Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here 138 ITP patients (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range, IQR, 56-80 years). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166 months). The median number of therapies prior to fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%) and intravenous immunoglobulins (IVIG) (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month prior to treatment initiation. 79.0% of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 x 109 /L). Eighty-three patients (60.1%) received fostamatinib monotherapy achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21 days). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1-2, the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Jastrow correlated and quantum Monte Carlo calculations for the low-lying states of the carbon atom.

Different computational methods are employed to calculate excitation energies of the carbon atom. Explicitly correlated wave functions have been obtained in a Variational Monte Carlo calculation. Fixed node Diffusion Monte Carlo calculations for the lowest energy excited states of a given symmetry are reported. A systematic and quantitative analysis of the performance of the different schemes in the calculation of the excitation energy of up to 27 excited states of the carbon atom is carried out. The quality of the different methods have been studied in terms of the deviation with respect to the experimental excitation energies. A good agreement with the experimental values has been reached.

Quantum Monte Carlo ground state energies for the singly charged ions from Li through Ar.

Nonrelativistic frozen nucleus all-electron Quantum Monte Carlo ground state energies of positive and negative ions Li(+) to Ar(+) and Li(-) to Cl(-), respectively, are reported. Explicitly correlated wave functions with a single configuration model function times a Jastrow factor are employed for all of the systems studied. The accuracy obtained for the ions in the third period is similar to that reached for the ions in the second one. For those ions with a stronger multiconfiguration nature a restricted multiconfiguration expansion has been employed. The ground state energy here obtained for the charged species shows a similar quality to that reached for neutral atoms. Starting from those results, ionization potentials and electron affinities are calculated.

Near degeneracy effects on the low-lying spectrum of the iron atom.

The ground state and the LS terms coming from the ground-state configuration, [Ar]-3d(6)4s(2), of the iron atom are studied by carrying out an all electron Variational Monte Carlo calculation. Explicitly correlated trial functions including near degeneracy effects are used. The effect of electronic correlations and the importance of near degeneracy effects are systematically analyzed for the states here considered and compared with the experimental values. Correlations are important to reproduce, even qualitatively, the low-lying spectrum of this atom. A significant quantitative improvement when comparing with the experimental values is achieved when near degeneracy is considered along with dynamic correlations in the variational trial wave function. Finally, the effect of relativity on the results here reported is discussed.

Quantum Monte Carlo ground state energies for the atoms Li through Ar.

All-electron quantum Monte Carlo energies are reported for the ground state of the atoms Li to Ar. The present work is mainly focused on the atoms Na to Ar as well as in those that have a stronger multiconfiguration nature, i.e., Be, B, and C and Mg, Al, and Si. Explicitly correlated wave functions with a single configuration model function times a Jastrow factor are employed for all of the atoms studied. The accuracy obtained for the atoms Na to Ar is similar to that reached for the atoms Li to Ne. In addition, a restricted multiconfiguration expansion has been employed for the atoms Be, B, and C and Mg, Al, and Si obtaining accurate results. Near degeneracy and the effect of other configurations are systematically analyzed for these systems, at both variational and diffusion Monte Carlo levels.

Quantum Monte Carlo for 3d transition-metal atoms.

The domain Green's function Monte Carlo method has been used to calculate the ground-state energy of the atoms Sc through Zn. The fixed node approximation with single-configuration explicitly correlated wave functions is used. A comparison with variational Monte Carlo energies is carried out. The quality of the ground-state energies reported here is similar to that achieved for few-electron atoms using similar techniques.

Correlated wave functions for the ground and some excited states of the iron atom.

We study the states arising from the [Ar]4s(2)3d6 and [Ar]4s(1)3d7 configurations of iron atom with explicitly correlated wave functions. The variational wave function is the product of the Jastrow correlation factor times a model function obtained within the parametrized optimized effective potential framework. A systematic analysis of the dependence of both the effective potential and the correlation factor on the configuration and on the term is carried out. The ground state of both, the cation, Fe+, and anion, Fe-, are calculated with correlated wave functions and the ionization potential and the electron affinity are obtained.

One- and two-body densities of carbon isoelectronic series in their low-lying multiplet states from explicitly correlated wave functions.

The (3)P ground state and both the (1)D and (1)S excited states arising from the low-lying 1s(2)2s(2)2p(2) configuration of the carbon isoelectronic series are studied starting from explicitly correlated multiconfigurational wave functions. One- and two-body densities in position space have been calculated and different one- and two-body expectation values have been obtained. The effects of electronic correlations have been systematically studied. All the calculations have been done by means of variational Monte Carlo.

1s22p3 and 1s22s23l, l = s,p,d, excited states of boron isoelectronic series from explicitly correlated wave functions.

For some members of the boron isoelectronic series and starting from explicitly correlated wave functions, six low-lying excited states have been studied. Three of them arise from the 1s(2)2p(3) configuration, and the other three from the 1s(2)2s(2)3l, l = s,p,d, configurations. This work follows a previous one on both the 1s(2)2s(2)2p-(2)P ground state and the four excited states coming from the 1s(2)2s2p(2) configuration. Energies, one- and two-body densities in position space and some other two-body properties in position and momentum spaces have been obtained. A systematic analysis of the energetic ordering of the states as a function of the total orbital angular momentum and spin is performed in terms of the electron-nucleus and electron-electron potential energies and the role of the angular correlation is discussed. All calculations have been carried out by using the Monte Carlo algorithm.

Excited states of boron isoelectronic series from explicitly correlated wave functions.

The ground state and some low-lying excited states arising from the 1s2 2s2p2 configuration of the boron isoelectronic series are studied starting from explicitly correlated multideterminant wave functions. One- and two-body densities in position space have been calculated and different expectation values such as , , , , , and , where r, r12, and R stand for the electron-nucleus, interelectronic, and two electron center of mass coordinates, respectively, have been obtained. The energetic ordering of the excited states and the fulfillment of the Hund's rules is analyzed systematically along the isoelectronic series in terms of the electron-electron and electron-nucleus potential energies. The effects of electronic correlations have been systematically studied by comparing the correlated results with the corresponding noncorrelated ones. All the calculations have been done by using the variational Monte Carlo method.