To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between ...hormonotherapy and pelvic nodes irradiation.
Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: "low risk" (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus "high risk" (T3 or Gleason score >6 or prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression.
With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy.
Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.
Objectives This study assessed pharmacodynamic (PD) response to the reduced prasugrel maintenance dose of 5 mg in very elderly (VE) patients (≥75 years of age). Background In the TRITON–TIMI 38 ...(TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel–Thrombolysis In Myocardial Infarction 38) study prasugrel 10 mg reduced ischemic events versus clopidogrel 75 mg, but increased bleeding in VE patients. Methods We examined PD and active metabolite pharmacokinetics (PKs) with prasugrel 5 and 10 mg and clopidogrel 75 mg in a 3-period (12 days each) blinded, crossover study in VE (n = 73; mean: 79 ± 3 years of age) or (n = 82) nonelderly (NE) (≥45 to <65 years of age; mean: 56 ± 5 years of age) stable coronary artery disease (CAD) patients receiving background aspirin. Assays included light transmission aggregometry (LTA), VerifyNow P2Y12 (VN-P2Y12), and vasodilator-associated stimulated phosphoprotein (VASP). The primary comparison was noninferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5 mg in VE versus the 75th percentile for prasugrel 10 mg in NE, using a pre-specified 1-sided 97.5% confidence interval for the difference <15%. Results Prasugrel 5 mg in VE met the primary PD noninferiority criterion versus prasugrel 10 mg in NE. For prasugrel 5 mg, MPA was significantly lower (57 ± 14%) than clopidogrel (63 ± 14%; p < 0.001) in VE but higher than prasugrel 10 mg in NE (46 ± 12%; p < 0.001). PD response by LTA, VN-P2Y12, and VASP during all treatments appeared similar between age cohorts. Prasugrel 5 mg resulted in fewer VE poor responders than clopidogrel. Rates of mild bleeding were higher with prasugrel 10 mg but similar for prasugrel 5 mg versus clopidogrel 75 mg. Conclusions In aspirin-treated stable CAD patients, prasugrel 5 mg in VE attenuated platelet inhibition while meeting pre-specified noninferiority criterion versus prasugrel 10 mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75 mg in VE. (Comparison of Prasugrel and Clopidogrel in Very Elderly and Non-Elderly Patients With Stable Coronary Artery Disease GENERATIONS; NCT01107912 )
Objectives The aim of this study was to confirm prior modeling data suggesting that prasugrel 5 mg in low-body-weight (LBW) patients would be noninferior to prasugrel 10 mg in higher-body-weight ...(HBW) patients as assessed by maximal platelet aggregation (MPA). Background Prasugrel 10 mg reduced ischemic events compared with clopidogrel 75 mg but increased bleeding, particularly in LBW patients. Methods In this blinded, 3-period, crossover study in stable patients with coronary artery disease (CAD) taking aspirin, prasugrel 5 and 10 mg and clopidogrel 75 mg were administered to LBW (56.4 ± 3.7 kg; n = 34) and HBW patients (84.7 ± 14.9 kg; n = 38). Assays included light transmission aggregometry (LTA), VerifyNow P2Y12 (VN), and vasodilator-associated stimulated phosphoprotein (VASP) level measured predose and after each 12-day treatment. Results Median MPA by LTA for prasugrel 5 mg in LBW patients was noninferior to the 75th percentile for prasugrel 10 mg in HBW patients (primary endpoint) and mean MPA was similar, but active metabolite exposure was lowered by 38%. Within LBW patients, prasugrel 5 mg lowered MPA more than clopidogrel (least squares mean difference 95% confidence interval: −3.7% −6.72%, −0.69%) and resulted in lower rates of high on-treatment platelet reactivity (HPR). Within HBW patients, prasugrel 10 mg lowered MPA more than clopidogrel (−16.9% −22.3%, −11.5%). Similar results were observed by VN and VASP. Prasugrel 10 mg in LBW patients was associated with more mild to moderate bleeding (mainly bruising) compared with prasugrel 5 mg and clopidogrel. Conclusions In aspirin-treated patients with CAD, prasugrel 5 mg in LBW patients reduced platelet reactivity to a similar extent as prasugrel 10 mg in HBW patients and resulted in greater platelet inhibition, lower HPR, and similar bleeding rates compared with clopidogrel. (Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease FEATHER; NCT01107925 )
Optimal transcatheter aortic valve (TAVI) results require accurate valve positioning, including anatomically correct orientation and secure fixation within the aortic annulus, thereby potentially ...decreasing paravalvular regurgitation. The new Engager (Medtronic 3F Therapeutics, Santa Ana, CA) transapical valve system captures the native leaflets for sealing and allows for tactile feedback during valve placement. We report initial safety and performance outcomes of the Engager system through 6 months in patients with severe aortic valve stenosis at high risk for surgical aortic valve replacement.
An interim analysis was performed on the first 61 enrolled September 2011 through May 2012. Inclusion criteria comprised severe aortic stenosis, New York Heart Association functional class of II or greater, logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 20% or greater, or contraindication to surgical aortic valve replacement. The primary endpoint was all-cause mortality at 30 days. Patients were evaluated 24 to 48 hours post-procedure, at hospital discharge, 30 days and 6 months. Follow-up is planned annually through five years.
Baseline characteristics for the 61 patients were mean age 81.9 ± 4.4 years, 62.3% female, 88.5% New York Heart Association class III/IV, 52.5% coronary artery disease, and 54.2% extracardiac arteriopathy. For all of the attempted implantations (n = 60), the Engager prosthesis was positioned in the correct anatomic position without conversions to surgery, second valve implantation, device malposition, aortic annular rupture, or coronary obstruction. All-cause mortality was 9.9% at 30 days and 16.9% at 6 months. The baseline mean aortic valve gradient was 43.7 ± 16.7 mm Hg and 11.5 ± 5.0 mm Hg at 30 days, and showed similar reduction at 6 months (13.9 ± 6.2 mm Hg). There was no paravalvular regurgitation greater than mild through 6 months.
Early postoperative results support implantation success and valve safety. Analysis for 6 month outcomes shows stable hemodynamic performance and clinical outcome. (Transapical Implantation of the Medtronic Engager Transcatheter Aortic Valve Implantation System-the Engager European Pivotal Trial; NCT01348438).
We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor C1-INH deficiency) in 2004.
To ensure that this ...consensus remains current.
In collaboration with the Canadian Network of Rare Blood Disorder Organizations, we held the second Canadian Consensus discussion with our international colleagues in Toronto, Ontario, on February 3, 2006, and reviewed its content at the Fifth C1 Inhibitor Deficiency Workshop in Budapest on June 2, 2007. Papers were presented by international investigators, and this consensus algorithm approach resulted.
This consensus algorithm outlines the approach recommended for the diagnosis, therapy, and management of HAE, which was agreed on by the authors of this report. This document is only a consensus algorithm approach and continues to require validation. As such, participants agreed to make this a living 2007 algorithm, a work in progress, and to review its content at future international HAE meetings.
There is a paucity of double-blind, placebo-controlled trials on the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Controlled trials currently under way will provide further insight into the management of HAE. As with our Canadian 2003 Consensus, this 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of HAE was formed through the meeting and agreement of patient care professionals along with patient group representatives and individual patients.
Abstract On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress ...and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis ( http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm ). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program, and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. Here we summarize the outcomes from the extensive premeeting deliberations and final workshop recommendations, including (1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex, (2) the key gaps, needs, and challenges that hinder progress in tuberous sclerosis complex research, and (3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five to ten year time frame.
Results A Florida (FL)-born infant from a midwife-attended home birth was referred for a specialist immunology consultation at 9 months of age after recurrent infections, failure to thrive and PJP ...pneumonitis.
Background The purpose of this study was to examine the effect of smoking on the incidence of complications after primary anatomic total shoulder arthroplasty (TSA) and reverse shoulder arthroplasty ...(RSA). Methods All patients who underwent primary TSA or RSA at our institution between 2002 and 2011 and had a minimum 2-year follow-up were included. Smoking status was assessed at the time of surgery. Current smokers, former smokers, and nonsmokers were compared for periprosthetic infection, fractures (intraoperative and postoperative), and loosening after surgery. Results The cohort included 1834 shoulders in 1614 patients (814 in smokers and 1020 in nonsmokers). Complications occurred in 73 patients (75 shoulders; 44 in smokers and 31 in nonsmokers). There were 20 periprosthetic infections (16 in smokers and 4 in nonsmokers), 27 periprosthetic fractures (14 in smokers and 13 in nonsmokers), and 28 loosenings (14 in smokers and 14 in nonsmokers). Smokers had lower periprosthetic infection-free survival rates (95.3%-99.4% at 10 years; P = .001) and overall complication-free survival rates (78.4%-90.2%; P = .012) than nonsmokers. Multivariable analyses showed that both current and former smokers had significantly higher risk of periprosthetic infection in comparison with nonsmokers (hazard ratio HR, 7.27 and 4.56, respectively). In addition, current smokers showed a higher risk of postoperative fractures than both former smokers (HR, 3.63) and nonsmokers (HR, 6.99). Conclusions This study demonstrates that smoking is a significant risk factor of complications after TSA and RSA. These findings emphasize the need for preoperative collaborative interventions, including smoking cessation programs.
An obituary for Galen S. Wagner, the editor-in-chief of the Journal of Electrocardiology who died on Jul 13, 2016, is presented. Being active as the director of the Cardiac Care Unit of the Duke ...University Medical Center from 1968 to 1981, Wagner was instrumental in the development of the world renowned Duke Cardiovascular Databank. He also helped establish the International Research Interdisciplinary School that offers outcome-research training programs in countries throughout the world that has been ongoing for the past eleven years.
PDF
