Year: 2015

Hyperhidrosis (HH) is excessive sweating that usually interferes with the patient's social life. In more than 80% of the cases, the symptoms start in childhood. Early detection and management can significantly improve the patient's quality of life; however, HH remains widely underdiagnosed and undertreated, particularly among children. Many patients do not realize that they have a treatable condition and reports have shown that only 38% of the patients had discussed their condition with a healthcare professional. The aim of this article was to improve awareness on the significant sequel of HH in children and highlight its effects on their quality of life and various available treatment options. © 2015 Annals of Pediatric Surgery. Source

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