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Changes in Self-Care Behaviour of Heart Failure Patients Receiving Remote Patient Management: A Pre-stratified Analysis of the TIM-HF2 Trial
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Die chronische Herzinsuffizienz ist sowohl für Betroffene als auch Gesundheitssysteme eine erhebliche Herausforderung. Patient:innen entwickeln individuelle Selbstpflegestrategien, um mit ihrer Erkrankung umzugehen und Therapie- sowie Verhaltensempfehlungen zu folgen. Angesichts der zunehmenden Bedeutung telemedizinischer Mitbetreuung (RPM) untersucht diese Arbeit, ob RPM signifikante Veränderungen im Selbstpflegeverhalten bei chronischer Herzinsuffizienz bewirkt. Methodik:
Diese prästratifizierte Analyse ist Teil der randomisierten, kontrollierten, multizentrischen Telemedical Interventional Management in Heart Failure II Studie (TIM-HF2, ClinicalTrials.gov ID: NCT 01878630), durchgeführt von 2013 bis 2018. Eingeschlossen wurden ambulante Patient:innen mit chronischer Herzinsuffizienz, die kürzlich wegen Dekompensation hospitalisiert waren und keine schwere Depression aufwiesen. Patient:innen wurden randomisiert einer Gruppe mit leitliniengerechter Standardversorgung plus RPM (n = 796) oder ausschließlich leitliniengerechter Standardversorgung (UC) (n = 775) zugewiesen, mit einem Follow-up von 12 Monaten. Das Selbstpflegeverhalten wurde zu Beginn und Ende der Studie mit der European Heart Failure Self-care Behaviour Scale (EHFScBS-9) gemessen, standardisierter Summenscore von 0-100, höhere Werte signalisieren besseres Selbstpflegeverhalten. Veränderungen im Selbstpflegeverhalten wurden mit ANCOVA und Regressionsmodellen analysiert.
Ergebnisse:
Von 1538 Patient:innen (Alter 70,3 ± 10,5 Jahre, 70% Männer, 52% NYHA II, 47% NYHA III, 65% LVEF ≤ 45%) wurden 1321 mit gültigen Fragebögen zu Studienbeginn und -ende analysiert. EHFScBS-Gesamtscores stiegen in der RPM-Gruppe (n = 667) von 78,7 ± 17 auf 84,5 ± 14 und in der UC-Gruppe (n = 654) von 79,0 ± 17 auf 80,0 ± 16, [Mittelwertdifferenz (MD) 4,58; 95% KI (3,02, 6,14); P < 0,001]. Größter Anstieg [MD 8,66 (3,52; 13,81)] bei allein lebenden Patient:innen mit inadäquatem Ausgangswert (<70) der EHFScBS. Gruppenunterschiede bei Item ‚Ich wiege mich jeden Tag‘ [MD -1,13 (-1,24, - 1,02); P < 0,001] und Item ‚Ich nehme meine Medikamente wie verordnet ein‘ [MD -0,06 (-0,10, -0,01); P = 0,014]. Es wurde kein Zusammenhang zwischen EHFScBS-Score und Wirksamkeit des RPM auf primären Endpunkt und sekundäre Hauptendpunkte der TIM-HF2-Studie (prozentualer Anteil verlorener Tage aufgrund kardiovaskulärer Hospitalisierung und Tod, Gesamtmortalität, kardiovaskuläre Mortalität, ungeplante Hospitalisierung wegen Herzinsuffizienz) gefunden.
Schlussfolgerungen:
Die Ergebnisse deuten darauf hin, dass RPM herzinsuffizienzspezifisches Selbstpflegeverhalten signifikant verbessert. Die Erkenntnisse legen nahe, dass Patient:innen unter RPM eine bessere Einhaltung des empfohlenen Herzinsuffizienz- Behandlungsregimes erreichen. In der untersuchten Population ließ sich kein direkter Zusammenhang zwischen Selbstpflegeverhalten und Hospitalisierung oder Mortalität nachweisen; hier besteht weiterer Forschungsbedarf.Background:
Chronic heart failure is a major challenge for both patients and healthcare systems. Patients develop individual self-care strategies to manage their condition and adhere to therapeutic and behavioural recommendations. In view of the increasing importance of remote patient management (RPM), this study aims to analyse whether RPM leads to significant changes in self-care behaviour in chronic heart failure.
Methods:
This pre-stratified analysis is part of the randomised, controlled, multicentre Telemedical Interventional Management in Heart Failure II trial (TIM-HF2, ClinicalTrials.gov ID: NCT 01878630), conducted from 2013 to 2018. Outpatients with chronic heart failure, recently hospitalised for decompensation and without severe depression were enrolled. Patients were randomly assigned to a group with usual care plus RPM (n = 796) or a group with usual care only (UC) (n = 775), with 12-month follow-up. Self-care behaviour was assessed at baseline and end of study with the European Heart Failure Self-care Behaviour Scale (EHFScBS-9), using a standardised sum score of 0-100, with higher scores indicating better self-care behaviour. ANCOVA and regression models were used to analyse changes in self-care behaviour.
Results:
Of 1538 patients (age 70.3 ± 10.5 years, 70% men, 52% NYHA II, 47% NYHA III, 65% LVEF ≤ 45%), 1321 were analysed with valid questionnaires at baseline and end of study. EHFScBS sum scores increased in the RPM group (n = 667) from 78.7±17 to 84.5±14 and in the UC group (n = 654) from 79.0 ± 17 to 80.0 ± 16, [difference in means (MD) 4.58; 95% CI (3.02, 6.14); P < 0.001]. Highest increase [MD 8.66 (3.52; 13.81)] in patients living alone with inadequate (<70) baseline EHFScBS sum score. Differences between groups for item ‘I weigh myself every day’ [MD -1.13 (-1.24, -1.02); P < 0.001] and item ‘I take my medication as prescribed’ [MD -0.06 (-0.10, -0.01); P = 0.014]. No correlation found between EHFScBS score and effectiveness of RPM on primary endpoint and secondary main endpoints (percentage of days lost due to cardiovascular hospitalisation and death, all-cause mortality, cardiovascular mortality, unplanned hospitalisation for heart failure) of the TIM-HF2 trial.
Conclusions:
The results suggest that RPM significantly improves heart failure-specific self-care behaviour. These findings also suggest that patients under RPM achieve better adherence to the recommended heart failure treatment regime. Self-care behaviour was not directly related to hospitalisation or mortality in the population studied and further research is needed
ganon2: up-to-date and scalable metagenomics analysis
Get PDFThe fast growth of public genomic sequence repositories greatly contributes to the success of metagenomics. However, they are growing at a faster pace than the computational resources to use them. This challenges current methods, which struggle to take full advantage of massive and fast data generation. We propose a generational leap in performance and usability with ganon2, a sequence classification method that performs taxonomic binning and profiling for metagenomics analysis. It indexes large datasets with a small memory footprint, maintaining fast, sensitive, and precise classification results. Based on the full NCBI RefSeq and its subsets, ganon2 indices are on average 50% smaller than state-of-the-art methods. Using 16 simulated samples from various studies, including the CAMI 1+2 challenge, ganon2 achieved up to 0.15 higher median F1-score in taxonomic binning. In profiling, improvements in the F1-score median are up to 0.35, keeping a balanced L1-norm error in the abundance estimation. ganon2 is one of the fastest tools evaluated and enables the use of larger, more diverse, and up-to-date reference sets in daily microbiome analysis, improving the resolution of results. The code is open-source and available with documentation at https://github.com/pirovc/ganon
Haploblocks contribute to parallel climate adaptation following global invasion of a cosmopolitan plant
Get PDFThe role of rapid adaptation during species invasions has historically been minimized with the assumption that introductions consist of few colonists and limited genetic diversity. While overwhelming evidence suggests that rapid adaptation is more prevalent than originally assumed, the demographic and adaptive processes underlying successful invasions remain unresolved. Here we leverage a large whole-genome sequence dataset to investigate the relative roles of colonization history and adaptation during the worldwide invasion of the forage crop, Trifolium repens (Fabaceae). We show that introduced populations encompass high levels of genetic variation with little evidence of bottlenecks. Independent colonization histories on different continents are evident from genome-wide population structure. Five haploblocks—large haplotypes with limited recombination—on three chromosomes exist as standing genetic variation within the native and introduced ranges and exhibit strong signatures of parallel climate-associated adaptation across continents. Field experiments in the native and introduced ranges demonstrate that three of the haploblocks strongly affect fitness and exhibit patterns of selection consistent with local adaptation across each range. Our results provide strong evidence that large-effect structural variants contribute substantially to rapid and parallel adaptation of an introduced species throughout the world
Untersuchungen über den Nachweis des Pferdefleisches in Koch- und Bratwürsten mittels des biologischen Verfahrens
Get PDFDigitalisat der Ausgabe von 1912, erschienen 202
Enhancement of neutralizing antibodies against SARS-CoV-2 through dose-intensified mRNA vaccinations in rheumatic low-responders with B-cell depletion
Get PDFVor dem Hintergrund der weltweiten SARS-CoV-2 Pandemie und neuartigen Impfstoffen startete im Jahr 2021 in der Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie die VACCIMMUN Studie. Diese übergeordnete Studie setzte sich zum Ziel, bei der vulnerablen und immunologisch besonderen Kohorte der Patienten mit Autoimmunerkrankungen die Auswirkungen der neu zugelassenen COVID-19-Impfstoffe zu erforschen. Von einem initialen Pool von über 390 Probanden wurden Blutproben akquiriert und untersucht. Es entstanden mehrere Subanalysen, an denen der Promovend als Koautor beteiligt war, die sich z.B. mit dem Einfluss von Methotrexat auf den Erfolg der Grundimmunisierung und der Boosterimpfungen beschäftigte, oder auch den Einfluss von Diagnose und Therapie untersuchten. Der größte eigenständige Beitrag zu diesen Forschungsbemühungen resultierte in der Erstautorenschaft der Publikation „Improvement of humoral immunity by repeated dose-intensified COVID-19 vaccinations in primary non- to low-responders and B cell deficient rheumatic disease patients“ veröffentlicht im Januar 2023 im Journal of Autoimmunity.1 Dort wurde sich der Frage gewidmet: Wie geht man mit schwer immunsupprimierten Risikopatienten um, die nach der Grundimmunisierung low-reponder sind und nur geringe neutralisierende Antikörper vorweisen? Man beobachtete, beschrieb und analysierte dabei eine mögliche Vorgehensweise, bestehend aus Impferfolgskontrollen gefolgt von wiederholten, dosis-intensivierten mRNA-Impfungen. Dieses Vorgehen wurde bis einschließlich der 5. Impfung verfolgt, nach der nur eine Person von 38 nicht eine hohe Immunität erreichte. Jede der zusätzlichen Impfungen erzeugte einen signifikanten Anstieg der Neutralisationskapazität. Keine erkennbaren Eigenschaften schlossen dabei kategorisch einen Impferfolg aus - insbesondere auch ein Mangel an peripheren B-Zellen nicht. Die Schlussfolgerungen dieser Studie müssen eingeordnet werden und folgende Schwächen bedacht werden: Teils niedrige Fallzahlen durch dropouts, die Schwierigkeit der präzisen Unterscheidung zwischen low-respone und high-response und die fehlende Messung der zellulären Immunität. Bei einem sich schließenden Zeitfenster sinnvoller Impfungen, nachgewiesen hoher Vulnerabilität und hoher Dringlichkeit bot dieses Forschungsbemühen trotzdem für diese, und auch für künftige Pandemien, einige aufschlussreiche Erkenntnisse und Inspirationen.Against the backdrop of the worldwide SARS-CoV-2 pandemic and novel vaccines, in 2021 in the „Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immuno-logie“ the VACCIMMUN study started. This study aimed to explore the impact of the new Covid-19 vaccines in the vulnerable and immunologically special cohort of patients with autoimmune diseases. Blood samples were collected and analysed from an initial pool of over 390 subjects. In addition to several smaller publications, various sub-analyses were conducted, among others on the influence of methotrexate on the basic vaccination and on booster vaccinations, and on the influence of diagnosis versus therapy for vaccination success. The biggest independent contribution to this research effort resulted in the publication "Improvement of humoral immunity by repeated dose-intensified COVID-19 vaccinations in primary non- to low-responders and B cell deficient rheumatic disease patients", of which the candidate is the first author, published in January 2023 in the Journal of Autoimmunity.1 The following question was addressed: How should one manage patients with autoimmune diseases who are low-responders with little neutralizing antibodies after primary immunisation? One possible approach consisting of frequently checking the effectiveness of the immunisation followed by repeated dose-intensified mRNA vaccinations was observed, described, and analysed. This approach was followed to the fifth vaccination, after which only one person out of 38 had not achieved high immunity. Each of the additional vaccinations produced a significant increase in neutralising capacity and no identifiable characteristics categorically precluded vaccination success, even a lack of peripheral B cells. The conclusions of this study must be put into context and the following weaknesses must be considered: low case numbers due to dropouts, the difficulty of precisely distinguishing between low-response and high-response, and the lack of measurement of cellular immunity. Nevertheless, with a closing window of opportunity for meaningful vaccination, proven high vulnerability and high urgency, this research effort provided insight and inspiration for this, and future, pandemics
Über das Verhalten von Jodfettsäurederivation des Cholesterins im Organismus des Hundes
No full textDigitalisat der Ausgabe von 1913, erschienen 202
Exploring the formation and alteration of organics in ice: experimental insights for astrochemistry and space missions
Get PDFThe formation and alteration of organic molecules within the Solar System and beyond is closely related to the life cycle of ice in space. Cold molecular clouds in the interstellar medium (ISM) are regions, where volatile molecules condense onto submicron-sized dust grains. Throughout their lifetime, these interstellar ice particles are exposed to energetic photons, charged particles and thermal processing, which catalyze the formation of increasingly complex organic compounds and induce the desorption of volatile species. The accretion of these compounds into comets and asteroids would allow their delivery on planetary surfaces, making them potential precursors of the building blocks of life. Alongside comets and asteroids, complex organics are also present on the icy moons of giant planets which are targets in both NASA’s and ESA’s space exploration programs. In this paper, we present a new experimental setup, built to study the formation and alteration of complex organic molecules of astrobiological-relevance in cryogenic environments. Possible samples include inorganic and organic molecules, in contact with various ice mixtures (e.g., H2O, NH3, CO, CO2, CH3OH) which can be exposed to UV photons, electron bombardment and undergo thermal processing. The setup allows continuous monitoring by Fourier transform-infrared (FT-IR) transmission spectroscopy during the ice formation, irradiation-, and warm-up. We present FT-IR measurements of pure H2O, pure NH3 and pure CH3OH ice samples deposited at 15 K and we show the main spectral changes induced by heating and electron bombardment. Furthermore, we show the formation of new molecular species within NH3:CH3OH and NH3:CH3OH:H2O ice mixture under electron bombardment, and outline an experimental design used to investigate the stability of organic molecules under simulated conditions on icy moons. With our setup we envision to provide spectral information on astrobiologically-relevant molecules, such as organic species fundamental for living organisms and potential biosignatures, in contact with ices of relevance for astrophysics and planetary science
One Health aspects in rural Rwanda: Prevalence and risk factors for ESBL-PE among community members, livestock, animal products and environment
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Der unkontrollierte Einsatz von Antibiotika fördert bakterielle Resistenzmechanismen wie genetische Mutationen oder enzymatische Inaktivierung, die sich durch horizonta-len Gentransfer verbreiten. One Health stellt einen multidimensionalen Ansatz zur Überwachung von antimikrobieller Resistenz (AMR) dar, indem es Wechselwirkungen zwischen Menschen, Tieren und ihrer Umwelt berücksichtigt. Die vorliegende Arbeit möchte anhand von Daten aus einer afrikanischen Gemeinde untersuchen, wie One Health-Prinzipien angewendet werden können, um die Prävalenz von Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae (ESBL-PE) bei Gemeinde-mitgliedern und ihrer Umwelt zu erheben und potenzielle Risikofaktoren für die Be-siedelung mit resistenten Keimen zu identifizieren.
Methodik
Da Daten zu AMR aus afrikanischen Ländern besonders in nicht-hospitalisierten Be-reichen selten sind, führten wir eine nicht-interventionelle Beobachtungsstudie in So-vu, Ruanda, durch. Um One Health-Aspekte aufzugreifen, umfasste die Probenakqui-se in 312 randomisierten Haushalten neben Rektalabstrichen von 620 Tieren und 643 Menschen auch je ca. 300 Isolate von Wasser, Boden, Gemüse und Tierprodukten. Bakteriologische Speziesidentifizierung mit Fokus auf ESBL-PE sowie Antibiotika-Resistenztestungen mittels Agardiffusionstests wurden durchgeführt. Lokale Health Worker erhoben soziodemografische Informationen mittels standardisierter Fragebö-gen.
Ergebnisse
Von insgesamt 2508 gesammelten Proben zeigte sich in 14,8% Wachstum auf ESBL-PE, vornehmlich Escherichia coli sowie Klebsiella pneumoniae.
Bei Menschen war eine rektale Besiedlung mit ESBL-PE mehr als doppelt so häufig wie bei Tieren (37,9 % vs. 15,6 %). Gemüse, tierische Produkte und Boden waren zu 2-4% kontaminiert. Isolate von E. coli und K. pneumoniae zeigten hohe Resistenzra-ten gegen Ampicillin/Sulbactam, Ciprofloxacin und Cotrimoxazol.
Als Risikofaktoren für eine Besiedlung mit ESBL wurden ein Alter über 18 Jahre, län-gere Transportzeiten für Wasser, akute Durchfallerkrankungen oder ein ESBL-PE-positives Haushaltsmitglied identifiziert. Sozioökonomische Merkmale wie der Besitz eines Radios oder die Fähigkeit, Schulgebühren zu zahlen, hatten ebenso Einfluss auf eine Kolonisierung mit ESBL-PE wie Ernährungsgewohnheiten. Es wurden keine signifikanten Assoziationen mit kürzlicher Antibiotikaeinnahme, Bildungsgrad, Vieh-zucht oder Haushaltsgröße festgestellt.
Schlussfolgerung
Unsere Forschungsergebnisse betonen die Wichtigkeit eines One Health-Ansatzes im Kontext von AMR, da Risikofaktoren für die Besiedelung mit resistenten Bakterien in der Umgebung und Lebensweise von Menschen zu finden sind. Wir empfehlen, auch zukünftig das Resistenzgeschehen von Mechanismen wie ESBL in der Gemeinschaft unter dem Aspekt von One Health mit Hinzunahme von Tier- und Umweltgesundheit zu überwachen, um Aufschlüsse über die Entwicklung sowohl von Prävalenzen als auch Risikofaktoren zu erhalten und diese in einen globalen Kontext zu setzen.Background
Antibiotics are the cornerstone of treatment for bacterial infections, but their excessive use promotes resistance mechanisms such as genetic mutations or enzymatic inacti-vation, which spread via horizontal gene transfer. One Health represents a multidi-mensional approach to monitoring antimicrobial resistance (AMR) by considering in-teractions between humans, animals, and their environment. This study aims to inves-tigate, using data from an African community, how One Health principles can be ap-plied to assess the prevalence of Extended-Spectrum Beta-Lactamase-Producing En-terobacteriaceae (ESBL-PE) among community members and their environment and to identify potential risk factors for colonization with resistant bacteria.
Methods
Since data on AMR from African countries, especially in non-hospitalized settings, are scarce, we conducted a non-interventional observational study in Sovu, Rwanda. To address One Health aspects, sample collection in 312 randomized households in-cluded rectal swabs from 620 animals and 643 humans, as well as approximately 300 isolates each from water, soil, vegetables, and animal products. Bacteriological spe-cies identification focusing on ESBL-PE and antibiotic resistance testing using agar diffusion tests were performed. Local health workers collected sociodemographic in-formation from participants using standardized questionnaires.
Results
Out of a total of 2508 collected samples, growth of ESBL-PE was observed in 14.8%, mainly Escherichia coli and Klebsiella pneumoniae. Rectal colonization with ESBL-PE was more than twice as common in humans compared to animals (37.9% vs. 15.6%). Animal products, vegetables and soil exhibited contamination levels ranging from 2% to 4%. Isolates of E. coli and K. pneumoniae showed high resistance rates to Ampicil-lin/Sulbactam, Ciprofloxacin, and Cotrimoxazole. Risk factors for colonization with ESBL included age over 18 years, longer time to fetch water, acute diarrheal diseases or a household member positive for ESBL-PE. Socioeconomic characteristics such as owning a radio or ability to pay school fees, as well as dietary habits, also influenced colonization with ESBL-PE. No significant associations were found with recent antibi-otic intake, education level, livestock farming, or household size.
Conclusions
Our research findings highlight the importance of a One Health approach in the con-text of AMR, as risk factors for colonization with resistant bacteria are found in the sur-roundings and lifestyle of humans. We recommend continued surveillance of re-sistance mechanisms such as ESBL in the community from a One Health perspective, incorporating animal and environmental health, to gain insights into the evolution of prevalence as well as risk factors and to contextualize them on a global scale
Glycerolbasierte Polymere für die Inhibition von Typ 2 Entzündung und für biosensorische Anwendungen
No full textThis dissertation focuses on the development and application of polyglycerol (PG)-based polymers for the modulation of type 2 inflammation as well as their use as innovative materials for biosensor analysis using surface plasmon resonance (SPR) spectroscopy.
Dysregulated type 2 inflammation forms the pathophysiological basis of atopic diseases such as atopic dermatitis or allergic asthma. Among other factors, disease progression is influenced by increased levels of cytokines such as thymic stromal lymphopoietin (TSLP) and extracellular matrix proteins such as fibronectin (FN). Both molecules exhibit cationic regions on their surface and therefore offer potential for electrostatic interactions with polyanions.
In the first part of this work, linear and dendritic PGs were carboxylated and sulfated and subsequently analyzed via SPR with regard to their interactions with FN and TSLP. Highly sulfated polymers showed high-affinity binding to both target molecules. The most promising polymer candidates were further investigated to assess the extent to which they can modulate or suppress the inflammatory effects mediated by TSLP and FN. Even at low concentrations (10 ng/mL), TSLP-neutralizing effects were observed with respect to the proinflammatory type 2 polarization of T cells. In contrast, significantly higher concentrations were required for FN-neutralizing effects in inflamed bronchial epithelium tissue models.
As these biochemical investigations require highly sensitive and selective analytical methods, the second part of the work focused on the development of innovative SPR biosensors based on a PG-polyethylene glycol (PEG) hydrogel. The main requirements were high ligand loading capacity and minimal nonspecific binding. Heparin-binding proteins such as the described FN or lectins often lead to nonspecific interactions with the carboxymethyldextran (CMD) matrix of conventional SPR biosensors, which complicates analysis. In contrast, the newly developed PG-PEG SPR biosensors exhibited significantly reduced nonspecific binding while maintaining high loading capacity. Furthermore, they were validated for the analysis of both small (222 Da) and large (150 kDa) biomolecules by comparing the determined binding constants with those obtained using CMD-based biosensors