[Knowledge and misconceptions on advance directives-results of a citizen survey]. / Wissensstand und Fehlvorstellungen zu Vorsorgedokumenten ­ Ergebnisse einer Bürgerbefragung.

BACKGROUND: Advance directives (ADs) such as living wills or healthcare powers of attorney are important tools to anticipate medical treatment decisions when decision-making capacity is lost in the future. Although a rising number of citizens in Germany are creating such documents, little is known about their knowledge of the purpose, types, and use of ADs. After more than 10 years since legislation on ADs came into force, this study intends to measure the objective knowledge of citizens and detect deficits in knowledge. METHODS: We conducted a cross-sectional quantitative survey of citizens aged 18+ in the city and county of Wuerzburg. The questionnaire included, among other things, possession, experience, and knowledge of ADs. Sampling was conducted via advertising and local networking. RESULTS: Of the 282 participants who took part in the survey (Mage = 50 years, 2/3 female), 43.4% reported having created a minimum of one document. In the knowledge test, an average of 22/34 points was achieved. While questions about the specific application of ADs based on a case study were often answered correctly, we found deficits about the single document types. The results in the knowledge test and the variables on the subjective level of knowledge correlate positively. DISCUSSION: The relatively high rate of ADs in this sample indicates their rapid dissemination during the past few years in Germany. Overall, the level of knowledge ADs appears to be low, revealing misconceptions about the creator's and involved people's rights and obligations. The measured knowledge level contradicts with the frequently expressed desire of citizens to preserve their autonomy by creating ADs for themselves.

Universal Conditions for the Controlled Polymerization of Acrylates, Methacrylates, and Styrene via Cu(0)-RDRP.

Atom transfer radical polymerization (ATRP) typically requires various parameters to be optimized in order to achieve a high degree of control over molecular weight and dispersity (such as the type of initiator, transition metal, ligand, solvent, temperature, deactivator, added salts, and reducing agents). These components play a major role when switching monomers, e.g., from acrylic to methacrylic and/or styrenic monomers during the synthesis of homo- and block copolymers as the stability and reactivity of the carbon centered propagating radical dramatically changes. This is a challenge for both "experts" and nonexperts as choosing the appropriate conditions for successful polymerization can be time-consuming and overall an arduous task. In this work, we describe one set of universal conditions for the efficacious polymerization of acrylates, methacrylates and styrene (using an identical initiator, ligand, copper salt, and solvent) based on commercially available and inexpensive reagents (PMDETA, IPA, Cu(0) wire). The versatility of these conditions is demonstrated by the near quantitative polymerization of these monomer families to yield well-defined materials over a range of molecular weights with low dispersities (∼1.1-1.2). The control and high end group fidelity is further exemplified by in situ block copolymerization upon sequential monomer addition for the case of methacrylates and styrene furnishing higher molecular weight copolymers with minimal termination. The facile nature of these conditions, combined with readily available reagents, will greatly expand the access and availability of tailored polymeric materials to all researchers.

Light-Mediated Atom Transfer Radical Polymerization of Semi-Fluorinated (Meth)acrylates: Facile Access to Functional Materials.

A highly efficient photomediated atom transfer radical polymerization protocol is reported for semi-fluorinated acrylates and methacrylates. Use of the commercially available solvent, 2-trifluoromethyl-2-propanol, optimally balances monomer, polymer, and catalyst solubility while eliminating transesterification as a detrimental side reaction. In the presence of UV irradiation and ppm concentrations of copper(II) bromide and Me6-TREN (TREN = tris(2-aminoethyl amine)), semi-fluorinated monomers with side chains containing between three and 21 fluorine atoms readily polymerize under controlled conditions. The resulting polymers exhibit narrow molar mass distributions (D ≈ 1.1) and high end group fidelity, even at conversions greater than 95%. This level of control permits the in situ generation of chain-end functional homopolymers and diblock copolymers, providing facile access to semi-fluorinated macromolecules using a single methodology with unprecedented monomer scope. The results disclosed herein should create opportunities across a variety of fields that exploit fluorine-containing polymers for tailored bulk, interfacial, and solution properties.

Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations.

RATIONALE: Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale. OBJECTIVES: To estimate the worldwide incidence and mortality of sepsis and identify knowledge gaps based on available evidence from observational studies. METHODS: We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years. MEASUREMENTS AND MAIN RESULTS: The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval [CI], 215-386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98-226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334-571; τ = 0.38) for sepsis and 270 (95% CI, 176-412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually. CONCLUSIONS: Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.

A Versatile and Scalable Strategy to Discrete Oligomers.

A versatile strategy is reported for the multigram synthesis of discrete oligomers from commercially available monomer families, e.g., acrylates, styrenics, and siloxanes. Central to this strategy is the identification of reproducible procedures for the separation of oligomer mixtures using automated flash chromatography systems with the effectiveness of this approach demonstrated through the multigram preparation of discrete oligomer libraries (D = 1.0). Synthetic availability, coupled with accurate structural control, allows these functional building blocks to be harnessed for both fundamental studies as well as targeted technological applications.

End group functionalization of poly(ethylene glycol) with phenolphthalein: towards star-shaped polymers based on supramolecular interactions.

The synthesis of a new phenolphthalein azide derivative, which can be easily utilized in polymer analogous reactions, is presented. The subsequent cycloaddition reaction with propargyl-functionalized methoxypoly(ethylene glycol) yielded polymers bearing phenolphthalein as the covalently attached end group. In presence of per-ß-cyclodextrin-dipentaerythritol, the formation of stable inclusion complexes was observed, representing an interesting approach towards the formation of star shaped polymers. The decolorization of a basic polymer solution caused by the complexation was of great advantage since this behavior enabled following the complex formation by UV-vis spectroscopy and even the naked eye.

Color indicator for supramolecular polymer chemistry: phenolphthalein-containing thermo- and pH-sensitive N-(Isopropyl)acrylamide copolymers and ß-cyclodextrin complexation.

The copolymerization parameters of N-(isopropyl)acrylamide (1) and N-(2-hydroxy-5-(1-(4-hydroxyphenyl)-3-oxo-1,3-dihydroisobenzofuran-1-yl)benzyl)acrylamide (2) are determined. For both monomers, the homoaddition proceeds slightly faster than the heteroaddition step; however, the polymer formation occurs in a statistic fashion. Copolymers of different compositions are prepared and the cloud points are determined. Thereby, a significant influence of the concentration of monomer 2 and the pH value is found. For the first time, the complexation of polymer attached phenolphthalein by ß-cyclodextrins is shown. Furthermore, it is possible to achieve a decomplexation by the addition of suitable guest molecules. Both procedures can be followed with the naked eye.

[What do health care professionals know about advance directives?] / Was wissen Fachkräfte im Gesundheitswesen über Vorsorgedokumente?

BACKGROUND: Advance directives are important to preserve the autonomy of patients for future situations in which they are uncapable of expressing their will. They are considered helpful by many healthcare professionals in their professional practice. However, their knowledge on these documents is not well known. Misconceptions can adversely affect decisions at the end of life. This study examines healthcare professionals' knowledge of advance directives and relevant correlates. METHODS: In 2021 healthcare professionals from various professions and institutions in Wuerzburg were surveyed using a standardized questionnaire on previous experiences with, advice on and use of advance directives, as well as an objective knowledge test containing 30 questions. Apart from the descriptive analysis of single questions out of the knowledge test, various parameters were screened for their influence on knowledge level. RESULTS: 363 healthcare professionals from different care settings participated in the study, including physicians, social workers, nurses and emergency services personnel. 77.5% work in patient care, of which 39.8% make decisions based on living wills daily to several times a month. High rates of incorrect answers in the knowledge test show lack in knowledge about decisions concerning patients who are unable to give consent; an average of 18 out of 30 points was achieved. Physicians, male healthcare professionals and respondents with more personal experience regarding advance directives had significantly better results in the knowledge test. CONCLUSION: Healthcare professionals have ethically and practically relevant knowledge deficits and a high need for further training on advance directives. Advance directives play an important role in maintaining patient autonomy and should receive more attention in training and further education equally involving non-medical professional groups.

Standing strong amid a pandemic: How a global online team project stands up to the public health crisis.

The annual instructional virtual team Project X brings together professors and students from across the globe to engage in client projects. The 2020 project was challenged by the global disruption of the COVID-19 pandemic. This paper draws on a quantitative dataset from a post-project survey among 500 participating students and a qualitative narrative inquiry of personal experiences of the faculty members. The findings reveal how innovative use of a variety of collaboration and communication technologies helped students and their professors in building emotional connection and compassion to support each other in the midst of the crisis, and to accomplish the project despite connectivity disruptions. The results suggest that the role of an instructor changed to a coach and mentor, and technology was used to create a greater sense of inclusion and co-presence in student-faculty interactions. Ultimately, the paper highlights the role of technology to help the participants navigate sudden crisis affecting a global online instructional team project. The adaptive instructional teaching strategies and technologies depicted in this study offer transformative potential for future developments in higher education.

Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis.

BACKGROUND: Neonates are at major risk of sepsis, but data on neonatal sepsis incidence are scarce. We aimed to assess the incidence and mortality of neonatal sepsis worldwide. METHODS: We performed a systematic review and meta-analysis. 13 databases were searched for the period January 1979-May 2019, updating the search of a previous systematic review and extending it in order to increase data inputs from low-income and middle-income countries (LMICs). We included studies on the population-level neonatal sepsis incidence that used a clinical sepsis definition, such as the 2005 consensus definition, or relevant ICD codes. We performed a random-effects meta-analysis on neonatal sepsis incidence and mortality, stratified according to sepsis onset, birth weight, prematurity, study setting, WHO region and World Bank income level. RESULTS: The search yielded 4737 publications, of which 26 were included. They accounted for 2 797 879 live births and 29 608 sepsis cases in 14 countries, most of which were middle-income countries. Random-effects estimator for neonatal sepsis incidence in the overall time frame was 2824 (95% CI 1892 to 4194) cases per 100 000 live births, of which an estimated 17.6% 9 (95% CI 10.3% to 28.6%) died. In the last decade (2009-2018), the incidence was 3930 (95% CI 1937 to 7812) per 100 000 live births based on four studies from LMICs. In the overall time frame, estimated incidence and mortality was higher in early-onset than late-onset neonatal sepsis cases. There was substantial between-study heterogeneity in all analyses. Studies were at moderate to high risk of bias. CONCLUSION: Neonatal sepsis is common and often fatal. Its incidence remains unknown in most countries and existing studies show marked heterogeneity, indicating the need to increase the number of epidemiological studies, harmonise neonatal sepsis definitions and improve the quality of research in this field. This can help to design and implement targeted interventions, which are urgently needed to reduce the high incidence of neonatal sepsis worldwide.

Direct Access to Functional (Meth)acrylate Copolymers through Transesterification with Lithium Alkoxides.

A straightforward and efficient synthetic method that transforms poly(methyl methacrylate) (PMMA) into value-added materials is presented. Specifically, PMMA is modified by transesterification to produce a variety of functional copolymers from a single starting material. Key to the reaction is the use of lithium alkoxides, prepared by treatment of primary alcohols with LDA, to displace the methyl esters. Under optimized conditions, up to 65% functionalization was achieved and copolymers containing alkyl, alkene, alkyne, benzyl, and (poly)ether side groups could be prepared. The versatility of this protocol was further demonstrated through the functionalization of both PMMA homo and block copolymers obtained through either radical polymerization (traditional and controlled) or anionic procedures. The scope of this strategy was illustrated by extension to a range of architectures and polymer backbones.

A patient cohort on long-term sequelae of sepsis survivors: study protocol of the Mid-German Sepsis Cohort.

INTRODUCTION: An increasing number of patients survive sepsis; however, we lack valid data on the long-term impact on morbidity from prospective observational studies. Therefore, we designed an observational cohort to quantify mid-term and long-term functional disabilities after intensive care unit (ICU)-treated sepsis. Ultimately, findings for the Mid-German Sepsis Cohort (MSC) will serve as basis for the implementation of follow-up structures for patients with sepsis and help to increase quality of care for sepsis survivors. METHODS AND ANALYSIS: All patients surviving ICU-treated sepsis are eligible and are recruited from five study centres in Germany (acute care hospital setting in Jena, Halle/Saale, Leipzig, Bad Berka, Erfurt; large long-term acute care hospital and rehabilitation setting in Klinik Bavaria Kreischa). Screening is performed by trained study nurses. Data are collected on ICU management of sepsis. On written informed consent provided by patients or proxies, follow-up is carried out by trained research staff at 3, 6 and 12 months and yearly thereafter. The primary outcome is functional disability as assessed by (instrumental) activities of daily living. Other outcomes cover domains like mortality, cognitive, emotional and physical impairment, and resource use. The estimated sample size of 3000 ICU survivors is calculated to allow detection of relevant changes in the primary outcome in sepsis survivors longitudinally. ETHICS AND DISSEMINATION: The study is conducted according to the current version of the Declaration of Helsinki and has been approved by four local/federal responsible institutional ethics committees and by the respective federal data protection commissioners. Results of MSC will be fed back to the patients and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry DRKS00010050.

How safe is gelatin? A systematic review and meta-analysis of gelatin-containing plasma expanders vs crystalloids and albumin.

Gelatin is a widely used synthetic colloid resuscitation fluid. We undertook a systematic review and meta-analysis of adverse effects in randomized and nonrandomized studies comparing gelatin with crystalloid or albumin for treatment of hypovolemia. Multiple databases were searched systematically without language restrictions until August 2015. We assessed risk of bias of individual studies and certainty in evidence assessment by the Grading of Recommendations Assessment, Development, and Evaluation approach. Sixty studies were eligible, including 30 randomized controlled trials, 8 nonrandomized studies, and 22 animal studies. After gelatin administration, the risk ratios were 1.15 (95% confidence interval, 0.96-1.38) for mortality, 1.10 (0.86-1.41) for requiring allogeneic blood transfusion, 1.35 (0.58-3.14) for acute kidney injury, and 3.01 (1.27-7.14) for anaphylaxis. Well-performed nonrandomized trials found increased rates of hospital mortality and acute kidney injury or renal replacement therapy in the gelatin intervention periods. Between 17% and 31% of administered gelatin was taken up extravascularly. The mean crystalloid-to-colloid ratio was 1.4. Gelatin solutions increase the risk of anaphylaxis and may be harmful by increasing mortality, renal failure, and bleeding possibly due to extravascular uptake and coagulation impairment. Until well-designed randomized controlled trials show that gelatin is safe, we caution against the use of gelatins because cheaper and safer fluid alternatives are available.

Hospital Incidence and Mortality Rates of Sepsis.

BACKGROUND: Sepsis, the most severe manifestation of acute infection, poses a major challenge to health care systems around the world. To date, adequate data on the incidence and mortality of sepsis in Germany have been lacking. METHODS: Nationwide case-related hospital DRG statistics for the years 2007-2013 were used to determine the in-hospital incidence and mortality of sepsis. Cases were identified on the basis of the clinical and pathogen-based ICD-10 codes for sepsis. The statistical evaluation was standardized for age and sex and carried out separately for each age group. RESULTS: The number of cases of sepsis rose by an average of 5.7% per year, from 200 535 in 2007 to 279 530 in 2013, corresponding to an increase in the adjusted in-hospital incidence from 256 to 335 cases per 100 000 persons per year. The percentage of patients with severe sepsis rose from 27% to 41%. The in-hospital mortality of sepsis fell over the same period by 2.7%, to 24.3%. In 2013, 67 849 persons died of sepsis in German hospitals (or died of another disease, but also had sepsis). The incidence was highest in the youngest and oldest age groups, and the in-hospital mortality rose nearly linearly with age from age 40 onward. CONCLUSION: Sepsis and death from sepsis are markedly more common in Germany than previously assumed, and they are on the rise. Sepsis statistics should become a standard component of federal statistical reports on public health, as well as of hospital statistics. Preventive measures and evidencebased treatment should be implemented across the nation.

A robust platform for functional microgels via thiol-ene achemistry with reactive polyether-based nanoparticles.

We herein report the development of crosslinked polyether particles as a reactive platform for the preparation of functional microgels. Thiol-ene crosslinking of poly(allyl glycidyl ether) in miniemulsion droplets - stabilized by a surface active, bio-compatible polyethylene glycol block copolymer - resulted in colloidal gels with a PEG corona and an inner polymeric network containing reactive allyl units. The stability of the allyl groups allows the microgels to be purified and stored before a second, subsequent thiol-ene functionalization step allows a wide variety of pH- and chemically-responsive groups to be introduced into the nanoparticles. The facile nature of this synthetic platform enables the preparation of microgel libraries that are responsive to different triggers but are characterized by the same size distribution, surface functionality, and crosslinking density. In addition, the utilization of a crosslinker containing cleavable ester groups renders the resulting hydrogel particles degradable at elevated pH or in the presence of esterase under physiological conditions.