The European medicines agency review of abiraterone for the treatment of metastatic castration-resistant prostate cancer in adult men after docetaxel chemotherapy and in chemotherapy-naïve disease: Summary of the scientific assessment of the committee for medicinal products for human use
Gravanis I.,European Medicines Agency |
Sancho Lopez A.,Hospital Universitario Puerta Of Hierro |
Hemmings R.J.,Medicines and Healthcare Products Regulatory Agency |
Camarero Jimenez J.,Agencia Espanola de Medicamentos y Productos Sanitarios |
And 7 more authors.
Oncologist | Year: 2013
On September 5, 2011, abiraterone was approved in the European Union in combination with prednisone or prednisolone for the treatment of metastatic castration-resistant prostate cancer (CRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen. On December 18, 2012, the therapeutic indication was extended to include the use of abiraterone in combination with prednisone or prednisolone for the treatment of metastatic CRPC in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. Abiraterone is a selective, irreversible inhibitor of cytochrome P450 17α, an enzyme that is key in the production of androgens. Inhibition of androgen biosynthesis deprives prostate cancer cells from important signals for growth, even in cases of resistance to castration. At the time of European Union approval and in a phase III trial in CRPC patients who had failed at least one docetaxel-based chemotherapy regimen, median overall survival for patients treated with abiraterone was 14.8 months versus 10.9 months for those receiving placebo (hazard ratio, 0.65; 95% confidence interval 0.54 - 0.77; p<.0001). In a subsequent phase III trial in a similar but chemotherapy-naïve patient population, median radiographic progression-free survival was 16.5 months for patients in the abiraterone treatment arm versus 8.3 months for patients in the placebo arm (hazard ratio, 0.53; 95% confidence interval, 0.45-0.62; p<.0001). Abiraterone was most commonly associated with adverse reactions resulting from increased or excessive mineralocorticoid activity. These were generally manageable with basic medical interventions. The most common side effects (affecting more than 10% of patients) were urinary tract infection, hypokalemia, hypertension, and peripheral edema. © AlphaMed Press 2013.
Regelsberger J.,Universatsklinikum Hamburg Eppendorf |
Eicker S.,Universatsklinikum Hamburg Eppendorf |
Siasios I.,University Hospital of Larissa |
Hanggi D.,Heinrich Heine University Dusseldorf |
And 11 more authors.
Neurosurgical Review | Year: 2015
Supplemental education is desirable for neurosurgical training, and the use of human cadaver specimen and virtual reality models is routine. An in vivo porcine training model for cranial neurosurgery was introduced in 2005, and our recent experience with this unique model is outlined here. For the first time, porcine anatomy is illustrated with particular respect to neurosurgical procedures. The pros and cons of this model are described. The aim of the course was to set up a laboratory scenery imitating an almost realistic operating room in which anatomy of the brain and neurosurgical techniques in a mentored environment free from time constraints could be trained. Learning objectives of the course were to learn about the microsurgical techniques in cranial neurosurgery and the management of complications. Participants were asked to evaluate the quality and utility of the programme via standardized questionnaires by a grading scale from A (best) to E (worst). In total, 154 residents have been trained on the porcine model to date. None of the participants regarded his own residency programme as structured. The bleeding and complication management (97 %), the realistic laboratory set-up (89 %) and the working environment (94 %) were favoured by the vast majority of trainees and confirmed our previous findings. After finishing the course, the participants graded that their skills in bone drilling, dissecting the brain and preserving cerebral vessels under microscopic magnification had improved to level A and B. In vivo hands-on courses, fully equipped with microsurgical instruments, offer an outstanding training opportunity in which bleeding management on a pulsating, vital brain represents a unique training approach. Our results have shown that education programmes still lack practical training facilities in which in vivo models may act as a complementary approach in surgical training. © 2014, Springer-Verlag Berlin Heidelberg.
Multicenter comparison of high concentration contrast agent iomeprol-400 with iso-osmolar iodixanol-320: Contrast enhancement and heart rate variation in coronary dual-source computed tomographic angiography
Becker C.R.,Ludwig Maximilians University of Munich |
Vanzulli A.,Hospital Niguarda Ca Granda |
Fink C.,University of Mannheim |
De Faveri D.,Hospital of Padua |
And 6 more authors.
Investigative Radiology | Year: 2011
Objectives: To compare a contrast agent with high iodine concentration with an iso-osmolar contrast agent for coronary dual-source computed tomography angiography (DS-CTA), and to assess whether the contrast agent characteristics may affect the diagnostic quality of coronary DS-CTA. Materials and Methods: Patients were randomized to receive either 80 mL of iodixanol-320 (Visipaque, GE Healthcare, Chalfont St. Giles, United Kingdom) or iomeprol-400 (Iomeron, Bracco Imaging SpA, Milan, Italy) at 5 mL/s. Mean, minimum, maximum heart rate, and its variation (max-min) were assessed during calcium scoring scan and coronary DS-CTA. Three off-site readers independently evaluated the image sets in terms of technical adequacy, reasons for inadequacy, vessel visualization, diagnostic confidence (based on a 5-point scale), and arterial contrast opacification in Hounsfield units (HUs). Results: Ninety-six patients were included in the final evaluation. No significant differences were observed for pre-and postdose heart rate values for iomeron-400 compared with iodixanol-320, and changes in heart rate variation were also not significantly different (-2.3 ± 11.7 vs.-2.5 ± 7.3 bpm, P > 0.1). Contrast measurements in all analyzed vessels were significantly higher for iomeprol-400 (mean, 391.5-441.4 HU) compared with iodixanol-320 (mean, 332.3-365.5 HU, all P ≤ 0.0038). There was no significant difference in qualitative visualization of coronary arteries (mean scores, 4.3-4.5 for iomeprol, 4.1-4.3 for iodixanol, P = 0.15-0.28), or in diagnostic confidence scores. HU were inversely correlated with the number of insufficiently opacified segments (all readers P ≤ 0.0006). Conclusions: The high-iodine concentration contrast medium iomeprol-400 demonstrated significant benefit for coronary arterial enhancement compared with the iso-osmolar contrast medium iodixanol-320 when administered at identical flow rates and volumes for coronary DS-CTA. In addition, higher enhancement levels were found to be associated with lower numbers of inadequately visualized segments. Finally, observed mean heart rate changes after intravenous contrast injection were generally small during the examination and comparable for both agents. Copyright © 2011 Lippincott Williams & Wilkins.
Biviano I.,University of Rome La Sapienza |
Badiali D.,University of Rome La Sapienza |
Candeloro L.,University of Rome La Sapienza |
Habib F.I.,University of Rome La Sapienza |
And 4 more authors.
World Journal of Gastroenterology | Year: 2011
AIM: To prospectively assess the efficacy and safety of stapled trans-anal rectal resection (STARR) compared to standard conservative treatment, and whether preoperative symptoms and findings at defecography and anorectal manometry can predict the outcome of STARR. METHODS: Thirty patients (Female, 28; age: 51 ± 9 years) with rectocele or rectal intussusception, a defecation disorder, and functional constipation were submitted for STARR. Thirty comparable patients (Female, 30; age 53 ± 13 years), who presented with symptoms of rectocele or rectal intussusception and were treated with macrogol, were assessed. Patients were interviewed with a standardized questionnaire at study enrollment and 38 ± 18 mo after the STARR procedure or during macrogol treatment. A responder was defined as an absence of the Rome III diagnostic criteria for functional constipation. Defecography and rectoanal manometry were performed before and after the STARR procedure in 16 and 12 patients, respectively. RESULTS: After STARR, 53% of patients were responders; during conservative treatment, 75% were responders. After STARR, 30% of the patients reported the use of laxatives, 17% had intermittent anal pain, 13% had anal leakage, 13% required digital facilitation, 6% experienced defecatory urgency, 6% experienced fecal incontinence, and 6% required re-intervention. During macrogol therapy, 23% of the patients complained of abdominal bloating and 13% of borborygmi, and 3% required digital facilitation.No preoperative symptom, defecographic, or manometric finding predicted the outcome of STARR. Post-operative defecography showed a statistically significant reduction (P < 0.05) of the rectal diameter and rectocele. The post-operative anorectal manometry showed that anal pressure and rectal sensitivity were not significantly modified, and that rectal compliance was reduced (P = 0.01). CONCLUSION: STARR is not better and is less safe than macrogol in the treatment of defecation disorders. It could be considered as an alternative therapy in patients unresponsive to macrogol. © 2011 Baishideng.
Evangelista A.,Hospital Universitario Vall dHebron |
Czerny M.,University of Zurich |
Nienaber C.,University of Rostock |
Schepens M.,A.Z. St. Jan Hospital |
And 4 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2014
An expert panel on the treatment of type B intramural haematoma (IMH) and penetrating atherosclerotic ulcer (PAU) consisting of cardiologists, cardiothoracic surgeons, vascular surgeons and interventional radiologists reviewed the literature to develop treatment algorithms using a consensus method. Data from 46 studies considered relevant were retrieved for a total of 1386 patients consisting of 925 with IMH, and 461 with PAU. The weighted mean 30-day mortality from IMH was 3.9%, 3-year aortic event-related mortality with medical treatment 5.4%, open surgery 23.2% and endovascular therapy 7.1%. In patients with PAU early and 3-year aortic event-mortality rates with open surgery were 15.9 and 25.0%, respectively, and with TEVAR were 7.2 and 10.4%, respectively. According to panel consensus statements, haemodynamic instability, persistent pain, signs of impending rupture and progressive periaortic haemorrhage in two successive imaging studies require immediate surgical or endovascular treatment. In the absence of these complications, medical treatment is warranted, with imaging control at 7 days, 3 and 6 months and annually thereafter. In the chronic phase, aortic diameter >55 mm or a yearly increase ≥5 mm should be considered indications for open surgery or thoracic endovascular treatment, with the latter being preferred. In complicated type B aortic PAU and IMH, endovascular repair is the best treatment option in the presence of suitable anatomy. © The Author 2014.