Institute of Child Life and Health

Bristol, United Kingdom

Institute of Child Life and Health

Bristol, United Kingdom

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Reguerre Y.,University of Angers | Martelli H.,University Paris - Sud | Rey A.,CNRS Gustave Roussy Institute | Rogers T.,Institute of Child Life and Health | And 6 more authors.
European Journal of Cancer | Year: 2012

Background: Localised pelvic rhabdomyosarcomas (pRMS) are rare tumours with a poorer prognosis than the majority of RMS. This study analysed patient outcome according to the type of local therapy delivered and the effect of disease-related factors on prognosis. Patients and methods: 97 children with localised pRMS were enrolled in the SIOP-MMT84, 89 and 95 studies. After primary surgery or biopsy, all children received ifosfamide/actinomycin/vincristine- based chemotherapy. Radiotherapy and surgery were planned in patients failing to achieve complete remission. Results: Median age at diagnosis was 52 months [5 months-18 years]. IRS staging was I for five patients, II for 15 and III for 77. Patients had embryonal RMS (N = 41), alveolar RMS (N = 29), botryoid RMS (N = 3), or not otherwise specified RMS (N = 24). Outcome: 87 patients achieved local control (90%), 37 relapsed (43%), mainly locally (84%). With a median follow-up of more than 10 years [4-22 years], 5-year OS was 66% (95% CI: 56-75%) and EFS was 52% (95% CI: 42-61%). Among the 18 IRS-I/II patients treated without radiotherapy, 15 survived. Seven out of the 20 IRS-III patients treated without local therapy died. In multivariate analysis, IRS staging, age greater than 10 years and lymph node involvement had a negative impact on OS. Perineal/perianal locations had a trend towards a worse prognosis. Conclusion: pRMS still have a relatively poor prognosis. Radiotherapy or brachytherapy is necessary for all IRS-III patients including those with radiological complete remission after neoadjuvant chemotherapy with or without surgery. Radiotherapy may be withheld in IRS-I patients and children under 3 years with IRS-II pRMS. © 2012 Elsevier B.V. All rights reserved.


Chisholm J.C.,Royal Marsden Hospital | Chisholm J.C.,Institute of Child Life and Health | Chisholm J.C.,Institute Gustave Roussy | Chisholm J.C.,Hospital Of Pediatria Jp Garrahan | And 59 more authors.
Journal of Clinical Oncology | Year: 2011

Purpose: Previous studies suggest poor outcome in children with relapsed rhabdomyosarcoma (RMS). A better understanding is needed of which patients can be salvaged after first relapse Patients and Methods: The analysis included children with nonmetastatic RMS and embryonal sarcoma enrolled onto the International Society of Paediatric Oncology (SIOP) Malignant Mesenchymal Tumor (MMT) 84, 89, and 95 studies who relapsed after achieving complete local control with primary therapy. All patients included in the analysis had follow-up for ≥ 3.0 years after the last event. The clinical features, initial treatment characteristics, and features of the relapse were correlated with surviva in univariate and multivariate analyses. Results: In all, 474 eligible patients were identified for the study. At ≥ 3.0 years from the last event, 176 (37%) were alive ("cured"). In a full-model multivariate analysis, the factors identified at first relapse that most strongly associated with poor outcome were metastatic relapse (odds ratio [OR], 4.19; 95% CI, 2.0 to 8.5), prior radiotherapy treatment (OR, 3.64; 95% CI, 2.1 to 6.4), initial tumor size > 5 cm (OR, 2.53; 95% CI, 1.5 to 4.1), and time of relapse < 18 months from diagnosis (OR, 2.20; 95% CI, 1.3 to 3.6). Unfavorable primary disease site, noda nvolvement at diagnosis, alveolar histology, and previous three-or six-drug chemotherapy were also independently associated with poor outcome. To estimate chance of cure for ndividual patients, a nomogram was developed, which allowed for weighting of these significant factors Conclusion: Some children with relapsed RMS remain curable. It is now possible to estimate the chance of salvage for individual children to direct therapy appropriately toward cure, use of experimenta therapies, and/or palliation. © 2011 by American Society of Clinical Oncology.


Siassakos D.,Southmead Hospital | Siassakos D.,University of Bristol | Bristowe K.,University of the West of England | Hambly H.,Speech Kingdom | And 6 more authors.
Simulation in Healthcare | Year: 2011

Introduction: Patient satisfaction is an important healthcare outcome and communication with clinical staff is an important determinant. Simulation could identify problems and inform corrective action to improve patient experience. Methods: One hundred eight randomly selected maternity professionals in 18 teams were videoed managing a patient-actor with a simulated emergency. The trained patient-actor assessed the quality of staff-patient interaction. Clinicians scored teams for their teamwork skills and behaviors. Results: There was significant variation in staff-patient interaction, with some teams not having exchanged a single word and others striving to interact with the patientactor in the heat of the emergency. There was significant correlation between patientactor perceptions of communication, respect, and safety and individual and team behaviors: number, duration, and content of communication episodes, as well as generic teamwork skills and teamwork behaviors. The patient-actor perception of safety was better when the content of the communication episodes with them included certain items of information, but most teams failed to communicate these to the patient-actor. Conclusion: Some aspects of staff-patient interaction and teamwork during management of a simulated emergency varied significantly and were often inadequate in this study, indicating a need for better training of individuals and teams. © 2011 Society for Simulation in Healthcare.


Marcovecchio M.L.,University of Cambridge | Tossavainen P.H.,University of Cambridge | Acerini C.L.,University of Cambridge | Barrett T.G.,University of Birmingham | And 6 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - Familial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was associated with ABP and albumin excretion in young offspring with type 1 diabetes. RESEARCH DESIGN AND METHODS - Twenty-four-hour ABP monitoring was performed in 509 young offspring (mean ± SD age 15.8 ± 2.3 years) with type 1 diabetes, 311 fathers, and 444 mothers. Systolic (SBP) and diastolic blood pressure (DBP) measurements during 24 h, daytime, and nighttime were calculated. Three early morning urinary albumin-tocreatinine ratios (ACRs), A1C, and anthropometric parameters were available for the offspring. RESULTS - All paternal ABP parameters, except for nighttime SBP, were independently related to the offspring's ABP (24-h SBP β = 0.18, 24-h DBP β = 0.22, daytime SBP β = 0.25, daytime DBP β = 0.23, and nighttime DBP β = 0.18; all P < 0.01). Maternal 24-h DBP (β = 0.19, P = 0.004), daytime DBP (β = 0.09, P = 0.04), and nighttime SBP (β = 0.24 P = 0.001) were related to the corresponding ABP parameter in the offspring. Significant associations were found between the offspring's logACR and maternal ABP. The association with 24-h DBP (β = 0.16, P = 0.02), daytime DBP (β = 0.16 P = 0.02), and nighttime DBP (β = 0.15 P =0.03) persisted even after adjustment for the offspring's ABP. Mothers of offspring with microalbuminuria had higher ABP than mothers of offspring without microalbuminuria (all P < 0.05). CONCLUSIONS - In this cohort, parental ABP significantly influenced offspring blood pressure, therefore confirming familial influences on this trait. In addition, maternal ABP, particularly DBP, was closely related to ACR in the offspring, suggesting a dominant effect of maternal genes or an effect of the intrauterine environment on microalbuminuria risk. © 2010 by the American Diabetes Association.


Siassakos D.,Southmead Hospital | Draycott T.J.,Southmead Hospital | Crofts J.F.,Southmead Hospital | Hunt L.P.,Institute of Child Life and Health | And 2 more authors.
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2010

Objective To assess whether team performance in simulated eclampsia is related to the knowledge, skills and attitudes of individual team members. Design Cross-sectional analysis of data from the Simulation and Fire Drill Evaluation randomised controlled trial. Setting Six secondary and tertiary maternity units in south-west England. Participants One hundred and fourteen maternity professionals in 19 teams of six members; one senior and one junior obstetrician; two senior and two junior midwives. Methods We validated a team performance ranking scheme with respect to magnesium administration (Magnesium Administration Rank, MAR) by expert consensus (face validity) and correlation with clinical measures (construct validity). We tested for correlation between MAR and measures of knowledge, skills and attitudes. Main outcome measures Correlation between team performance (MAR) and scores in validated multiple-choice questionnaires (MCQs) (knowledge), a measure of individual manual skill to manage an obstetric emergency (skill) and scores in a widely used teamworksafety attitude questionnaire (attitude). Results There was no relationship between team performance and cumulative individual MCQs, skill or teamworksafety attitude scores. Conclusions The knowledge, manual skills and attitudes of the individuals comprising each team, measured by established methods, did not correlate in this study with the team's clinical efficiency in the management of simulated eclampsia. The inference is that unidentified characteristic(s) play a crucial part in the efficiency of teams managing emergencies. Any emphasis of training programmes to promote individual knowledge, skills and attitudes alone may have to be re-examined. This highlights a need to understand what makes a team efficient in dealing with clinical emergencies. © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.


Siassakos D.,Southmead Hospital | Fox R.,Taunton and Somerset Hospital | Hunt L.,Institute of Child Life and Health | Farey J.,Southmead Hospital | And 3 more authors.
American Journal of Medical Quality | Year: 2011

The objective of this study was to identify any residual challenges in a unit with a track record of good clinical performance. A cross-sectional survey of frontline caregiver attitudes was conducted using a validated psychometric instrument. A total of 69% (91 of 132) of eligible participants completed questionnaires. The results indicated positive safety culture, teamwork climate, and job satisfaction. Perceptions of high workload and insufficient staffing levels were the most prominent negative observations but not to the detriment of job satisfaction or perception of work conditions. Male staff had consistently better safety attitudes in multivariate analyses. The authors identified 24-hour consultant (attending) presence and better support by management as prerequisites for further improvement. Teamwork and safety attitudes are positive in a unit with established interprofessional team training. Establishing better support by senior clinical and management leaders was identified as a necessary intervention to improve attitudes and safety. © 2011 by the American College of Medical Quality.


Phillips R.J.,University of Bristol | Al-Zamil H.,University of Bristol | Hunt L.P.,Institute of Child Life and Health | Fortier M.A.,Laval University | And 2 more authors.
Molecular Human Reproduction | Year: 2011

Prostaglandins (PGs) are important factors in the physiology of human parturition and the control of uterine contractility. We have characterized the expression of 15 genes from all stages of the PG pathway in human pregnant and non-pregnant (NP) myometrium and in other uterine tissues at delivery, and the results show patterns indicative of different capacities for PG synthesis and catabolism in each tissue. In placenta, the PG synthase expression profile favours production of PGD 2, PGE 2 and PGF 2, with high levels of PG transporters and catabolic PG dehydrogenase suggesting rapid PG turnover. Choriodecidua is primed for PGE 2, PGF 2 and PGD 2 production and high PG turnover, whereas amnion expresses genes for PGE 2 synthesis with low levels of PG transporters and dehydrogenase. In umbilical cord, PGI 2 synthase is highly expressed. In pregnant myometrium, PGI 2, PGD 2 and PGF 2 synthases are highly expressed, whereas PG dehydrogenase is underexpressed. Myometrium from women with spontaneous or induced labour had higher expression of the PGH 2 synthase PTGS2 than tissue from women not-in-labour. Myometrium from NP women had lower levels of PG synthases and higher levels of PG dehydrogenase than pregnant myometrium. Discriminant function analysis showed that expression of selected genes in myometrium could distinguish groups of women with different modes of labour from each other and from NP women. In cultured myometrial cells, there was a dose-dependent stimulatory effect of interleukin 1β and tumour necrosis factor α on PTGS2, PTGES and AKR1B1 (PGF synthase) expression. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

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