Neurobiologische Korrelate der Belohnungs- und Suchtreizverarbeitung im Rahmen der Alkoholabhängigkeit und deren pharmakologische Modifikation mit Baclofen

Hintergrund: In der Erforschung alkoholbezogener psychischer Störungen konnte festgestellt werden, dass eine veränderte neurobiologische Verarbeitung des mesokortikolimbischen dopaminergen Systems, des sogenannten Belohnungssystems, vorliegt. In den letzten Jahren rückten vermehrt pharmakologische Behandlungsansätze der Alkoholabhängigkeit in den Fokus, mit überwiegend moderaten Effekten. Einen derzeit diskutierten Therapieansatz stellt die Off-Label Behandlung mit dem GABAB-Rezeptor Agonisten Baclofen zur Abstinenzerhaltung als auch zur Trinkmengenreduktion dar. Methodik: In dieser publikationsbasierten Dissertationsschrift wurden zunächst die pharmakologischen Effekte von individuell titriertem Hochdosis-Baclofen bezüglich der assoziierten Abstinenzraten bei alkoholabhängigen Patient*innen in einer klinischen Studie analysiert (Publikation 1). Diese Patient*innen wurden in Publikation 2 mittels sogenannten pharmako-fMRT-Ansatzes untersucht. Dieser Ansatz umfasst die Kombination aus der Behandlung mit Baclofen und der neurobiologischen Untersuchung mittels funktioneller Magnetresonanztomografie (fMRT) zu zwei Messzeitpunkten; vor und nach zweiwöchiger Behandlung mit Baclofen oder Placebo. Gegenstand von Publikation 2 war demnach die zusätzliche Aussage über die assoziierte neuronale Sucht-Reiz-Verarbeitung dieser Patient*innen mittels Cue-Reactivity Paradigma, welches die Reaktion auf alkoholbezogene Reize abbildet. Im Gegensatz dazu wurde in Publikation 3 die nicht-sucht-relatierte neuronale Belohnungsverarbeitung während der Belohnungsantizipation von Geldgewinnen im MRT bei gesunden Jugendlichen mit dem Slot Machine Paradigma untersucht, einem herkömmlich als „einarmigen Banditen“ bezeichneten Spielautomaten. Ergebnisse: Bei der Behandlung mit individuellem Hochdosis-Baclofen konnten signifikant höhere Abstinenzraten in der Baclofen- als in der Placebo-Gruppe berichtet werden (Publikation 1). Mittels Pharmako-fMRT-Ansatzes konnte eine Reduktion der neuronalen Aktivierung bei der Verarbeitung alkohol-relatierter Reize in der Baclofen- im Vergleich zur Placebo-Gruppe beobachtet werden (Publikation 2). Gesunde Jugendliche wiesen eine veränderte Belohnungsantizipation auf, wenn sie eine irrtümliche Kontrollüberzeugung, den Spielautomaten beeinflussen zu können („Illusion of Control; IOC“), innehatten (Publikation 3). Diskussion: Die genannten Studienergebnisse leisten einen wichtigen Beitrag in der Evaluierung der Behandlung mit Baclofen bei alkoholabhängigen Patient*innen und geben zudem Hinweise auf die zugrundeliegenden neurobiologischen Mechanismen, im Speziellen auf die Verarbeitung belohnungsanzeigender, alkohol-relatierter Reize. Bei gesunden Jugendlichen führte der Faktor einer irrtümlichen Kontrollüberzeugung („IOC“) zu einer veränderten Belohnungsverarbeitung und könnte eine mögliche Prädisposition für eine spätere Suchtentwicklung (z. B. Spielsucht) darstellen. Zusammenfassend trägt die publikationsbasierte Arbeit zum weiteren Verständnis der Alkoholabhängigkeit bei und gibt wichtige Hinweise auf die neurobiologische Funktionsweise eines vielversprechenden pharmakologischen Behandlungsansatzes mit Baclofen.Background: In the course of alcohol dependence, an altered neurobiological processing in the mesocorticolimbic dopaminergic system – the so-called reward system – has been shown. The current pharmacological treatment options for alcohol-dependent patients showed only modest effects. Newsworthy, baclofen a GABAB-receptor agonist has been investigated to prevent relapse behavior or to support alcohol reduction in alcohol-dependent patients. Methods: In this publication-based dissertation, the pharmacological effects of baclofen on abstinence rates in alcohol-dependent patients have been investigated in a clinical trial (publication 1). These patients were also enrolled with a so-called pharmaco-fMRI approach in publication 2. Pharmaco-fMRI is described as a combination of pharmacological treatment with baclofen or placebo and the neurobiological investigation using functional magnetic resonance imaging (fMRI) at baseline and after two weeks of individual titrated high-dose intake. During fMRI, a cue-reactivity paradigm comprising the presentation of alcohol- and non-alcohol-related stimuli, has been conducted twice. In publication 3, the processing of non-drug-related stimuli has been investigated via a slot machine paradigm with a focus on the anticipation phase of monetary gains. Results: Pharmacological treatment with individual high-dose baclofen revealed superiority over placebo in terms of abstinence rates (publication 1). Using pharmaco-fMRI, a reduced activation was observed during an alcohol-associated cue-reactivity paradigm in the baclofen compared to placebo group (study 2). FMRI investigation during non-drug-related gain anticipation revealed higher fronto-striatal activation in adolescents who misconceived an “illusion of control” (IOC group) compared to the noIOC group (adolescents who had no illusion of control). Discussion: The results significantly contribute to the evaluation of the treatment with individual high-dose baclofen in alcohol-dependent patients sustaining abstinence behavior. Furthermore, the associated neurobiological findings might indicate a rehabilitation effect. Illusion of control during neural gain anticipation might further predispose adolescents to a development of addiction-related problems like gambling disorders. In summary, the present publication-based dissertation contributes to the understanding of alcohol dependence and provides important new insights into the neurobiological mode of action during a new promising pharmacological treatment with baclofen

Classroom Interpreting and Visual Information Processing in Mainstream Education for Deaf Students: Live or Memorex?

This study examined visual information processing and learning in classrooms including both deaf and hearing students. Of particular interest were the effects on deaf students’ learning of live (threedimensional) versus video-recorded (two-dimensional) sign language interpreting and the visual attention strategies of more and less experienced deaf signers exposed to simultaneous, multiple sources of visual information. Results from three experiments consistently indicated no differences in learning between three-dimensional and two-dimensional presentations among hearing or deaf students. Analyses of students’ allocation of visual attention and the influence of various demographic and experimental variables suggested considerable flexibility in deaf students’ receptive communication skills. Nevertheless, the findings also revealed a robust advantage in learning in favor of hearing students

Measuring self-regulation in everyday life: reliability and validity of smartphone-based experiments in alcohol use disorder

Self-regulation, the ability to guide behavior according to one’s goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test–retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures’ construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks

Measuring self-regulation in everyday life: Reliability and validity of smartphone-based experiments in alcohol use disorder

Self-regulation, the ability to guide behavior according to one's goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test-retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures' construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks

Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany

Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002). Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Patrones de emisión de gases de efecto invernadero y medidas de mitigación en el Delta del Paraná, Argentina

El objetivo general del presente informe técnico es conocer los patrones de emisión y las absorciones de gases de efecto invernadero en el Delta superior, medio e inferior del Paraná, considerando aquellos actores y actrices que tienen más incidencia en la toma de decisiones y responsabilidad en las emisiones y la absorción de gases efecto invernadero (GEI) en el área. El Delta del Paraná es un mosaico de humedales que cubren una superficie aproximada de 27500 km2 que se despliega sobre las provincias de Buenos Aires, Santa Fe y Entre Ríos, siendo esta última la que mayor porcentaje de superficie abarca. El Delta brinda una variedad de servicios ambientales que permiten llevar adelante distintas actividades socioeconómicas. El conflicto de intereses entre estos dos aspectos pone de relieve la tensión que existe entre la protección de los humedales y las actividades productivas. El análisis de los patrones de emisión y de absorción de GEI de las tres provincias objeto del estudio muestra que el sector de energía y el subsector de ganadería (perteneciente al sector Agricultura, Ganadería, Silvicultura y Otros Usos de la Tierra [AGSyOUT]) son los que más GEI emiten. Para este informe, se tuvo en cuenta el mapeo de actores y actrices con mayor incidencia en el Delta del Paraná en cuanto a emisiones y absorciones de GEI, y a los responsables de la mitigación a nivel local. Sólo Santa Fe y Buenos Aires elaboraron sus propios inventarios de GEI. Y se trabajó con la información proveniente del inventario de GEI nacional con base en el año 2016. Vale aclarar que en ningún inventario, a la fecha, se ha incorporado el subsector humedales. En este informe, se incluyen algunas de las medidas de mitigación a nivel nacional propuestas en los diferentes planes de acción nacional y, luego, se especifican dichas propuestas haciendo foco en nuestro caso de estudio, poniendo especial énfasis en la transversalidad de género.Fil: Bianco, Cecilia. Universidad Nacional de Rosario; Argentina.Fil: Guitman, Stephanie. Universidad Nacional de Rosario; Argentina.Fil: Pelz, Claudia Patricia. Universidad Nacional de Rosario; Argentina.Fil: Tarragona, Verónica. Universidad Nacional de Rosario; Argentina