Development of a pulsed, variable-energy positron beam for atomic scale defect studies.

Positron annihilation spectroscopy provides a sensitive means of non-destructive characterization of materials, capable of probing single atom vacancies in solids with 10 sensitivity. We detail here the development of a magnetically guided, variable energy, pulsed positron beam designed to conduct depth-dependent defect studies in metals, semiconductors, and dielectrics, which will be the first of its kind in the United States. The design of the target stage provides capabilities for measurements during in situ annealing up to 800 °C and incorporates a new approach to minimize the background due to energetic backscattered positrons.

Two-Year Safety and Effectiveness of Peficitinib in Moderate-To-Severe Rheumatoid Arthritis: A Phase IIb, Open-Label Extension Study.

Introduction: Peficitinib is a novel orally bioavailable, once-daily Janus kinase (JAK) inhibitor approved in Japan for the treatment of rheumatoid arthritis (RA). This 2-year extension study of two global phase IIb trials investigated the long-term safety and effectiveness of peficitinib.

Methods: All eligible patients with moderate-to-severe RA including patients in the placebo group who participated in one of two global phase IIb trials ('with methotrexate' or 'without methotrexate') were included in this 2-year open-label extension study and were converted to peficitinib 100 mg once daily.

Secukinumab in Active Rheumatoid Arthritis: A Phase III Randomized, Double-Blind, Active Comparator- and Placebo-Controlled Study.

Objective: To evaluate the efficacy and safety of secukinumab in patients with active rheumatoid arthritis (RA) who had an inadequate response to or intolerance of tumor necrosis factor (TNF) inhibitors.

Methods: In this phase III study, 551 patients were randomized (1:1:1:1) to receive intravenous secukinumab at a dose of 10 mg/kg (at baseline and weeks 2 and 4) followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks or, alternatively, abatacept or placebo on the same dosing schedule. The primary end point was the proportion of patients achieving 20% improvement in disease activity according to the American College of Rheumatology response criteria (ACR20) at week 24 in the secukinumab 150 mg or 75 mg treatment groups as compared with placebo.

Peficitinib, a JAK Inhibitor, in Combination With Limited Conventional Synthetic Disease-Modifying Antirheumatic Drugs in the Treatment of Moderate-to-Severe Rheumatoid Arthritis.

Objective: To evaluate the efficacy and safety of orally administered once-daily peficitinib in combination with limited conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with moderate-to-severe rheumatoid arthritis (RA).

Methods: In this randomized, double-blind, phase IIb trial, patients with RA (n = 289) were treated with peficitinib 25 mg, 50 mg, 100 mg, or 150 mg or matching placebo once daily for 12 weeks. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 12.

Parallelization of photocatalytic gas-producing reactions.

High-throughput screening has been widely utilized in the pharmaceutical and manufacturing industry targeting the development of new molecules and materials for numerous applications. To enable more rapid progress in photocatalytic water-splitting reactions, the construction of high-throughput combinatorial photoreactors enabling the parallel optimization of relevant compositions under varieties of experimental conditions seems appropriate. This contribution describes a 16-photoreactor apparatus permitting the kinetic evaluation of photocatalytic gas-producing reactions using head-space pressure, gas chromatography, and mass spectrometry operating in parallel, illustrated with molecular-based homogeneous photocatalytic H2-generating compositions.

One-year efficacy and safety results of secukinumab in patients with rheumatoid arthritis: phase II, dose-finding, double-blind, randomized, placebo-controlled study.

Objective: To evaluate the longer-term safety and efficacy of secukinumab, a fully human monoclonal antiinterleukin-17A antibody, in patients with rheumatoid arthritis.

Methods: In this 52-week, double-blind, placebo-controlled (up to Week 20) study (NCT00928512), patients responding inadequately to disease-modifying antirheumatic drugs (DMARD) or biologics were randomized to receive monthly subcutaneous injections of secukinumab (25, 75, 150, or 300 mg), or placebo. The efficacy and safety results up to Week 20 have been reported previously.

Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study.

Objectives: The interleukin-6 receptor (IL-6R) blocker tocilizumab (TCZ) reduces inflammatory disease activity in rheumatoid arthritis (RA) but elevates lipid concentrations in some patients. We aimed to characterise the impact of IL-6R inhibition on established and novel risk factors in active RA.

Methods: Randomised, multicentre, two-part, phase III trial (24-week double-blind, 80-week open-label), MEASURE, evaluated lipid and lipoprotein levels, high-density lipoprotein (HDL) particle composition, markers of coagulation, thrombosis and vascular function by pulse wave velocity (PWV) in 132 patients with RA who received TCZ or placebo.

Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study.

Objective: To assess the safety and efficacy of secukinumab, a fully human monoclonal anti-interleukin-17A antibody, in patients with rheumatoid arthritis (RA).

Methods: Patients (n=237) with inadequate response to methotrexate were randomly assigned to receive monthly subcutaneous injections of secukinumab 25 mg, 75 mg, 150 mg, 300 mg or placebo. The primary endpoint was the American College of Rheumatology 20% response (ACR20) at week 16.

Clinical response and tolerability to abatacept in patients with rheumatoid arthritis previously treated with infliximab or abatacept: open-label extension of the ATTEST Study.

Objective: To assess the efficacy and safety of abatacept in biological-naive patients with rheumatoid arthritis and an inadequate response to methotrexate treated in the long-term extension (LTE) of the ATTEST trial.

Methods: Patients randomly assigned to abatacept, placebo or infliximab completing the 1-year double-blind period were eligible to receive abatacept ∼10 mg/kg in the open-label LTE. Efficacy to year 2 is presented for patients randomly assigned to abatacept or infliximab who switched to open-label abatacept.

Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial.

Objective: To examine immunization responses in patients with rheumatoid arthritis (RA) treated with rituximab and to investigate the effects of rituximab-induced CD20+ B cell depletion on immune responses to tetanus toxoid (T cell-dependent antigen), pneumococcal polysaccharide (T cell-independent antigen), and keyhole limpet hemocyanin (KLH) (neoantigen) and on delayed-type hypersensitivity (DTH).

Methods: In a controlled trial, we enrolled 103 patients with active RA receiving a stable dose of methotrexate (MTX). Tetanus toxoid, pneumococcal polysaccharide, and KLH vaccines as well as a Candida albicans skin test were administered to 1 group of patients receiving rituximab plus MTX (called rituximab-treated patients) for 36 weeks and to 1 group of patients receiving MTX alone for 12 weeks.

Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate.

Objectives: This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo. The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score (based on erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups at day 197.

Methods: Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) were randomised 3:3:2 to abatacept ( approximately 10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or placebo (every 4 weeks, n = 110) and background MTX.

Economic evaluation of controlled-release oxycodone vs oxycodone-acetaminophen for osteoarthritis pain of the hip or knee.

Objective: To examine, in routine practice, the effectiveness and cost-effectiveness of oxycodone (OxyContin) compared with standard therapy for osteoarthritis pain.

Study Design: Open-label active-controlled randomized naturalistic 4-month study of oxycodone vs a combination of oxycodone-acetaminophen (Percocet).

Methods: Outcomes and health resource utilization data were collected by telephone interview.

Topical lidocaine patch 5% may target a novel underlying pain mechanism in osteoarthritis.

Recent literature and animal research has provided insight to potentially new analgesic targets for managing osteoarthritis (OA) pain. Primary afferent neurons located in affected joints express excessive amounts of abnormally functioning sodium (Na) channels on their surface in response to the inflammatory process. These Na channels may play an integral role in production of pain and hyperalgesia.

Differences in the fine specificity of anti-Ro (SS-A) in relation to the presence of other precipitating autoantibodies.

In sera from patients with systemic lupus erythematosus or Sjögren's syndrome, we determined the fraction of antibody that remained reactive with human Ro (SS-A) after absorption with bovine spleen extract, and the reactivity with the 60-kd and 54-kd red blood cell Ro (SS-A) bands by Western blot. Of the 3 groups of sera studied, those containing anti-Ro (SS-A) alone had the highest degree of reactivity with human Ro (SS-A) after absorption with bovine spleen extract, followed, in descending order, by sera containing anti-Ro (SS-A) and anti-La (SS-B), and sera containing anti-Ro (SS-A) and anti-nuclear RNP. The groups of sera could be distinguished on this basis.

Tubulointerstitial nephritis due to vancomycin.

Vancomycin was used to treat a patient with Staphylococcus aureus endocarditis. After 3 weeks of therapy, the patient developed a diffuse maculopapular rash, which resolved upon stopping the drug. Rechallenge with vancomycin several days later resulted in reappearance of the rash and rapid onset of acute anuric renal failure.