Vitamin D and Disease Severity in Multiple Sclerosis-Baseline Data From the Randomized Controlled Trial (EVIDIMS)

Objective: To investigate the associations between hypovitaminosis D and disease activity in a cohort of relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) patients. Methods: In 51 RRMS and 2 CIS patients on stable interferon-β-1b (IFN-β-1b) treatment recruited to the EVIDIMS study (Efficacy of Vitamin D Supplementation in Multiple Sclerosis (NCT01440062) baseline serum vitamin D levels were evaluated. Patients were dichotomized based on the definition of vitamin D deficiency which is reflected by a < 30 vs. ≥ 30 ng/ml level of 25-hydroxyvitamin D (25(OH)D). Possible associations between vitamin D deficiency and both clinical and MRI features of the disease were analyzed. Results: Median (25, 75% quartiles, Q) 25(OH)D level was 18 ng/ml (12, 24). Forty eight out of 53 (91%) patients had 25(OH)D levels < 30 ng/ml (p < 0.001). Patients with 25(OH)D ≥ 30 ng/ml had lower median (25, 75% Q) T2-weighted lesion counts [25 (24, 33)] compared to patients with 25(OH)D < 30 ng/ml [60 (36, 84), p = 0.03; adjusted for age, gender and disease duration: p < 0.001]. Expanded disability status scale (EDSS) score was negatively associated with serum 25(OH)D levels in a multiple linear regression, including age, sex, and disease duration (adjusted: p < 0.001). Interpretation: Most patients recruited in the EVIDIMS study were vitamin D deficient. Higher 25(OH)D levels were associated with reduced T2 weighted lesion count and lower EDSS scores

End-of-life decisions in acute stroke patients: an observational cohort study

Background: Crucial issues of modern stroke care include best practice end-of-life-decision (EOLD)-making procedures and the provision of high-quality palliative care for dying stroke patients. Methods: We retrospectively analyzed records of those patients who died over a 4-year period (2011–2014) on our Stroke Unit concerning EOLD, focusing on the factors that most probably guided decisions to induce limitation of life-sustaining therapy and subsequently end-of-life-care procedures thereafter. Results: Of all patients treated at our Stroke Unit, 120 (2.71 %) died. In 101 (86.3 %), a do-not-resuscitate-order (DNRO) was made during early treatment. A decision to withdraw/withhold further life supportive therapy was made in 40 patients (34.2 %) after a mean of 5.0 days (range 0–29). Overall patient death occurred after a mean time of 7.0 days (range 1–30) and 2.6 days after therapy restrictions. Disturbance of consciousness at presentation, dysphagia on day 1 and large supratentorial stroke were possible indicators of decisions to therapeutic withdrawing/withholding. Proceedings of EOL care in these patients were heterogeneous; in most cases monitoring (95 %), medical procedures (90 %), oral medication (88 %), parenteral nutrition (98 %) and antibiotic therapy (86 %) were either not ordered or withdrawn, however IV fluids were continued in all patients. Conclusions: A high percentage of stroke patients were rated as terminally ill and died in the course of caregiving. Disturbance of consciousness at presentation, dysphagia on day 1 and large supratentorial stroke facilitated decisions to change therapeutic goals thus initiating end-of-life-care. However, there is further need to foster research on this field in order to ameliorate outcome prognostication, to understand the dynamics of EOLD-making procedures and to educate staff to provide high-quality patient-centred palliative care in stroke medicine

Neutralität, Transparenz und Kompetenz: rechtliche Ansatzpunkte für eine Neuregulierung des Suchmaschinenmarktes

Die Frage nach den gesellschaftlichen Implikationen der Google-Dienste steht schon länger auf der wissenschaftlichen Agenda. Auch die Rechtswissenschaft hat sich dieser Frage in der Vergangenheit bereits angenommen: Ansatz waren dabei häufig Fragen des Datenschutzes und des Rechts der Nutzer auf informationelle Selbstbestimmung. Eine Evaluierung der Relevanz des Suchmaschinendienstes als ein zentrales Funktionselement im Internet für die öffentliche Meinungsbildung steht allerdings noch aus. Dieser Frage versucht sich der Aufsatz unter Rückgriff auf neue Forschungsergebnisse aus der Kommunikationswissenschaft rechtswissenschaftlich zu nähern. Danach ist die Suchmaschine wegen ihrer Relevanz für die Meinungsvielfaltssicherung in eine gesellschaftliche Verantwortung hineingewachsen, deren Erfüllung der Gesetzgeber aufgrund seiner Gewährleistungsverantwortung absichern muss. Hierfür werden erste Regulierungsansätze vorgeschlagen, an denen sich eine Neuregulierung orientieren könnte.Scientific research on the societal implications of Google’s manifold set of services has a long-standing tradition. Legal scholars have so far mainly focused on data protection, privacy and the "right to informational self-determination". Search engines’ role in opinion formation, however, has rarely if ever been the subject of a rigorous analysis. This article draws on recent research from mass communication research in order to provide a first assessment of the necessity and possible approaches to search engine regulation from the perspective of media law and plurality

Multinuclear magnetic resonance study of sterically crowded stannylphosphines and stannylamines : stereochemical influences on chemical shielding and spin-spin couplings

Multinuclear (1H, 15N, 29Si, 31P, 119Sn) NMR data of sterically crowded acyclic stannylphosphines tBu3SnPHY (Y = H, SnMe3, SntBu3, SiMe3; 1-3, 10), (tBu2RSn)2PH (R = Me, Cl; 4, 5), tBu3SnPY2 (Y = SnMe3, SiMe3; 6, 11), PH(SntBu2PHSntBu3)2 (7), SntBu2(PY2)2 (Y = H, SiMe3, PHSntBu3; 8, 9, 12), cyclic stannylphosphines (tBu2SnPY)n (n = 2, Y = H, C3H6Cl, tBu, SnMe3; 13-16; n = 3, Y = H; 18), (Me2SnPSntBu3)2 (17), and stannylamines tBu3SnNHY (Y = H, SnMe3, SntBu3; 19-21) were obtained by various 1D- and 2D-techniques. 31P- and 15N-shieldings may be explained qualitatively in terms of two counteracting influences, viz electronegativity differences and steric requirements of the substituents. In a similar manner, the trends in one-bond coupling 1KSnP and 1KSnM may be rationalized using a simple model based on the deformation of bond angles by sterically demanding substituents. The signs of long-range couplings 2KSnPH and 1KPSnCCH could be determined, which may be useful for future structural studies. Temperature-dependent effects in the spectra of 13, 18 allow conclusions about the conformational dynamics of the molecules

Disease modification in multiple sclerosis by flupirtine-results of a randomized placebo controlled phase II trial

Central nervous system inflammation and neurodegeneration are the pathophysiological hallmarks of multiple sclerosis (MS). While inflammation can readily be targeted by current disease modifying drugs, neurodegeneration is by far less accessible to treatment. Based on suggested additional neuroprotective capacities of the orally available non-opioid and centrally acting analgesic drug flupirtine maleate we hypothesized that treatment with flupirtine maleate might be beneficial in MS patients. The flupirtine as oral treatment in multiple sclerosis (FLORIMS) study was a multi-center, randomized and stratified, placebo-controlled double-blind phase II trial to investigate safety and efficacy in terms of clinical and radiographical activity of flupirtine maleate (300 mg per day) given orally for 12 months, add-on to interferon beta 1b subcutaneously in patients with relapsing remitting MS. Due to a substantial delay in recruitment, enrolment of patients was prematurely terminated after randomization of only 30 of the originally planned 80 patients. Of these, 24 regularly terminated study after 12 months of treatment. Data were analyzed as originally planned. Treatment with flupirtine maleate was overall well tolerated. We observed moderate and asymptomatic elevations of liver enzymes in several cases but no overt hepatotoxicity. Neither the intention to treat nor the per protocol analysis revealed any significant treatment effects of flupirtine maleate with respect to occurrence of MS relapses, disability progression, or development of new lesions on cranial MRI. However, substantial methodological limitations need to be considered when interpreting these results. In conclusion, the results of the FLORIMS study neither add further evidence to nor argue against the hypothesized neuroprotective or disease modifying effects of flupirtine maleate in MS

A Randomized, Placebo-Controlled Trial

Objective: To examine whether treatment with epigallocatechin gallate (EGCG) influences progression of brain atrophy, reduces clinical and further radiologic disease activity markers, and is safe in patients with progressive multiple sclerosis (PMS). Methods: We enrolled 61 patients with primary or secondary PMS in a randomized double-blind, parallel-group, phase II trial on oral EGCG (up to 1,200 mg daily) or placebo for 36 months with an optional open-label EGCG treatment extension (OE) of 12-month duration. The primary end point was the rate of brain atrophy, quantified as brain parenchymal fraction (BPF). The secondary end points were radiologic and clinical disease parameters and safety assessments. Results: In our cohort, 30 patients were randomized to EGCG treatment and 31 to placebo. Thirty-eight patients (19 from each group) completed the study. The primary endpoint was not met, as in 36 months the rate of decrease in BPF was 0.0092 +/- 0.0152 in the treatment group and -0.0078 +/- 0.0159 in placebo-treated patients. None of the secondary MRI and clinical end points revealed group differences. Adverse events of EGCG were mostly mild and occurred with a similar incidence in the placebo group. One patient in the EGCG group had to stop treatment due to elevated aminotransferases (>3.5 times above normal limit). Conclusions: In a phase II trial including patients with multiple sclerosis (MS) with progressive disease course, we were unable to demonstrate a treatment effect of EGCG on the primary and secondary radiologic and clinical disease parameters while confirming on overall beneficial safety profile. Clinicaltrial.gov Identifier NCT00799890. Classification of Evidence This phase II trial provides Class II evidence that for patients with PMS, EGCG was safe, well tolerated, and did not significantly reduce the rate of brain atrophy