Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease : A Fabry Outcome Survey analysis

Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m 2 had a mean (standard error of the mean [SEM]) annualized change in eGFR of − 2.86 (0.53) mL/min/1.73 m 2 /y compared with − 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m 2.7 /y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into account that they are based on retrospective comparisons with previously published data

Treatment adherence with the easypod™ growth hormone electronic auto-injector and patient acceptance: survey results from 824 children and their parents

<p>Abstract</p> <p>Background</p> <p>Accurately monitoring adherence to treatment with recombinant human growth hormone (r-hGH) enables appropriate intervention in cases of poor adherence. The electronic r-hGH auto-injector, easypod™, automatically records the patient's adherence to treatment. This study evaluated adherence to treatment of children who started using the auto-injector and assessed opinions about the device.</p> <p>Methods</p> <p>A multicentre, multinational, observational 3-month survey in which children received r-hGH as part of their normal care. Physicians reviewed the recorded dose history and children (with or without parental assistance) completed a questionnaire-based survey. Children missing ≤2 injections per month (92% of injections given) were considered adherent to treatment. Adherence was compared between GH treatment-naïve and treatment-experienced children.</p> <p>Results</p> <p>Of 834 recruited participants, 824 were evaluated. The median (range) age was 11 (1-18) years. From the recorded dose history, 87.5% of children were adherent to treatment over the 3-month period. Recorded adherence was higher in treatment-naïve (89.7%, n = 445/496) than in treatment-experienced children (81.7%, n = 152/186) [Fisher's exact test FI(X) = 7.577; <it>p </it>= 0.0062]. According to self-reported data, 90.2% (607/673) of children were adherent over 3 months; 51.5% (421/817) missed ≥1 injection over this period (mainly due to forgetfulness). Concordance between reported and recorded adherence was 84.3%, with a trend towards self-reported adherence being higher than recorded adherence. Most children liked the auto-injector: over 80% gave the top two responses from five options for ease of use (720/779), speed (684/805) and comfort (716/804). Although 38.5% (300/780) of children reported pain on injection, over half of children (210/363) considered the pain to be less or much less than expected. Given the choice, 91.8% (732/797) of children/parents would continue using the device.</p> <p>Conclusions</p> <p>easypod™ provides an accurate method of monitoring adherence to treatment with r-hGH. In children who received treatment with r-hGH using easypod™, short-term adherence is good, and significantly higher in treatment-naïve children compared with experienced children. Children/parents rate the device highly. The high level of acceptability of the device is reflected by a desire to continue using it by over 90% of the children in the survey.</p

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Ionisation de molécules chirales en champ fort

This work concerns the ionization of chiral molecules by strong fields, and par­ticularly the electron dynamics involved in this process at the attosecond timescale. We have developed a spectral approach to solve the time-dependent Schrëidinger equation, well suited to describe the laser-molecule interaction for fixed nuclear geometry in an effectively monoelectronic mean-field framework. We present our methodology, as well as its implementations for various chiral ionizing fields, in close collaboration with experimental works. We show that strong-field ionization, occurring in terms of tunneling through the potential barrier lowered by the laser field, is sensitive to the target chirality. The instantaneous chirality of the interaction is encoded in both the amplitude and the phase of the ejected wavepackets. The subsequent scattering of the electron onto the chiral potential eventually further modify the amplitude and the phase of the wavepackets. Therefore, our results unambiguously show that strong-field ionization dyna­mics are influenced by the target potential, whatever is the target beyond chiral species.Le travail présenté dans ce manuscrit concerne l'ionisation de molécules chirales en champ fort, et plus particulièrement la dynamique électronique impliquée dans ce processus à l'échelle attoseconde. Nous avons développé une approche spectrale de résolution de l'équation de Schrëidinger dépendante du temps, apte à décrire l'interaction laser-molécule à géométrie nu­cléaire figée dans un cadre de champ moyen, effectivement monoélectronique. Nous présentons la méthodologie que nous avons mise en place, et son application à divers types de champs ionisants chiraux dans le cadre d'un effort conjoint théorie/expérience. On montre alors que l'ionisation en champ fort, se produisant par effet tunnel au travers de la barrière de potentiel abaissée par le champ, est sensible à la chiralité de la cible. Les paquets d'onde éjectés du tunnel ont une amplitude et une phase dans lesquelles est encodée la chiralité instantanée de l'interaction. La diffusion de l'électron dans le potentiel chiral, intervenant après éjection du tunnel, est à-même de modifier l'amplitude et la phase des paquets d'onde. Nos résultats montrent alors sans ambi­guïté que bien que principalement guidée par le champ, l'ionisation en champ fort est largement influencée par le potentiel ionique, quelle que soit la cible considérée

Strong field ionization of chiral molecules

Le travail présenté dans ce manuscrit concerne l'ionisation de molécules chirales en champ fort, et plus particulièrement la dynamique électronique impliquée dans ce processus à l'échelle attoseconde. Nous avons développé une approche spectrale de résolution de l'équation de Schrëidinger dépendante du temps, apte à décrire l'interaction laser-molécule à géométrie nu­cléaire figée dans un cadre de champ moyen, effectivement monoélectronique. Nous présentons la méthodologie que nous avons mise en place, et son application à divers types de champs ionisants chiraux dans le cadre d'un effort conjoint théorie/expérience. On montre alors que l'ionisation en champ fort, se produisant par effet tunnel au travers de la barrière de potentiel abaissée par le champ, est sensible à la chiralité de la cible. Les paquets d'onde éjectés du tunnel ont une amplitude et une phase dans lesquelles est encodée la chiralité instantanée de l'interaction. La diffusion de l'électron dans le potentiel chiral, intervenant après éjection du tunnel, est à-même de modifier l'amplitude et la phase des paquets d'onde. Nos résultats montrent alors sans ambi­guïté que bien que principalement guidée par le champ, l'ionisation en champ fort est largement influencée par le potentiel ionique, quelle que soit la cible considérée.This work concerns the ionization of chiral molecules by strong fields, and par­ticularly the electron dynamics involved in this process at the attosecond timescale. We have developed a spectral approach to solve the time-dependent Schrëidinger equation, well suited to describe the laser-molecule interaction for fixed nuclear geometry in an effectively monoelectronic mean-field framework. We present our methodology, as well as its implementations for various chiral ionizing fields, in close collaboration with experimental works. We show that strong-field ionization, occurring in terms of tunneling through the potential barrier lowered by the laser field, is sensitive to the target chirality. The instantaneous chirality of the interaction is encoded in both the amplitude and the phase of the ejected wavepackets. The subsequent scattering of the electron onto the chiral potential eventually further modify the amplitude and the phase of the wavepackets. Therefore, our results unambiguously show that strong-field ionization dyna­mics are influenced by the target potential, whatever is the target beyond chiral species

Strong field ionization of chiral molecules

Le travail présenté dans ce manuscrit concerne l'ionisation de molécules chirales en champ fort, et plus particulièrement la dynamique électronique impliquée dans ce processus à l'échelle attoseconde. Nous avons développé une approche spectrale de résolution de l'équation de Schrëidinger dépendante du temps, apte à décrire l'interaction laser-molécule à géométrie nu­cléaire figée dans un cadre de champ moyen, effectivement monoélectronique. Nous présentons la méthodologie que nous avons mise en place, et son application à divers types de champs ionisants chiraux dans le cadre d'un effort conjoint théorie/expérience. On montre alors que l'ionisation en champ fort, se produisant par effet tunnel au travers de la barrière de potentiel abaissée par le champ, est sensible à la chiralité de la cible. Les paquets d'onde éjectés du tunnel ont une amplitude et une phase dans lesquelles est encodée la chiralité instantanée de l'interaction. La diffusion de l'électron dans le potentiel chiral, intervenant après éjection du tunnel, est à-même de modifier l'amplitude et la phase des paquets d'onde. Nos résultats montrent alors sans ambi­guïté que bien que principalement guidée par le champ, l'ionisation en champ fort est largement influencée par le potentiel ionique, quelle que soit la cible considérée.This work concerns the ionization of chiral molecules by strong fields, and par­ticularly the electron dynamics involved in this process at the attosecond timescale. We have developed a spectral approach to solve the time-dependent Schrëidinger equation, well suited to describe the laser-molecule interaction for fixed nuclear geometry in an effectively monoelectronic mean-field framework. We present our methodology, as well as its implementations for various chiral ionizing fields, in close collaboration with experimental works. We show that strong-field ionization, occurring in terms of tunneling through the potential barrier lowered by the laser field, is sensitive to the target chirality. The instantaneous chirality of the interaction is encoded in both the amplitude and the phase of the ejected wavepackets. The subsequent scattering of the electron onto the chiral potential eventually further modify the amplitude and the phase of the wavepackets. Therefore, our results unambiguously show that strong-field ionization dyna­mics are influenced by the target potential, whatever is the target beyond chiral species

Ionisation de molécules chirales en champ fort

This work concerns the ionization of chiral molecules by strong fields, and par­ticularly the electron dynamics involved in this process at the attosecond timescale. We have developed a spectral approach to solve the time-dependent Schrëidinger equation, well suited to describe the laser-molecule interaction for fixed nuclear geometry in an effectively monoelectronic mean-field framework. We present our methodology, as well as its implementations for various chiral ionizing fields, in close collaboration with experimental works. We show that strong-field ionization, occurring in terms of tunneling through the potential barrier lowered by the laser field, is sensitive to the target chirality. The instantaneous chirality of the interaction is encoded in both the amplitude and the phase of the ejected wavepackets. The subsequent scattering of the electron onto the chiral potential eventually further modify the amplitude and the phase of the wavepackets. Therefore, our results unambiguously show that strong-field ionization dyna­mics are influenced by the target potential, whatever is the target beyond chiral species.Le travail présenté dans ce manuscrit concerne l'ionisation de molécules chirales en champ fort, et plus particulièrement la dynamique électronique impliquée dans ce processus à l'échelle attoseconde. Nous avons développé une approche spectrale de résolution de l'équation de Schrëidinger dépendante du temps, apte à décrire l'interaction laser-molécule à géométrie nu­cléaire figée dans un cadre de champ moyen, effectivement monoélectronique. Nous présentons la méthodologie que nous avons mise en place, et son application à divers types de champs ionisants chiraux dans le cadre d'un effort conjoint théorie/expérience. On montre alors que l'ionisation en champ fort, se produisant par effet tunnel au travers de la barrière de potentiel abaissée par le champ, est sensible à la chiralité de la cible. Les paquets d'onde éjectés du tunnel ont une amplitude et une phase dans lesquelles est encodée la chiralité instantanée de l'interaction. La diffusion de l'électron dans le potentiel chiral, intervenant après éjection du tunnel, est à-même de modifier l'amplitude et la phase des paquets d'onde. Nos résultats montrent alors sans ambi­guïté que bien que principalement guidée par le champ, l'ionisation en champ fort est largement influencée par le potentiel ionique, quelle que soit la cible considérée

Tubulin and Microtubule Study under Hydrostatic Pressure

International audienc

Silencing of the Tandem Pore Domain Halothane-inhibited K + Channel 2 (THIK2) Relies on Combined Intracellular Retention and Low Intrinsic Activity at the Plasma Membrane

International audienc