Prevalence and pharmacologic management of familial hypercholesterolemia in an unselected contemporary cohort of patients with stable coronary artery disease

INTRODUCTION: Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) associated with premature cardiovascular disease. METHODS: Using the data from the START (STable Coronary Artery Diseases RegisTry) study, a nationwide, prospective survey on patients with stable coronary artery disease (CAD), we described prevalence and lipid lowering strategies commonly employed in these patients. The study population was divided into "definite/probable FH," defined as a Dutch Lipid Clinic Network (DLCN) score ≥6, "possible FH" with DLCN 3-5, and "unlikely FH" in presence of a DLCN <3. RESULTS: Among the 4030 patients with the DLCN score available, 132 (3.3%) were classified as FH (2.3% with definite/probable and 1.0% with possible FH) and 3898 (96.7%) had unlikely FH. Patients with both definite/probable and possible FH were younger compared to patients not presenting FH. Mean on-treatment LDL-C levels were 107.8 ± 41.5, 84.4 ± 40.9, and 85.8 ± 32.3 (P < 0.0001) and a target of ≤70 mg/dL was reached in 10.9%, 30.0%, and 22.0% (P < 0.0001) of patents with definite/probable, possible FH, and unlikely FH, respectively. Statin therapy was prescribed in 85 (92.4%) patients with definite/probable FH, in 38 (95.0%) with possible FH, and in 3621 (92.9%) with unlikely FH (P = 0.86). The association of statin and ezetimibe, in absence of other lipid-lowering therapy, was more frequently used in patients with definite/probable FH compared to patients without FH (31.5% vs 17.5% vs 9.5%; P < 0.0001). CONCLUSIONS: In this large cohort of consecutive patients with stable CAD, FH was highly prevalent and generally undertreated with lipid lowering therapies

Effects of finish line design and fatigue cyclic loading on phase transformation of zirconia dental ceramics: A qualitative micro-raman spectroscopic analysis

Objectives: Stresses produced during the fabrication of copings and by chewing activity can induce a tetragonal-to-monoclinic (t-m) transformation of zirconia. As a consequence, in the m-phase, the material is not able to hinder possible cracks by the favorable mechanism known as "transformation toughening". This study aimed at evaluating if different marginal preparations of zirconia copings can cause a premature phase transformation immediately after manufacturing milling and after chewing simulation. Methods: Ninety copings using three commercial zirconia ceramics (Nobel Procera Zirconia, Nobel Biocare Management AG; Lava Classic, 3M ESPE; Lava Plus, 3M ESPE) were prepared with deep-chamfer, slight-chamfer, or feather-edge finish lines (n = 10). Specimens were tested in a chewing simulator (CS-4.4, SD Mechatronik) under cyclic occlusal loads simulating one year of clinical service. Raman spectra were acquired and analyzed for each specimen along the finish lines and at the top of each coping before and after chewing simulation, respectively. Results: Raman analysis did not show any t-m transformation both before and after chewing simulation, as the typical monoclinic bands at 181 cm -1 and 192 cm -1 were not detected in any of the tested specimens. Conclusions: After a one-year simulation of chewing activity, irrespective of preparation geometry, zirconia copings did not show any sign of t-m transformation, either in the load application areas or at the margins. Consequently, manufacturing milling even in thin thickness did not cause any structural modification of zirconia ceramics "as received by manufacturers" both before and after chewing simulation

A new integrated approach to cardiac mechanics: reference values for normal left ventricle

The association between left ventricular (LV) myocardial deformation and hemodynamic forces is still mostly unexplored. The normative values and the effects of demographic and technical factors on hemodynamic forces are not known. The authors studied the association between LV myocardial deformation and hemodynamic forces in a large cohort of healthy volunteers. One-hundred seventy-six consecutive subjects (age range, 16\u201382; 51% women), with no cardiovascular risk factors or any relevant diseases, were enrolled. All subjects underwent an echo-Doppler examination. Both 2D global myocardial and endocardial longitudinal strain (GLS), circumferential strain (GCS), and the hemodynamic forces were measured with new software that enabled to calculate all these values and parameters from the three apical views. Higher LV mass index and larger LV volumes were found in males compared to females (85 \ub1 17 vs 74 \ub1 15\ua0g/m2 and 127 \ub1 28 vs 85 \ub1 18\ua0ml, p < 0.0001 respectively) while no differences of the mean values of endocardial and myocardial GLS and of myocardial GCS were found (p = ns) and higher endocardial GCS in women ( 12\ua030.6 \ub1 4.2 vs 12\ua031.8 \ub1 3.7; p = 0.05). LV longitudinal force, LV systolic longitudinal force and LV impulse were higher in men (16.2 \ub1 5.3 vs 13.2 \ub1 3.6; 25.1 \ub1 7.9 vs 19.4 \ub1 5.6 and 20.4 \ub1 7 vs 16.6 \ub1 5.2, p < 0.0001, respectively). A weak but statistically significant decline with age (p < 0.0001) was also found for these force parameters. This new integrated approach could differentiate normality from pathology by providing average deformation values and hemodynamic forces parameters, differentiated by age and gender

Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET.

BACKGROUND: It is unclear whether beta-blocker therapy should be reduced or withdrawn in patients who develop acute decompensated heart failure (HF). We studied the relationship between changes in beta-blocker dose and outcome in patients surviving a HF hospitalisation in COMET. METHODS: Patients hospitalised for HF were subdivided on the basis of the beta-blocker dose administered at the visit following hospitalisation, compared to that administered before. RESULTS: In COMET, 752/3029 patients (25%, 361 carvedilol and 391 metoprolol) had a non-fatal HF hospitalisation while on study treatment. Of these, 61 patients (8%) had beta-blocker treatment withdrawn, 162 (22%) had a dose reduction and 529 (70%) were maintained on the same dose. One-and two-year cumulative mortality rates were 28.7% and 44.6% for patients withdrawn from study medication, 37.4% and 51.4% for those with a reduced dosage (n.s.) and 19.1% and 32.5% for those maintained on the same dose (HR,1.59; 95%CI, 1.28-1.98; p<0.001, compared to the others). The result remained significant in a multivariable model: (HR, 1.30; 95%CI, 1.02-1.66; p=0.0318). No interaction with the beneficial effects of carvedilol, compared to metoprolol, on outcome was observed (p=0.8436). CONCLUSIONS: HF hospitalisations are associated with a high subsequent mortality. The risk of death is higher in patients who discontinue beta-blocker therapy or have their dose reduced. The increase in mortality is only partially explained by the worse prognostic profile of these patients

The physics, dosimetry and microdosimetry of boron neutron capture therapy

A validated experimental and numerical procedure is described detailing macroscopic and microscopic dose calculations forming the basis of a protocol for the pre-clinical biological characterisation of the University of Birmingham’s BNCT facility. Fundamental reference dosimetric measurements have been carried out at the University of Birmingham’s accelerator based NCT facility and the Massachusetts Institute of Technology (MIT) research reactor to characterise macroscopic and microscopic doses and derive correction factors for the irradiation of V79 cells incubated in boric acid and irradiated as monolayers. On and off-axis thermal neutron, fast neutron and photon doses have been measured and calculated with standard macroscopic dosimetry techniques (foils and ion chambers) from which normalised MCNPX calculations are used to derive perturbation factors and off-axis corrections for cell flask irradiations. Microdosimetric correction factors are calculated for the boron dose component using Monte Carlo methods to simulate lithium ion and alpha particle tracks in semi-stochastic geometries representative of cell monolayer irradiations, incubated in a medium with 50ppm boric acid. Further simulations of recoil protons from nitrogen capture reactions allow for the calculation of correction factors for the non-uniform distribution of the nitrogen dose at the cellular level.EThOS - Electronic Theses Online ServiceGBUnited Kingdo