Changes in overlap of subjective and objective cognition over time in epilepsy surgery candidates.

Purpose: Subjective and objective cognition often show weak overlap in persons with epilepsy (PWE). Over- as well as underestimation may occur. In particular after epilepsy surgery, objective memory decline is often not subjectively reported.

German questionnaires assessing quality of life and psycho-social status in people with epilepsy: Reliable change and intercorrelations.

Objectives: People with epilepsy (PWE) not only suffer from seizures but also from various psycho-social issues containing facets such as social functioning, anxiety, depression or stigmatization, and consequently quality of life. (1) Assessing reliable change of these issues is crucial to evaluate their course and potential treatment effects. As most psycho-social self-report questionnaires have been validated in separate samples, their clinical-socio-demographic differences may limit the comparability and generalizability of the scales' internal consistency, which is important for the reliable change index (RCI).

Domain-specific relationships of subjective and objective cognition in epilepsy.

Objective: Many people with epilepsy report subjective cognitive impairment (SCI), i.e., problems with memory, attention, or executive functions, reducing quality of life.

Subjective cognition is linked to everyday functioning in epilepsy.

Objective: Many people with epilepsy (PWE) suffer from reduced everyday functioning such as unemployment, relationship difficulties, or lifestyle limitations. To identify whether subjective cognitive impairment (SCI) is a potential source of these impairments, associations with restrictions of daily life (RDL) and reduced daily activities (DA) were examined.

Methods: In a prospective cross-sectional sample of 316 adult in-patients with epilepsy, multiple regression analyses were calculated predicting RDL and DA.

Interleukin-6 receptor blockade or TNFα inhibition for reducing glycaemia in patients with RA and diabetes: post hoc analyses of three randomised, controlled trials.

Background: Diabetes is common in patients with rheumatoid arthritis (RA). Interleukin (IL)-6 is implicated in both the pathogenesis of RA and in glucose homeostasis; this post hoc analysis investigated the effects of IL-6 receptor vs. tumour necrosis factor inhibition on glycosylated haemoglobin (HbA1c) in patients with RA with or without diabetes.

Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial.

Background: Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis.

Impact of tocilizumab administered intravenously or subcutaneously on patient-reported quality-of-life outcomes in patients with rheumatoid arthritis.

Objective: Randomised controlled trials (RCTs) have shown tocilizumab (TCZ) administered intravenously or subcutaneously with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to be superior to csDMARDs alone for improving rheumatoid arthritis (RA) disease activity. This study evaluated the effect of TCZ-intravenous and TCZ-subcutaneous on patient-reported outcomes (PROs) in three RCT populations.

Methods: OPTION (NCT00106548), BREVACTA (NCT01232569) and SUMMACTA (NCT01194414) were independent RCTs evaluating the efficacy and safety of TCZ-intravenous and/or TCZ-subcutaneous with csDMARDs in patients with RA.

Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III Studies.

Objective: Tofacitinib has been investigated for the treatment of rheumatoid arthritis (RA) in phase III studies in which concomitant glucocorticoids (GC) were allowed. We analyzed the effect of GC use on efficacy outcomes in patients with RA receiving tofacitinib and/or methotrexate (MTX) or conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in these studies.

Methods: Our posthoc analysis included data from 6 phase III studies (NCT01039688; NCT00814307; NCT00847613; NCT00853385; NCT00856544; NCT00960440).

Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial.

Objective: Investigate whether the efficacy and safety of intravenous tocilizumab (TCZ) demonstrated at week 52 in patients with early rheumatoid arthritis (RA) are maintained to week 104.

Methods: Methotrexate (MTX)-naive patients with early progressive RA were randomly assigned to double-blind 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo or placebo+MTX for 104 weeks. Patients not receiving 8 mg/kg TCZ and not achieving Disease Activity Score-28 joints (DAS28-erythrocyte sedimentation rate (ESR)) ≤3.

Low immunogenicity of tocilizumab in patients with rheumatoid arthritis.

Objective: Subcutaneous (SC) and intravenous formulations of tocilizumab (TCZ) are available for the treatment of patients with rheumatoid arthritis (RA), based on the efficacy and safety observed in clinical trials. Anti-TCZ antibody development and its impact on safety and efficacy were evaluated in adult patients with RA treated with intravenous TCZ (TCZ-IV) or TCZ-SC as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Methods: Data from 5 TCZ-SC and 8 TCZ-IV phase III clinical trials and 1 TCZ-IV clinical pharmacology safety study (>50 000 samples) were pooled to assess the immunogenicity profile of TCZ-SC and TCZ-IV (8974 total patients).

Pharmacokinetic and Pharmacodynamic Analysis of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis From 2 Randomized, Controlled Trials: SUMMACTA and BREVACTA.

Tocilizumab is a humanized anti-interleukin-6 receptor antibody for treating rheumatoid arthritis. Pharmacokinetic/pharmacodynamic analysis was performed on the 24-week double-blind parts of 2 randomized, controlled trials: SUMMACTA and BREVACTA. SUMMACTA compared subcutaneous tocilizumab 162 mg every week to intravenous tocilizumab 8 mg/kg every 4 weeks, whereas BREVACTA evaluated 162 mg subcutaneous tocilizumab every 2 weeks versus placebo.

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis.

Background: Adalimumab has been used in patients with moderately to severely active rheumatoid arthritis (RA) for over 10 years and has a well-established safety profile across multiple indications.

Objective: To update adverse events (AEs) of special interest from global adalimumab clinical trials in patients with RA.

Methods: This analysis includes 15 132 patients exposed to adalimumab in global RA clinical trials.

Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial.

Objectives: The efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA).

Methods: In a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28-erythrocyte sedimentation rate (ESR) <2.

Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA).

Objectives: To evaluate the long-term efficacy and safety of subcutaneous (SC) tocilizumab (TCZ) versus intravenous (IV) TCZ, including switching formulations, in patients with rheumatoid arthritis (RA) and inadequate response to disease-modifying antirheumatic drugs (DMARDs).

Methods: Patients (n=1262) were randomised 1:1 to receive TCZ-SC 162 mg weekly (qw)+placebo-IV every four weeks (q4w) or TCZ-IV 8 mg/kg q4w+placebo-SC qw in combination with DMARD(s). After a 24-week double-blind period, patients receiving TCZ-SC were re-randomised 11:1 to TCZ-SC (n=521) or TCZ-IV (TCZ-SC-IV, n=48), and patients receiving TCZ-IV were re-randomised 2:1 to TCZ-IV (n=372) or TCZ-SC (TCZ-IV-SC; n=186).

Improvement of contraction force in injured skeletal muscle after autologous mesenchymal stroma cell transplantation is accompanied by slow to fast fiber type shift.

Background: Skeletal muscle trauma leads to severe functional deficits, which cannot be addressed by current treatment options. Previous investigation could show the efficacy of a local transplantation (TX) of mesenchymal stroma cells (MSCs) for the therapy of muscle injury. Underlying mechanisms remain to be elucidated.

A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe rheumatoid arthritis (SUMMACTA study).

Objectives: This study compared the efficacy and safety of subcutaneous (SC) versus intravenous (IV) formulations of tocilizumab in patients with rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs (DMARD).

Methods: Patients (n=1262) were randomly assigned to receive tocilizumab-SC 162 mg weekly+placebo-IV every 4 weeks or tocilizumab-IV 8 mg/kg every 4 weeks+placebo-SC weekly in combination with traditional DMARD. The primary outcome was to demonstrate the non-inferiority of tocilizumab-SC to tocilizumab-IV with regard to the proportion of patients in each group achieving an American College of Rheumatology (ACR) 20 response at week 24 using a 12% non-inferiority margin (NIM).

Small molecules targeting JAKs--a new approach in the treatment of rheumatoid arthritis.

Advances in the treatment of RA in the past decade have been achieved mainly by using combinations of different conventional and biologic DMARDs. However, until now no final victory has been achieved over this organ damaging and potentially life-threatening systemic autoimmune disease. Few patients, notably those with established disease, stay in remission permanently, even using advanced treatment concepts.

Effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab after 4 and 24 weeks in patients with active rheumatoid arthritis: the first phase IIIb real-life study (TAMARA).

Objectives: To confirm the effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) in a setting close to real-life medical care in Germany.

Methods: A multicentre open-label phase IIIb study was undertaken. Patients with active RA with a 28-joint Disease Activity Score (DAS28) >3.

Expression of proteasomal immunosubunit beta1i is dysregulated in inflammatory infiltrates of minor salivary glands in Sjogren's syndrome.

Objective: Minor salivary gland specimens were analyzed to investigate dysregulation of the proteasome system in patients with Sjögren's syndrome (SS) and patients with sicca syndrome.

Methods: Labial biopsy specimens from 17 patients with SS and 11 patients with non-autoimmunesicca syndrome were analyzed by immunohistochemistry for expression of the inducible proteasomal subunits ss1i, ss2i, and ss5i. The infiltrating subsets of lymphocytes were characterized using immunofluorescence stainings against the cell-surface markers CD20 and CD27.

Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases.

Objectives: Clinical trials of tumour necrosis factor antagonists have raised questions about the potential risk of certain serious adverse events (SAE). To assess the safety of adalimumab in rheumatoid arthritis (RA) over time and across five other immune-mediated inflammatory diseases and to compare adalimumab malignancy and mortality rates with data on the general population.

Methods: This analysis included 19,041 patients exposed to adalimumab in 36 global clinical trials in RA, psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis and juvenile idiopathic arthritis (JIA) to 15 April 2007.

The toxicity of cadmium and resulting hazards for human health.

Cadmium (Cd) has been in industrial use for a long period of time. Its serious toxicity moved into scientific focus during the middle of the last century. In this review, we discuss historic and recent developments of toxicological and epidemiological questions, including exposition sources, resorption pathways and organ damage processes.

Early diagnosis of colorectal cancer: a preventive task in occupational health.

Morbidity of colorectal cancer is still accreting; therefore in 2003 a total of 57000 patients fell ill and about 28000 died due to colorectal carcinoma. According to the etiology, many different factors are currently in discussion. However, as in about 25-30% of the cases familial clustering can be observed one of the most probable might be the genetic predisposition.