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Background:Adults with systemic right ventricle have a significant risk for long-term complications such as arrhythmias or heart failure.Methods:A nationwide retrospective study based on the German National Register for Congenital Heart Disease was performed. Patients with transposition of the great arteries after atrial switch operation or congenitally corrected TGA were included.Results:Two hundred and eight-five patients with transposition of the great arteries after atrial switch operation and 95 patients with congenitally corrected transposition of the great arteries were included (mean age 33 years). Systolic function of the systemic ventricle was moderately or severely reduced in 25.5 % after atrial switch operation and in 35.1% in patients with congenitally corrected transposition. Regurgitation of the systemic atrioventricular valve was present in 39.5% and 43.2% of the cases, respectively. A significant percentage of patients also had a history for supraventricular or ventricular arrhythmias. However, polypharmacy of cardiovascular drugs was rare (4.5%) and 38.5 % of the patients did not take any cardiovascular medication. The amount of cardiovascular drugs taken was associated with NYHA class as well as systemic right ventricular dysfunction. Patients with congenitally corrected transposition were more likely to receive pharmacological treatment than patients after atrial switch operation.Conclusion:A significant portion of patients with systemic right ventricle suffer from a relevant systemic ventricular dysfunction, systemic atrioventricular valve regurgitation, and arrhythmias. Despite this, medication for heart failure treatment is not universally used in this cohort. This emphasises the need for randomised trials in patient with systemic right ventricle.

Nursing home residents tend to have lower medical specialist utilization than other groups of older people; however, as yet there is little evidence whether nursing home residents obtain adequate medical specialist care. This study investigated whether nursing home residents receive adequate oral health care, ophthalmological care, otorhinolaryngologist care and neurological care. The unmet needs of the nursing home population in Germany was extrapolated.Audiometry, eye examinations and oral visual inspection were performed in 409 residents from 44 nursing homes. Medical care in the previous 12 months as well as existing diagnoses were retrieved from the nursing documentation. Teams of physicians evaluated for each resident based on all collected data if the resident obtained specialist care that was adequate to the needs.Between 15% and 45% of the residents with need for medical specialist care did not receive adequate specialist care. Of all residents 27% had unmet need of specialist care in at least one of the investigated medical specialties. It is projected that up to 205,000 nursing home residents in Germany do not receive adequate medical specialist care.Given a considerable proportion of nursing home residents with unmet need of specialist care, interventions should be developed that help reduce the level of unmet needs.HINTERGRUND: Bisherige Studien deuten darauf hin, dass Pflegebedürftige eine geringere fachärztliche Versorgung aufweisen als Nichtpflegebedürftige. Insbesondere im stationären Setting ist die fachärztliche Versorgungsintensität gering. Aus den bestehenden quantitativen Versorgungsunterschieden lässt sich bislang jedoch nicht ableiten, inwieweit von einer Unterversorgung bei Pflegebedürftigen ausgegangen werden muss. Für die Versorgungsbereiche Sehfähigkeit, Hörfähigkeit, Mundgesundheit und Parkinson-Syndrom wird geprüft, inwieweit Heimbewohner fachärztlich unterversorgt sind.In 44 Pflegeheimen in Bremen und Niedersachsen wurde der Gesundheitszustand von 409 Pflegebedürftigen mittels standardisierter Assessments und Befragungen erhoben; zusätzlich wurden Diagnosen und die medizinische Versorgung aus der Pflegedokumentation ausgewertet. Ärzteteams beurteilten auf dieser Grundlage für jeden Pflegebedürftigen, inwieweit eine bedarfsgerechte fachärztliche Versorgung vorlag oder nicht.Gemäß ärztlichem Urteil zeigt sich bei 45 % (Sehfähigkeit), 19 % (Parkinson-Syndrom), 16 % (Mundgesundheit) und 15 % (Hörfähigkeit) der Bewohner mit entsprechendem Versorgungsbedarf eine fachärztliche Unterversorgung. Bei 27 % aller Bewohner zeigt sich in mindestens einem der 4 Versorgungsbereiche eine fachärztliche Unterversorgung. Hochgerechnet entspricht dies bis zu 205.000 fachärztlich unterversorgten Pflegeheimbewohnern in Deutschland.Die Studie liefert für ausgewählte Versorgungsbereiche die ersten empirischen Belege über das Ausmaß fachärztlicher Unterversorgung von Pflegeheimbewohnern. Daher erscheint es notwendig, entsprechende Interventionen zur Reduktion der Unterversorgung zu entwickeln und zu erproben.

Introduction Knowledge, once acquired, degrades over time. Exams that contain questions related to previously acquired knowledge (‘retrieval practice questions’) may promote retrieval practice and spaced learning, and subsequently prevent knowledge loss. To investigate this hypothesis, we compare the score of retrieval practice questions to regular questions in exams of a two-year (bio)medical study program. Methods The two-year “Mechanisms of Health and Disease”-program for biomedical sciences and medical students in Nijmegen (the Netherlands) contains 14 spaced exams of 80 questions each. The percentages of correct-, false-, and non-answers were compared between regular questions and retrieval practice questions. Using Pearson correlations between question scores and exam scores (RiT-values), the impact of retrieval practice questions on the internal consistency of exams was determined. Mixed model analyses determined changes in outcomes across time. Results Analysis of 2006 regular questions and 1728 retrieval practice questions revealed a significantly higher percentage of correct and false answers, and a significantly lower percentage of non-answers, in retrieval practice questions versus regular questions (all P RiT-values were slightly lower in retrieval practice questions, with a small inverse trend across time. Conclusion Our data indicate preservation of knowledge, possibly related to retrieval practice and/or spaced learning. Although the RiT-values of retrieval practice questions were slightly lower than those of regular questions, the discriminative capacity was well within acceptable range. These data highlight the potency of retrieval practice questions to prevent knowledge decrement, without altering exam quality.

Fetal alcohol spectrum disorder (FASD) is a major problem worldwide and dysmorphic facial features may be a prenatal biomarker for FASD. Deviations from normal facial development cannot be explored before establishing the normal variation in a specific population, since ethnic differences may exist. Objectives: Main objective: to establish reference standards for 23 facial measurements on 3D ultrasound volumes obtained between days 196 and 224 of gestation in healthy unexposed South African fetuses from an area with historically high alcohol consumption prevalence and a population group with no existing normative values. Secondary objective: to assess the confounding effect of maternal and fetal characteristics. Design: This study involves 97 women (including 43 smokers) who had been enrolled in the Safe Passage Study (SPS), a large prospective multinational cohort study assessing the effects of prenatal alcohol exposure. They had adequate 3 D ultrasound volumes of the fetal face acquired at 28+0–31+6 weeks in singleton pregnancies without comorbidities, congenital abnormalities or exposure to alcohol, marijuana, or methamphetamines from 4 weeks before conception. Participants, materials, setting, methods: The participants were recruited from two residential areas of low socioeconomic status in Cape Town. Meticulous information was collected on maternal and pregnancy characteristics, including alcohol use at different time points. Gestational age (GA) was based on ultrasound biometry before 24 weeks, and 3D ultrasound volumes were acquired trans-abdominally from a sagittal and axial plane of the fetal face. Volumes were independently assessed offline by two observers and the image with the best landmark definition was used for 23 facial measurements, representing features previously described in children with FASD. The relation to the exact GA was assessed by regression analysis, the expected mean value and standard error of the estimate (SEE) was determined to transform all raw measurements into z-scores, and the effect of possible confounders on z-scores was assessed by ANOVA. Results: Ten variables changed significantly with advancing GA (extraocular diameter, anteroposterior, medio-lateral and supero-inferior ocular diameter, ocular volume, interlens distance, prenasal thickness, nasal bone length, nose length and nose protrusion) and thirteen did not (interocular distance; interocular: extraocular diameter ratio, prenasal thickness: nasal bone length ratio, pronasal-subnasal distance, subnasal-mouth distance, philtrum length, upper vermillion thickness, nose-philtrum angle, maxillary angle, facial height, facial protrusion, frontomaxillary facial angle and maxilla-nasion-mandible angle). Reference values (expected mean and SEE) for the 23 measurements were established for each day. The z-scores of all facial measurements were not independently affected by maternal age, parity, gravidity, smoking or body mass index, but infant sex and birthweight z-score significantly influenced several z-scores (infant sex for extraocular, medio-lateral, and supero-inferior ocular diameter, ocular volume, prenasal thickness and nose protrusion; birthweight z-score for extraocular diameter, interocular and interlens distance, nose protrusion and maxillary angle). Limitations: GA was not always confirmed by first trimester ultrasound and some measurements could not be obtained in all cases due to suboptimal image quality. The cohort included few heavy smokers so an effect of heavy or continued smoking cannot be ruled out, and the effect of ethnicity was not assessed. Conclusions: These are the first local reference standards for fetal facial measurements and, to our knowledge, the first reference standards for the supero-inferior ocular diameter, face protrusion, upper vermillion thickness, maxillary angle, and nose-philtrum angle. They were broadly in keeping with published references, with small discrepancies explained by minor differences in technique. Even in this narrow GA window, the distribution of many variables changed over time and normal variation was significantly influenced by fetal sex and birthweight z-score. The possible confounding effect of these factors needs to be considered when assessing the impact of harmful exposures like alcohol on facial development.

Background Nursing home residents have high medical care needs. Their medical care utilization is, however, lower compared to community-dwelling elderly and varies widely among nursing homes. This study quantified the utilization of general practitioners (GPs), dentists, and medical specialists among nursing homes and residents, and investigated whether dentist utilization is associated with individual and nursing home characteristics. Methods Forty-four nursing homes invited 2124 residents to participate in a cross-sectional study. For 10 medical specialties, data on contacts in nursing homes, practices, and by telephone in the last 12 months were assessed at individual and nursing home level. The proportion of nursing homes and residents with any form of contact, and the median number and interquartile range (IQR) of contacts among individuals with contact were determined. Using multilevel logistic regression, associations between the probability of individual dental care utilization and sex, age, LTC grade, years of residence, sponsorship, number of nursing home beds, and transport and medical escort services for consultations at a practice were investigated. Results The proportion of nursing homes with any form of contact with physicians ranged from 100% for GPs, dentists, and urologists to 76.7% for gynecologists and orthopedists. Among the nursing homes, 442 residents participated (20.8% response). The proportion of residents with any contact varied from 97.8% for GPs, 38.5% for neurologists/psychiatrists, and 32.3% for dentists to 3.0% for gynecologists. Only for GPs, neurologists/psychiatrists, dentists, otorhinolaryngologists, urologists, and dermatologists, the proportion was higher for nursing home contacts than for practice and telephone contacts. Among residents with any contact, the median number of contacts was highest for GPs (11.0 [IQR 7.0-16.0]), urologists (4.0 [IQR 2.0-7.0]), and neurologists/psychiatrists (3.0 [IQR 2.0-5.0]). Dentist utilization varied widely among nursing homes (median odds ratio 2.5) and was associated with higher age. Conclusions Almost all residents had regular contact to GPs, but only one third had contact with dentists. Lower proportions with contact were found for medical specialists, except for neurologists/psychiatrists. Reasons for the large variations in dental care utilization among nursing homes should be identified. Trial registration DRKS00012383 [2017/12/06].

Background Dementia is a multi-factorial condition rather than a natural and inevitable consequence of ageing. Some factors related to dementia have been studied much more extensively than others. To gain an overview of known or suspected influential factors is a prerequisite to design studies that aim to identify causal relationships and interactions between factors. This article aims to develop a visual model that a) identifies factors related to cognitive decline that signal the onset of dementia, b) structures them by different domains and c) reflects on and visualizes the possible causal links and interactions between these factors based on expert input using a causal loop diagram. Method We used a mixed-method, step-wise approach: 1. A systematic literature review on factors related to cognitive decline; 2. A group model building (GMB) workshop with experts from different disciplines; 3. Structured discussions within the group of researchers. The results were continuously synthesized and graphically transformed into a causal loop diagram. Results The causal loop diagram comprises 73 factors that were structured into six domains: physical (medical) factors (23), social health factors (21), psychological factors (14), environmental factors (5), demographic factors (5) and lifestyle factors (3). 57 factors were identified in the systematic literature review, additionally 16 factors, mostly of the social health cluster, were identified during the GMB session and the feedback rounds. Conclusion The causal loop diagram offers a comprehensive visualisation of factors related to cognitive decline and their interactions. It supports the generation of hypotheses on causal relationships and interactions of factors within and between domains.

Healthcare managers are confronted with various Capacity Management decisions to determine appropriate levels of resources such as equipment and staff. Given the significant impact of these decisions, they should be taken with great care. The increasing amount of process execution data – i.e. event logs – stored in Hospital Information Systems (HIS) can be leveraged using Data-Driven Process Simulation (DDPS), an emerging field of Process Mining, to provide decision-support information to healthcare managers. While existing research on DDPS mainly focuses on the fully automated discovery of simulation models from event logs, the interaction between process execution data and domain expertise has received little attention. Nevertheless, data quality issues in real-life process execution data stored in HIS prevent the discovery of accurate and reliable models from this data. Therefore, complementary information from domain experts is necessary. In this paper, we describe the application of DDPS in healthcare by means of an extensive real-life case study at the radiology department of a Belgium hospital. In addition to formulating our recommendations towards the radiology management, we will elaborate on the experienced challenges and formulate recommendations to move research on DDPS within a healthcare context forward. In this respect, explicit attention is attributed to data quality assessment, as well as the interaction between the use of process execution data and domain expertise.

Contact tracing is currently one of the most effective measures to contain the COVID-19 pandemic. In order to identify persons that would otherwise not be known or remembered and to keep the time delay when reporting an infection and when contacting people as short as possible, digital contact tracing using smartphones seems to be a reasonable measure additional to manual contact tracing. Although first modelling studies predicted a positive effect in terms of prompt contact tracing, no empirically reliable data are as yet available, neither on the population-wide benefit nor on the potential risks of contact tracing apps. Risk-benefit assessment of such an app includes investigating whether such an app fulfils its purpose, as also research on the effectiveness, risks and side effects, and implementation processes (e. g. planning and inclusion of different participants). The aim of this article was to give an overview of possible public health benefits as well as technical, social, legal and ethical aspects of a contact-tracing app in the context of the COVID-19 pandemic. Furthermore, conditions for the widest possible use of the app are presented.Die Kontaktpersonennachverfolgung ist derzeit eine der wirksamsten Maßnahmen zur Eindämmung der COVID-19 Pandemie. Digitales Contact Tracing mittels Smartphones scheint eine sinnvolle zusätzliche Maßnahme zur manuellen Kontaktpersonennachverfolgung zu sein, um Personen zu identifizieren, die nicht bekannt oder nicht erinnerlich sind und um den zeitlichen Verzug beim Melden eines Infektionsfalles und beim Benachrichtigen von Kontaktpersonen so gering wie möglich zu halten. Obwohl erste Modellierungsstudien eine positive Wirkung in Bezug auf eine zeitnahe Kontaktpersonennachverfolgung nahelegen, gibt es bislang keine empirisch belastbaren Daten, weder zum bevölkerungsweiten Nutzen noch zum potenziellen Schaden von Contact-Tracing-Apps. Die Beurteilung der Zweckerfüllung und eine wissenschaftliche interdisziplinäre Begleitforschung sowohl zur Wirksamkeit, Risiken und Nebenwirkungen als auch zu Implementierungsprozessen (z. B. Planung und Einbezug verschiedener Beteiligter) sind wesentliche Bestandteile einer Nutzen-Risiko Bewertung. Dieser Beitrag betrachtet daher den möglichen Public-Health-Nutzen sowie technische, soziale, rechtliche und ethische Aspekte einer Contact-Tracing-App zur Kontaktpersonennachverfolgung im Rahmen der COVID-19-Pandemie. Weiterhin werden Bedingungen für eine möglichst breite Nutzung der App aufgezeigt.

Research projects in the health sciences often involve ethically sensitive areas. The rise in the number of empirically oriented theses and concepts such as research-based learning has led to an increasing need for ethics approvals also for student research projects. There is no standardised procedure for dealing with student research projects in Germany. This can lead to research projects being carried out without an ethics approval, even though this might have been necessary. This study aims to investigate how different universities deal with ethical aspects in students' research. In addition, we present examples of existing approaches.An online-based questionnaire was sent to 132 departments offering degree programmes in public health, health and nursing science, and psychology at 112 universities. Additionally, telephone interviews were conducted with the coordinators of four such degree programmes.Coordinators of 55 such degree programmes participated in the survey; 84% of the participating of these offered support to students with ethical questions concerning their research. However, only 39% provided a structured procedure for dealing with ethical assessments of research projects led by students. Several approaches were presented in depth by the coordinators of four degree programmes, among them the use of checklists, the establishment of internal ethics committees, and ethics advisory services. All respondents agreed on a need to deal with ethics approvals related to students' research projects.Structured procedures exist at some but not all degree programmes, faculties, and universities. Some of these procedures can serve as models for other universities.Forschungsprojekte in den Gesundheitswissenschaften berühren häufig ethisch sensible Bereiche. Mit zunehmend empirisch angelegten Abschlussarbeiten und Konzepten wie dem Forschenden Lernen steigt der Bedarf an Ethikvoten bei studentischen Arbeiten. Ein einheitliches Verfahren für den Umgang mit studentische Arbeiten liegt in Deutschland nicht vor. Dies kann dazu führen, dass Forschungsarbeiten ohne ein Ethikvotum durchgeführt werden, obwohl es notwendig gewesen wäre. ZIEL: dieser Studie war es, zu erfahren wie verschiedene Hochschulen mit der ethischen Bewertung bei studentischen Forschungsarbeiten umgehen. Methode Von Mai bis Juni 2018 wurden Online-Fragebögen an 132 Studiengänge an 112 Hochschulen mit Public Health, gesundheits- und pflegewissenschaftlichem Bezug sowie universitäre Studiengänge der Psychologie geschickt. Zusätzlich wurden telefonische Interviews mit vier ausgewählten Studiengangsverantwortlichen geführt.Studiengangsverantwortliche von 55 der 132 angeschriebenen Studiengänge nahmen an der Befragung teil. Unterstützungen für Studierende bei ethischen Fragestellungen ihrer Forschungsarbeiten werden von 84% der Antwortenden gewährleistet. Ein festgelegtes Verfahren für den Umgang mit (möglicherweise) ethisch beurteilungsbedürftigen studentischen Forschungsarbeiten existiert nur bei 39% der Antwortenden. Unterschiedliche Lösungsansätze wurden von ausgewählten Studiengangsverantwortlichen ausführlich vorgestellt, wie z. B. der Einsatz von Checklisten, die Einrichtung studiengangsinterner Ethikkommissionen oder Ethikberatungen.Alle befragten Studiengangsverantwortlichen erkennen die Notwendigkeit sich mit der Frage von Ethikvoten bei studentischen Forschungsarbeiten zu beschäftigen. An einigen Hochschulen existieren bereits Verfahren um damit umzugehen. Diese können als Orientierung für andere Hochschulen dienen.

Objectives: Rotational thromboelastometry (ROTEM)-guided transfusion algorithms in cardiac surgery have been proven to be successful in reducing blood loss in randomized controlled trials. Using an institutional hemostasis registry of patients in cardiac surgery (HEROES-CS), the authors hypothesized that the use of ROTEM-guided transfusion algorithms would save blood products and overall costs in cardiac surgery in every day practice.Design: Observational, prospective open cohort database.Setting: Single-center academic hospital.Participants: Cardiac surgery patients.Interventions: Implementation of ROTEM-guided bleeding management.Measurements and Main Results: A classical-guided algorithm and a ROTEM-guided algorithm were used for patient blood management in 2 cohorts. Primary outcome was the use and amount of blood products and hemostatic medication. Secondary outcomes were amount of rethoracotomies, length of stay, and 30-day mortality. Finally, costs and savings were calculated. The classical -guided cohort comprised 204 patients, and ROTEM-guided cohort comprised 151 patients. Baseline characteristics showed excellent similarities after propensity score matching of 202 patients. Blood loss was lower after ROTEM guidance (p Conclusions: Implementation of a ROTEM-guided transfusion algorithm in cardiac surgery patients reduced the use of blood products and hemostatic medication, hereby saving costs. Reductions in mortality and rethoracotomy rates could not be found. (C) 2018 The Authors. Published by Elsevier Inc.

Hypoxia is a hallmark of solid cancers, supporting proliferation, angiogenesis, and escape from apoptosis. There is still limited understanding of how cancer cells adapt to hypoxic conditions and survive. We analyzed transcriptome changes of human lung and breast cancer cells under chronic hypoxia. Hypoxia induced highly concordant changes in transcript abundance, but divergent splicing responses, underlining the cell type-specificity of alternative splicing programs. While RNA-binding proteins were predominantly reduced, hypoxia specifically induced muscleblind-like protein 2 (MBNL2). Strikingly, MBNL2 induction was critical for hypoxia adaptation by controlling the transcript abundance of hypoxia response genes, such as vascular endothelial growth factor A (VEGFA). MBNL2 depletion reduced the proliferation and migration of cancer cells, demonstrating an important role of MBNL2 as cancer driver. Hypoxia control is specific for MBNL2 and not shared by its paralog MBNL1. Thus, our study revealed MBNL2 as central mediator of cancer cell responses to hypoxia, regulating the expression and alternative splicing of hypoxia-induced genes.

ObjectivesThe aim of this study was to provide an overview of the methodological characteristics and compare the assessment methods applied in health technology assessments (HTAs) of public health interventions (PHIs).MethodsWe defined a PHI as a population-based intervention on health promotion or for primary prevention of chronic or nonchronic diseases. HTAs on PHIs were identified by systematically searching the Web pages of members of international HTA networks. We included only full HTA reports published between 2012 and 2016. Two reviewers extracted data on the methods used to assess effectiveness/safety, as well as on economic, social, cultural, ethical, and legal aspects using a-priori standardized tables.ResultsWe included ten HTAs provided by four different organizations. Of these, all reports assessed the effectiveness of the interventions and conducted economic evaluations, seven investigated social/cultural aspects, and four each considered legal and ethical aspects, respectively. Some reports addressed applicability, context/setting, and intervention fidelity issues in different ways. We found that most HTAs adapted their methods to some extent, for example, by including nonrandomized studies, expanding the search strategy, involving stakeholders, or applying a framework to guide the HTA process.ConclusionsOur analysis provides a comprehensive overview of methods applied in HTAs on public health interventions. We found that a heterogeneous set of approaches is used to deal with the challenges of evaluating complex public health interventions.

The clinical logbook is the currently accepted tool for evaluating experiential learning (EL) in postgraduate radiology training programs internationally. The role of the picture archiving and communication system/radiology information system (PACS/RIS) in defining the complete EL portfolio of radiology residents has not been explored. To conduct a PACS/RIS-based analysis of the comprehensive clinical outputs of radiology residents, and to correlate outputs with residency recruitment criteria and exit examination performance. Retrospective, customized searches of the institutional PACS/RIS were conducted to determine the clinical outputs of radiology residents completing a standardized 4-year training program at a single institution in a middle-income country. The association between outputs and prior-to-residency radiology experience, prior-to residency completion of the primary examination, and performance in the exit examination were determined. Fifteen residents were included. Average clinical output was 8286 cases, with a wide range (6268-10460). Total output was not associated with first-time exit examination success (p=0.16). Residents with prior radiology experience tended to greater success at first exit examination attempt (10/11, 91% versus 2/4, 50%; p=0.09), despite lower average outputs (8138 versus 8695). Outputs were not associated with prior completion of the radiology primary examination (8263 versus 8378; p=0.87). This first PACS/RIS-based analysis of the complete clinical outputs of any radiology residency training program provides important baseline educational data, with the potential to inform discourses on specialty training internationally. It demonstrates the potential for the modern PACS/RIS to supersede the traditional logbook and to serve as a comprehensive EL portfolio for radiology residents.

The potential of capillary electrophoresis (CE) with ultraviolet (UV)-excited fluorescence detection for sensitive chiral analysis of amino acids (AAs) was investigated. dl-AAs were derivatized with 9-fluorenylmethoxycarbonyl chloride (FMOC)-Cl to allow their fluorescence detection and enhance enantioseparation. Fluorescence detection was achieved employing optical fibers, leading UV excitation light (< 300 nm) from a Xe-Hg lamp to the capillary window, and fluorescence emission to a spectrograph equipped with a charge-coupled device (CCD). Signal averaging over time and emission wavelength intervals was carried out to improve the signal-to-noise ratio of the FMOC-AAs. A background electrolyte (BGE) of 40 mM sodium tetraborate (pH 9.5), containing 15% isopropanol (v/v), 30 mM sodium dodecyl sulfate (SDS), and 30 mM β-cyclodextrin (β-CD), was found optimal for AA chemo- and enantioseparation. Enantioresolutions of 1.0 or higher were achieved for 16 proteinogenic dl-AAs. Limits of detection (LODs) were in the 10–100-nM range (injected concentration) for the d-AA enantiomers, except for FMOC-d-tryptophan (536 nM) which showed intramolecular fluorescence quenching. Linearity (R2 > 0.997) and repeatability for peak height (relative standard deviations (RSDs) < 7.0%; n = 5) and electrophoretic mobility (RSDs < 0.6%; n = 5) of individual AA enantiomers were established for chiral analysis of dl-AA mixtures. The applicability of the method was investigated by the analysis of cerebrospinal fluid (CSF). Next to l-AAs, endogenous levels of d-glutamine and d-aspartic acid could be measured in CSF revealing enantiomeric ratios of 0.35 and 19.6%, respectively. This indicates the method’s potential for the analysis of low concentrations of d-AAs in presence of abundant l-AAs.

Background Kidney biopsy can result in bleeding complications. Pre-biopsy testing using bleeding time (BT) is controversial. New whole blood haemostasis tests, like platelet function analyser 100 (PFA-100) and multiple electrode aggregometer (MEA) might perform better. We postulated that PFA-100 would be suitable to replace BT pre-biopsy. Methods In 154 patients, transplanted kidney biopsies were performed after measurement of bleeding time, PFA-100, MEA, and mean platelet volume (MPV). Bleeding outcome (haemoglobin (Hb) drop, haematuria (±bladder catherization), ultrasound finding of a bleeding, need for (non-)surgical intervention, and/or transfusion) after the biopsy was correlated to each test. Results Male-female ratio was 2:1. 50% had a surveillance biopsy at either three or 12 months. Around 17% (had) used acetylsalicylic acid (ASA) pre-biopsy. Of 17 bleeding events one subject needed a transfusion. Most bleeding events were Hb reductions over 1 mmol/L and all resolved uneventful. BT, PFA-100, MEA, and MPV did not predict a bleeding outcome; prior ASA use however could (odds ratio 3.19; 95%-CI 1.06 to 9.61). Diagnostic performance data and Bland-Altman analysis showed that BT could not be substituted by PFA-100. Conclusions ASA use was the best determinant of bleeding after kidney biopsy. Routine haemostasis testing pre-biopsy has no added value. This article is protected by copyright. All rights reserved.

Contains fulltext : 190759.pdf (Publisher’s version ) (Closed access) The complexity associated with how interventions result-or fail to result-in outcomes and how context matters is increasingly recognised. Logic models provide an important tool for handling complexity, with contrasting uses in programme evaluation and evidence synthesis. To reconcile these, we developed an approach that combines the strengths of both traditions, propose a taxonomy of logic models, and provide guidance on how to choose between approaches and types of logic models in systematic reviews and health technology assessments (HTA). The taxonomy distinguishes 3 approaches (a priori, staged, and iterative) and 2 types (systems-based and process-orientated) of logic models. An a priori logic model is specified at the start of the systematic review/HTA and remains unchanged. With a staged logic model, the reviewer prespecifies several points, at which major data inputs require a subsequent version. An iterative logic model is continuously modified throughout the systematic review/HTA process. System-based logic models describe the system, in which the interaction between participants, intervention, and context takes place; process-orientated models display the causal pathways leading from the intervention to multiple outcomes. The proposed taxonomy of logic models offers an improved understanding of the advantages and limitations of logic models across the spectrum from a priori to fully iterative approaches. Choice of logic model should be informed by scope of evidence synthesis, presence/absence of clearly defined population, intervention, comparison, outcome (PICO) elements, and feasibility considerations. Applications across distinct interventions and methodological approaches will deliver good practice case studies and offer further insights on the choice and implementation of logic modelling approaches.

The evaluation of complex interventions such as palliative care is challenging. Methods guidance such as the guidance documents of the Integrated Health Technology Assessment for the Evaluation of Complex Technologies (INTEGRATE-HTA) project help address specific challenges. The INTEGRATE-guidance was developed cooperatively by various international stakeholders and it was applied in a case study on palliative care. The presented study was part of the INTEGRATE-HTA project. ObjectivesThe objective was to identify important assessment aspects of palliative care in Germany from the perspective of patients, relatives and professional providers.Applying the structured consensus method of the Improved Nominal Group Technique, we conducted interviews with two focus groups - one with relatives and one with professionals. Additionally, we conducted 4 interviews with patients. We used an open coding procedure to analyze the data and a dialogical approach to validate the results.8 assessment aspects were found to be important. These are the definition and legitimacy of the term benefit, understanding of palliative care, patient-centered and holistic care approach, access to palliative care, continuity and flexibility of care, education of palliative care providers, and multidisciplinary approach. A central point was the need to address the intervention in its complexity and to include interactions between the different components.To be able to integrate various models and different perspectives of palliative care, it is important to have the involvement of different stakeholders. This also enhances the incorporation of important aspects during the development of assessment instruments.Komplexe Interventionen wie die Palliativversorgung (PV) stellen besondere Ansprüche an die Evaluation. Methodenleitfäden wie die des Projektes Integrated Health Technology Assessment for Evaluating Complex Technologies (INTEGRATE-HTA) helfen, diesen gerecht zu werden. Letztere wurden am Beispiel von PV in 7 europäischen Ländern entwickelt. ZIEL: Ziel der vorliegenden Studie war es, wichtige Aspekte für die Nutzenbewertung von PV aus Sicht von Patienten, Angehörigen und (professionell) Versorgenden in Deutschland zu identifizieren.Unter Anwendung der strukturierten Konsensfindung der Improved Nominal Group Technique führten wir je eine Fokusgruppe mit Angehörigen und mit in der PV tätigen Versorgern durch. Patienten befragten wir in 4 offenen Leitfadeninterviews. Die Analyse erfolgte unter Anwendung des offenen Kodierens.Die Ergebnisse wurden kommunikativ validiert. Wir identifizierten die Bestimmung und Legitimität des Nutzenbegriffs, das Verständnis von PV, den patientenzentrierten und ganzheitlichen Ansatz, den Zugang zu PV, die Kontinuität und Flexibilität der Versorgung, die Ausbildung von Palliativkräften und die Multiprofessionalität als wichtige Nutzenaspekte. SchlussfolgerungDeutlich wird, dass ein Aufbrechen der Intervention in weniger komplexe Teile PV nicht adäquat erfasst. Die frühe Integration unterschiedlicher Stakeholder hilft wichtige Nutzenaspekte zu identifizieren, die so bereits in die Entwicklung von Bewertungsinstrumenten einfließen können.

Patient involvement in health research is an integral part of health care in many countries. It promotes the relevance and quality of research and increases the meaningfulness of research results. Meanwhile, the value of patient involvement has also been recognised in Germany. The lack of a common understanding of patient involvement and appropriate methods make implementation difficult. In Germany, patients are still rarely involved in the planning and conduct of health research. Vulnerable patient groups such as the elderly and the very old are considered particularly challenging for researchers in active patient involvement due to their special needs, which is why they are often neglected. Especially nursing home residents suffer from a variety of health impairments which are accompanied by a high number of prescription drugs and adverse events and can therefore make patient involvement more difficult. The present project aims to test the method of patient advisory boards for the involvement of nursing home residents. Using the design of a clinical trial to optimise medication for nursing home residents as a case study, we will assess the feasibility of the method for this target group. We will also install a patient advocate as moderator of the advisory board. The study plan is described in the present study protocol.Two patient advisory boards with nursing home residents will be established. With a patient advocate acting as moderator, the essential elements of a clinical trial to optimise medication will be discussed and passed on to the study planning team via the patient advocate. The overall topic of the clinical trial is the optimisation of medication in cardiovascular disease. The nursing home residents are informed about the contents and ideas of the study to be planned and the interests of the researchers, respectively, and will discuss the proposals of the study planning team. Nursing home residents', the patient advocate's and the researchers' expectations and experiences will be examined in individual interviews.The study will provide a potentially suitable method to involve nursing home residents in the research process. The jointly developed study design will be incorporated into a new project proposal. The results will be used to inform the development of a German handbook on active public and patient involvement.

Introduction Nursing home residents typically have greater needs for medical care than community-dwelling elderly. However, restricted cognitive abilities and limited mobility may impede their access to general practitioners and medical specialists. The provision of medical care in nursing homes may therefore be inappropriate in some areas of medical care. The purpose of this mixed-methods study is to systematically assess, evaluate and explain met and unmet medical care needs in German nursing homes and to develop solutions where medical care is found to be inappropriate. Methods and analysis First, statutory health insurance claims data are analysed to identify differences in the utilisation of medical care between nursing home residents and community-dwelling elderly with and without need for long-term care. Second, the health status and medical care of 500 nursing home residents are assessed and evaluated to quantify met and unmet medical care needs. Third, qualitative expert interviews and case conferences and, fourth, quantitative analyses of linked data are used to provide structural, case-specific and generalisable explanations of inappropriate medical care among nursing home residents. Fifth, a modified Delphi study is employed to develop pilot projects aiming to improve medical care in nursing homes. Ethics and dissemination This study was approved by the Ethics Committee of the University of Bremen on 23 November 2017. Research findings are disseminated through presentations at national and international conferences and publications in peer-reviewed scientific journals. Trial registration number DRKS00012383.

Low platelet counts and hematocrit levels hinder whole blood point-of-care testing of platelet function. Thus far, no reference ranges for MEA (multiple electrode aggregometry) and PFA-100 (platelet function analyzer 100) devices exist for low ranges. Through dilution methods of volunteer whole blood, platelet function at low ranges of platelet count and hematocrit levels was assessed on MEA for four agonists and for PFA-100 in two cartridges. Using (multiple) regression analysis, 95% reference intervals were computed for these low ranges. Low platelet counts affected MEA in a positive correlation (all agonists showed r(2) >= 0.75) and PFA-100 in an inverse correlation (closure times were prolonged with lower platelet counts). Lowered hematocrit did not affect MEA testing, except for arachidonic acid activation (ASPI), which showed a weak positive correlation (r(2) = 0.14). Closure time on PFA-100 testing was inversely correlated with hematocrit for both cartridges. Regression analysis revealed different 95% reference intervals in comparison with originally established intervals for both MEA and PFA-100 in low platelet or hematocrit conditions. Multiple regression analysis of ASPI and both tests on the PFA-100 for combined low platelet and hematocrit conditions revealed that only PFA-100 testing should be adjusted for both thrombocytopenia and anemia. 95% reference intervals were calculated using multiple regression analysis. However, coefficients of determination of PFA-100 were poor, and some variance remained unexplained. Thus, in this pilot study using (multiple) regression analysis, we could establish reference intervals of platelet function in anemia and thrombocytopenia conditions on PFA-100 and in thrombocytopenia conditions on MEA.

CE–MS can be considered a useful analytical technique for the global profiling of (highly) polar and charged metabolites in various samples. Over the past few years, significant advancements have been made in CE–MS approaches for metabolomics studies. In this paper, which is a follow-up of a previous review paper covering the years 2012–2014 (Electrophoresis 2015, 36, 212–224), recent CE–MS strategies developed for metabolomics covering the literature from July 2014 to June 2016 are outlined. Attention will be paid to new CE–MS approaches for the profiling of anionic metabolites and the potential of SPE coupled to CE–MS is also demonstrated. Representative examples illustrate the applicability of CE–MS in the fields of biomedical, clinical, microbial, plant, and food metabolomics. A complete overview of recent CE–MS-based metabolomics studies is given in a table, which provides information on sample type and pretreatment, capillary coatings, and MS detection mode. Finally, general conclusions and perspectives are given.

Objectives: A comprehensive health technology assessment (HTA) enables a patient-centered assessment of the effectiveness, economic, ethical, socio-cultural, and legal issues of health technologies that takes context and implementation into account. A question is whether these various pieces of evidence need to be integrated, and if so, how that might be achieved. The objective of our study is to discuss the meaning of integration in the context of HTA and suggest how it may be achieved in a more structured way.Methods: An analysis of the concept of integration in the context of HTA and a review of approaches that were adopted in the INTEGRATE-HTA project that may support integration.Results: Current approaches to integration in HTA are mainly methods of commensuration, which are not optimally geared to support public deliberation. In contrast, articulating evaluative frameworks could be an important means of integration which allows for exploring how facts and values can be brought to bear on each other.Conclusions: Integration is not something that only needs to be addressed at the end, but rather throughout an HTA, right from the start. Integration can be conceived as a matter of accounting for the relevance of empirical evidence in view of a commitment to a set of potentially conflicting values. Various elements of the INTEGRATE-HTA project, such as scoping and the development of logic models, can help to achieve integration in HTA.

Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) is frequently associated with low platelet count (PC) and disturbed platelet function (PF). While PC is easy to measure, PF is more difficult to assess. Moreover, the time-related platelet dysfunction and recovery after CPB is not fully elucidated. Platelet dysfunction could lead to bleeding but also to coronary graft failure. Laboratory tests could provide more insights into PF after CABG. The aim of the current study was to investigate the time-related PF induced by CPB. Blood samples of 20 patients with a preoperative PC of more than 250 x 10(9)/L were collected before incision, after weaning from CPB, and 24 h postoperative. Platelet contribution to coagulation was quantified by PLTEM (calculated by means of EXTEM and FIBTEM results). PF was assessed by multiple electrode impedance aggregometry (MEIA) in whole blood and by light transmission aggregometry (LTA) in platelet-rich plasma after stimulation with arachidonic acid (AA), adenosine diphosphate, collagen, and thrombin-receptor-activating peptide. LTA and MEIA analysis demonstrated significant platelet dysfunction after CPB, with partial recovery within 24 h after surgery. AA-induced platelet aggregation increased to higher levels within 24 h after surgery compared to baseline values as measured by LTA. PLTEM maximum clot firmness remained unchanged throughout the study. Correlation analyses revealed that MEIA and rotational thromboelastometry (ROTEM), but not LTA, were dependent on PC and hematocrit. No correlations were found between LTA, MEIA, ROTEM, PC, and clinical outcome parameters. Our results demonstrate a reversible platelet dysfunction recovering within 24 h after CPB. Interestingly, AA-induced platelet aggregation increases to higher levels during the first 24 h postoperatively, which might be important for early initiation of antiplatelet therapy after CABG. MEIA as POC test is able to detect platelet dysfunction during cardiac surgery with a PC of >= 150 x 10(9)/L.

Practitioners and providers who want to apply evidence from studies will usually face the following two questions: 1) 'Are the study results valid?', and 2) 'Will these results be the same in my setting?' Major progress has been achieved in regard to the first question. An array of tools to assess the validity has been developed. Much less effort, though, has been put into developing and applying methods to assess the transferability of evidence from one setting to another. Existing concepts to assess transferability aim at identifying similarities and differences between the study context and the context in which the study findings are supposed to be applied. In a second step, the impact of the differences on the outcomes are estimated. Context can be distinguished into 'implementation' (how is an intervention applied?), 'target group' (who will receive the intervention?), and 'setting.' In this article selected tools to identify context variables and to assess transferability are presented.

Human breast milk (HBM) is considered inadequate in meeting protein requirements, especially for very low birth weight (VLBW) infants, which could affect body composition.The primary objective was to determine the effect of HBM on body composition of HIV-exposed and unexposed preterm VLBW and extremely low birth weight infants. The secondary objectives were to ascertain the effect breast milk fortification and days nil per os (NPO) have on body composition.A descriptive cross-sectional study was conducted. Preterm infants with a birth weight of ≤1,200 g were included. Infant nutritional intakes and body composition measurements were recorded during the 28-day follow-up period.One hundred ten of 113 preterm infants received HBM and 91 infants received fortified HBM. HIV-exposed and unexposed infants receiving fortified HBM displayed differences in fat mass percentage (FM%) (0.88% versus 1.36%, p = 0.01; 0.97% versus 1.49%, p = 0.03) and fat-free mass percentage (FFM%) (98.98% versus 98.68%, p = 0.03; 99.02% versus 98.49%, p = 0.02) on days 21 and 28, respectively. Infants kept NPO displayed differences in FM% on days 7, 21, and 28 (0.9% versus 1.3%, p = 0.03; 0.99% versus 1.4%, p = 0.02; and 0.9% versus 1.6%, p = 0.0004) as well as differences in FFM% (99.1% versus 98.4%; p = 0.0005) on day 28 of life.There were no significant differences in the body composition of infants who received HBM versus fortified HBM. However, significant differences in body composition were reported between HIV exposure groups for infants who received fortified HBM. Infants who were kept NPO were generally smaller, shorter, and had lower FM% and more FFM%.

Objectives Social and cultural aspects are rarely assessed in health technology assessments (HTA), despite being part of most HTA definitions. One hypothesis for the reason why they are hardly considered in HTA is that we lack relevant assessment methods. Accordingly, this review aims at providing an overview of methodological approaches to address social and cultural aspects related to health technologies in HTA. Methods We conducted a comprehensive literature search by searching fourteen databases and a hand-search of two pertinent journals. Additionally, we sent a query to all member agencies of the International Network of Agencies for Health Technology Assessment (INAHTA) asking them for methods they use to assess social and cultural aspects. Results A total of 125 publications met our inclusion criteria. We grouped the methodological approaches into checklists for experts, literature reviews, stakeholder participatory approaches, primary data collection methods, and combinations of methodological approaches. Conclusions There is a wide variety of methods available for assessing social and cultural aspects of health technologies, some of which have been applied in HTA. The presented overview of the different approaches and their merits can facilitate the assessment of these aspects, and improve the knowledge regarding (potential) success and failure of the implementation of a health technology. © Cambridge University Press 2019. This is an Open Access article, distributed under the terms of the Creative Commons AttributionNonCommercial-NoDerivatives licence (http:// creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.

Background Conducting a health technology assessment (HTA) of public health interventions (PHIs) poses some challenges. PHIs are often complex interventions, which affect the number and degree of interactions of the aspects to be assessed. Randomized controlled trials on PHIs are rare as they are difficult to conduct because of ethical or feasibility issues. The aim of this study is to provide an overview of the methodological characteristics and to compare the applied assessment methods in HTAs on PHIs. Methods We will systematically search HTA agencies for HTAs on PHIs published between 2012 and 2016. We will identify the HTAs by screening the webpages of members of international HTA organizations. One reviewer will screen the list of HTAs on the webpages of members of international HTA organization, and a second review will double-check the excluded records. For this methodological review, we define a PHI as a population-based intervention on health promotion or for primary prevention of chronic or non-chronic diseases. Only full HTA reports will be included. At maximum, we will include a sample of 100 HTAs. In the case that we identify more than 100 relevant HTAs, we will perform a random selection. We will extract data on effectiveness, safety and economic as well as on social, cultural, ethical and legal aspects in a priori piloted standardized tables. We will not assess the risk of bias as we focus on exploring methodological features. Data extraction will be performed by one reviewer and verified by a second. We will synthesize data using tables and in a structured narrative way. Discussion Our analysis will provide a comprehensive and current overview of methods applied in HTAs on PHIs. We will discuss approaches that may be promising to overcome the challenges of evaluating PHIs. Electronic supplementary material The online version of this article (10.1186/s13643-018-0743-4) contains supplementary material, which is available to authorized users.

Background: cancellation of planned surgery impacts substantially on patients and health systems. This study describes the incidence and reasons for cancellation of inpatient surgery in the UK NHS. Methods: we conducted a prospective observational cohort study over 7 consecutive days in March 2017 in 245 NHS hospitals. Occurrences and reasons for previous surgical cancellations were recorded. Using multilevel logistic regression, we identified patient- and hospital-level factors associated with cancellation due to inadequate bed capacity. Results: we analysed data from 14 936 patients undergoing planned surgery. A total of 1499 patients (10.0%) reported previous cancellation for the same procedure; contemporaneous hospital census data indicated that 13.9% patients attending inpatient operations were cancelled on the day of surgery. Non-clinical reasons, predominantly inadequate bed capacity, accounted for a large proportion of previous cancellations. Independent risk factors for cancellation due to inadequate bed capacity included requirement for postoperative critical care [odds ratio (OR)=2.92; 95% confidence interval (CI), 2.12–4.02; PConclusions: a significant proportion of patients presenting for surgery have experienced a previous cancellation for the same procedure. Cancer surgery is relatively protected, but bed capacity, including postoperative critical care requirements, are significant risk factors for previous cancellations.

Contains fulltext : 168280.pdf (Publisher’s version ) (Open Access) Ethics has been identified as a key element in Health Technology Assessment (HTA) since its conception. However, ethical issues are still not frequently addressed explicitly in HTA. Several valuable reasons have been identified. The basis of the article is the claim that ethics is often not part of HTA for "epistemological reasons". Hence, the main aim of the contribution is to explore in more details and emphasize them by using the fact/value dichotomy. Our conclusion is that current HTA configuration is predominantly based on the comparison among objective and empirically testable "facts", whilst ethics is not empirically testable. In this sense, there is a sort of "epistemological gap", which can explain why it is so difficult to integrate ethics in HTA. We suggest that the epistemological differences among the various domains of HTA are addressed more explicitly.

Background Evidence from first world contexts support the notion that strong primary health care teams contain family physicians (FPs). African leaders are looking for evidence from their own context. The roles and scope of practice of FPs are also contextually defined. The South African family medicine discipline has agreed on six roles. These roles were incorporated into a family physician impact assessment tool, previously validated in the Western Cape Province. Methods A cross-sectional study design was used to assess the perceived impact of family physicians across seven South African provinces. All FPs working in the district health system (DHS) of these seven provinces were invited to participate. Sixteen respondents (including the FP) per enrolled FP were asked to complete the validated 360-degree assessment tool. Results A total number of 52 FPs enrolled for the survey (a response rate of 56.5%) with a total number of 542 respondents. The mean number of respondents per FP was 10.4 (SD = 3.9). The perceived impact made by FPs was high for five of the six roles. Co-workers rated their FP’s impact across all six roles as higher, compared to the other doctors at the same facility. The perceived beneficial impact was experienced equally across the whole study setting, with no significant differences when comparing location (rural vs. metropolitan), facility type or training model (graduation before and ≥ 2011). Conclusions The findings support the need to increase the deployment of family physicians in the DHS and to increase the number being trained as per the national position paper. Electronic supplementary material The online version of this article (10.1186/s12875-018-0710-0) contains supplementary material, which is available to authorized users.

Burkholderia pseudomallei and B. thailandensis are in the soil; a novel B. pseudomallei sequence type causes lethal septic shock., Burkholderia pseudomallei, an environmental gram-negative bacillus, is the causative agent of melioidosis and a bio-threat agent. Reports of B. pseudomallei isolation from soil and animals in East and West Africa suggest that melioidosis might be more widely distributed than previously thought. Because it has been found in equatorial areas with tropical climates, we hypothesized that B. pseudomallei could exist in Gabon. During 2012–2013, we conducted a seroprevalance study in which we set up microbiology facilities at a large clinical referral center and prospectively screened all febrile patients by conducting blood cultures and testing for B. pseudomallei and related species; we also determined whether B. pseudomallei could be isolated from soil. We discovered a novel B. pseudomallei sequence type that caused lethal septic shock and identified B. pseudomallei and B. thailandensis in the environment. Our data suggest that melioidosis is emerging in Central Africa but is unrecognized because of the lack of diagnostic microbiology facilities.

Objectives: The aim of this study was to identify and discuss appropriate approaches to integrate ethical inquiry in health technology assessment (HTA).Methods: The key question is how ethics can be integrated in HTA. This is addressed in two steps: by investigating what it means to integrate ethics in HTA, and by assessing how suitable the various methods in ethics are to be integrated in HTA according to these meanings of integration.Results: In the first step, we found that integrating ethics can mean that ethics is (a) subsumed under or (b) combined with other parts of the HTA process; that it can be (c) coordinated with other parts; or that (d) ethics actively interacts and changes other parts of the HTA process. For the second step, we found that the various methods in ethics have different merits with respect to the four conceptions of integration in HTA.Conclusions: Traditional approaches in moral philosophy tend to be most suited to be subsumed or combined, while processual approaches being close to the HTA or implementation process appear to be most suited to coordinated and interactive types of integration. The article provides a guide for choosing the ethics approach that appears most appropriate for the goals and process of a particular HTA.

The need for a qualified public health workforce can only be met by appropriate provision of a wide spectrum of basic, advanced and continuing education and training programs on public health that meet international standards. At the same time, efforts must be made to offer young academics attractive career opportunities. Training in public health competences must also be provided for allied professionals in health care and for professions with influence on the determinants of health such as urban planning or agricultural science. This report from a working group meeting at the 'Public Health Zukunftsforum 2016' in Berlin presents ideas for the further development of training in public health in Germany.Der Bedarf an Public-Health-Expertinnen und -Experten kann nur durch ein abgestimmtes Angebot von Aus-, Fort- und Weiterbildung auf Basis internationaler didaktischer Standards gedeckt werden. Zugleich sollten den Absolventinnen und Absolventen attraktive Karrierewege offenstehen. Auch in der Ausbildung der Gesundheitsberufe sowie in Studienfächern mit Bezug zur Bevölkerungsgesundheit (z. B. Stadtplanung, Agrarwissenschaften) sollten Public-Health-Kompetenzen eine wichtige Rolle spielen. Um diese Ziele zu erreichen, hat eine Arbeitsgruppe des Zukunftsforums erste Vorschläge für Strategien erarbeitet und in diesem Beitrag zusammengefasst.

OBJECTIVES Transcatheter aortic valve implantation (TAVI) in patients with low coronary heights is generally denied but is not impossible. Information about these high-risk procedures is sparse. METHODS Since May 2008, data of more than 3000 patients who had TAVI were prospectively collected in the institutional TAVI Karlsruhe registry. Characteristics, peri- and postoperative outcome of patients with low coronary heights of ≤7 mm were analysed according to the Valve Academic Research Consortium-2. RESULTS Eighty-six patients with an average coronary height of 6.4 ± 1.1 mm (mean age 81.0 ± 5.3 years, logistic EuroSCORE I 19.6 ± 13.3%) were treated. TAVI was performed in 72 transfemoral (83.7%) and 14 transapical (16.3%) cases using 44 CoreValve/Evolut R (51.2%), 21 Sapien XT/S3 (24.4%), 14 ACURATE (16.3%), 5 Lotus (5.8%) and 2 Portico (2.3%) prostheses. Ten procedures were valve-in-valve (VinV) TAVI (VinV, 11.6%). The 72-h, 30-day, 1-year and follow-up (3.0 ± 1.6 years) mortality rates were 2.3%, 8.0%, 10.5% and 26.7%, respectively. Within 30 days, 4 cardiac deaths and 3 non-cardiac deaths occurred (4.7% and 3.5%). Three coronary obstructions (3.5%) occurred-2 during VinV TAVI. One patient was connected to extracorporeal circulation that could not be weaned later due to an unsuccessful percutaneous coronary intervention. Another patient, the only conversion (1.2%), required delayed surgical valve replacement. The third patient died of right heart failure after aortic dissection. The procedural success rate was 95.3%. VinV procedures were associated with increased follow-up deaths (P

Objectives: The INTEGRATE-HTA project provided methodology to evaluate complex technologies. This study provides guidance on how to retrieve and critically appraise available evidence on moderators and predictors of treatment effects and on patient preferences for treatment outcomes as a source of complexity.Methods: Search filters for PubMed were developed by hand-searching a large volume of articles reporting on relevant aspects. Search terms were retrieved from selected papers and algorithmically combined to find the optimal combination of search terms. For the development of the appraisal checklists literature was searched in PubMed and Google Scholar together with citation chasing. For the CHecklist for the Appraisal of Moderators and Predictors (CHAMP) a Delphi procedure was used to value a set of eligible appraisal criteria retrieved from the literature.Results: Search filters were developed optimized for different accuracy measures. The final version of CHAMP consists of a seventeen questions covering the design, analysis, results and transferability of results of moderator and predictor analysis. The final checklist for appraisal of literature on patient preferences for treatment outcomes consist of six questions meant to help the user to identify relevant quality issues together with a guidance toward existing tools concerning the appraisal of specific preference elicitation methods.Conclusions: Incorporating knowledge on subgroups for whom a specific treatment will produce more benefit holds the promise of better targeting and, ultimately, enhancing overall effectiveness and efficiency of healthcare technology. Finally, incorporating information on preferences for treatment outcomes will foster health technology assessment that addresses outcomes that are important to patients.

Demographic change has increased the need for research on healthcare for older people. Recently there has been a growing awareness that research might benefit from actively involving patients and the public in study design and conduct. Besides empowering patients and democratizing research, involvement enhances the quality of research and the development of equitable healthcare solutions. Little is known about how to involve older people. This review aims to support scientists intending to involve older people in health research by systematically identifying and describing studies involving older people and analyzing associated facilitators and challenges. Old people were operationalized as people living with old-age-related conditions. We conducted a systematic search in PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane library for the period 2007 to July 2017 and also manually searched reference lists of the nine retrieved articles and other relevant sources. While involvement of older people in research is feasible, specific challenges related to this group need be taken into account. Strategies to enhance effective involvement comprise a thoughtful choice of location, use of visualization and accessible communication, building good relationships and flexible approaches. Further research is needed on the involvement of people in care homes or with vision, hearing or mobility limitations.

Objectives:The translation of research findings into policy and practice is crucially dependent on the applicability of such findings in a given decision-making context. We explored in a case study whether a generic consultation guide to assess the applicability of a health technology could be rapidly deployed and deliver useful insights.Methods:A consultation guide based on the context and implementation for complex interventions (CICI) framework was developed and piloted to assess the applicability of reinforced home-based palliative care in three European countries. Individual consultations in England and Germany and a panel discussion in Poland were completed.Results:Various barriers may hinder successful implementation of reinforced home-based palliative care in the three countries. Whilst the experts across all countries emphasized the lack of funding along with organization and structure as major barriers, information varied by country for many of the other identified barriers and facilitators. Participants in the pilot study provided positive feedback in terms of understanding the topic and purpose of the consultation, and both individual and panel consultations could be easily implemented.Conclusions:In this case study, the consultation guide presented a pragmatic, ready-to-use tool to assess the applicability of a health technology. As shown here, it can be used in a generic manner without discrete empirical information on the technology in question or, ideally, makes use of specific information collected as part of a HTA. Further studies are needed to validate this guide and apply it to other types of health technologies and more diverse decision-making contexts.

INTRODUCTION: The Cochrane Collaboration aims to produce relevant and top priority evidence that responds to existing evidence gaps. Hence, research priority setting (RPS) is important to identify which potential research gaps are deemed most important. Moreover, RPS supports future health research to conform both health and health evidence needs. However, studies that are prioritising systematic review topics in public health are surprisingly rare. Therefore, to inform the research agenda of Cochrane Public Health Europe (CPHE), we introduce the protocol of a priority setting study on systematic review topics in several European countries, which is conceptualised as pilot. METHODS AND ANALYSIS: We will conduct a two-round modified Delphi study in Switzerland, incorporating an anonymous web-based questionnaire, to assess which topics should be prioritised for systematic reviews in public health. In the first Delphi round public health stakeholders will suggest relevant assessment criteria and potential priority topics. In the second Delphi round the participants indicate their (dis)agreement to the aggregated results of the first round and rate the potential review topics with the predetermined criteria on a four-point Likert scale. As we invite a wide variety of stakeholders we will compare the results between the different stakeholder groups. ETHICS AND DISSEMINATION: We have received ethical approval from the ethical board of the University of Bremen, Germany (principal investigation is conducted at the University of Bremen) and a certificate of non-objection from the Canton of Zurich, Switzerland (fieldwork will be conducted in Switzerland). The results of this study will be further disseminated through peer reviewed publication and will support systematic review author groups (i.a. CPHE) to improve the relevance of the groups´ future review work. Finally, the proposed priority setting study can be used as a framework by other systematic review groups when conducting a priority setting study in a different context.

UNLABELLED A systematic review and meta-analysis were performed to determine the effect of therapeutic hypothermia using low-technology methods, in settings with facilities for intensive care, in term or near-term infants with hypoxic-ischaemic encephalopathy on mortality, neurological morbidity at discharge and neurological morbidity at 6-24 months. CONCLUSION Meta-analysis of three randomised controlled studies showed that low-technology therapeutic hypothermia in an intensive care setting significantly reduced the mortality and the neurological morbidity in survivors at discharge.

Background Evidence synthesis has seen major methodological advances in reducing uncertainty and estimating the sizes of the effects. Much less is known about how to assess the relative value of different outcomes. Objective To identify studies that assessed preferences for outcomes in health conditions. Methods Search strategy: we searched MEDLINE, EMBASE, PsycINFO and the Cochrane Library in February 2014. Inclusion criteria: eligible studies investigated preferences of patients, family members, the general population or healthcare professionals for health outcomes. The intention of this review was to include studies which focus on theoretical alternatives; studies which assessed preferences for distinct treatments were excluded. Data extraction: study characteristics as study objective, health condition, participants, elicitation method, and outcomes assessed in the study were extracted. Main results One hundred and twenty-four studies were identified and categorized into four groups: (1) multi criteria decision analysis (MCDA) (n = 71), (2) rating or ranking (n = 25), (3) utility eliciting (n = 5) and (4) studies comparing different methods (n = 23). The number of outcomes assessed by method group varied. The comparison of different methods or subgroups within one study often resulted in different hierarchies of outcomes. Conclusions A dominant method most suitable for application in evidence syntheses was not identified. As preferences of patients differ from those of other stakeholders (especially medical professionals), the choice of the group to be questioned is consequential. Further research needs to focus on validity and applicability of the identified methods.

Aortic rupture of the device landing zone is a rare complication of transcatheter aortic valve implantation (TAVI) and it is associated with significant mortality.This study reports on the experience of a single-center in a case series of more than 1,000 implants. We explored patient and procedural characteristics aiming at identifying variables that increase the risk for aortic root rupture.Among a total of 1,000 TAVI procedures, six patients (0.6 %) had a rupture of the device landing zone. Five of these patients received the balloon-expandable Edwards SAPIEN valve (5/813; 0.62 %) of which four had a supraannular and one a subannular rupture. One patient received the self-expanding Medtronic CoreValve (1/199; 0.5 %; p = n.s. vs. SAPIEN) and had an annular rupture. Factors that were associated with aortic rupture were: (1) the relative size of the valve compared with the aortic annulus and its geometric form; (2) the need for post-dilation of the new valve because of paravalvular leakage; and (3) the location and severity of calcification. We determined, to avoid aortic rupture, caution may be necessary in the presence of the following conditions: (1) flat sinuses of Valsalva and severe calcifications of either the body or the free edge of the aortic cusps (supraannular rupture); (2) an ellipsoid annulus and bulky calcifications on either the base of the cusps or the rim of the annulus (annular rupture); and (3) a narrow left-ventricular outflow tract (LVOT) and bulky calcification of the LVOT (subannular rupture). After considering these precautions, we observed no case of aortic root rupture in the following 600 cases.The data indicate that to reduce the frequency of aortic rupture, a careful pre-procedural planning appears essential to avoid this serious and potentially deleterious complication.

Objectives: In the present study, the authors have investigated whether rotational thromboelastometry (ROTEM) could predict thrombocytopenia and hypofibrinogenemia in cardiac surgery using the clot amplitude after 5 minutes (A5). Another parameter, PLTEM, in which the contribution of fibrinogen is eliminated by subtracting a fibrin-specific ROTEM test (FIBTEM) from an extrinsically-activated ROTEM test (EXTEM), was investigated. Furthermore, the turnaround time of ROTEM was compared to conventional laboratory tests.Design: Prospective cohort study.Setting: Single academic medical center.Participants: Ninety-seven patients undergoing cardiac surgery between July 2011 until August 2012.Interventions: The correlations between EXTEM/FIBTEM A5, A10, and maximal clot formation (MCF), EXTEM/PLTEM (A5/A10, and MCF) and platelet count, and FIBTEM (A5/A10, and MCF) and fibrinogen were evaluated using the Pearson's correlation coefficient and receiver-operating characteristic curves. Turnaround times of ROTEM tests and conventional laboratory tests were assessed in the central laboratory.Measurements and Main Results: EXTEM AS and FIBTEM A5 showed an excellent correlation with A10 (R:0.99/1.00) and MCF (R:0.97/0.99). The correlation between EXTEM AS and platelet count (R:0.74) was comparable with the correlation of A10 (R:0.73) and MCF (R:0.70) with platelet count. FIBTEM AS predicted fibrinogen levels (R:0.87) as well as A10 (R:0.86) and MCF (R:0.87). PLTEM AS (R:0.85) correlated better with platelet count than EXTEM A5 (R:0.74; p = 0.04) and showed significantly better area under the curve values than EXTEM for predicting thrombocytopenia (A5 p = 0.012, A10 p = 0.019). Turnaround time for ROTEM tests, 12 minutes, was comparable with emergency requests for platelet count, 13 minutes, and shorter than emergency requests for fibrinogen levels, 37 minutes.Conclusions: Implementation of PLTEM and FIBTEM AS in ROTEM-guided transfusion protocols may improve transfusion management.

Capillary electrophoresis (CE) played an important role in developments in the life sciences. The technique is nowadays used for the analysis of both large and small molecules in applications where it performs better than or is complementary to liquid chromatographic techniques. In this review, principles of different electromigration techniques, especially capillary isoelectric focusing (CIEF), capillary gel (CGE) and capillary zone electrophoresis (CZE), are described and recent developments in instrumentation, with an emphasis on mass spectrometry (MS) coupling and microchip CE, are discussed. The role of CE in the life sciences is shown with applications in which it had a high impact over the past few decades. In this context, current practice for the characterization of biopharmaceuticals (therapeutic proteins) is shown with CIEF, CGE and CZE using different detection techniques, including MS. Subsequently, the application of CGE and CZE, in combination with laser induced fluorescence detection and CZE-MS are demonstrated for the analysis of protein-released glycans in the characterization of biopharmaceuticals and glycan biomarker discovery in biological samples. Special attention is paid to developments in capillary coatings and derivatization strategies for glycans. Finally, routine CE analysis in clinical chemistry and latest developments in metabolomics approaches for the profiling of small molecules in biological samples are discussed. The large number of CE applications published for these topics in recent years clearly demonstrates the established role of CE in life sciences.

SummaryBlood dilution after transfusion fluids leads to diminished coagulant activity monitored by rotational thromboelastometry, assessing elastic fibrin clot formation, or by thrombin generation testing. We aimed to determine the contributions of blood cells (platelets, red blood cells) and plasma factors (fibrinogen, prothrombin complex concentrate) to fibrin clot formation under conditions of haemodilution in vitro or in vivo. Whole blood or plasma diluted in vitro was supplemented with platelets, red cells, fibrinogen or prothrombin complex concentrate (PCC). Thromboelastometry was measured in whole blood as well as plasma; thrombin generation was determined in parallel. Similar tests were performed with blood from 48 patients, obtained before and after massive fluid infusion during cardiothoracic surgery. Addition of platelets or fibrinogen, in additive and independent ways, reversed the impaired fibrin clot formation (thromboelastometry) in diluted whole blood. In contrast, supplementation of red blood cells or prothrombin complex concentrate was ineffective. Platelets and fibrinogen independently restored clot formation in diluted plasma, resulting in thromboelastometry curves approaching those in whole blood. In whole blood from patients undergoing dilution during surgery, elastic clot formation was determined by both the platelet count and the fibrinogen level. Thrombin generation in diluted (patient) plasma was not changed by fibrinogen, but improved markedly by prothrombin complex concentrate. In conclusion, in dilutional coagulopathy, platelets and fibrinogen, but not red blood cells or vitamin K-dependent coagulation factors, independently determine thromboelastometry parameters measured in whole blood and plasma. Clinical decisions for transfusion based on thromboelastometry should take into account the platelet concentration.

A new MEKC-ESI-MS method for the analysis of amino acids (AAs) in human urine was developed employing ammonium perfluorooctanoate (APFO) as volatile surfactant. The influence of APFO on the MS signal of AAs was evaluated by infusion experiments, which showed that APFO hardly affects analyte responses and presents significantly less ion suppression than equal concentrations of ammonium acetate. In order to obtain efficient separation of AAs, MEKC parameters such as the pH and APFO concentration of the BGE, were optimized. Optimum AA resolution, including baseline separation of leucine and isoleucine, was obtained using 150 mM APFO (pH 9.0) as BGE, representing a considerable selectivity improvement over CE using 50 mM ammonium acetate (pH 9.0). Optimization of CE-MS parameters, such as sheath liquid composition and flow rate, and ESI and MS settings, led to LODs ranging from 9 to 26 ng/mL for the 20 tested AAs, which is highly favorable for an MEKC-MS method. Good linearity (r(2) > 0.99) and repeatability were obtained for all AAs tested with RSD values of 3.0-6.7% for peak area and