Predictive modeling identifies total bleeds at 12-weeks postswitch to N8-GP prophylaxis as a predictor of treatment response

Predicting annualized bleeding rate (ABR) during factor VIII (FVIII) prophylaxis for severe hemophilia A (SHA) is important for long-term outcomes. This study used supervised machine learning-based predictive modeling to identify predictors of long-term ABR during prophylaxis with an extended half-life FVIII. Methods  Data were from 166 SHA patients who received N8-GP prophylaxis (50 IU/kg every 4 days) in the pathfinder 2 study. Predictive models were developed to identify variables associated with an ABR of ≤1 versus >1 during the trial's main phase (median follow-up of 469 days). Model performance was assessed using area under the receiver operator characteristic curve (AUROC). Pre-N8-GP prophylaxis models learned from data collected at baseline; post-N8-GP prophylaxis models learned from data collected up to 12-weeks postswitch to N8-GP, and predicted ABR at the end of the outcome period (final year of treatment in the main phase). Results  The predictive model using baseline variables had moderate performance (AUROC = 0.64) for predicting observed ABR. The most performant model used data collected at 12-weeks postswitch (AUROC = 0.79) with cumulative bleed count up to 12 weeks as the most informative variable, followed by baseline von Willebrand factor and mean FVIII at 30 minutes postdose. Univariate cumulative bleed count at 12 weeks performed equally well to the 12-weeks postswitch model (AUROC = 0.75). Pharmacokinetic measures were indicative, but not essential, to predict ABR. Conclusion  Cumulative bleed count up to 12-weeks postswitch was as informative as the 12-week post-switch predictive model for predicting long-term ABR, supporting alterations in prophylaxis based on treatment responseThis analysis and medical writing support for the article was funded by Novo Nordisk A/S (Bagsværd, Denmark

Ablative therapy for people with localised prostate cancer : a systematic review and economic evaluation

The research reported in this issue of the journal was funded by the HTA programme as project number 10/136/01. The contractual start date was in April 2012. The draft report began editorial review in October 2013 and was accepted for publication in April 2014. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements We thank l the people recruited from the local UCAN for providing valuable consumer insight and advice through their participation as members of the project focus group: - Mark Emberton (Professor of Interventional Oncology), Damian Greene (consultant urologist), Axel Heidenreich (Professor and Director of Department of Urology), Christoph von Klot (specialist in brachytherapy), Roger Kockelbergh (BAUS chairman and Clinical Director of Urology) and Axel Merserburger (Deputy Clinical Director of Urology and Urologic Oncology) for providing their clinical expertise as members of the project advisory group - Edgar Paez (consultant urologist) and Gill Lawrence (Head of Radiotherapy Physics) for providing a list of staff time by grade and specialty involved in EBRT - Debbie Bennett (Radiotherapy Service Manager) for providing estimates for the expected number of uses for EBRT - Ian Pedley (clinical director/clinical oncologist) and Gill Lawrence for providing a list of all resource inputs relevant to brachytherapy - Steve Locks (Consultant Clinical Scientist in Radiotherapy) for providing a list of reusable equipment and consumables used during brachytherapy, along with their unit costs - Sue Asterling (urology research nurse) and Mark Kelly (Acting Divisional General Manager – Theatres) for providing a list of all resource inputs relevant to cryotherapy - Lara Kemp for providing secretarial support. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewedPublisher PD

Métabolisme d'anti-cancéreux par des enzymes extrahépatiques

La chimiothérapie des cancers a été l'une des avancées médicales majeures dans les dernières décennies. Toutefois, les médicaments utilisés pour cette thérapie ont un index thérapeutique étroit, et souvent les réponses produites sont juste palliatives ainsi que imprévisibles. En revanche, les thérapies ciblées qui ont été introduites ces dernières années sont directement dirigées contre des molécules spécifiques du cancer et ont ainsi réduit l'apparition d'effets indésirables. Tel est le cas des inhibiteurs des protéines kinases (PKIs), ces dernières étant une cible particulièrement importantes car elles jouent un rôle important dans la modulation de la signalisation des facteurs de croissance. Cependant, des résistances apparaissent et de multiples causes ont été identifiées. L'une d'elles est la rapide dégradation de ces PKIs par des enzymes extra-hépatiques, particulièrement des enzymes surexprimées dans les cellules tumorales, qui sont les CYP1A1, CYP1B1 et le CYP2J2

Approche diagnostique et classification des traumatismes du rachis cervical inférieur (série multicentrique prospective de 284 blessés)

NICE-BU Médecine Odontologie (060882102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Cinétique et variation du PSA > 4ng/ml après une première série de biopsies négatives (prédiction du risque de cancer significatif)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF