22 research outputs found
Heats of formation of perchloric acid, HClO, and perchloric anhydride, ClO. Probing the limits of W1 and W2 theory
The heats of formation of HClO and ClO have been determined to
chemical accuracy for the first time by means of W1 and W2 theory. These
molecules exhibit particularly severe degrees of inner polarization, and as
such obtaining a basis-set limit SCF component to the total atomization energy
becomes a challenge. (Adding high-exponent functions to a standard
basis set has an effect on the order of 100 kcal/mol for ClO.) Wilson's
aug-cc-pV(n+d)Z basis sets represent a dramatic improvement over the standard
aug-cc-pVnZ basis sets, while the aug-cc-pVnZ+2d1f sequence converges still
more rapidly. Jensen's polarization consistent basis sets still require
additional high-exponent functions: for smooth convergence we suggest the
\{aug-pc1+3d,aug-pc2+2d,aug-pc3+d,aug-pc4\} sequence. The role of the tight
functions is shown to be an improved description of the Cl (3d) Rydberg
orbital, enhancing its ability to receive back-bonding from the oxygen lone
pairs. In problematic cases like this (or indeed in general), a single
SCF/aug-cc-pV6Z+2d1f calculation may be preferable over empirically motivated
extrapolations. Our best estimate heats of formation are HClO(g)1 kcal/mol and ClO(g)2 kcal/mol, the largest source of
uncertainty being our inability to account for post-CCSD(T) correlation
effects. While G2 and G3 theory have fairly large errors, G3X theory reproduces
both values to within 2 kcal/mol.Comment: J. Mol. Struct. (THEOCHEM), in press (WATOC'05 special issue
6 YEARS' DENOSUMAB TREATMENT IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS: FIRST 3 YEARS OF THE FREEDOM EXTENSION
Bone and mineral researc
DENOSUMAB TREATMENT OF POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS FOR 6 YEARS: RESULTS FROM THE FIRST 3 YEARS OF THE FREEDOM EXTENSION
Bone and mineral researc
Six years of denosumab treatment in postmenopausal women with osteoporosis: results from the first three years of the freedom extension
Background/Purpose: Denosumab (DMAb) is an approved therapy for the treatment of postmenopausal women with osteoporosis at increased risk for fracture. A favorable risk/benefit profile was demonstrated in the pivotal, 3-year FREEDOM trial (Cummings et al NEJM 2009). The open-label, active-treatment FREEDOM Extension study is investigating the efficacy and safety of DMAb for up to 10 years. The Extension trial enrolled women who had received DMAb or placebo in FREEDOM and provides an opportunity to evaluate the long-term efficacy and safety of continuous DMAb treatment (long-term group), and to replicate the DMAb findings observed in FREEDOM (cross-over group). Here, we report the results from the first 3 years of the Extension, representing up to 6 continuous years of DMAb exposure.Methods: During the Extension, each woman is scheduled to receive 60 mg DMAb every 6 months and supplemental calcium and vitamin D daily. For the analyses reported here, women from the FREEDOM DMAb group received 3 more years of DMAb for a total of 6 years of exposure (long-term group) and women from the FREEDOM placebo group received 3 years of DMAb exposure (cross-over group).Results: Of the 5928 women eligible for the Extension, 4550 (77%) enrolled (N_2343 long-term; N_2207 cross-over). In the long-term group, further significant mean increases in bone mineral density (BMD) occurred 4044 for cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip (Figure). During the first 3 years of DMAb treatment during the Extension, the cross-over group had significant mean gains in BMD at the lumbar spine (9.4%) and total hip (4.8%), similar to those observed in the long-term DMAb group during the first 3 years of FREEDOM (lumbar spine, 10.1%; total hip, 5.7%). Serum CTX was rapidly and similarly reduced after the 1st (cross-over) or 7th (long-term) DMAb dose with the characteristic attenuation observed at the end of the dosing period. In the cross-over group, yearly incidences of new vertebral and nonvertebral fractures were lower than in the FREEDOM placebo group. Fracture incidence remained low in the long-term group. Incidences of adverse events (AEs) and serious AEs did not increase over time with DMAb treatment. There were 2 subjects with AEs adjudicated to ONJ in the cross-over group and 2 in the long-term group. Both cases in the cross-over group healed completely and without further complications; 1 of these subjects continues to receive DMAb. Both women in the long-term group continue to be followed. No atypical femur fractures have been observed to date. Figure. Percent changes in bone mineral density during FREEDOM and the Extension Conclusion: DMAb treatment for 6 continuous years (long-term group) remained well tolerated, maintained reduced bone turnover, and continued to significantly increase BMD. Fracture incidence remained low. DMAb treatment for 3 years in the cross-over group reproduced the original observations in FREEDOM
TEN YEARS OF DENOSUMAB (DMAB) TREATMENT IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS: RESULTS FROM THE FREEDOM EXTENSION TRIAL
Bone and mineral researc
Ten years of Denosumab (DMAB) treatment in postmenopausal women with osteoporosis. Results from the FREEDOM Extension trial.
Bone and mineral researc
EFFECT OF EIGHT YEARS OF DENOSUMAB TREATMENT IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS: FIVE-YEAR RESULTS FROM THE FREEDOM EXTENSION
Bone and mineral researc