IB Hochschule

The concurrent delivery of multiple infusion solutions (Y-site administration) through asingle catheter lumen in intensive care patients is often unavoidable. This may lead to physicochemical incompatibilities, significantly affecting the efficacy and safety of drug therapy. The objective of this study is to develop and formulate an infusion regimen that considers the number of access points and avoids incompatibilities for adult intensive care patients. Acomprehensive literature search was conducted following the ADKA-DIVI standard concentration list for continuous infusions. Manufacturer information and databases, such as STABILIS, Kingguide, and Trissel's TM2IV Compatibility, were used to evaluate compatibility. For frequently used combinations for which no compatibility data were available, stability data on physical compatibility were compiled. Based on this, considering 34common active ingredients and their standard concentrations, a4-lumen central venous catheter (CVC) infusion regimen was developed to help avoid incompatibilities in the adult intensive care unit.

Abstract Objective People with Parkinson’s disease (PD) who carry a pathogenic GBA1 variant (PD GBA1 ) are at higher risk of cognitive impairment than those without the variant (PD GBA1_wildtype ). To date, little is known about the pattern and evolution of cognitive decline in PD GBA1 . This multi-center study characterized the cognitive profile of PD GBA , focusing on the longitudinal trajectories and the group-specific onset times among cognitive functions, as well as their clinical relevance. Methods In this longitudinal multicohort-study (PPMI, ABC-PD, Luxembourg Parkinson’s Study), comprehensive neuropsychological assessments were standardized across 548 healthy controls (follow-up-years=2.84±4.33), 906 PD GBA1_wildtype (follow-up-years=4.29±4.16), and 210 PD GBA1 (follow-up-years=4.09±3.35). We evaluated performance across age and disease duration using regression (generalized) linear mixed models within each cognitive domain. Time-to-first-event models, assessing risks of clinically relevant performance impairment (test-score z ≤-1.5, MoCA<26), and an expanding-time-window approach identified the course of cognitive impairment. Additionally, correlations between cognitive functions were calculated. Results At baseline, PD GBA1 showed lower performance in attention (processing speed) and memory (verbal learning) than PD GBA1_wildtype , but more widespread probability of performance impairment. Over time, attention, visuoperception, memory, and semantic fluency performance declined more rapidly in PD GBA1 compared to PD GBA1_wildtype . Impairment in processing speed occurred earlier in the disease process of PD GBA1 . Risks for clinically relevant cognitive impairment in PD GBA1 during the disease course were generally increased. Moderate-to-strong correlations between cognitive functions were observed within and across cognitive domains in PD GBA1 and PD GBA1_wildtype , particularly in attentional-executive functions. Interpretation PD GBA1 exhibits accelerated domain-generalized cognitive decline compared to PD GBA1_wildtype , with susceptibility of semantic fluency, attention, and memory. Summary for Social Media If you and/or a co-author has a X handle that you would like to be tagged, please enter it here. (format: @AUTHORSHANDLE) . None What is the current knowledge on the topic? (one to two sentences) Pathogenic coding variants in the Glucocerebrosidase (GBA1) gene in Parkinson’s Disease (PD-GBA1) are linked to more severe cognitive impairment. However, the domain-specific trajectories of cognitive decline are currently unknown. What question did this study address? (one to two sentences) This study aimed to analyze the course of longitudinal cognitive profile in PD-GBA1 across disease duration and age in regard to cognitive domains and clinical relevance. What does this study add to our knowledge? (one to two sentences) PD-GBA1 exhibits accelerated cognitive decline with susceptibility of semantic fluency, attention, and memory. Cognitive decline risk elevated 2-to-3 years post-diagnosis. How might this potentially impact on the practice of neurology? (one to two sentences) The results can help to identify individuals at risk of cognitive decline and to better design clinical trials aiming at disease modification with cognition as endpoint.

One-third of Parkinson disease (PD) patients with PD-mild cognitive impairment (PD-MCI) convert to dementia within a few years. Markers with a high prognostic value for dementia conversion are needed. Loss of everyday function primarily caused by cognitive dysfunction is the core criterion for the diagnosis of PD dementia, with an onset of more complex instrumental activities of daily living (IADL) dysfunction in the prodromal stage. This study evaluated the phenotype associated with cognitive IADL impairment and its predictive value for defining a high-risk group for PD dementia. An observational longitudinal study using cognitive and clinical scores in addition to genetic and CSF biomarkers was conducted. The Functional Activities Questionnaire quotient (cut-off ≥1), indicating more cognitive than motor-driven IADL impairment, defined cognitive IADL impairment status at baseline. Hazard ratios (HRs) were used to compare the impact of baseline classifications on dementia conversion. Of 268 patients with PD assessed at baseline, 108 (40.3%) had PD-MCI. After a period of 3.78 ± 0.84 years, 164 (61.2%) patients were reassessed. At follow-up, 93 (56.7%) patients had no cognitive impairment, 54 (32.9%) fulfilled PD-MCI criteria, and 17 (10.4%) had developed dementia. The HR of baseline cognitive IADL impairment (n = 37) for dementia conversion was descriptively higher than for PD-MCI, but highest in patients with both markers (HR = 12.01, 95% CI 4.47-32.22, p < 0.001). In the follow-up sample, nearly half of the patients (n = 10, 47.6%) with baseline classification of cognitive IADL impairment and PD-MCI converted to dementia. Baseline status of cognitive IADL impairment was associated with higher nonmotor burden, worse cognitive performance, and more severe IADL progression over the study period. The importance of differentiating between cognitive and motor aspects on ADL function in PD and monitoring cognitive ADL impairment in the prodromal stage of dementia is paramount. Patients with PD-MCI and cognitive IADL impairment may be a valuable target group for clinical trials aiming to slow down the development of dementia. ClinicalTrials.gov NCT03687203. This study provides Class II evidence that impairment of cognitive activities of daily living is associated with progression from MCI to dementia among patients with Parkinson disease.

Cognitive impairment is among the most burdensome non-motor symptoms in Parkinson's disease (PD) and has been associated with hippocampal atrophy. Exercise has been reported to enhance neuroplasticity in the hippocampus in correlation with an improvement of cognitive function. We present data from the Training-PD study, which was designed to evaluate effects of an "" training protocol on neuronal plasticity in PD. We initiated a 6-week exergaming training program, combining visually stimulating computer games with physical exercise in 17 PD patients and 18matched healthy controls. Volumetric segmentation of hippocampal subfields on T1- and T2-weighted magnetic resonance imaging and brain-derived neurotrophic factor (BDNF) serum levels were analyzed before and after the training protocol. The PD group showed a group-dependent significant volume increase of the left hippocampal subfields CA1, CA4/dentate gyrus (DG) and subiculum after the 6-week training protocol. The effect was most pronounced in the left DG of PD patients, who showed a significantly smaller percentage volume compared to healthy controls at baseline, but not at follow-up. Both groups had a significant increase in serum BDNF levels after training. The results of the present study indicate that exergaming might be a suitable approach to induce hippocampal volume changes in PD patients. Further and larger studies are needed to verify our findings.

BackgroundThe MIDAS is the most used questionnaire to evaluate migraine-related disability, but its utility to assess treatment response remains unclear. Our aim was to estimate the MIDAS’ minimal important change (MIC) value and its responsiveness.MethodsA total of 103 patients were enrolled in a non-pharmacological, preference-based clinical trial. MIDAS and global rating of self-perceived change (GRoC) scores were collected at baseline, after 5 weeks of treatment, 4-weeks and 3-months follow-up after treatment. Anchor-based approaches were used to establish MIC values and responsiveness.FindingsIn all 3 timepoint comparisons, MIDAS presented a MIC of 4.5 points. A moderate positive correlation was identified between the MIDAS change and GRoC scores. The area under the curve ranged from 0.63 to 0.68.ConclusionsThis study showed that MIDAS has a limited responsiveness to change. A change of 4.5 points or more represents a clinically important change for patients with high frequent migraine and chronic migraine receiving non-pharmacological treatment.