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Background & Aim: The resistance profile of anti-hepatitis C virus (HCV) agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT)-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor), deleobuvir (HCV polymerase non-nucleoside inhibitor), and ribavirin in multiple clinical studies.
Methods: HCV NS3/4A and NS5B population sequencing (Sanger method) was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B) and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b). Persistence and time to loss of resistance-associated variants (RAVs) was estimated using Kaplan–Meier analysis.
Results: Faldaprevir RAVs (NS3 R155 and D168) and deleobuvir RAVs (NS5B 495 and 496) were rare (<1%) at baseline. Virologic response to faldaprevir/deleobuvir/ribavirin was not compromised by common baseline NS3 polymorphisms (e.g. Q80K in 17.5% of GT-1a) or by NS5B A421V, present in 20% of GT-1a. In GT-1b, alanine at NS5B codon 499 (present in 15% of baseline sequences) was associated with reduced response. Treatment-emergent RAVs consolidated previous findings: NS3 R155 and D168 were key faldaprevir RAVs; NS5B A421 and P495 were key deleobuvir RAVs. Among on-treatment virologic breakthroughs, RAVs emerged in both NS3 and NS5B (>90%). Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b); some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b). Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months) was less than that of GT-1b NS3 D168 (8.5 months) and GT-1a R155 RAVs (11.5 months).
Conclusion: Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a, polymorphism in GT-1b) may reduce response to this deleobuvir-based regimen.
Multimorbidity is a health issue mostly dealt with in primary care practice. As a result of their generalist and patient-centered approach, long-lasting relationships with patients, and responsibility for continuity and coordination of care, family physicians are particularly well placed to manage patients with multimorbidity. However, conflicts arising from the application of multiple disease oriented guidelines and the burden of diseases and treatments often make consultations challenging. To provide orientation in decision making in multimorbidity during primary care consultations, we developed guiding principles and named them after the Greek mythological figure Ariadne. For this purpose, we convened a two-day expert workshop accompanied by an international symposium in October 2012 in Frankfurt, Germany. Against the background of the current state of knowledge presented and discussed at the symposium, 19 experts from North America, Europe, and Australia identified the key issues of concern in the management of multimorbidity in primary care in panel and small group sessions and agreed upon making use of formal and informal consensus methods. The proposed preliminary principles were refined during a multistage feedback process and discussed using a case example. The sharing of realistic treatment goals by physicians and patients is at the core of the Ariadne principles. These result from i) a thorough interaction assessment of the patient’s conditions, treatments, constitution, and context; ii) the prioritization of health problems that take into account the patient's preferences – his or her most and least desired outcomes; and iii) individualized management realizes the best options of care in diagnostics, treatment, and prevention to achieve the goals. Goal attainment is followed-up in accordance with a re-assessment in planned visits. The occurrence of new or changed conditions, such as an increase in severity, or a changed context may trigger the (re-)start of the process. Further work is needed on the implementation of the formulated principles, but they were recognized and appreciated as important by family physicians and primary care researchers.
Purpose: While more advanced COVID-19 necessitates medical interventions and hospitalization, patients with mild COVID-19 do not require this. Identifying patients at risk of progressing to advanced COVID-19 might guide treatment decisions, particularly for better prioritizing patients in need for hospitalization.
Methods: We developed a machine learning-based predictor for deriving a clinical score identifying patients with asymptomatic/mild COVID-19 at risk of progressing to advanced COVID-19. Clinical data from SARS-CoV-2 positive patients from the multicenter Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) were used for discovery (2020-03-16 to 2020-07-14) and validation (data from 2020-07-15 to 2021-02-16).
Results: The LEOSS dataset contains 473 baseline patient parameters measured at the first patient contact. After training the predictor model on a training dataset comprising 1233 patients, 20 of the 473 parameters were selected for the predictor model. From the predictor model, we delineated a composite predictive score (SACOV-19, Score for the prediction of an Advanced stage of COVID-19) with eleven variables. In the validation cohort (n = 2264 patients), we observed good prediction performance with an area under the curve (AUC) of 0.73 ± 0.01. Besides temperature, age, body mass index and smoking habit, variables indicating pulmonary involvement (respiration rate, oxygen saturation, dyspnea), inflammation (CRP, LDH, lymphocyte counts), and acute kidney injury at diagnosis were identified. For better interpretability, the predictor was translated into a web interface.
Conclusion: We present a machine learning-based predictor model and a clinical score for identifying patients at risk of developing advanced COVID-19.
Feeding type and development drive the ingestion of microplastics by freshwater invertebrates
(2017)
Microscopic plastic items (microplastics) are ubiquitously present in aquatic ecosystems. With decreasing size their availability and potential to accumulate throughout food webs increase. However, little is known on the uptake of microplastics by freshwater invertebrates. To address this, we exposed species with different feeding strategies to 1, 10 and 90 µm fluorescent polystyrene spheres (3–3 000 particles mL−1). Additionally, we investigated how developmental stages and a co-exposure to natural particles (e.g., food) modulate microplastic ingestion. All species ingested microplastics in a concentration-dependent manner with Daphnia magna consuming up to 6 180 particles h−1, followed by Chironomus riparius (226 particles h−1), Physella acuta (118 particles h−1), Gammarus pulex (10 particles h−1) and Lumbriculus variegatus (8 particles h−1). D. magna did not ingest 90 µm microplastics whereas the other species preferred larger microplastics over 1 µm in size. In C. riparius and D. magna, size preference depended on the life stage with larger specimens ingesting more and larger microplastics. The presence of natural particles generally reduced the microplastics uptake. Our results demonstrate that freshwater invertebrates have the capacity to ingest microplastics. However, the quantity of uptake depends on their feeding type and morphology as well as on the availability of microplastics.
Background: While the use of plastic materials has generated huge societal benefits, the "plastic age" comes with downsides: One issue of emerging concern is the accumulation of plastics in the aquatic environment. Here, so-called microplastics (MP), fragments smaller than 5 mm, are of special concern because they can be ingested throughout the food web more readily than larger particles. Focusing on freshwater MP, we briefly review the state of the science to identify gaps of knowledge and deduce research needs.
State of the science: Environmental scientists started investigating marine (micro)plastics in the early 2000s. Today, a wealth of studies demonstrates that MP have ubiquitously permeated the marine ecosystem, including the polar regions and the deep sea. MP ingestion has been documented for an increasing number of marine species. However, to date, only few studies investigate their biological effects. The majority of marine plastics are considered to originate from land-based sources, including surface waters. Although they may be important transport pathways of MP, data from freshwater ecosystems is scarce. So far, only few studies provide evidence for the presence of MP in rivers and lakes. Data on MP uptake by freshwater invertebrates and fish is very limited.
Knowledge gaps: While the research on marine MP is more advanced, there are immense gaps of knowledge regarding freshwater MP. Data on their abundance is fragmentary for large and absent for small surface waters. Likewise, relevant sources and the environmental fate remain to be investigated. Data on the biological effects of MP in freshwater species is completely lacking. The accumulation of other freshwater contaminants on MP is of special interest because ingestion might increase the chemical exposure. Again, data is unavailable on this important issue.
Conclusions: MP represent freshwater contaminants of emerging concern. However, to assess the environmental risk associated with MP, comprehensive data on their abundance, fate, sources, and biological effects in freshwater ecosystems are needed. Establishing such data critically depends on a collaborative effort by environmental scientists from diverse disciplines (chemistry, hydrology, ecotoxicology, etc.) and, unsurprisingly, on the allocation of sufficient public funding.
Microplastics (MP) are contaminants of emerging concern in aquatic ecosystems. While the number of studies is rapidly increasing, a comparison of the toxicity of MP and natural particulate matter is largely missing. In addition, research focusses on the impacts of hydrophobic chemicals sorbed to plastics. However, the interactive effects of MP and hydrophilic, dissolved chemicals remain largely unknown. Therefore, we conducted chronic toxicity studies with larvae of the freshwater dipteran Chironomus riparius exposed to unplasticised polyvinyl chloride MP (PVC-MP) as well as kaolin and diatomite as reference materials for 28 days. In addition, we investigated the effects of particles in combination with the neonicotinoid imidacloprid in a multiple-stressor experiment. High concentrations of kaolin positively affected the chironomids. In contrast, exposure to diatomite and PVC-MP reduced the emergence and mass of C. riparius. Likewise, the toxicity of imidacloprid was enhanced in the presence of PVC-MP and slightly decreased in the co-exposure with kaolin. Overall, parallel experiments and chemical analysis indicate that the toxicity of PVC-MP was not caused by leached or sorbed chemicals. Our study demonstrates that PVC-MP induce more severe effects than both natural particulate materials. However, the latter are not benign per se, as the case of diatomite highlights. Considering the high, environmentally irrelevant concentrations needed to induce adverse effects, C. riparius is insensitive to exposures to PVC-MP.
Background: The elderly population deals with multimorbidity (three chronic conditions) and increasinged drug use with age. A comprehensive characterisation of the medication – including prescription and over-the-counter (OTC) drugs – of elderly patients in primary care is still insufficient.
Objectives: This study aims to characterise the medication (prescription and OTC) of multimorbid elderly patients in primary care and living at home by identifying drug patterns to evaluate the relationship between drugs and drug groups and reveal associations with recently published multimorbidity clusters of the same cohort.
Methods: MultiCare was a multicentre, prospective, observational cohort study of 3189 multimorbid patients aged 65 to 85 years in primary care in Germany. Patients and general practitioners were interviewed between 2008 and 2009. Drug patterns were identified using exploratory factor analysis. The relations between the drug patterns with the three multimorbidity clusters were analysed with Spearman-Rank-Correlation.
Results: Patients (59.3% female) used in mean 7.7 drugs; in total 24,535 drugs (23.7% OTC) were detected. Five drug patterns for men (drugs for obstructive pulmonary diseases (D-OPD), drugs for coronary heart diseases and hypertension (D-CHD), drugs for osteoporosis (D-Osteo), drugs for heart failure and drugs for pain) and four drug patterns for women (D-Osteo, D-CHD, D-OPD and drugs for diuretics and gout) were detected. Significant associations between multimorbidity clusters and drug patterns were detectable (D-CHD and CMD: male: ρ = 0.376, CI 0.322–0.430; female: ρ = 0.301, CI 0.624–0.340).
Conclusion: The drug patterns demonstrate non-random relations in drug use in multimorbid elderly patients and systematic associations between drug patterns and multimorbidity clusters were found in primary care.
The toxicity of microplastics on Daphnia magna as key model for freshwater zooplankton is well described. While several studies predict population-level effects based on short-term, individual-level responses, only very few have validated these predictions experimentally. Thus, we exposed D. magna populations to irregular polystyrene microplastics and diatomite as natural particle (both ≤63 µm) over 50 days. We used mixtures of both particle types at fixed particle concentrations (50,000 mL-1) and recorded the overall population density, the size of the individual animals, and resting egg production. Particle exposure adversely affected the population density and structure and induced resting egg production. The terminal population size was 31–42% lower in exposed compared to control populations. Interestingly, mixtures containing diatomite induced stronger effects than microplastics alone highlighting that natural particles are not per se less toxic than microplastics. Our results demonstrate that an exposure to synthetic and natural particles has negative population-level effects on zooplankton. Understanding the mixture toxicity of microplastics and natural particles is important given that aquatic organisms will experience exposure to both. Just as for chemical pollutants, better knowledge of such joint effects is essential to fully understand the environmental risks of complex particle mixtures.
Environmental Implications While microplastics are commonly considered hazardous based on individual-level effects, there is a dearth of information on how they affect populations. Since the latter is key for understanding the environmental impacts of microplastics, we investigated how particle exposures affect the population size and structure of Daphnia magna. In addition, we used mixtures of microplastics and natural particles because neither occurs alone in nature and joint effects can expected in an environmentally realistic scenario. We show that such mixtures adversely affect daphnid populations and highlight that population-level and mixture-toxicity designs are one important step towards more environmental realism in microplastics research.
The toxicity of microplastics on Daphnia magna as a key model for freshwater zooplankton is well described. While several studies predict population-level effects based on short-term, individual-level responses, only very few have validated these predictions experimentally. Thus, we exposed D. magna populations to irregular polystyrene microplastics and diatomite as natural particle (both ≤ 63 μm) over 50 days. We used mixtures of both particle types at fixed particle concentrations (50,000 mL-1) and recorded the effects on overall population size and structure, the size of the individual animals, and resting egg production. Particle exposure adversely affected the population density and structure, and induced resting egg production. The terminal population size was 28–42% lower in exposed compared to control populations. Interestingly, mixtures containing diatomite induced stronger effects than microplastics alone, highlighting that natural particles are not per se less toxic than microplastics. Our results demonstrate that an exposure to synthetic and natural particles has negative population-level effects on zooplankton. Understanding the mixture toxicity of microplastics and natural particles is important given that aquatic organisms will experience exposure to both. Just as for chemical pollutants, better knowledge of such joint effects is essential to fully understand the environmental impacts of complex particle mixtures.
Environmental Implications While microplastics are commonly considered hazardous based on individual-level effects, there is a dearth of information on how they affect populations. Since the latter is key for understanding the environmental impacts of microplastics, we investigated how particle exposures affect the population size and structure of Daphnia magna. In addition, we used mixtures of microplastics and natural particles because neither occurs alone in nature and joint effects can be expected in an environmentally realistic scenario. We show that such mixtures adversely affect daphnid populations and highlight that population-level and mixture-toxicity designs are one important step towards more environmental realism in microplastics research.
Background: Critical organ shortage results in the utilization of extended donor criteria (EDC) liver grafts. These marginal liver grafts are prone to increased ischemia reperfusion injury (IRI) which may contribute to deteriorated graft function and survival. Experimental data have shown that the calcineurin inhibitor tacrolimus exerts protective effects on hepatic IRI when applied intravenously or directly as a hepatic rinse. Therefore, the aim of the present study is to examine the effects of an ex vivo tacrolimus perfusion on IRI in transplantation of EDC liver grafts.
Methods/Design: The TOP-Study (tacrolimus organ perfusion) is a randomized multicenter trial comparing the ex vivo tacrolimus perfusion of marginal liver grafts with placebo. We hypothesize that a tacrolimus rinse reduces IRI, potentially improving organ survival following transplantation of EDC livers. The study includes livers with two or more EDC, according to Eurotransplant International Foundation’s definition of EDC livers. Prior to implantation, livers randomized to the treatment group are rinsed with tacrolimus at a concentration of 20 ng/ml in 1000 ml Custodiol solution and in the placebo group with Custodiol alone. The primary endpoint is the maximum serum alanine transamninase (ALT) level within the first 48 hours after surgery; however, the study design also includes a 1-year observation period following transplantation. The TOP-Study is an investigator-initiated trial sponsored by the University of Munich Hospital. Seven other German transplant centers are participating (Berlin, Frankfurt, Heidelberg, Mainz, Münster, Regensburg, Tübingen) and aim to include a total of 86 patients.
Discussion: Tacrolimus organ perfusion represents a promising strategy to reduce hepatic IRI following the transplantation of marginal liver grafts. This treatment may help to improve the function of EDC grafts and therefore safely expand the donor pool in light of critical organ shortage.
Trial register: EudraCT number: 2010-021333-31, ClinicalTrials.gov identifier: NCT01564095
Aquatic ecosystems are globally contaminated with microplastics (MP). However, comparative data on MP levels in freshwater systems is still scarce. Therefore, the aim of this study is to quantify MP abundance in water and sediment of the German river Elbe using visual, spectroscopic (Fourier-transform infrared spectroscopy) and thermo analytical (pyrolysis gas chromatography mass spectrometry) methods. Samples from eleven German sites along the German part of the Elbe were collected, both in the water and sediment phase, in order to better understand MP sinks and transport mechanisms. MP concentrations differed between the water and sediment phase. Sediment concentrations (mean: 3,350,000 particles m−3, 125–5000 μm MP) were in average 600,000-fold higher than water concentrations (mean: 5.57 particles m−3, 150–5000 μm MP). The abundance varied between the sampling sites: In sediments, the abundance decreased in the course of the river while in water samples no such clear trend was observed. This may be explained by a barrage retaining sediments and limiting tidal influence in the upstream parts of the river. Particle shape differed site-specifically with one site having exceptionally high quantities of spheres, most probably due to industrial emissions of PS-DVB resin beads. Suspended MP consisted predominantly of polyethylene and polypropylene whereas sediments contained a higher diversity of polymer types. Determined MP concentrations correspond well to previous results from other European rivers. In a global context, MP levels in the Elbe relate to the lower (water) to middle section (sediment) of the global range of MP concentrations determined for rivers worldwide. This highlights that elevated MP levels are not only found in single countries or continents, but that MP pollution is an issue of global concern.
The ubiquitous detection of microplastics in aquatic ecosystems promotes the concern for adverse impacts on freshwater ecosystems. The wide variety of material types, sizes, shapes, and physicochemical properties renders interactions with biota via multiple pathways probable.
So far, our knowledge about the uptake and biological effects of microplastics comes from laboratory studies, applying simplified exposure regimes (e.g., one polymer and size, spherical shape, high concentrations) often with limited environmental relevance. However, the available data illustrates species- and material-related interactions and highlights that microplastics represent a multifaceted stressor. Particle-related toxicities will be driven by polymer type, size, and shape. Chemical toxicity is driven by the adsorption-desorption kinetics of additives and pollutants. In addition, microbial colonization, the formation of hetero-aggregates, and the evolutionary adaptations of the biological receptor further increase the complexity of microplastics as stressors. Therefore, the aim of this chapter is to synthesize and critically revisit these aspects based on the state of the science in freshwater research. Where unavailable we supplement this with data on marine biota. This provides an insight into the direction of future research.
In this regard, the challenge is to understand the complex interactions of biota and plastic materials and to identify the toxicologically most relevant characteristics of the plethora of microplastics. Importantly, as the direct biological impacts of natural particles may be similar, future research needs to benchmark synthetic against natural materials. Finally, given the scale of the research question, we need a multidisciplinary approach to understand the role of microplastics in a multiple-particle world.
Rezensionen [2017]
(2017)
156 Ansari, Christine (Hrsg.): Adoleszenz in Medienkontexten. Literaturrezeption, Medienwirkung und Jugendmedienschutz (judith mathez)
158 Bachmann, Christian A. / Emans, Laura / Schmitz-Emans, Monika (Hrsg.): Bewegungsbücher. Spielformen, Poetiken, Konstellationen (gundel mattenklott)
160 Ballis, Anja /Schlachter, Birgit (Hrsg.): Schätze der Kinder- und Jugendliteratur wiederentdeckt. Frühe Lektüreerfahrung und Kanonbildung im akademischen Kontext (ernst seibert)
162 Benner, Julia: Federkrieg. Kinder- und Jugendliteratur gegen den Nationalsozialismus 1933 – 1945 (linde storm)
164 Born, Stefan: Allgemeinliterarische Adoleszenzromane. Untersuchungen zu Herrndorf, Regener, Strunk, Kehlmann und anderen (lena hoffmann)
166 Börnchen, Stefan: Poetik der Linie. Wilhelm Busch, Max und Moritz und die Tradition (lukas sarvari)
168 Burwitz-Melzer, Eva /O’Sullivan, Emer (Hrsg.): Einfachheit in der Kinder- und Jugendliteratur. Ein Gewinn für den Fremdsprachenunterricht (roland alexander issler)
169 Emde, Oliver /Möller, Lukas /Wicke, Andreas (Hrsg.): Von »Bibi Blocksberg« bis »TKKG«. Kinderhörspiele aus gesellschafts- und kulturwissenschaftlicher Perspektive (anika ullmann)
171 Ferstl, Paul /Walach, Thomas / Zahlmann, Stefan (Hrsg.): Fantasy Studies (maren bonacker)
173 Giesa, Felix: Graphisches Erzählen von Adoleszenz. Deutschsprachige Autorencomics nach 2000 (michael staiger)
175 Hahn, Heidi / Laudenberg, Beate / Rösch, Heidi (Hrsg.): »Wörter raus!?« Zur Debatte um eine diskriminierungsfreie Sprache im Kinderbuch (julia benner)
177 Haug, Christine / Frimmel, Johannes (Hrsg.): Schulbücher um 1800. Ein Spezialmarkt zwischen staatlichem, volksaufklärerischem und konfessionellem Auftrag (ortwin beisbart)
179 Hollerweger, Elisabeth /Stemmann, Anna (Hrsg.): Narrative Delikatessen. Kulturelle Dimensionen von Ernährung (sonja loidl)
180 Hopp, Margarete: Sterben, Tod und Trauer im Bilderbuch seit 1945 (iris schäfer)
182 Huemer, Georg: Mira Lobe. Doyenne der österreichischen Kinder- und Jugendliteratur (andreas schumann)
183 Josting, Petra (Hrsg.): Andreas Steinhöfel, Bielefelder Poet in Residence 2014 (heinke kilian)
185 Josting, Petra /Roeder, Caroline /Dettmar, Ute (Hrsg.): Immer Trouble mit Gender. Genderperspektiven in Kinder- und Jugendliteraturforschung und -medien (jana mikota)
187 Kurwinkel, Tobias /Schmerheim, Philipp /Sevi, Annika (Hrsg.): Michael Ende intermedial. Von Lokomotivführern, Glücksdrachen und dem (phantastischen) Spiel mit Mediengrenzen (michael stierstorfer)
188 Mikota, Jana / Pecher, Claudia Maria / von Glasenapp, Gabriele (Hrsg.): Literarisch-kulturelle Begegnungen mit dem Judentum. Beiträge zur kinderliterarischen Fachöffentlichkeit (susanne blumesberger)
190 Müller, Karla / Decker, Jan-Oliver / Krah, Hans / Schilcher, Anita (Hrsg.): Genderkompetenz mit Kinder- und Jugendliteratur entwickeln: Grundlagen – Analysen – Modelle (annette kliewer)
192 Nikolajeva, Maria: Reading for Learning. Cognitive Approaches to Children’s Literature (sabine fuchs)
194 Paul, Lissa / Johnston, Rosemary R. / Short, Emma (Hrsg.):Children’s Literature and Culture of the First World War.(julia benner)
195 Payrhuber, Franz-Josef / Meier, Bernhard(Hrsg.): Franz, Kurt: Kinderlyrik. Geschichte, Formen, Rezeption(ludger scherer)
197 Payrhuber, Franz-Josef:Gedichte entdecken. Wege zu Gedichten in der ersten bis sechsten Klasse (andreas schumann)
198 Pohlmann, Carola (Hrsg): Kinder- und Jugendliteratur. Sammeln und Erwerben (wolfgang wangerin)
200 Pompe, Anja (Hrsg): Kind und Gedicht. Wie wir lesen lernen (heinz-jürgen kliewer)
202 Preindl, Nadia:Russische Kinderliteratur im europäischen Exil der Zwischenkriegszeit (verena rutschmann)
204 Richter, Karin: Die Kinder- und Jugend-literatur der DDR. Entwicklungslinien – Themen und Genres. Autorenporträts und Textanalysen (maria becker)
206 Riemhofer, Andra:Interkulturelle Kinder- und Jugendliteratur in Deutschland. Lesen auf eigene Gefahr (roger meyer)
208Roeder, Caroline (Hrsg.): Himmel und Hölle. Raumerkundungen – interdisziplinär & in schulischer Praxis (claudia blei-hoch)
210 Ruzicka Kenfel, Vejka (Hrsg.): New Trends in Children’s Literature Research. Twenty-first Century Approaches (2000–2012) from the University of Vigo (Spain) (susanne blumesberger)
212 Schäfer, Iris:Von der Hysterie zur Magersucht. Adoleszenz und Krankheit in Romanen und Erzählungen der Jahrhundert- und der Jahrtausendwende (philipp schmerheim)
214 Scherer, Gabriela / Volz, Steffen (Hrsg.): Im Bildungsfokus: Bilderbuchrezeptions-forschung (margarete hopp)
216 Schmitt, Susann Sophie:Nachwuchs für die Literatur. Kinder- und Jugendprogramme ausgewählter Literaturhäuser Deutschlands, Österreichs und der Schweiz (renate grubert)
217 Seelinger Trites, Roberta:Literary Conceptu-alizations of Growth. Metaphors and Cogni-tion in Adolescent Literature (iris schäfer)
219 Seifert, Martina:Die Bilderfalle. Kanada in der deutschsprachigen Kinder- und Jugend-literatur: Produktion und Rezeption (sabine planka)
222 Stein, Daniel / Thon, Jan-Noël (Hrsg.): From Comic Strips to Graphic Novels. Contributions to the Theory and History of Graphic Narrative (anna stemmann)
223 Tomberg, Markus (Hrsg.): Alle wichtigen Bücher handeln von Gott. Religiöse Spuren in aktueller Kinder- und Jugendliteratur (martin anker)
Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.
Background: In primary care, patients with multiple chronic conditions are the rule rather than the exception. The Chronic Care Model (CCM) is an evidence-based framework for improving chronic illness care, but little is known about the extent to which it has been implemented in routine primary care. The aim of this study was to describe how multimorbid older patients assess the routine chronic care they receive in primary care practices in Germany, and to explore the extent to which factors at both the practice and patient level determine their views.
Methods: This cross-sectional study used baseline data from an observational cohort study involving 158 general practitioners (GP) and 3189 multimorbid patients. Standardized questionnaires were employed to collect data, and the Patient Assessment of Chronic Illness Care (PACIC) questionnaire used to assess the quality of care received. Multilevel hierarchical modeling was used to identify any existing association between the dependent variable, PACIC, and independent variables at the patient level (socio-economic factors, weighted count of chronic conditions, instrumental activities of daily living, health-related quality of life, graded chronic pain, no. of contacts with GP, existence of a disease management program (DMP) disease, self-efficacy, and social support) and the practice level (age and sex of GP, years in current practice, size and type of practice).
Results: The overall mean PACIC score was 2.4 (SD 0.8), with the mean subscale scores ranging from 2.0 (SD 1.0, subscale goal setting/tailoring) to 3.5 (SD 0.7, delivery system design). At the patient level, higher PACIC scores were associated with a DMP disease, more frequent GP contacts, higher social support, and higher autonomy of past occupation. At the practice level, solo practices were associated with higher PACIC values than other types of practice.
Conclusions: This study shows that from the perspective of multimorbid patients receiving care in German primary care practices, the implementation of structured care and counseling could be improved, particularly by helping patients set specific goals, coordinating care, and arranging follow-up contacts. Studies evaluating chronic care should take into consideration that a patient’s assessment is associated not only with practice-level factors, but also with individual, patient-level factors.
Background: It is not well established how psychosocial factors like social support and depression affect health-related quality of life in multimorbid and elderly patients. We investigated whether depressive mood mediates the influence of social support on health-related quality of life.
Methods: Cross-sectional data of 3,189 multimorbid patients from the baseline assessment of the German MultiCare cohort study were used. Mediation was tested using the approach described by Baron and Kenny based on multiple linear regression, and controlling for socioeconomic variables and burden of multimorbidity.
Results: Mediation analyses confirmed that depressive mood mediates the influence of social support on health-related quality of life (Sobel's p < 0.001). Multiple linear regression showed that the influence of depressive mood (beta = -0.341, p < 0.01) on health-related quality of life is greater than the influence of multimorbidity (beta = -0.234, p < 0.01).
Conclusion: Social support influences health-related quality of life, but this association is strongly mediated by depressive mood. Depression should be taken into consideration in research on multimorbidity, and clinicians should be aware of its importance when caring for multimorbid patients.
Introduction: In this article three research questions are addressed: (1) Is there an association between socioeconomic status (SES) and patient-reported outcomes in a cohort of multimorbid patients? (2) Does the association vary according to SES indicator used (income, education, occupational position)? (3) Can the association between SES and patient-reported outcomes (self-rated health, health-related quality of life and functional status) be (partly) explained by burden of disease?
Methods: Analyses are based on the MultiCare Cohort Study, a German multicentre, prospective, observational cohort study of multimorbid patients from general practice. We analysed baseline data and data from the first follow-up after 15 months (N = 2,729). To assess burden of disease we used the patients’ morbidity data from standardized general practitioner (GP) interviews based on a list of 46 groups of chronic conditions including the GP’s severity rating of each chronic condition ranging from marginal to very severe.
Results: In the cross-sectional analyses SES was significantly associated with the patient-reported outcomes at baseline. Associations with income were more consistent and stronger than with education and occupational position. Associations were partly explained (17% to 44%) by burden of disease. In the longitudinal analyses only income (but not education and occupational position) was significantly related to the patient-reported outcomes at follow-up. Associations between income and the outcomes were reduced by 18% to 27% after adjustment for burden of disease.
Conclusions: Results indicate social inequalities in self-rated health, functional status and health related quality of life among older multimorbid patients. As associations with education and occupational position were inconsistent, these inequalities were mainly due to income. Inequalities were partly explained by burden of disease. However, even among patients with a similar disease burden, those with a low income were worse off in terms of the three patient-reported outcomes under study.
Obesity and associated lifestyle in a large sample of multi-morbid German primary care attendees
(2014)
Background: Obesity and the accompanying increased morbidity and mortality risk is highly prevalent among older adults. As obese elderly might benefit from intentional weight reduction, it is necessary to determine associated and potentially modifiable factors on senior obesity. This cross-sectional study focuses on multi-morbid patients which make up the majority in primary care. It reports on the prevalence of senior obesity and its associations with lifestyle behaviors.
Methods: A total of 3,189 non-demented, multi-morbid participants aged 65–85 years were recruited in primary care within the German MultiCare-study. Physical activity, smoking, alcohol consumption and quantity and quality of nutritional intake were classified as relevant lifestyle factors. Body Mass Index (BMI, general obesity) and waist circumference (WC, abdominal obesity) were used as outcome measures and regression analyses were conducted.
Results: About one third of all patients were classified as obese according to BMI. The prevalence of abdominal obesity was 73.5%. Adjusted for socio-demographic variables and objective and subjective disease burden, participants with low physical activity had a 1.6 kg/m2 higher BMI as well as a higher WC (4.9 cm, p<0.001). Current smoking and high alcohol consumption were associated with a lower BMI and WC. In multivariate logistic regression, using elevated WC and BMI as categorical outcomes, the same pattern in lifestyle factors was observed. Only for WC, not current but former smoking was associated with a higher probability for elevated WC. Dietary intake in quantity and quality was not associated with BMI or WC in either model.
Conclusions: Further research is needed to clarify if the huge prevalence discrepancy between BMI and WC also reflects a difference in obesity-related morbidity and mortality. Yet, age-specific thresholds for the BMI are needed likewise. Encouraging and promoting physical activity in older adults might a starting point for weight reduction efforts.
Background: Multimorbidity is a common phenomenon in primary care. Until now, no clinical guidelines for multimorbidity exist. For the development of these guidelines, it is necessary to know whether or not patients are aware of their diseases and to what extent they agree with their doctor. The objectives of this paper are to analyze the agreement of self-reported and general practitioner-reported chronic conditions among multimorbid patients in primary care, and to discover which patient characteristics are associated with positive agreement.
Methods: The MultiCare Cohort Study is a multicenter, prospective, observational cohort study of 3,189 multimorbid patients, ages 65 to 85. Data was collected in personal interviews with patients and GPs. The prevalence proportions for 32 diagnosis groups, kappa coefficients and proportions of specific agreement were calculated in order to examine the agreement of patient self-reported and general practitioner-reported chronic conditions. Logistic regression models were calculated to analyze which patient characteristics can be associated with positive agreement.
Results: We identified four chronic conditions with good agreement (e.g. diabetes mellitus κ = 0.80;PA = 0,87), seven with moderate agreement (e.g. cerebral ischemia/chronic stroke κ = 0.55;PA = 0.60), seventeen with fair agreement (e.g. cardiac insufficiency κ = 0.24;PA = 0.36) and four with poor agreement (e.g. gynecological problems κ = 0.05;PA = 0.10).Factors associated with positive agreement concerning different chronic diseases were sex, age, education, income, disease count, depression, EQ VAS score and nursing care dependency. For example: Women had higher odds ratios for positive agreement with their GP regarding osteoporosis (OR = 7.16). The odds ratios for positive agreement increase with increasing multimorbidity in almost all of the observed chronic conditions (OR = 1.22-2.41).
Conclusions: For multimorbidity research, the knowledge of diseases with high disagreement levels between the patients' perceived illnesses and their physicians' reports is important. The analysis shows that different patient characteristics have an impact on the agreement. Findings from this study should be included in the development of clinical guidelines for multimorbidity aiming to optimize health care. Further research is needed to identify more reasons for disagreement and their consequences in health care.
Background: With increasing life expectancy the number of people affected by multimorbidity rises. Knowledge of factors associated with health-related quality of life in multimorbid people is scarce. We aimed to identify the factors that are associated with self-rated health (SRH) in aged multimorbid primary care patients.
Methods: Cross-sectional study with 3,189 multimorbid primary care patients aged from 65 to 85 years recruited in 158 general practices in 8 study centers in Germany. Information about morbidity, risk factors, resources, functional status and socio-economic data were collected in face-to-face interviews. Factors associated with SRH were identified by multivariable regression analyses.
Results: Depression, somatization, pain, limitations of instrumental activities (iADL), age, distress and Body Mass Index (BMI) were inversely related with SRH. Higher levels of physical activity, income and self-efficacy expectation had a positive association with SRH. The only chronic diseases remaining in the final model were Parkinson's disease and neuropathies. The final model accounted for 35% variance of SRH. Separate analyses for men and women detected some similarities; however, gender specific variation existed for several factors.
Conclusion: In multimorbid patients symptoms and consequences of diseases such as pain and activity limitations, as well as depression, seem to be far stronger associated with SRH than the diseases themselves. High income and self-efficacy expectation are independently associated with better SRH and high BMI and age with low SRH.
Background: Multimorbidity is a phenomenon with high burden and high prevalence in the elderly. Our previous research has shown that multimorbidity can be divided into the multimorbidity patterns of 1) anxiety, depression, somatoform disorders (ADS) and pain, and 2) cardiovascular and metabolic disorders. However, it is not yet known, how these patterns are influenced by patient characteristics. The objective of this paper is to analyze the association of socio-demographic variables, and especially socio-economic status with multimorbidity in general and with each multimorbidity pattern.
Methods: The MultiCare Cohort Study is a multicentre, prospective, observational cohort study of 3.189 multimorbid patients aged 65+ randomly selected from 158 GP practices. Data were collected in GP interviews and comprehensive patient interviews. Missing values have been imputed by hot deck imputation based on Gower distance in morbidity and other variables. The association of patient characteristics with the number of chronic conditions is analysed by multilevel mixed-effects linear regression analyses.
Results: Multimorbidity in general is associated with age (+0.07 chronic conditions per year), gender (-0.27 conditions for female), education (-0.26 conditions for medium and -0.29 conditions for high level vs. low level) and income (-0.27 conditions per logarithmic unit). The pattern of cardiovascular and metabolic disorders shows comparable associations with a higher coefficient for gender (-1.29 conditions for female), while multimorbidity within the pattern of ADS and pain correlates with gender (+0.79 conditions for female), but not with age or socioeconomic status.
Conclusions: Our study confirms that the morbidity load of multimorbid patients is associated with age, gender and the socioeconomic status of the patients, but there were no effects of living arrangements and marital status. We could also show that the influence of patient characteristics is dependent on the multimorbidity pattern concerned, i.e. there seem to be at least two types of elderly multimorbid patients. First, there are patients with mainly cardiovascular and metabolic disorders, who are more often male, have an older age and a lower socio-economic status. Second, there are patients mainly with ADS and pain-related morbidity, who are more often female and equally distributed across age and socio-economic groups.
Objectives Our study aimed to assess the frequency of potentially inappropriate medication (PIM) use (according to three PIM lists) and to examine the association between PIM use and cognitive function among participants in the MultiCare cohort. Design MultiCare is conducted as a longitudinal, multicentre, observational cohort study. Setting The MultiCare study is located in eight different study centres in Germany. Participants 3189 patients (59.3% female). Primary and secondary outcome measures The study had a cross-sectional design using baseline data from the German MultiCare study. Prescribed and over-the-counter drugs were classified using FORTA (Fit fOR The Aged), PRISCUS (Latin for ‘time-honoured’) and EU(7)-PIM lists. A mixed-effect multivariate linear regression was performed to calculate the association between PIM use patients’ cognitive function (measured with (LDST)). Results Patients (3189) used 2152 FORTA PIM (mean 0.9±1.03 per patient), 936 PRISCUS PIM (0.3±0.58) and 4311 EU(7)-PIM (1.4±1.29). The most common FORTA PIM was phenprocoumon (13.8%); the most prevalent PRISCUS PIM was amitriptyline (2.8%); the most common EU(7)-PIM was omeprazole (14.0%). The lists rate PIM differently, with an overall overlap of 6.6%. Increasing use of PIM is significantly associated with reduced cognitive function that was detected with a correlation coefficient of −0.60 for FORTA PIM (p=0.002), −0.72 for PRISCUS PIM (p=0.025) and −0.44 for EU(7)-PIM (p=0.005). Conclusion We identified PIM using FORTA, PRISCUS and EU(7)-PIM lists differently and found that PIM use is associated with cognitive impairment according to LDST, whereby the FORTA list best explained cognitive decline for the German population. These findings are consistent with a negative impact of PIM use on multimorbid elderly patient outcomes.
Objective: The objective of this study was to describe and analyze the effects of depression on health care utilization and costs in a sample of multimorbid elderly patients.
Method: This cross-sectional analysis used data of a prospective cohort study, consisting of 1,050 randomly selected multimorbid primary care patients aged 65 to 85 years. Depression was defined as a score of six points or more on the Geriatric Depression Scale (GDS-15). Subjects passed a geriatric assessment, including a questionnaire for health care utilization. The impact of depression on health care costs was analyzed using multiple linear regression models. A societal perspective was adopted.
Results: Prevalence of depression was 10.7%. Mean total costs per six-month period were €8,144 (95% CI: €6,199-€10,090) in patients with depression as compared to €3,137 (95% CI: €2,735-€3,538; p<0.001) in patients without depression. The positive association between depression and total costs persisted after controlling for socio-economic variables, functional status and level of multimorbidity. In particular, multiple regression analyses showed a significant positive association between depression and pharmaceutical costs.
Conclusion: Among multimorbid elderly patients, depression was associated with significantly higher health care utilization and costs. The effect of depression on costs was even greater than reported by previous studies conducted in less morbid patients.
Objectives The aims of our study were to examine the anticholinergic drug use and to assess the association between anticholinergic burden and cognitive function in the multimorbid elderly patients of the MultiCare cohort.
Setting MultiCare was conducted as a longitudinal cohort study in primary care, located in eight different study centres in Germany.
Participants 3189 patients (59.3% female).
Primary and secondary outcome measures Baseline data were used for the following analyses. Drugs were classified according to the well-established anticholinergic drug scale (ADS) and the recently published German anticholinergic burden (German ACB). Cognitive function was measured using a letter digit substitution test (LDST) and a mixed-effect multivariate linear regression was performed to calculate the influence of anticholinergic burden on the cognitive function.
Results Patients used 1764 anticholinergic drugs according to ADS and 2750 anticholinergics according to the German ACB score (prevalence 38.4% and 53.7%, respectively). The mean ADS score was 0.8 (±1.3), and the mean German ACB score was 1.2 (±1.6) per patient. The most common ADS anticholinergic was furosemide (5.8%) and the most common ACB anticholinergic was metformin (13.7%). The majority of the identified anticholinergics were drugs with low anticholinergic potential: 80.2% (ADS) and 73.4% (ACB), respectively. An increasing ADS and German ACB score was associated with reduced cognitive function according to the LDST (−0.26; p=0.008 and −0.24; p=0.003, respectively).
Conclusion Multimorbid elderly patients are in a high risk for using anticholinergic drugs according to ADS and German ACB score. We especially need to gain greater awareness for the contribution of drugs with low anticholinergic potential from the cardiovascular system. As anticholinergic drug use is associated with reduced cognitive function in multimorbid elderly patients, the importance of rational prescribing and also deprescribing needs to be further evaluated.
Trial registration number ISRCTN89818205.
The toxicity of microplastics on Daphnia magna as a key model for freshwater zooplankton is well described. While several studies predict population-level effects based on short-term, individual-level responses, only very few have validated these predictions experimentally. Thus, we exposed D. magna populations to irregular polystyrene microplastics and diatomite as natural particle (both ≤ 63 μm) over 50 days. We used mixtures of both particle types at fixed particle concentrations (50,000 particles mL-1) and recorded the effects on overall population size and structure, the size of the individual animals, and resting egg production. Particle exposure adversely affected the population size and structure and induced resting egg production. The terminal population size was 28–42% lower in exposed compared to control populations. Interestingly, mixtures containing diatomite induced stronger effects than microplastics alone, highlighting that natural particles are not per se less toxic than microplastics. Our results demonstrate that an exposure to synthetic and natural particles has negative population-level effects on zooplankton. Understanding the mixture toxicity of microplastics and natural particles is important given that aquatic organisms will experience exposure to both. Just as for chemical pollutants, better knowledge of such joint effects is essential to fully understand the environmental impacts of complex particle mixtures.
Environmental Implications While microplastics are commonly considered hazardous based on individual-level effects, there is a dearth of information on how they affect populations. Since the latter is key for understanding the environmental impacts of microplastics, we investigated how particle exposures affect the population size and structure of Daphnia magna. In addition, we used mixtures of microplastics and natural particles because neither occurs alone in nature and joint effects can be expected in an environmentally realistic scenario. We show that such mixtures adversely affect daphnid populations and highlight that population-level and mixture-toxicity designs are one important step towards more environmental realism in microplastics research.