Beeinflussung des Essentiellen Tremors durch kontinuierliche Theta- Burst- Stimulation des Primär motorischen Kortex

Ziel dieser Studie war es, die Beeinflussbarkeit des Essentiellen Tremors über den Primär motorischen Kortex (M1) zu untersuchen und damit einerseits dessen Stellenwert für die Tremorentstehung und andererseits sein Potential als therapeutisches Zielgebiet zu überprüfen. Mittels der Theta- Burst- Stimulation, einem besonders effektiven Stimulationsprotokoll der repetitiven Transkraniellen Magnetstimulation, wurde der rechte Primärmotorische Kortex von 10 Patienten mit Essentiellem Tremor und 10 Normalprobanden einmal mit einer efektiven Intensität und einmal mit einer anzunehmend nicht effektiven Intensität gereitzt. Bei den mit hoher Intensität stimulierten Patienten konnte eine signifikante Tremorreduktion nachgewiesen werden, welche über 45 Minuten nach der Stimulation fortbestand. Nach nicht effektiver Stimulation und bei den Normalprobanden fanden sich keine signifikanten Tremoränderungen. Eine Exzitabilitätsminderung des Motorkortex konnte nur bei den Normalprobanden gezeigt werden. Den Ergebnissen zu Folge ist eine direkte oder indirekte Beteiligung des Primärmotorischen Kortex an der Entstehung des Essentiellen Tremors anzunehmen

Frequency and potential reasons

Background: Generic substitution can have unintended consequences. In Germany, brand name to generic or generic to generic switching is mainly driven by rebate contracts. Frequent switching may raise concerns about bio-and therapeutic equivalence. Expected patient confusion may result in compromised medication adherence or new onset of other drug-related problems. Since 2008, pharmacists are allowed to deviate from rebate contracts by denying substitution due to pharmaceutical concerns on an individual basis. Objectives: To explore the frequency of documented pharmaceutical concerns in Germany between July 2011 and December 2013 and to identify the medicines most frequently related to pharmaceutical concerns in 2013. Methods: We analyzed documented pharmaceutical concerns in all prescribed drugs at the expense of any statutory health insurance company requiring pharmacies’ generic substitution according to rebate contracts. Results: Since July 2011, the frequency of documented pharmaceutical concerns in relation to prescribed drug products with rebate contracts requiring substitution increased consistently and doubled between July 2011 and July 2013. Overall in 2013, the trend of the two previous years continued and reached approximately 1.5%. The most affected drugs/drug classes were thyroid hormones (in particular combinations with iodide; 15.9%) followed by ondansetron (12.5%), and levothyroxine (11.3%). For all drugs/drug classes under investigation, product-, patient-or disease- related aspects could be identified which are potential reasons to deny substitution and to document pharmaceutical concerns. Conclusions: Although there is no electronic recording of the specific reasons for pharmaceutical concerns in claims data, our analyses support the assumption that pharmacists make use of this instrument based on individual clinical decisions and as required by contract. Pharmaceutical concerns are, therefore, an important instrument for pharmacies to refuse generic substitution. They are considered to prevent compromised medication safety and to assure pharmacotherapy effectiveness in a generic substitution environment driven by low drug prizes above all. © 2016, Grupo de Investigacion en Atencion Farmaceutica. All rights reserved

Die Rolle der Texturanalyse in der Computertomographie zur Beurteilung der Krankheitsaktivität bei Patienten mit Multiplem Myelom

Retrospektive Studie zur Identifizierung von Texturmerkmalen auf DECT-basierten Knochenmarkbildern beim Multiplen Myelom, die Aussage über den Plasmazellinfiltrationsgrad im Knochenmark geben und auf diesem Wege wiederum die Krankheitsaktivität und das Progressionsrisiko dieser Erkrankung widerspiegeln

Evaluation of pharmaceutical concerns in Germany: frequency and potential reasons

Background: Generic substitution can have unintended consequences. In Germany, brand name to generic or generic to generic switching is mainly driven by rebate contracts. Frequent switching may raise concerns about bio- and therapeutic equivalence. Expected patient confusion may result in compromised medication adherence or new onset of other drug-related problems. Since 2008, pharmacists are allowed to deviate from rebate contracts by denying substitution due to pharmaceutical concerns on an individual basis.Objectives: To explore the frequency of documented pharmaceutical concerns in Germany between July 2011 and December 2013 and to identify the medicines most frequently related to pharmaceutical concerns in 2013.Methods: We analyzed documented pharmaceutical concerns in all prescribed drugs at the expense of any statutory health insurance company requiring pharmacies’ generic substitution according to rebate contracts.Results: Since July 2011, the frequency of documented pharmaceutical concerns in relation to prescribed drug products with rebate contracts requiring substitution increased consistently and doubled between July 2011 and July 2013. Overall in 2013, the trend of the two previous years continued and reached approximately 1.5%. The most affected drugs/drug classes were thyroid hormones (in particular combinations with iodide; 15.9%) followed by ondansetron (12.5%), and levothyroxine (11.3%). For all drugs/drug classes under investigation, product-, patient- or disease-related aspects could be identified which are potential reasons to deny substitution and to document pharmaceutical concerns.Conclusions: Although there is no electronic recording of the specific reasons for pharmaceutical concerns in claims data, our analyses support the assumption that pharmacists make use of this instrument based on individual clinical decisions and as required by contract. Pharmaceutical concerns are, therefore, an important instrument for pharmacies to refuse generic substitution. They are considered to prevent compromised medication safety and to assure pharmacotherapy effectiveness in a generic substitution environment driven by low drug prizes above all

Role of computed tomography texture analysis using dual-energy-based bone marrow imaging for multiple myeloma characterization: comparison with histology and established serologic parameters

Objective!#!To identify textural features on dual-energy CT (DECT)-based bone marrow images in myeloma which correlate with serum markers of myeloma activity and the degree of medullary involvement.!##!Methods!#!A total of 110 patients (63.0 ± 11.0 years, 51 female) who underwent unenhanced whole-body DECT between September 2015 and February 2019 were retrospectively included, which was approved by our institutional ethics committee with a waiver of the informed consent requirement. All patients had current hematologic laboratory tests. Using DECT post-processing, non-calcium bone marrow images were reconstructed. The vertebral bodies T10-L5 were segmented for quantification of textural features, which were compared with serologic parameters and myeloma stages by the Mann-Whitney U test. In a subgroup of 56/110 patients with current bone marrow biopsies, textural features were correlated with the degree of bone marrow infiltration.!##!Results!#!First-order features were higher in patients with advanced stage of myeloma (p < .02), whereas the 2nd-order 'gray-level co-occurrence matrix (GLCM) cluster prominence' was lower (p < .04). In patients with elevated serum-free light chains (SFLC) or kappa/lambda SFLC ratio above 1.56, the 'entropy' and 2nd-order GLCM features were lower (p < .03). The degree of bone marrow infiltration correlated with 1st-order features (e.g., 'uniformity'; r!##!Conclusions!#!CT textural features applied on non-calcium bone marrow images correlate well with myeloma-related serologic parameters and histology showing a more uniform tissue structure and higher attenuation with increasing medullary infiltration and could therefore be used as additional imaging biomarkers for non-invasive assessment of medullary involvement.!##!Key points!#!• Texture analysis applied on dual-energy reconstructed non-calcium bone marrow images provides information about marrow structure and attenuation. • Myeloma-related serologic parameters and the degree of myeloma cell infiltration correlate with 1st- and 2nd-order features which could be useful as additional imaging biomarkers for non-invasive assessment of medullary involvement

Treatments for intracranial hypertension in acute brain-injured patients: grading, timing, and association with outcome. Data from the SYNAPSE-ICU study

Purpose: Uncertainties remain about the safety and efficacy of therapies for managing intracranial hypertension in acute brain injured (ABI) patients. This study aims to describe the therapeutical approaches used in ABI, with/without intracranial pressure (ICP) monitoring, among different pathologies and across different countries, and their association with six months mortality and neurological outcome. Methods: A preplanned subanalysis of the SYNAPSE-ICU study, a multicentre, prospective, international, observational cohort study, describing the ICP treatment, graded according to Therapy Intensity Level (TIL) scale, in patients with ABI during the first week of intensive care unit (ICU) admission. Results: 2320 patients were included in the analysis. The median age was 55 (I-III quartiles = 39-69) years, and 800 (34.5%) were female. During the first week from ICU admission, no-basic TIL was used in 382 (16.5%) patients, mild-moderate in 1643 (70.8%), and extreme in 295 cases (eTIL, 12.7%). Patients who received eTIL were younger (median age 49 (I-III quartiles = 35-62) vs 56 (40-69) years, p < 0.001), with less cardiovascular pre-injury comorbidities (859 (44%) vs 90 (31.4%), p < 0.001), with more episodes of neuroworsening (160 (56.1%) vs 653 (33.3%), p < 0.001), and were more frequently monitored with an ICP device (221 (74.9%) vs 1037 (51.2%), p < 0.001). Considerable variability in the frequency of use and type of eTIL adopted was observed between centres and countries. At six months, patients who received no-basic TIL had an increased risk of mortality (Hazard ratio, HR = 1.612, 95% Confidence Interval, CI = 1.243-2.091, p < 0.001) compared to patients who received eTIL. No difference was observed when comparing mild-moderate TIL with eTIL (HR = 1.017, 95% CI = 0.823-1.257, p = 0.873). No significant association between the use of TIL and neurological outcome was observed. Conclusions: During the first week of ICU admission, therapies to control high ICP are frequently used, especially mild-moderate TIL. In selected patients, the use of aggressive strategies can have a beneficial effect on six months mortality but not on neurological outcome