A prospective, randomized evaluation of a novel everolimus-eluting coronary stent: The PLATINUM (a prospective, randomized, multicenter trial to assess an everolimus-eluting coronary stent system [PROMUS element] for the treatment of up to two de novo coronary artery lesions) trial
Stone G.W.,Columbia University Medical Center |
Teirstein P.S.,Scripps Research Institute |
Meredith I.T.,Monash Medical Center |
Farah B.,Clinique Pasteur |
And 6 more authors.
Journal of the American College of Cardiology | Year: 2011
Objectives: We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI). Background: Randomized trials have demonstrated an excellent safety and efficacy profile for the CoCr-EES. The PtCr-EES uses the identical antiproliferative agent and polymer but with a novel platinum chromium scaffold designed for enhanced deliverability, vessel conformability, side-branch access, radiopacity, radial strength, and fracture resistance. Methods: A total of 1,530 patients undergoing PCI of 1 or 2 de novo native lesions were randomized at 132 worldwide sites to CoCr-EES (n = 762) or PtCr-EES (n = 768). The primary endpoint was the 12-month rate of target lesion failure (TLF), the composite of target vessel-related cardiac death, target vessel-related myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR) in the per-protocol population (patients who received <1 assigned study stent), powered for noninferiority. Results: The 12-month rate of TLF in the per-protocol population occurred in 2.9% versus 3.4% of patients assigned to CoCr-EES versus PtCr-EES, respectively (difference: 0.5%, 95% confidence interval: -1.3% to 2.3%, pnoninferiority = 0.001, psuperiority = 0.60). By intention-to-treat, there were no significant differences between CoCr-EES and PtCr-EES in the 12-month rates of TLF (3.2% vs. 3.5%, p = 0.72), cardiac death or MI (2.5% vs. 2.0%, p = 0.56), TLR (1.9% vs. 1.9%, p = 0.96), or Academic Research Consortium definite or probable stent thrombosis (0.4% vs. 0.4%, p = 1.00). Conclusions: In this large-scale, prospective, single-blind randomized trial, a novel PtCr-EES was noninferior to the predicate CoCr-EES for TLF, with nonsignificant differences in measures of safety and efficacy through 12-month follow-up after PCI. (A Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of up to Two De Novo Coronary Artery Lesions: NCT00823212) © 2011 American College of Cardiology Foundation.
Hermans M.P.,Cliniques Universitaires St Luc |
Elisaf M.,University of Ioannina |
Michel G.,Center Hospitalier Of Luxembourg |
Muls E.,UZ Gasthuisberg |
And 3 more authors.
Diabetes Care | Year: 2013
OBJECTIVE-To assess prospectively the effect of benchmarking on quality of primary care for patients with type 2 diabetes by using three major modifiable cardiovascular risk factors as critical quality indicators. RESEARCH DESIGN ANDMETHODSdPrimary care physicians treating patients with type 2 diabetes in six European countries were randomized to give standard care (control group) or standard care with feedback benchmarked against other centers in each country (benchmarking group). In both groups, laboratory tests were performed every 4 months. The primary end point was the percentage of patients achieving preset targets of the critical quality indicators HbA1c, LDL cholesterol, and systolic blood pressure (SBP) after 12 months of follow-up. RESULTS-Of 4,027 patients enrolled, 3,996 patients were evaluable and 3,487 completed 12 months of follow-up. Primary end point of HbA1c target was achieved in the benchmarking group by 58.9 vs. 62.1% in the control group (P = 0.398) after 12 months; 40.0 vs. 30.1% patients met the SBP target (P < 0.001); 54.3 vs. 49.7% met the LDL cholesterol target (P = 0.006). Percentages of patients meeting all three targets increased during the study in both groups, with a statistically significant increase observed in the benchmarking group. The percentage of patients achieving all three targets at month 12 was significantly larger in the benchmarking group than in the control group (12.5 vs. 8.1%; P < 0.001). CONCLUSIONS-In this prospective, randomized, controlled study, benchmarking was shown to be an effective tool for increasing achievement of critical quality indicators and potentially reducing patient cardiovascular residual risk profile. © 2013 by the American Diabetes Association.
Cockmartin L.,UZ Gasthuisberg |
Bosmans H.,UZ Gasthuisberg |
Marshall N.W.,UZ Gasthuisberg
Medical Physics | Year: 2013
Purpose: This work characterizes three candidate mammography phantoms with structured background in terms of power law analysis in the low frequency region of the power spectrum for 2D (planar) mammography and digital breast tomosynthesis (DBT). Methods: The study was performed using three phantoms (spheres in water, Voxmam, and BR3D CIRS phantoms) on two DBT systems from two different vendors (Siemens Inspiration and Hologic Selenia Dimensions). Power spectra (PS) were calculated for planar projection, DBT projection, and reconstructed images and curve fitted in the low frequency region from 0.2 to 0.7 mm-1 with a power law function characterized by an exponent β and magnitude κ. The influence of acquisition dose and tube voltage on the power law parameters was first explored. Then power law parameters were calculated from images acquired with the same anode/filter combination and tube voltage for the three test objects, and compared with each other. Finally, PS curves for automatic exposure controlled acquisitions (anode/filter combination and tube voltages selected by the systems based on the breast equivalent thickness of the test objects) were compared against PS analysis performed on patient data (for Siemens 80 and for Hologic 48 mammograms and DBT series). Dosimetric aspects of the three test objects were also examined. Results: The power law exponent (β) was found to be independent of acquisition dose for planar mammography but varied more for DBT projections of the sphere-phantom. Systematic increase of tube voltage did not affect β but decreased κ, both in planar and DBT projection phantom images. Power spectra of the BR3D phantom were closer to those of the patients than these of the Voxmam phantom; the Voxmam phantom gave high values of κ compared to the other phantoms and the patient series. The magnitude of the PS curves of the BR3D phantom was within the patient range but β was lower than the average patient value. Finally, PS magnitude for the sphere-phantom coincided with the patient curves for Siemens but was lower for the Hologic system. Close agreement of doses for all three phantoms with patient doses was found. Conclusions: Power law parameters of the phantoms were close to those of the patients but no single phantom matched in terms of both magnitude (κ) and texture (β) for the x-ray systems in this work. PS analysis of structured phantoms is feasible and this methodology can be used to suggest improvements in phantom design. © 2013 American Association of Physicists in Medicine.
Marshall N.W.,UZ Gasthuisberg |
Lemmens K.,UZ Gasthuisberg |
Bosmans H.,UZ Gasthuisberg
Medical Physics | Year: 2012
Purpose: Needle phosphor based computed radiography (CR) systems promise improved image quality compared to powder phosphor based CR units for x-ray screening mammography. This paper compares the imaging performance of needle CR cassettes, powder based CR cassettes and a well established amorphous selenium (a-Se) based flat panel based mammography system, using consistent beam qualities. Methods: Detector performance was assessed using modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE). Mammography system performance was assessed against levels from the European Guidelines, including threshold gold thickness (c-d), relative signal difference to noise (SdNR) and mean glandular dose, for automatic exposure control settings suggested by the manufacturers. The needle based Agfa HM5.0 CR detector was compared against the single sided readout Agfa MM3.0R and dual sided readout Fuji Profect CS powder CR plates using a 28 kV Mo/Rh spectrum, while a 28 kV W/Rh spectrum was used to compare the Agfa HM5.0 against the Siemens MAMMOMAT Inspiration a-Se based system. Results: MTF at 5 mm -1 was 0.16 and 0.24 for the needle CR detector in the fast and slow scan directions, respectively, indicating a slight improvement (∼20) over the two powder CR systems but remained 50 lower than the result at 5 mm -1 for the a-Se detector (∼0.55). Structured screen noise was lower for the needle phosphor compared to the powder plates. CR system gain, estimated from the measured absorption fraction and NNPS results, was 6.3 for the (single sided) needle phosphor and 5.1 and 7.2 for the single sided and dual sided powder phosphor systems. Peak DQE at ∼100 Gy was 0.47 for the needle system compared to peak DQE figures of 0.33 and 0.46 for the single sided readout powder plates and dual sided readout plates. The high frequency DQE (at 5 mm -1) was 0.19 for the needle CR plates, a factor of approximately 3 greater than for the powder CR plates. At 28 kV W/Rh, 2 mm Al, peak DQE for the needle CR system was 0.45 against a value of 0.50 for the a-Se detector. The needle CR detector reached the Acceptable limit for 0.1 mm details in the European Guidelines at a mean glandular dose (MGD) of approximately 1.31 mGy imaged at 28 kV Mo/Rh, compared to figures of 2.19 and 1.43 mGy for the single sided and dual sided readout powder CR systems. The a-Se detector could reach the limit at 0.65 mGy using a 28 kV W/Rh spectrum, while the needle CR system required 1.09 mGy for the same spectrum. Conclusions: Imaging performance for the needle CR phosphor technology, characterized using MTF and DQE and threshold gold thickness demonstrated a clear improvement compared to both single and dual sided reading powder phosphor based CR systems. © 2012 American Association of Physicists in Medicine.
Peeters K.,UZ Gasthuisberg |
Sahai A.,Guys Hospital |
De Ridder D.,UZ Gasthuisberg |
De Ridder D.,Catholic University of Leuven |
And 2 more authors.
BJU International | Year: 2014
Objective To report our long-term experience of sacral neuromodulation (SNM) for various lower urinary tract dysfunctions but with a focus on efficacy, safety, re-interventions and degree of success. Patients and Methods This is a single tertiary referral centre study that included 217 patients (86% female) who received an implantable pulse generator (IPG) (Interstim™, Medtronic, Minneapolis, USA) between 1996 and 2010. Success was considered if the initial ≥50% improvement in any of primary voiding diary variables persisted compared with baseline, but was further stratified. Results The mean duration of follow-up was 46.88 months. Success and cure rates were ≈70% and 20% for urgency incontinence, 68% and 33% for urgency frequency syndrome and 73% and 58% for idiopathic retention. In those patients with an unsuccessful therapy outcome, the mean time to failure was 24.6 months after implantation. There were 88 (41%) patients who had at least one device or treatment related surgical re-intervention. The re-intervention rate was 1.7 per patient with most of them (47%) occurring ≤2 years of follow-up. Conclusions SNM appears effective in the long-term with a success rate after definitive IPG implant of ≈70% and complete cure rates ranging between 20% and 58% depending on indication. Patients with idiopathic retention appear to do best. The re-intervention rate is high with most occurring ≤2 years of implantation. It is likely that with the newer techniques used, efficacy and re-intervention rates will improve. © 2013 The Authors. BJU International © 2013 BJU International.
Cuypers J.,UZ Gasthuisberg |
Mathieu C.,UZ Gasthuisberg |
Benhalima K.,UZ Gasthuisberg
Acta Clinica Belgica | Year: 2013
Treatment of type 2 diabetes (T2DM) continues to present challenges, with significant proportion of patients failing to achieve and maintain glycemic targets. Despite the availability of many oral antidiabetic agents, therapeutic efficacy is offset by side effects such as weight gain and hypoglycemia. Therefore, the search for novel therapeutic agents with an improved benefitrisk profile continues. Recent research has focused on the kidney as a potential therapeutic target, especially because maximal renal glucose reabsorption is increased in T2DM. Under normal physiological conditions, nearly all filtered glucose is reabsorbed in the proximal tubule of the nephron, principally via the sodium-glucose cotransporter 2 (SGLT2). SGLT2- inhibitors are a new class of oral antidiabetics, which reduce hyperglycemia by increasing urinary glucose excretion independently of insulin secretion or action. Clinical results are promising with significant lowering of HbA1c without increased risk of hypoglycemia, reduction of body weight and reduction of systolic blood pressure. Dapagliflozin is the first highly selective SGLT2-inhibitor approved by the European Medecine Agency. Canagliflozin and empagliflozin are undergoing phase III trials. Actual safety issues are an increased risk for genital- and urinary tract infections and a possible increased risk for bladder and breast cancer. This led to refusal of dapagliflozin by the Food and Drug Administration (FDA). A large randomized control trial is therefore warranted by the FDA. This review provides an overview of the current evidence available so far on the therapeutic potential of the SGLT2-inhibitors for the treatment of T2DM.
Van Remoortel H.,Catholic University of Leuven |
Hornikx M.,Catholic University of Leuven |
Demeyer H.,Catholic University of Leuven |
Langer D.,Catholic University of Leuven |
And 5 more authors.
Thorax | Year: 2013
Rationale Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce. This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD. Methods Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male). PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry. Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics. Results PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765 ±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05). Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA. Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD. Conclusions The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD. Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity.
Peeters C.,UZ Gasthuisberg
Urologia Internationalis | Year: 2014
Prostate cancer is the most common male malignancy. Radiation therapy and radical prostatectomy are the main curative treatment options for organ confined disease. Despite the good long-term oncologic outcomes, roughly 40% of patients undergoing surgery develop biochemical recurrence, manifested as a rising prostate-specific antigen (PSA). Those patients are at higher risk of developing a local or distant recurrence. The diagnosis of a nodal recurrence is challenging. This report is about a 66-year-old male, who had a radical prostatectomy in 2006. Postoperatively, the PSA was never undetectable. Radiotherapy was delivered in 2007, but the PSA rose again. Anti-androgen therapy was started, but he developed painful mastodynia. A (11C) choline PET-CT showed an enlarged suspicious lymph node at the left common iliac and a salvage pelvic lymphadenectomy was performed. Postoperatively, the PSA remained undetectable for the last 5 years. The use of lesion - targeted therapy for oligometastatic disease is a new concept in urology, aiming at reducing the tumor burden. Therefore, even though this surgical approach might not be associated with a durable response over time, the tumor load is decreased and further cancer progression might be delayed, allowing to postpone the delivery of hormone therapy. © 2014 S. Karger AG, Basel Copyright © 2014, S. Karger AG. All rights reserved.
Peene B.,Catholic University of Leuven |
Benhalima K.,UZ Gasthuisberg
Therapeutic Advances in Endocrinology and Metabolism | Year: 2014
Type 2 diabetes mellitus (T2DM) is increasing worldwide. Treatment of T2DM continues to present challenges, with a significant proportion of patients failing to achieve and maintain glycemic targets. Despite the availability of many oral antidiabetic agents, therapeutic efficacy is also offset by side effects such as weight gain and hypoglycemia. Therefore, the search for novel therapeutic agents with an improved benefit–risk profile continues. In the following review we focus on a novel class of oral antidiabetic drugs, the sodium glucose transporter protein 2 (SGLT2) inhibitors, which have unique characteristics. SGLT2 inhibitors focus on the kidney as a therapeutic target, where they inhibit the reabsorption of glucose in the proximal tubule, causing an increase in urinary glucose excretion. Doing this, they reduce plasma glucose independently of the β-cell function of the pancreas. SGLT2 inhibitors are effective at lowering hemoglobin A1c, but also induce weight loss and reduce blood pressure, with a low risk of hypoglycemia. In general, the SGLT2 inhibitors are well tolerated, with the most frequent adverse events being mild urinal and genital infections. Since their primary site of effect is the kidney, these drugs are less effective in patients with impaired kidney function but evidence is emerging that these drugs may also have a protective effect against diabetic nephropathy. This review focuses on the most extensively studied SGLT2 inhibitors dapagliflozin, canagliflozin and empagliflozin. Dapagliflozin and canagliflozin have already been approved for marketing by the US Food and Drug Administration. The European Medicines Agency has accepted all three drugs for marketing. © The Author(s), 2014.
Marshall N.W.,UZ Gasthuisberg |
Bosmans H.,UZ Gasthuisberg
Physics in Medicine and Biology | Year: 2012
The aim of this work was to propose system sharpness parameters for digital breast tomosynthesis (DBT) systems that include the influence of focus size and focus motion for use in quality assurance protocols. X-ray focus size was measured using a multiple pinhole test object, while detector presampling modulation transfer function (MTF) was measured from projection images of a 10cm×10cm, 1mm thick steel edge, for the Siemens Inspiration and Hologic Selenia Dimensions DBT systems. The height of the edge above the table was then varied from 1 to 78mm. The MTF expected from theory for the projection images was calculated from the measured detector MTF, focus size MTF and focus motion MTF and was compared against measured curves. Two methods were used to measure the in-plane MTF in the DBT volume: a tungsten wire of diameter 25m and an Al edge 0.2mm thick, both imaged with a 15mm thick poly(methyl methacrylate) (PMMA) plate. The in-depth point spread function (PSF) was measured using an angled tungsten wire. The full 3D MTF was estimated with a 0.5mm diameter aluminium bead held in a 45mm thick PMMA phantom, with the bead 15 and 65mm above the table. Inspiration DBT projection images are saved at native detector resolution (85m), while the Dimensions re-bins projections to 140m pixels (2×2 binning); both systems used 2×2 binning of projection data before reconstruction. The 50% point for the MTF (MTF 0.50) measured in the DBT projection images for the tube-travel direction fell as a function of height above the table from 3.60 to 0.90mm 1for the Inspiration system and from 2.50 to 1.20mm 1for the Dimensions unit. The maximum deviation of measured MTF 0.50from the calculated value was 13%. MTF 0.50measured in-plane (tube-travel direction) fell as a function of height above the table from 1.66 to 0.97mm 1for the Inspiration system and from 2.21 to 1.31mm 1for the Dimensions system. The full-width half-maximum for the in-depth PSF was 3.0 and 5.9mm for the Inspiration and Dimensions systems, respectively. There was no difference in the 3D MTF curves, sectioned in the tube-travel direction, for bead heights of 15 and 65mm above the table. A 25m tungsten wire held within a 15mm thick PMMA plate was found to be a suitable test object for measurement of in-plane MTF. Evaluation of MTF as a function of height above the table, both in the projection images and in the reconstructed planes, provides important information on the impact of focus size and focus motion on the DBT system's imaging performance. © 2012 Institute of Physics and Engineering in Medicine.