Background: In clinical studies, treatment with subcutaneous interferon beta-1a (IFN beta-1a) has been shown to reduce relapse rates and slow the progression of physical disability in patients with relapsing forms of multiple sclerosis (MS). A formulation of subcutaneous IFN beta-1a has been developed that is free of fetal bovine serum and human serum albumin. Objective: To evaluate (a) the impact on quality of life (QoL) and treatment satisfaction of transitioning from the original formulation of subcutaneous IFN beta-1a to the serum-free formulation in patients with relapsing forms of MS; and (b) the impact of dose titration versus non-titration during the transition on tolerability and patterns of analgesic use. QoL was measured by the Multiple Sclerosis Treatment Concerns Questionnaire Global Side Effects (GSE) score.Methods: Patients who had received the original formulation of IFN beta-1a subcutaneously for >= 24 weeks were randomized to receive the serum-free formulation of IFN beta-1a 44 mu g subcutaneously three times weekly for 12 weeks, with or without a dose titration over a 4-week period. After week 12, patients continued to receive serum-free subcutaneous IFN beta-1a during a safety extension phase until they completed between 84 and 112 weeks of treatment. The primary endpoint was the percentage change from baseline to week 12 in GSE score in all patients.Results: A total of 232 patients were randomized (titrated n=113; non-titrated n=119). The mean percent change (improvement) from baseline to week 12 in the GSE score was 5.0% (p<0.001 for mean change in GSE score from baseline); this change was similar between titrated and nontitrated patients and met criteria for non-inferiority to the original formulation. Adverse event (AE) incidence and use of analgesics for the treatment of flu-like symptoms (FLS) were less common in the titrated group. Few patients (<2%) discontinued due to AEs during weeks 0 to 12.Conclusion: Patients with relapsing forms of MS who transitioned from original-formulation subcutaneous IFN beta-1a to serum-free subcutaneous IFN beta-1a had overall improved QoL scores at 12 weeks of treatment. Titration during the transition resulted in a lower requirement for analgesic treatment of FLS and fewer AEs. (C) 2012 Elsevier B.V. All rights reserved.

In patients with relapsing–remitting multiple sclerosis (RRMS), subcutaneous (sc) interferon (IFN)β-1a and IFNβ-1b have been shown to reduce relapse rates. A formulation of IFNβ-1a has been produced without fetal bovine serum and without human serum albumin as an excipient (not currently approved for use in the US). The objectives of this study were to evaluate tolerability, injection-site redness, subject-reported satisfaction with therapy, and clinical safety and efficacy of the serum-free formulation of IFNβ-1a versus IFNβ-1b in IFNβ-treatment-naïve patients with RRMS. The objectives of the extension phase were to evaluate long-term safety and tolerability of IFNβ-1a.

It is common knowledge that the semiconductor industry continues to shrink the features contained in integrated circuits to increase speed and density. Each time the critical dimension (CD) shrinks, new challenges arise to impede the progress to attain smaller feature sizes, and control over surface reflectivity becomes even more important. Single-layer bottom anti-reflective coatings (BARCs) have been used in photolithography processes for years to reduce substrate reflectance, thus reducing or eliminating CD swing, reflective notching, and standing waves. Continued use of this solution is highly advantageous because it is well-known and cost-effective. This paper will describe a cutting-edge BARC system that has tailorable optical constants designed specifically to greatly improve immersion lithography process latitude. This BARC system can be easily modified to make formulations that match many different substrates that are being used in new devices, including highly absorbing substrates (nitrides), reflective substrates (oxide), metal layers, and hardmasks. The optimum optical parameters for this BARC system can be easily achieved through simulations. This paper will exhibit the correlation between optical simulations and lithography results.

Purpose Mitoxantrone was approved for treatment of multiple sclerosis (MS) in October 2000. Monitoring and dosing guidelines in the product labeling accompanying this indication include blood counts, liver function, and pregnancy tests at each administration. Due to potential cardiotoxicity, left ventricular ejection fraction (LVEF) testing prior to initial infusion and all infusions at a cumulative dose >= 100 mg/m(2) was recommended until April 2005 when LVEF testing before all infusions was recommended in the approved labeling. We sought to estimate provider adherence to dosing and monitoring guidelines and the effect of changes in LVEF monitoring guidelines.Methods MS patients who received mitoxantrone between October 2000 and June 2006 were selected from the claims of a large US health insurer. Claims for infusions and for specified tests prior to an infusion determined adherence to guidelines, with medical records providing additional information for a subset.Results There were 1827 mitoxantrone infusions to 548 eligible patients; medical records were obtained for 261 patients (1096 infusions). Most mitoxantrone recipients were 30-59 years of age and 73% were female. Adherence to recommended dosing was higher than for recommended monitoring. Blood counts were conducted for most infusions (78-83%), while liver function tests (LFT) were performed less often (47-54% of infusions). Pregnancy tests were performed for 10% or fewer of the infusions administered to reproductive age women. Adherence with LVEF testing guidelines improved following labeling changes.Conclusions Adherence to recommended monitoring was incomplete, but amenable to change. Automated assessment through insurance claims supplemented with medical record data provides a balanced means for studying adherence to recommendations. Copyright (C) 2010 John Wiley & Sons, Ltd.

OBJECTIVE: The ASRM considers oocyte cryopreservation as experimental because of limited efficacy and safety data. To address this need, EMD Serono has launched the HOPE Registry. The present aim is to report preliminary data from the initial cohort of enrolled patients from participating US IVF Centers. DESIGN: Phase IV, prospective, 5-year observational registry with a 3-year enrollment period and a baby follow-up at birth and at one year of age. MATERIALS AND METHODS: 75 women have already been enrolled. Descriptive statistics from 48 cycles are reported below. RESULTS: Table 1.Tabled 1Outcomes by Technique (cycles)Slow-Freezing (16)Vitrification (32)Age (yr), (Mean ± SD)41.6 ± 4.040.6 ± 4.4Oocytes Retrieved22.1 ± 5.331.1 ± 16.2Oocytes Frozen,21.9 ± 5.530.1 ± 15.5Oocytes Thawed6.4 ± 1.27.2 ± 2.9Oocyte Survival%89.8% ± 12.089.0% ± 14.32PN Oocytes (% of Thawed)79.4%73.8%Embryos Transferred3.8 ± 0.72.0 ± 0.7Embryos Cryopreserved0.3 ± 0.72.0 ± 1.8Implantation Rate %25.4% ± 30.250% ± 43.9Clinical Pregnancy (%)57.1%63.6%Miscarriage Rate (%)12.5%0%Mean ± SD per cycle Open table in a new tab CONCLUSIONS: Oocyte survival, fertilization and embryo development were similarly high in both groups. Both cryopreservation techniques had similarly high clinical pregnancy rates, though after slow-freeze there were more embryos transferred than after vitrification, a difference also reflected by the implantation rates. These initial excellent results may be obtained as a combination of type of patients (majority in both groups were recipients of donated frozen eggs) and advanced cryopreservation techniques. With the continuing incorporation of new patients, future inclusion of the data on offspring and a statistical comparison of the two techniques, the HOPE Registry will provide standardized data regarding efficiency and safety of oocyte cryopreservation to satisfy unmet needs from the medical community.

Objective: The EVIDENCE trial concluded that administering highdose/high-frequency subcutaneous (SC) interferon-beta-1a (IFNb1a) was more effective in preventing relapses among patients with relapsing multiple sclerosis (MS) than low-dose weekly intramuscular (IM) IFNb1a after 64 weeks. This analysis utilized discrete-event simulation (DES) to model the potential longer-term clinical and economic implications of this trial. Methods: A DES predicting the course of relapsing MS and incorporating the effect of IFNb1a therapy was developed. The model began by randomly reading in actual patient data from the trial to create 1000 patients. Each simulated patient was replicated — one was assigned to receive SC IFNb1a three times a week and the other to receive IM IFNb1a once a week. During the simulation, patients may (i) experience relapses, with associated short- and long-term impacts on costs and disability; (ii) develop new T2 lesions detected by a magnetic resonance imaging scan; (iii) discontinue treatment because of adverse events or lack of response; (iv) advance to secondary progressive MS; or (v) die. Model inputs were mainly obtained from the EVIDENCE trial, but were taken from published literature if they could not be obtained from the trial. Direct medical costs ($US, year 2006 values) to the US payers were primarily obtained by updating a published cost analysis. Costs and benefits were discounted at 3% per annum. Extensive sensitivity analyses were conducted to test the robustness of the model results. Results: Based on 100 replications of 1000 patient pairs over 4 years, SC IFNb1a was predicted to enable more patients to avoid relapse (216 vs 147). Total mean costs per patient (discounted) were $US79 890 with SC IFNb1a versus $US74 485 with IM administration, a net increase of $US5405 per patient. However, SC IFNb1a was estimated to prevent 0.50 relapses and save 23 relapse-free days per patient, yielding incremental cost-effectiveness ratios of $US10 755 per relapse prevented and $US232 per relapse-free day gained. Sensitivity analyses revealed that the result was most sensitive to the treatment efficacy, model time horizon and cost of IFNb1a treatment. Conclusion: Based on the results observed in the EVIDENCE trial, the model predicted that SC IFNb1a would yield greater health benefits over 4 years than IM IFNb1a, at a cost that would seem to be a reasonable trade-off.

Background: The EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) study was an international, randomized, open-label, assessor-blinded, parallel-group study assessing the efficacy and tolerability of interferon (IFN) beta-1a, 44 mcg subcutaneously (sc) three times weekly (tiw), and IFN beta-1a, 30 mcg intramuscularly (im) once weekly (qw), in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this analysis was to assess whether reductions in T2 burden of disease (BOD) were greater for patients receiving IFN beta-1a, 44 mcg sc tiw, than for those treated with IFN beta-1a, 30 mcg im qw, and to assess the impact of neutralizing antibodies (NAbs).Methods: A post-hoc analysis was performed on magnetic resonance imaging (MRI) data collected prospectively from the EVIDENCE study. The analysis included all patients with evaluable T2 MRI scans at the start of dosing and at week 48, and those who received at least one drug dose (n = 553). Lesions were identified by a radiologist blinded to treatment codes and the total volume of T2 lesions (BOD) was reported in mm3.Results: Both median percentage decreases and absolute reduction in BOD were greater in the IFN beta-1a, 44 mcg sc tiw, treatment group. The adjusted mean treatment difference in percentage change in BOD from baseline to week 48 showed a significant treatment benefit for patients treated with IFN beta-1a, 44 mcg sc tiw, over those treated with IFN beta-1a, 30 mcg im qw (-4.6%; standard error: 2.6%; p = 0.002). The presence of NAbs reduced the effect of IFN beta-1a 44, mcg sc tiw, on BOD, but BOD changes were still similar to those seen with IFN beta-1a, 30 mcg im qw.Conclusion: Patients with RRMS treated with IFN beta-1a, 44 mcg sc tiw, had greater reduction in T2 BOD after 48 weeks than those treated with IFN beta-1a, 30 mcg im qw, which is consistent with other clinical and MRI outcome measures in the EVIDENCE study. In patients testing positive for NAbs (NAb+) to IFN beta-1a 44 mcg sc tiw, changes in BOD were smaller than in NAb negative (NAb-) patients, but similar to those receiving IFN beta-1a, 30 mcg im qw.