Development and Validation of the FSIQ-RMS: A New Patient-Reported Questionnaire to Assess Symptoms and Impacts of Fatigue in Relapsing Multiple Sclerosis

Objectives: A new patient-reported outcome (PRO) instrument to measure fatigue symptoms and impacts in relapsing multiple sclerosis (RMS) was developed in a qualitative stage, followed by psychometric validation and migration from paper to an electronic format. Methods: Adult patients with relapsing-remitting multiple sclerosis (RRMS) were interviewed to elicit fatigue-related symptoms and impacts. A draft questionnaire was debriefed in cognitive interviews with further RRMS patients, and revised. Content confirmation interviews were conducted with patients with progressive-relapsing multiple sclerosis (PRMS) and relapsing secondary-progressive multiple sclerosis (RSPMS). Psychometric analyses used data from adult patients with different RMS subtypes and matched non-RMS controls in a multicenter, observational study. After item reduction, the final instrument was migrated to a smartphone (eDiary) and usability was confirmed in interviews with additional adult RMS patients. Results: The qualitative stage included 37 RRMS, 5 PRMS, and 5 RSPMS patients. Saturation of concepts was reached during concept elicitation. Cognitive interviews confirmed that participants understood the instructions, items, and response options of the instrument—named FSIQ-RMS—as intended. Psychometric validation included 164 RMS and 74 control patients. Internal consistency and test–retest reliability were demonstrated. The symptoms domain discriminated along the RMS symptom-severity continuum and between patients and controls. Patients were able to attribute fatigue-related symptoms to RMS. Usability and conceptual equivalence of the eDiary were confirmed (n = 10 participants). Conclusions: With 7 symptom items and 13 impact items (in 3 impacts subdomains: physical, cognitive and emotional, and coping) after item reduction, the FSIQ-RMS is a comprehensive, valid, and reliable measure of fatigue-related symptoms and impacts in RMS patients

WHAT BENEFITS DO THEY BRING? A CASE STUDY ANALYSIS ON ENTERPRISE SOCIAL NETWORKS

Over the last years, Enterprise Social Networks (ESN) have gained increasing attention both in academia and practice, resulting in a large number of publications dealing with ESN. Among them is a large number of case studies describing the benefits of ESN in each individual case. Based on the different research objects they focus, various benefits are described. However, an overview of the bene-fits achieved by using ESN is missing and will, thus, be elaborated in this article (research question 1). Further, we cluster the identified benefits to more generic categories and finally classify them to the capabilities of traditional IT as presented by Davenport and Short (1990) to determine if new capabilities of IT arise using ESN (research question 2). To address our research questions, we perform a qualitative content analysis on 37 ESN case studies. As a result, we identify 99 individual benefits, classify them to the capabilities of traditional IT, and define a new IT capability named Social Capital. Our results can, e.g., be used to align and expand current ESN success measurement approaches

Involvement of beta-chemokines in the development of inflammatory demyelination.

The importance of beta-chemokines (or CC chemokine ligands - CCL) in the development of inflammatory lesions in the central nervous system of patients with multiple sclerosis and rodents with experimental allergic encephalomyelitis is strongly supported by descriptive studies and experimental models. Our recent genetic scans in families identified haplotypes in the genes of CCL2, CCL3 and CCL11-CCL8-CCL13 which showed association with multiple sclerosis. Complementing the genetic associations, we also detected a distinct regional expression regulation for CCL2, CCL7 and CCL8 in correlation with chronic inflammation in multiple sclerosis brains. These observations are in consensus with previous studies, and add new data to support the involvement of CCL2, CCL7, CCL8 and CCL3 in the development of inflammatory demyelination. Along with our own data, here we review the literature implicating CCLs and their receptors (CCRs) in multiple sclerosis and experimental allergic encephalomyelitis. The survey reflects that the field is in a rapid expansion, and highlights some of the pathways which might be suitable to pharmaceutical interventions

Multiple sclerosis: relationship between locus of control and quality of life in persons with low versus high disability

Background: Health Locus of Control (HLOC) is the degree to which individuals believe that their health outcomes are controlled by \u27external\u27 factors - environmental forces, chance, fate, other people, or some higher power - or by \u27internal\u27 factors - their own behavior or action. Most of the literature on HLOC associates an Internal Health Locus of Control (IHLOC) to pro-health behaviors and better health outcomes. However, a few studies also suggest that in chronic illnesses, an External Health Locus of Control (EHLOC) could be beneficial with respect to pro-health behaviors and perceptions of Quality of Life (QoL), challenging assumptions about what leads to the most effective psychological coping in the face of difficult circumstances. Multiple sclerosis (MS) is a chronic immune condition of the central nervous system and the most frequent cause of non-traumatic disability in young adults, often despite treatment. Method: The primary goal of this non-experimental, cross-sectional, quantitative study of 89 individuals with MS was to explore the HLOC of individuals with MS, and to identify whether holding an EHLOC positively impacts the MS patients\u27 perceived QoL while taking into consideration their level of disability. Results: This research found that individuals with higher disability scores tended to hold more EHLOC beliefs, and that there was a significant correlation between QoL and holding EHLOC beliefs. Conclusion: This study was able to capture the importance of control beliefs in the QoL of individuals with MS with higher disability. The clinical implications of the findingare explored and areas for further research are suggested

Involvement of β-chemokines in the development of inflammatory demyelination

The importance of β-chemokines (or CC chemokine ligands – CCL) in the development of inflammatory lesions in the central nervous system of patients with multiple sclerosis and rodents with experimental allergic encephalomyelitis is strongly supported by descriptive studies and experimental models. Our recent genetic scans in families identified haplotypes in the genes of CCL2, CCL3 and CCL11-CCL8-CCL13 which showed association with multiple sclerosis. Complementing the genetic associations, we also detected a distinct regional expression regulation for CCL2, CCL7 and CCL8 in correlation with chronic inflammation in multiple sclerosis brains. These observations are in consensus with previous studies, and add new data to support the involvement of CCL2, CCL7, CCL8 and CCL3 in the development of inflammatory demyelination. Along with our own data, here we review the literature implicating CCLs and their receptors (CCRs) in multiple sclerosis and experimental allergic encephalomyelitis. The survey reflects that the field is in a rapid expansion, and highlights some of the pathways which might be suitable to pharmaceutical interventions

BPM ADOPTION IN SMALL AND MEDIUM-SIZED COMPANIES IN BAVARIA

Small and medium sized (SMEs) companies are a pillar of the Bavarian economy. With business process management (BPM) providing an important competitive advantage in the globalized economy, the adap-tion of BPM by SMEs has societal relevance. However, the reasons why, or why not, SMEs implement BPM measures are still not fully understood. Previous research addressed this topic either breadthwise as surveys or in depth as case studies, and thus only has a limited perspective. Therefore, in our work, we carry out a mixed method analysis. We conduct 10 case studies to analyse the current state of adoption as well as the reasons for or against implementing further BPM measures. The insights gained guide the design of the subsequent survey. 114 results allow us to evaluate how widespread a particular reason may be. Lastly, the combined discussion of the results of both the case studies and surveys allow us to identify reasons that hinder or foster BPM adoption in SMEs, which are in-depth as well as generalizable. The study results are analyzed to derive propositions to research and practitioners alike that support SMEs to introduce further measures of BPM and improve their global competitiveness. For example, we could identify that BPM is in some cases enforced by customers, that stricter certifications are nec-essary, and that BPM trainings aligned to the needs of SMEs are desirable

Evaluating Business Process Improvement Patterns by Simulation

Existing approaches for business process improvement often lack systematic guidelines to transform a business process into an enhanced state, which we refer to as the “act of improvement”. To close this gap, a pattern-based approach has been designed and developed in previous works. In this paper, the usefulness of “Business Process Improvement Patterns” (BPI-Patterns) as a means of improving business processes is analyzed. For this purpose, a simulation experiment is performed in which several BPI-Patterns are applied to evaluate whether their anticipated effects can be confirmed for real-life business processes. From the analysis of the simulation results, i.e. how the application of BPI-Patterns affects the business processes, we investigate enabling as well as hindering factors that influence the implementation of BPI-Patterns. These factors may serve as a means to further specify instances of BPI-Patterns and also contribute to the overall evaluation of the BPI-Pattern approach

The sensitivity of the zebrafish embryo coiling assay for the detection of neurotoxicity by compounds with diverse modes of action

Open Access via the Springer Agreement Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 681002 (EU-ToxRisk).Peer reviewedPublisher PD

РОЗВИТОК СИСТЕМИ ПОЧАТКОВОЇ ТА СЕРЕДНЬОЇ ОСВІТИ У МЕНОНІТСЬКИХ КОЛОНІЯХ КАТЕРИНОСЛАВСЬКОГО ПОВІТУ НАПРИКІНЦІ XIX – НА ПОЧАТКУ XX СТ.

Проблеми формування системи початкової освіти постійно знаходи-лись у фокусі громадської уваги менонітського соціуму, який намагався шля-хом надзвичайної концентрації інтелектуальних, фінансових та господарчих зусиль сприяти її всебічному становленню та розвитку. Ґенеза менонітсько-го віровчення, темпи та масштаб його поширення серед населення північ-них регіонів Західної Європи були об'єктивно зумовлені наявністю у пред-ставників даного релігійного руху елементарних освітянських навичок (вміння читати та писати), які були необхідні для раціонального тлумачен-ня біблійних та релігійних текстів. Поява розгалуженої освітянської системи в громадах менонітів була детермінована специфікою віровчення спільноти, її нагальними релігійними, церковними та громадськими потребами. Зазначимо, що меноніти розглядали шкільництво як один із засобів набуття «освічено-го благочестя»

Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis.

Abstract Background Treating patients with relapsing multiple sclerosis (MS) with cladribine tablets (two times 4 or 5 days of treatment each year for 2 years) results in long-lasting efficacy, with continued stability in many patients for 4 or more years. Safety and tolerability outcomes from individual clinical studies with cladribine tablets have been reported previously. Objective Report safety data from an integrated analysis of clinical trials and follow-up in patients with MS to further characterize the safety profile of cladribine tablets. Methods Data for patients treated with cladribine tablets 10 mg (MAVENCLAD®; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg) as monotherapy (n = 923) or placebo (n = 641) in Phase III clinical trials (CLARITY, CLARITY Extension and ORACLE-MS) and followed up in the PREMIERE registry were aggregated (Monotherapy Oral cohort). To better characterize rare events, additional data from earlier studies which involved the use of parenteral cladribine in patients with MS, and the ONWARD study, in which patients were given cladribine tablets in addition to interferon (IFN)-β or placebo plus IFN-β were included in an All Exposed cohort (cladribine, n = 1926; placebo, n = 802). Adjusted adverse events incidences per 100 patient-years (Adj-AE per 100 PY) were calculated for the integrated analyses. Results The incidence rate of treatment-emergent adverse events (TEAEs) in the Monotherapy Oral cohort was 103.29 vs. 94.26 Adj-AEs per 100 PY for placebo. TEAEs that occurred more frequently with cladribine tablets were mainly driven by the TEAEs of lymphopenia (Adj-AE per 100 PY 7.94 vs. 1.06 for placebo) and lymphocyte count decreased (Adj-AE per 100 PY 0.78 vs. 0.10 for placebo) as anticipated due to the mode of action of cladribine. An increase in TEAE incidence rate was also observed in the cladribine tablets 3.5 mg/kg group vs. placebo for herpes zoster (Adj-AE per 100 PY 0.83 vs. 0.20, respectively). There were no cases of systemic, serious disseminated herpes zoster attributed to treatment with cladribine tablets. In general there was no increase in the risk of infections including opportunistic infections with cladribine tablets versus placebo, except for herpes zoster. Periods of severe lymphopenia ( Conclusion The AE profile for cladribine tablets 3.5 mg/kg as a monotherapy has been well-characterized in a pooled population of patients from early to more advanced relapsing MS. There was no increased risk for infections in general except for a higher incidence of herpes zoster. Lymphopenia was amongst the most frequently observed TEAEs that occurred at a higher incidence with cladribine relative to placebo. There was also no increase in malignancy rates for cladribine relative to placebo