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Introduction: Hearing impairment concerns a relevant percentage of individuals with Osteogenesis Imperfecta (OI). When looking at the current literature, the percentage of affected individuals with OI varies greatly from 32 to 58% of patients having mild OI and 21% to 27% of patients having moderate to severe OI. Little is known about the German population with OI., Method: The goal of this study was to detect how many patients with OI, who visited the annual meeting of the German Association for Osteogenesis Imperfecta in 2023, proved to have a hearing impairment. In this prospective, cross-sectional study, each included individual obtained ear microscopy, audiometry, stapedius reflexes, tympanometry, and OAEs. Furthermore, each patient was asked a set of questions concerning the medical history., Results: Of the included patients, 33% had hearing impairment. A significant difference was found for the mean air-bone gap (ABG) as well as the hearing threshold of the right ears. The difference was found between OI type III and IV (p = 0.0127) for the mean ABG and OI type I and IV (p = 0.0138) as well as III and IV (p = 0.0281) for the hearing threshold. Spearman's rank correlation showed a high correlation between age and hearing threshold. Of the patients between 40 and 50 years old, 56% had hearing loss., Conclusion: Hearing loss in individuals with OI is still a relevant problem, especially age-related in OI type I. Audiometry should be performed at least when individuals experience subjective hearing loss. The implementation of a screening starting at 40 years should be discussed and studied., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. The authors have no relevant financial or non-financial interests to disclose. Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of University Hospital, LMU Munich (protocol code 22–0357 and date of approval 17.05.2022). Informed consent statement: Informed consent was obtained from all subjects involved in the study., (© 2024. The Author(s).)

Aims: Low-gradient (LG) aortic stenosis (AS) poses a diagnostic challenge. Aortic valve calcium score (AVCS) assessment has emerged as a complementary diagnostic method when echocardiography provides discordant results. However, the diagnostic and prognostic values of AVCS in LGAS have not been thoroughly studied. Our aims in this study were to investigate the prognostic importance of AVCS in LGAS and to assess whether symptomatic patients with LGAS and low AVCS may benefit from aortic valve intervention (AVI)., Methods and Results: A total of 327 symptomatic patients (78.5 ± 7.3 years, 51% women) with severe AS defined by the aortic valve area who underwent computed tomography for transcatheter aortic valve intervention (TAVI) planning were enrolled. AVCS was measured. AVCS < 2000AU in men and < 1200 AU in women was considered a low AVCS. A total of 243 patients had high gradient (HG) and 84 had LGAS. A low AVCS was present in 25 (10%) patients with HG and 34 (40%) with LGAS. Over a median follow-up period of 4.9 years, 194 deaths occurred. In multivariate analysis, AVCS was a significant independent predictor of all-cause mortality among patients with HGAS [adjusted hazard ratio (aHR): 2.317; CI: 1.104-4.861; P = 0.026] but not among those with LGAS (aHR: 0.848; CI: 0.434-1.658; P = 0.630). After propensity score matching between patients who underwent AVI and those who were medically treated, AVI (94% TAVI) was a significant and independent predictor of survival among LGAS patients with a low AVCS even after adjustment for clinical variables (aHR: 0.102, CI: 0.028-0.369; P < 0.001)., Conclusion: The prevalence of a low AVCS is much higher in patients with LGAS than in those with HGAS. In patients with symptomatic severe LGAS, a low AVCS does not entail a better prognosis. AVI is equally beneficial in LGAS patients with a high or low AVCS, similarly to those with HGAS., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Mortality is often assessed during ICU stay and early after, but rarely at later stage. We aimed to compare the long-term mortality between TBI and ICH patients., Materials and Methods: From an observational cohort, we studied 580 TBI patients and 435 ICH patients, admitted from January 2013 to February 2021 in 3 ICUs and alive at 7-days post-ICU discharge. We performed a Lasso-penalized Cox survival analysis., Results: We estimated 7-year survival rates at 72.8% (95%CI from 67.3% to 78.7%) for ICH patients and at 84.9% (95%CI from 80.9% to 89.1%) for TBI patients: ICH patients presenting a higher mortality risk than TBI patients. Additionally, we identified variables associated with higher mortality risk (age, ICU length of stay, tracheostomy, low GCS, absence of intracranial pressure monitoring). We also observed anisocoria related with the mortality risk in the early stage after ICU stay., Conclusions: In this ICU survivor population with a prolonged follow-up, we highlight an acute risk of death after ICU stay, which seems to last longer in ICH patients. Several variables characteristic of disease severity appeared associated with long-term mortality, raising the hypothesis that the most severe patients deserve closer follow-up after ICU stay., (Copyright © 2024. Published by Elsevier Inc.)

This article aims to explore the evolution of the debates surrounding human rights in the discourse(s) of major sporting events (MSEs), particularly the Olympics. The paper will first analyse the western-centric origins of the "universality" of the Olympic philosophy and how it affected the protection and promotion of human rights, as well as addressing practical challenges or limitations faced. It will then focus on unpacking the elements of sportswashing and soft power in the multi-discursive context of sport where power, privilege, politics, and position are (re)produced. In doing so it draws upon the emergent field of Sports Diplomacy as the most appropriate explanatory framework to share in this discourse. Finally, it will explore the potential impact of anti-corruption reforms on the establishment of a meaningful human rights legacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chatziefstathiou and Simon Rofe.)

Background: Forcibly displaced populations are highly vulnerable to psychosocial distress and mental disorders, including alcohol misuse. In an ongoing trial that seeks to develop a transdiagnostic intervention addressing psychological distress and alcohol use disorders among conflict-affected populations, we will carry out a cost-effectiveness evaluation using a capability-based Oxford Capabilities Mental Health (OxCAP-MH) measure. The OxCAP-MH is a 16-item questionnaire developed from the Capability Approach, that covers multiple domains of functioning and welfare. The aim of the current paper is to present the results of the translation, cultural adaptation and valuation of the OxCAP-MH into Juba Arabic for South Sudanese refugees living in Uganda. We adhered to the official Translation and Linguistic Validation process of the OxCAP-MH. To carry out the translation, the Concept Elaboration document, official English version of the OxCAP-MH, and the Back-Translation Review Template were used. Four independent translators were used for forward and back translations. The reconciled translated version was then piloted in two focus group discussions (N = 16) in Rhino refugee settlement. A most important to least important valuation of the sixteen capability domains covered in the OxCAP-MH was also done., Results: The Juba Arabic version of the OxCAP-MH was finalized following a systematic iterative process. The content of the Juba Arabic version remained unchanged, but key concepts were adapted to ensure cultural acceptability, feasibility, and comprehension of the measure in the local context of Rhino refugee settlement. Most participants had low levels of literacy and required support with filling in the tool. Participants suggested an additional capability that is currently not reflected in the OxCAP-MH, namely access to food. Furthermore, discussions around the valuation exercise of the sixteen domains led to two separate importance scales, which showed relevant differences., Conclusions: In this context, the OxCAP-MH was considered culturally acceptable. The valuation exercise proved cognitively demanding. Participants voiced confusion over how to answer the questions on the OxCAP-MH instrument due to low levels of literacy. These concerns invite consideration for future research to consider how measures such as the OxCAP-MH can be made more accessible to individuals with low literacy rates in resource poor settings., (© 2024. The Author(s).)

Background: In the past, the IIEF‑5 (International Index of Erectile Function 5 ) was predominantly used to measure erectile function in prostate cancer patients. Following international developments, the domain "sexuality" of the EPIC-26 (Expanded Prostate Cancer Index Composite 26) is increasingly used in Germany., Objective: The aim of this work is to create a practicable comparison of the domain "sexuality" of the EPIC-26 with the IIEF‑5 for treatment in Germany. This is particularly necessary for the evaluation of historical patient collectives., Materials and Methods: For the evaluation, 2123 patients with prostate cancer confirmed by biopsy from 2014-2017 who completed both the IIEF‑5 and the EPIC-26 were considered. Linear regression analyses are calculated to convert IIEF‑5 sum scores to EPIC-26 sexuality domain scores., Results: The correlation between IIEF‑5 and the EPIC-26 domain score "sexuality" was 0.74, suggesting a high degree of content convergence between the constructs measured. While the standard error of the predicted values is relatively small, the prediction intervals are very wide. For example, for the critical IIEF‑5 value of 22, the predicted value is 78.88 with a 95% prediction interval of 55.09 to 102.66., Conclusion: IIEF‑5 and the Sexuality scale of the EPIC-26 measure a similar construct. The analysis shows that conversion of individual values is associated with great uncertainty. However, at the group level, the observed EPIC-26 "sexuality" score could be predicted quite accurately. This opens up the possibility of comparing the erectile function of cohorts of patients/test persons, even if this was collected with different measuring instruments., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The think-aloud (TA) approach is a qualitative research method that allows for gaining insight into thoughts and cognitive processes. It can be used to incorporate a respondent's perspective when developing resource-use measurement (RUM) instruments. Currently, the application of TA methods in RUM research is limited, and so is the guidance on how to use them. Transparent publication of TA methods for RUM in health economics studies, which is the aim of this paper, can contribute to reducing the aforementioned gap., Methods: Methods for conducting TA interviews were iteratively developed by a multi-national working group of health economists and additional qualitative research expertise was sought. TA interviews were conducted in four countries to support this process. A ten-step process was outlined in three parts: Part A 'before the interview' (including translation, recruitment, training), Part B 'during the interview' (including setting, opening, completing the instrument, open-ended questions, closing), and part C 'after the interview' (including transcription and data analysis, trustworthiness)., Conclusions: This manuscript describes the step-by-step approach for conducting multi-national TA interviews with potential respondents of the PECUNIA RUM instrument. It increases the methodological transparency in RUM development and reduces the knowledge gap of using qualitative research methods in health economics.

There is widespread evidence for a worldwide trend of insect decline, but we have much fewer data about recent temporal trends in other arthropod groups, including spiders. Spiders can be hypothesised to similarly decline because of trophic dependence on insects and being equally sensitive to local and global environmental changes. Background trends in arthropod populations can be verified if we decouple large-scale environmental transitions, such as climate change, from local factors. To provide a case study on baseline spider community trends, we observed changes in the spider community of an unsprayed alfalfa field and its margin 23 years apart under largely unchanged local conditions. We aimed to determine whether there are changes in spider abundance, species richness and mean species characteristics. Spider abundance per unit effort decreased dramatically, by 45% in alfalfa and by 59% in the margin, but species richness and most characteristics remained unchanged. Community composition in both habitats shifted and became more similar by the current study period. The population decline was especially marked in certain farmland species. We propose that in the absence of local causative factors, spider abundance decline in our study indicates a reduction of spider populations at landscape and regional scales., (© 2023. The Author(s).)

Background: Sickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the intervention implementation. In this report, we describe engagement with stakeholders, planning of the implementation process, and final analytical plan to evaluate the implementation outcomes., Methods: During 19 meetings, a 16-member multidisciplinary SCDIC implementation team created, conceived, and implemented a project that utilized Intervention Mapping to guide designing an intervention and its evaluation plan. The process included five steps: (1) needs assessment of low hydroxyurea utilization, (2) conceptual framework development, (3) intervention design process, (4) selection of models and frameworks, and (5) designing evaluation of the intervention implementation., Results: Behavioral theories guided the needs assessment and the design of the multi-level mHealth intervention. In designing the evaluation approach, we combined two implementation frameworks to best account for the contextual complexity at the organizational, provider, and patient levels: (1) the Consolidated Framework for Implementation Research (CFIR) that details barriers and facilitators to implementing the mHealth intervention at multiple levels (users, organization, intervention characteristics, broader community), and (2) the Technology Acceptance Model (TAM), a conceptual model specific for explaining the intent to use new information technology (including mHealth). The Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM) framework was used to measure the outcomes., Discussion: Our research project can serve as a case study of a potential approach to combining different models/frameworks to help organize and plan the evaluation of interventions to increase medication adherence. The description of our process may serve as a blueprint for future studies developing and testing new strategies to foster evidence-based treatments for individuals living with SCD., Competing Interests: JSH receives consultancy fees from Forma Therapeutics, CVS Health, and Global Blood Therapeutics., (© 2023 Hankins, Potter, Fernandez, Melvin, DiMartino, Jacobs, Bosworth, King, Simon, Glassberg, Kutlar, Gordeuk, Shah, Baumann, Klesges and the Sickle Cell Disease Implementation Consortium.)

Background: The gastrointestinal (GI) microbiota has been linked to health consequences throughout life, from early life illnesses (e.g. sepsis and necrotising enterocolitis) to lifelong chronic conditions such as obesity and inflammatory bowel disease. It has also been observed that events in early life can lead to shifts in the microbiota, with some of these changes having been documented to persist into adulthood. A particularly extreme example of a divergent early GI microbiota occurs in premature neonates, who display a very different GI community to term infants. Certain characteristic patterns have been associated with negative health outcomes during the neonatal period, and these patterns may prove to have continual damaging effects if not resolved., Results: In this study we compared a set of premature infants with a paired set of term infants (n = 37 pairs) at 6 weeks of age and at 2 years of age. In the samples taken at 6 weeks of age we found microbial communities differing in both diversity and specific bacterial groups between the two infant cohorts. We identified clinical factors associated with over-abundance of potentially pathogenic organisms (e.g. Enterobacteriaceae) and reduced abundances of some beneficial organisms (e.g. Bifidobacterium). We contrasted these findings with samples taken at 2 years of age, which indicated that despite a very different initial gut microbiota, the two infant groups converged to a similar, more adult-like state. We identified clinical factors, including both prematurity and delivery method, which remain associated with components of the gut microbiota. Both clinical factors and microbial characteristics are compared to the occurrence of childhood wheeze and eczema, revealing associations between components of the GI microbiota and the development of these allergic conditions., Conclusions: The faecal microbiota differs greatly between infants born at term and those born prematurely during early life, yet it converges over time. Despite this, early clinical factors remain significantly associated with the abundance of some bacterial groups at 2 years of age. Given the associations made between health conditions and the microbiota, factors that alter the makeup of the gut microbiota, and potentially its trajectory through life, could have important lifelong consequences., (© 2023. The Author(s).)

Background: Health problems can lead to costs in the education sector. However, these costs are rarely incorporated in health economic evaluations due to the lack of reference unit costs (RUCs), cost per unit of service, of education services and of validated methods to obtain them. In this study, a standardized unit cost calculation tool developed in the PECUNIA project, the PECUNIA RUC Template for services, was applied to calculate the RUCs of selected education services in five European countries., Methods: The RUCs of special education services and of educational therapy were calculated using the information collected via an exploratory gray literature search and contact with service providers., Results: The RUCs of special education services ranged from €55 to €189 per school day. The RUCs of educational therapy ranged from €6 to €25 per contact and from €5 to €35 per day. Variation was observed in the type of input data and measurement unit, among other., Discussion: The tool helped reduce variability in the RUCs related to costing methodology and gain insights into other aspects that contribute to the variability (e.g. data availability). Further research and efforts to generate high quality input data are required to reduce the variability of the RUCs.

Aims: Health services research (HSR) is affected by a widespread problem related to service terminology including non-commensurability (using different units of analysis for comparisons) and terminological unclarity due to ambiguity and vagueness of terms. The aim of this study was to identify the magnitude of the terminological bias in health and social services research and health economics by applying an international classification system., Methods: This study, that was part of the PECUNIA project, followed an ontoterminology approach (disambiguation of technical and scientific terms using a taxonomy and a glossary of terms). A listing of 56 types of health and social services relevant for mental health was compiled from a systematic review of the literature and feedback provided by 29 experts in six European countries. The disambiguation of terms was performed using an ontology-based classification of services (Description and Evaluation of Services and DirectoriEs - DESDE), and its glossary of terms. The analysis focused on the commensurability and the clarity of definitions according to the reference classification system. Interrater reliability was analysed using κ ., Results: The disambiguation revealed that only 13 terms (23%) of the 56 services selected were accurate. Six terms (11%) were confusing as they did not correspond to services as defined in the reference classification system (non-commensurability bias), 27 (48%) did not include a clear definition of the target population for which the service was intended, and the definition of types of services was unclear in 59% of the terms: 15 were ambiguous and 11 vague. The κ analyses were significant for agreements in unit of analysis and assignment of DESDE codes and very high in definition of target population., Conclusions: Service terminology is a source of systematic bias in health service research, and certainly in mental healthcare. The magnitude of the problem is substantial. This finding has major implications for the international comparability of resource use in health economics, quality and equality research. The approach presented in this paper contributes to minimise differentiation between services by taking into account key features such as target population, care setting, main activities and type and number of professionals among others. This approach also contributes to support financial incentives for effective health promotion and disease prevention. A detailed analysis of services in terms of cost measurement for economic evaluations reveals the necessity and usefulness of defining services using a coding system and taxonomical criteria rather than by 'text-based descriptions'.

Radiological dispersion study is a key element in safety analysis report (SAR) of every nuclear facility for the purpose of emergency response planning. In this work, computational approach was used to determine the total effective dose and ground deposition at critical positions onsite and offsite of the Nigerian Research Reactor-1 (NIRR-1) facility which will be useful in the ongoing development of final SAR for NIRR-1 Low Enriched Uranium (LEU) core. In the methodology used, NIRR-1 LEU core was depleted with TRITON module of SCALE 6.2.3 code and the fission inventory in the core was calculated after a continuous operation at full power of 231.931MWD/MTU for 918 Effective Full Power Days (EFPD) at an operation regime of 3 h per day, 3 days per week and 48 weeks per year. Hot Spot was employed for atmospheric transport and dose calculations with consideration of different accidental scenarios in which 20%, 30%, 60% and 100% gaseous inventory was hypothetically released into the atmosphere. From the results obtained, the total effective dose to maximum exposed workers at 10 m and maximum exposed members of public at 300 m from the reactor were 3.10mSvand0.43mSv respectively for the worst-case scenario with 100% release while the maximum ground deposition was 5.5×10 6 Bq/m 2 with corresponding maximum ground shine dose rate of 7.5×10 -4 mSv/hr. This results are at least one order of magnitude below the dose limits recommended by the International Commission on Radiological Protection (ICRP) and indicate that the present LEU core of NIRR-1 is unlikely to cause any detectable health effect on workers and members of public in the event that 100% of its gaseous inventory is released into air in the environment. Hence it could unequivocally be said that the population is safe from the operation of NIRR-1 in its present location., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background & Aims: In hospital nutrition care the difficulty of translating knowledge to action often leads to inadequate management of patients with malnutrition. nutritionDay, an annual cross-sectional survey has been assessing nutrition care in healthcare institutions in 66 countries since 2006. While initial efforts led to increased awareness of malnutrition, specific local remedial actions rarely followed. Thus, reducing the Knowledge-to-action (KTA) gap in nutrition care requires more robust and focused strategies. This study describes the strategy, methods, instruments and experience of developing and implementing nutritionDay 2.0, an audit and feedback intervention that uses quality and economic indicators, feedback, benchmarking and self-defined action strategies to reduce the KTA gap in hospital nutrition care., Methods: We used an evidence based multi-professional mixed-methods approach to develop and implement nutritionDay 2.0 This audit and feedback intervention is driven by a Knowledge-to-Action framework complemented with robust stakeholder analysis. Further evidence was synthesized from the literature, online surveys, a pilot study, World Cafés and individual expert feedback involving international health care professionals, nutrition care scientists and patients., Results: The process of developing and implementing nutritionDay 2.0 over three years resulted in a new audit questionnaire based on 36 nutrition care quality and economic indicators at hospital, unit and patient levels, a new action-oriented feedback and benchmarking report and a unit-level personalizable action plan template. The evaluation of nutritionDay 2.0 is ongoing and will include satisfaction and utility of nutritionDay 2.0 tools and short-, mid- and long-term effects on the KTA gap., Conclusion: In clinical practice, nutritionDay 2.0 has the potential to promote behavioural and practice changes and improve hospital nutrition care outcomes. In research, the data generated advances knowledge about institutional malnutrition and quality of hospital nutrition care. The ongoing evaluation of the initiative will reveal how far the KTA gap in hospital nutrition care was addressed and facilitate the understanding of the mechanisms needed for successful audit and feedback., Trial Registration: Registration in clinicaltrials.gov: Identifier: NCT02820246., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The radial artery is commonly accessed for arterial blood sampling, invasive blood pressure monitoring, and vascular access for cardiac catheterization. Iatrogenic radial artery injury is a rare complication with potentially devastating outcomes. The purpose of our study was to identify the timing of these injuries and define a treatment algorithm. Methods: A retrospective chart review of all patients with iatrogenic radial artery injuries were identified between the years 2008 and 2018. Patient demographics, mechanism of injury, interventions, and outcomes were recorded. Results: A total of 18 patients were identified with iatrogenic radial artery injury over a 10-year period. Fifty percent of these resulted from arterial line cannulation, and 50% occurred after transradial cardiac catheterization. Thirty-three percent resulted in radial artery pseudoaneurysm (RAP), and 66% had acute radial artery thrombosis (RAT). Eleven of the 18 patients underwent operative intervention. Of the 12 patients with RAT, 4 were treated with systemic anticoagulation for 3 months. All patients with RAP who were surgically treated had resolution of symptoms on follow-up evaluation. Of the patients with RAT, 2 had persistent sensorimotor deficits after treatment, and 1 patient had multiple necrotic fingers requiring amputation. Conclusion: Radial artery injuries are an uncommon but potentially devastating complication of common invasive procedures resulting in thrombosis, pseudoaneurysm, or overt hand ischemia. The treatment options vary depending on presenting symptoms.

Objective: Quality indicators (QIs) can be used to assess and improve the quality of care in health care institutions. Although QIs about nutrition care in hospitals and nursing homes have been used in studies, no systematic catalogue exists to date. This systematic literature review identifies nutrition care QIs in hospitals and nursing homes and maps them according to QI type, stakeholder level and nutrition care theme. We also assess the level of consensus between studies and critically appraise the QIs presented therein based on two conceptual frameworks., Methods: Ovid, Scopus and grey literature were searched from 1995 to 2016 including studies in English and German. Papers were considered if they presented, developed, assessed, rated or applied nutrition care QIs in hospitals or nursing homes. We used Donabedian's framework to define structure, process and outcome indicators, the WHO (World Health Organization) definition to describe stakeholder levels, and a structured table to map indicators within themes. Further, we used the Institute of Medicine (IOM) and the Organisation for Economic Cooperation and Development (OECD) frameworks' key dimensions to measure the conceptual quality of the QIs. Results are summarised and presented tabulated and narratively., Results: From 536 identified studies, 46 were included. Eight hundred and twenty-two QIs were extracted and mapped into 19 themes and 151 sub-themes. Half were process indicators (49%) and about a quarter were outcome (28%) and structure (23%) indicators, respectively. The vast majority (71%) targeted micro level, while 28% meso level and only 1% macro level information. The nutrition themes meals/mealtimes (12%), treatment (adherence) (12%), nutrition screening (7%), assessment (7%) and monitoring (7%) were most frequently covered. 69% of indicators were cited by more than one study. Most frequent framework dimensions were patient-centeredness (33%), timeliness (30%), validity (30%) and actionability/feasibility (30%)., Conclusion: The large number of nutrition care QIs in hospitals and nursing homes indicates the high interest in and importance of better nutrition care provision in institutions. However, the great variability indicates little consensus of the nutrition community on how to best assess and measure the quality of nutrition care. The limited methodological and conceptual validity of presented QIs and the low representation of QIs at macro and meso levels make international consensus finding complicated. Increased efforts including all stakeholder levels and using conceptual frameworks to define a limited number of key QIs with high methodological validity, actionability and stakeholder relevance are needed. Registration in clinicaltrials.gov: Identifier: NCT02820246., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction:  Inhalative treatments with metered dose aerosols and dry powder inhalers are the backbone of the pharmacotherapy for asthma and COPD. In the last decade many new and generic inhalative bronchodilators were launched at the German market, both monotherapies and fixed dose double bronchodilator (LABA/LAMA, beta adrenergic and antimuscarinic) or LABA and inhaled corticosteroid (ICS) and triple (LABA/LAMA/ICS) combinations. According to two surveys in 2015 among respiratory physicians we expected a high proportion of patients receiving duplicate prescriptions, e. g. a fixed dose new LABA/LAMA combination in addition to an existing ICS/LABA fixed dose combination., Methodology:  We searched the database of a large mail order pharmacy (DocMorris) to identify duplicate prescriptions of inhalative drugs for a patient by the same or by two or more different physicians during a 3 months period., Results:  Unexpectedly, we found as little as around 1 % duplicate prescriptions for the same patient. Duplicate prescriptions involving combination products were found to be much more common than duplicate prescriptions of different mono-products. Irrespective the low percentage number of all prescriptions we saw in just one large mail order pharmacy several thousands of erroneous prescriptions., Conclusion:  At least in the setting of this mail order pharmacy duplicate (i. e. contraindicated and potentially dangerous) prescriptions are relatively rare. Prescribers and pharmacists should be aware of the issue of duplicates - especially when prescribing or filling prescriptions with combination products., Competing Interests: According to this paper the authors PK and HW declare no conflict of interest.FG, JS and CF are employees of DocMorris, Heerlen.UB is Executive manager of the German Airways League., (© Georg Thieme Verlag KG Stuttgart · New York.)

Here, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During the meeting, cross-speciality participants assessed critical aspects of non-invasive, quantitative biomarker development in view of the need to expand our understanding of disease mechanisms and the definition of appropriate strategies both for molecular diagnostics and personalised therapies. More specifically, panelists addressed the main topics, including the current status of disease characterisation by means of non-invasive imaging, histopathology and liquid biopsies as well as strategies of gaining new understanding of disease formation, modulation and plasticity to large-scale molecular imaging as well as integrative multi-platform approaches. Highlights of the 2018 meeting included dedicated sessions on non-invasive disease characterisation, development of disease and therapeutic tailored biomarkers, standardisation and quality measures in biospecimens, new therapeutic approaches and socio-economic challenges of biomarker developments. The scientific programme was accompanied by a roundtable discussion on identification and implementation of sustainable strategies to address the educational needs in the rapidly evolving field of molecular diagnostics. The central theme that emanated from the 2nd Donau Symposium was the importance of the conceptualisation and implementation of a convergent approach towards a disease characterisation beyond lesion-counting "lumpology" for a cost-effective and patient-centric diagnosis, therapy planning, guidance and monitoring. This involves a judicious choice of diagnostic means, the adoption of clinical decision support systems and, above all, a new way of communication involving all stakeholders across modalities and specialities. Moreover, complex diseases require a comprehensive diagnosis by converging parameters from different disciplines, which will finally yield to a precise therapeutic guidance and outcome prediction. While it is attractive to focus on technical advances alone, it is important to develop a patient-centric approach, thus asking "What can we do with our expertise to help patients?"

Background: In 2014, the Royal College of Anaesthetists (RCoA) launched the Perioperative Medicine Programme to facilitate the delivery of best preoperative, intraoperative and postoperative care through implementation of evidence-based medicine to reduce variation and improve postoperative outcomes. However, variation exists in the establishment of perioperative medicine services in the UK. This survey explored attitudes and behaviours of anaesthetists towards perioperative medicine, described current anaesthetic-led perioperative medicine services across the UK and explored barriers to anaesthetic involvement in perioperative medicine., Methods: Survey content based on the RCoA vision document was refined and validated using an expert panel. An anonymous electronic survey was then sent by email to the members of the RCoA., Results: Seven hundred fifty-eight UK anaesthetists (4.5% of the RCoA mailing list) responded to the survey. Of these, 64% considered themselves a perioperative doctor, with 65% having changed local services in response to the RCoA vision. Barriers to developing perioperative medicine included insufficient time (75%) and inadequate training (51%). Three quarters of respondents advocate anaesthetists leading the development of perioperative medicine., Conclusions: Despite evidence of emerging services, this survey describes barriers to ongoing development of perioperative medicine. Facilitators may include increased clinical exposure, targeted education and training and collaborative working with other specialties., Competing Interests: Competing interestsDW/JD/JP have been involved in the development of the Perioperative Medicine MSc at University Hospital College, London, UK. MS is joint clinical lead for Anaesthesia and Perioperative medicine, Getting It Right First Time., (© The Author(s). 2020.)

Objective: The introduction provisional approval strategies increases the approval of anticancer drugs with ambiguous benefit-risk profiles. Thus, in many instances, there is lacking evidence about overall survival (OS) at the time of marketing authorisation. Our objective was to monitor and characterise therapies with ambiguous benefit-risk profiles and identify any postapproval updates on median OS after at least 3 years of approval by the European Medicines Agency (EMA)., Methods: We included all originator anticancer drugs with initially ambiguous benefit-risk profiles that received marketing authorisation by the EMA between January 1, 2009 and May 31, 2015. Our monitoring timeframe was at least 3 years after EMA approval. To identify study updates, the following three sources were included: clinicaltrials.gov, European Public Assessments Reports and PubMed., Results: In total, we identified 102 eligible approval studies. Out of these, a negative difference in median OS or no information was available in 43 (42.2%) instances. During monitoring, 14 updates with accessible positive information on OS could be identified. Including monitoring results, there are still 29 remaining therapies (28.4%) where no or negative information (n = 24 [23.5%] and n = 5 [4.9%], respectively) regarding OS is present at least 3 years after EMA approval., Conclusion: One-third of oncology drugs with ambiguous benefit-risk profiles at the time of approval fail to demonstrate a survival benefit even after several years of marketing authorisation. Systematic and transparent postapproval monitoring mechanisms will be of high relevance to assure a clinically relevant patient benefit, since the trend towards faster access to medicines with uncertain benefit is increasing rather than declining., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Nanocarriers that are used for targeted drug delivery come in contact with biological liquids and subsequently proteins will adsorb to the nanocarriers' surface to form the so called 'protein corona'. The protein corona defines the biological identity and determines the biological response towards the nanocarriers in the body. To make nanomedicine safe and reliable it is required to get a better insight into this protein corona and, therefore, the adsorbed proteins have to be characterized. Currently, centrifugation is the common method to isolate the protein corona for further investigations. However, with this method it is only possible to investigate the strongly bound proteins, also referred to as 'hard protein corona'. Therefore, we want to introduce a new separation technique to separate nanoparticles including the soft protein corona containing also loosely bound proteins for further characterization. The used separation technique is the asymmetric flow field-flow fractionation (AF4). We were able to separate the nanoparticles with proteins forming the soft protein corona and were able to show that in our system only the hard protein corona directly influenced the cell uptake behavior., Statement of Significance: Currently, there is an ongoing debate whether only strongly bound proteins (hard corona) or also loosely bound proteins (soft corona) contribute to the biological identity of nanocarriers, because up to now isolation of the soft corona was not possible. Here, asymmetric flow field-flow fractionation was used to isolate nanoparticles with a preserved soft corona from the biological medium. This enabled the characterization of the soft corona composition and to evaluate its influence on cellular uptake. For our system we found that only the strongly bound proteins (hard corona) determined cell internalization. This method can now be used to evaluate the impact of the soft corona further and to characterize nanomaterials that cannot be separated from blood plasma by other means., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In mammals, insulin regulates blood glucose levels and plays a key regulatory role in appetite via the hypothalamus. In contrast, chickens are characterized by atypical glucose homeostasis, with relatively high blood glucose levels, reduced glucose sensitivity of pancreatic beta cells, and large resistance to exogenous insulin. The aim of the present study was to investigate in chickens the effects of 5 h fasting and 5 h insulin immuno-neutralization on hypothalamic mRNA levels of 23 genes associated with food intake, energy balance, and glucose metabolism. We observed that insulin immune-neutralization by administration of anti-porcine insulin guinea pig serum (AI) significantly decreased food intake and increased plasma glucose levels in chickens, while 5 h fasting produced a limited and non-significant reduction in plasma glucose. In addition, 5 h fasting increased levels of NPY, TAS1R1, DIO2, LEPR, GLUT1, GLUT3, GLUT8, and GCK mRNA. In contrast, AI had no impact on the levels of any selected mRNA. Therefore, our results demonstrate that in chickens, food intake inhibition or satiety mechanisms induced by insulin immuno-neutralization do not rely on hypothalamic abundance of the 23 transcripts analyzed. The hypothalamic transcripts that were increased in the fasted group are likely components of a mechanism of adaptation to fasting in chickens., (© The Author 2017. Published by Oxford University Press on behalf of Poultry Science Association.)

Objective: To evaluate the reliability of a four-level triage scale for obstetrics and gynaecology emergencies and to explore the factors associated with an optimal triage., Design: Thirty clinical vignettes presenting the most frequent indications for obstetrics and gynaecology emergency consultations were evaluated twice using a computerised simulator., Setting: The study was performed at the emergency unit of obstetrics and gynaecology at the Geneva University Hospitals., Sample: The vignettes were submitted to nurses and midwives., Methods: We assessed inter- and intra-rater reliability and agreement using a two-way mixed-effects intra-class correlation (ICC). We also performed a generalised linear mixed model to evaluate factors associated triage correctness., Main Outcome Measures: Triage acuity., Results: We obtained a total of 1191 evaluations. Inter-rater reliability was good (ICC 0.748; 95% CI 0.633-0.858) and intra-rater reliability was almost perfect (ICC 0.812; 95% CI 0.726-0.889). We observed a wide variability: the mean number of questions varied from 6.9 to 18.9 across individuals and from 8.4 to 16.9 across vignettes. Triage acuity was underestimated in 12.4% of cases and overestimated in 9.3%. Undertriage occurred less frequently for gynaecology compared with obstetric vignettes [odds ratio (OR) 0.45; 95% CI 0.23-0.91; P = 0.035] and decreased with the number of questions asked (OR 0.94; 95% CI 0.88-0.99; P = 0.047). Certification in obstetrics and gynaecology emergencies was an independent factor for the avoidance of undertriage (OR 0.35; 95% CI 0.17-0.70; P = 0.003)., Conclusion: The four-level triage scale is a valid and reliable tool for the integrated emergency management of obstetrics and gynaecology patients., Tweetable Abstract: The Swiss Emergency Triage Scale is a valid and reliable tool for obstetrics and gynaecology emergency triage., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Background: Remote monitoring of mood disorders may be an effective and low resource option for patient follow-up, but relevant evidence remains very limited. This study explores real-life compliance and health services impacts of mood monitoring among patients with bipolar disorder in the UK., Methods: Patients with a diagnosis of bipolar disorder who were registered users of the True Colours monitoring system for at least 12months at study assessment were included in this retrospective cohort study (n=79). Compliance was measured as the proportion of valid depression and mania scale messages received in comparison to their expected numbers over the first 12months of monitoring. Mental health service use data were extracted from case notes, costed using national unit costs, and compared 12months before (pre-TC period) and 12months after (TC period) patients' engagement with monitoring. Associations with relevant patient factors were investigated in a multiple regression model., Results: Average compliance with monitoring was 82%. Significant increases in the annual use and costs of psychiatrist contacts and total mental health services were shown for patients newly referred to the clinic during the pre-TC period but not for long-term patients of the clinic. Psychiatric medication costs increased significantly between the pre-TC and TC periods (£235, P=0.005) unrelated to patients' referral status., Conclusions: Remote mood monitoring has good compliance among consenting patients with bipolar disorder. We found no associations between observed changes in mental health service costs and the introduction of monitoring except for the increase in psychiatric medication costs., (Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Decades of intensive genetic selection in the domestic chicken (Gallus gallus domesticus) have enabled the remarkable rapid growth of today's broiler (meat-type) chickens. However, this enhanced growth rate was accompanied by several unfavorable traits (i.e., increased visceral fatness, leg weakness, and disorders of metabolism and reproduction). The present descriptive analysis of the abdominal fat transcriptome aimed to identify functional genes and biological pathways that likely contribute to an extreme difference in visceral fatness of divergently selected broiler chickens., Methods: We used the Del-Mar 14 K Chicken Integrated Systems microarray to take time-course snapshots of global gene transcription in abdominal fat of juvenile [1-11 weeks of age (wk)] chickens divergently selected on bodyweight at two ages (8 and 36 wk). Further, a RNA sequencing analysis was completed on the same abdominal fat samples taken from high-growth (HG) and low-growth (LG) cockerels at 7 wk, the age with the greatest divergence in body weight (3.2-fold) and visceral fatness (19.6-fold)., Results: Time-course microarray analysis revealed 312 differentially expressed genes (FDR ≤ 0.05) as the main effect of genotype (HG versus LG), 718 genes in the interaction of age and genotype, and 2918 genes as the main effect of age. The RNA sequencing analysis identified 2410 differentially expressed genes in abdominal fat of HG versus LG chickens at 7 wk. The HG chickens are fatter and over-express numerous genes that support higher rates of visceral adipogenesis and lipogenesis. In abdominal fat of LG chickens, we found higher expression of many genes involved in hemostasis, energy catabolism and endocrine signaling, which likely contribute to their leaner phenotype and slower growth. Many transcription factors and their direct target genes identified in HG and LG chickens could be involved in their divergence in adiposity and growth rate., Conclusions: The present analyses of the visceral fat transcriptome in chickens divergently selected for a large difference in growth rate and abdominal fatness clearly demonstrate that abdominal fat is a very dynamic metabolic and endocrine organ in the chicken. The HG chickens overexpress many transcription factors and their direct target genes, which should enhance in situ lipogenesis and ultimately adiposity. Our observation of enhanced expression of hemostasis and endocrine-signaling genes in diminished abdominal fat of LG cockerels provides insight into genetic mechanisms involved in divergence of abdominal fatness and somatic growth in avian and perhaps mammalian species, including humans.

Introduction: Adult scoliosis is a condition in which the spinal deformity occurs because of degeneration. Although various studies have agreed on the importance of restoring the sagittal balance, few have evaluated the relationship between functional scores and radiological parameters. The primary objective of this retrospective study was to demonstrate the correlation between radiographic parameters and functional outcomes in adult patients with lumbar or thoracolumbar degenerative scoliosis. The secondary objective was to assess the long-term effects of posterolateral fusion for treating this deformity., Study Outline: This single-centre retrospective study included 47 patients over 50years of age who had degenerative lumbar scoliosis treated with an instrumented posterolateral fusion; the mean follow-up was 6.4years (range 2 to 20)., Methods: Radiographic analysis of A/P and lateral full spine standing radiographs was carried out with the KEOPS software. Three pelvic parameters (pelvic tilt, pelvic incidence, sacral slope), two spinal parameters (lumbar lordosis and thoracic kyphosis) and three sagittal balance parameters (C7 sagittal tilt, C7 Barrey's ratio and spinosacral angle) were calculated. The functional outcomes were evaluated through three self-assessment questionnaires: Oswestry Disability Index, SRS-30 and SF-36. The correlation between clinical and radiographic parameters was calculated with Spearman's correlation test., Results: There was a significant correlation between the SF-36 (PCS) and the following three sagittal parameters: sacral slope (r=-0.31453; P=0.04), lumbar lordosis (r=-0.30198; P=0.0491) and spinosacral angle (r=-0.311967; P=0.0366). The mean ODI score was 33.61, which corresponds to minimal to moderate disability. The mean physical (PCS) and mental (MCS) component summary scores of the SF-36 were 37.70 and 38.40, respectively. The mean SRS-30 score was 3.07., Conclusion: It is essential that the sagittal balance be restored when treating degenerative lumbar scoliosis to generate better functional outcomes and better quality of life. To achieve this correction, instrumented posterolateral fusion appears to be a very reliable technique that leads to lasting improvement., Level of Evidence: IV., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Nanoparticles with long blood circulation time are a prerequisite for targeted drug delivery. To make the nanoparticles invisible for phagocytizing cells, functional moieties on the particle surface are believed to be necessary to attract specific so-called 'stealth' proteins forming a protein 'corona'. Currently, covalent attachment of those moieties represents the only way to achieve that attraction. However, that approach requires a high synthetic effort and is difficult to control. Therefore, we present the coating of model nanoparticles with biodegradable polymeric surfactants as an alternative method. The thermodynamic parameters of the coating process can be tuned by adjusting the surfactants' block lengths and hydrophilicity. Consequently, the unspecific protein adsorption and aggregation tendency of the particles can be controlled, and stealth proteins inhibiting cell uptake are enriched on their surface. This non-covalent approach could be applied to any particle type and thus facilitates tuning the protein corona and its biological impact., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Mutational analysis is commonly used to support the diagnosis and management of haemophilia. This has allowed for the generation of large mutation databases which provide unparalleled insight into genotype-phenotype relationships. Haemophilia is associated with inversions, deletions, insertions, nonsense and missense mutations. Both synonymous and non-synonymous mutations influence the base pairing of messenger RNA (mRNA), which can alter mRNA structure, cellular half-life and ribosome processivity/elongation. However, the role of mRNA structure in determining the pathogenicity of point mutations in haemophilia has not been evaluated., Aim: To evaluate mRNA thermodynamic stability and associated RNA prediction software as a means to distinguish between neutral and disease-associated mutations in haemophilia., Methods: Five mRNA structure prediction software programs were used to assess the thermodynamic stability of mRNA fragments carrying neutral vs. disease-associated and synonymous vs. non-synonymous point mutations in F8, F9 and a third X-linked gene, DMD (dystrophin)., Results: In F8 and DMD, disease-associated mutations tend to occur in more structurally stable mRNA regions, represented by lower MFE (minimum free energy) levels. In comparing multiple software packages for mRNA structure prediction, a 101-151 nucleotide fragment length appears to be a feasible range for structuring future studies., Conclusion: mRNA thermodynamic stability is one predictive characteristic, which when combined with other RNA and protein features, may offer significant insight when screening sequencing data for novel disease-associated mutations. Our results also suggest potential utility in evaluating the mRNA thermodynamic stability profile of a gene when determining the viability of interchanging codons for biological and therapeutic applications., Competing Interests: The authors stated that they had no interests which might be perceived as posing a conflict or bias., (© 2016 John Wiley & Sons Ltd.)

Background: To date, the Pediatric Emergency Care Applied Research Network (PECARN) rule for identifying children who are at very low risk of clinically-important traumatic brain injuries after minor head trauma has not been validated prospectively in an independent population. Our goal was to evaluate the diagnostic performance of the PECARN clinical decision rule in a French pediatric population in multiple clinical settings., Methods: We conducted a multicenter, prospective, non-interventional cohort study of patients with minor head trauma who presented to three emergency departments in France. We enrolled patients younger than 16 years of age seeking a consultation within 24 h of head trauma with Glasgow Coma Scale scores of 14-15., Results: During the study period, we included 1499 children of which 421 (28 %) were under 2 years of age, and 955 (64 %) were male. A cranial computed tomography (CT) scan was performed on 76 patients (5.1 %). Of the 1499 included patients, 9 children (0.6 %) had a clinically-important traumatic brain injury, and none were classified as very low risk by the PECARN rule. In our study, the sensitivity of this clinical decision rule was 100 % (95 % CI 66.4 to 100 %), the specificity was 69.9 % (95 % CI 67.5 to 72.2 %) and the negative predictive value was 100 % (95 % CI 99.7 to 100 %)., Discussion: Our study confirmed the good predictive performances of the PECARN clinical decision rule for minor head trauma in children. The PECARN rule performed similarly to our study and to its internal validation study., Conclusions: We conducted an external validation study of the PECARN clinical decision rule for the detection of clinically-important traumatic brain injuries in children with minor head trauma, according to the methodological standards. The PECARN rule successfully identified all patients with clinically-important traumatic brain injuries, with a limited use of CT scans. Conducting a broad validation study with a large cohort is a prerequisite to provide sufficient statistical power before authorizing its implementation and generalization., Trial Registration: This study has been registered in ClinicalTrials.gov with identifier number: NCT02752711 on April 27, 2016.

Nitrous oxide (N2O) is an important greenhouse gas (GHG) with substantial global warming potential and also contributes to ozone depletion through photochemical nitric oxide (NO) production in the stratosphere. The negative effects of N2O on climate and stratospheric ozone make N2O mitigation an international challenge. More than 60% of global N2O emissions are emitted from agricultural soils mainly due to the application of synthetic nitrogen-containing fertilizers. Thus, mitigation strategies must be developed which increase (or at least do not negatively impact) on agricultural efficiency whilst decrease the levels of N2O released. This aim is particularly important in the context of the ever expanding population and subsequent increased burden on the food chain. More than two-thirds of N2O emissions from soils can be attributed to bacterial and fungal denitrification and nitrification processes. In ammonia-oxidizing bacteria, N2O is formed through the oxidation of hydroxylamine to nitrite. In denitrifiers, nitrate is reduced to N2 via nitrite, NO and N2O production. In addition to denitrification, respiratory nitrate ammonification (also termed dissimilatory nitrate reduction to ammonium) is another important nitrate-reducing mechanism in soil, responsible for the loss of nitrate and production of N2O from reduction of NO that is formed as a by-product of the reduction process. This review will synthesize our current understanding of the environmental, regulatory and biochemical control of N2O emissions by nitrate-reducing bacteria and point to new solutions for agricultural GHG mitigation., (© 2016 Elsevier Ltd. All rights reserved.)

Objectives: To determine whether assessment of all moderate-to-severe symptoms at baseline gives a more accurate evaluation of the treatment effect of ospemifene in vulvovaginal atrophy (VVA) than the most bothersome symptom (MBS) approach., Methods: Data were pooled from two pivotal phase-III clinical trials evaluating the efficacy and safety of oral ospemifene 60 mg/day for the treatment of symptoms of VVA (n = 1463 subjects). Symptoms of vaginal dryness, dyspareunia, and vaginal and/or vulvar irritation/itching reported as moderate or severe at baseline were evaluated. Clinically relevant differences between ospemifene and placebo were analyzed using a four-point severity scoring system and presented as improvement, substantial improvement, or relief., Results: Subjects in these studies reported statistically significant improvement, substantial improvement, and relief for vaginal dryness (p < 0.00001), dyspareunia (p < 0.001) and statistically significant improvement and relief for vaginal and/or vulvar irritation/itching (p < 0.01) from baseline to week 12 with ospemifene compared with placebo. A similar trend was observed for women who reported substantial improvement of vaginal and/or vulvar irritation/itching., Conclusions: For drug registration purposes, the use of the MBS model is appealing because of its simplicity and ease of scientific validation. However, the MBS model may underestimate the total magnitude of the clinical benefit of ospemifene treatment for symptomatic women suffering from VVA.

What Is Known and Objective: Pharmacist-managed anticoagulation programmes have been shown to improve appropriate use of warfarin, but few programmes have included the new target-specific oral anticoagulants (TSOACs) in their protocols. A greater understanding of TSOAC prescribing, monitoring and administration is needed to identify common errors in the current outpatient practice. The objective of this study is to assess the rate of errors related to prescribing, baseline monitoring and patient administration of TSOACs., Methods: A retrospective chart review was conducted to identify patients on TSOAC therapy in each of four outpatient practice sites. Data were abstracted to include TSOAC indication, dosage and frequency prescribed, pertinent past medical history, and laboratory monitoring obtained at the time of TSOAC initiation. In addition, patients were contacted by telephone to assess TSOAC adherence, storage, administration and incidence of adverse events., Results and Discussion: A total of 395 patients were included in the evaluation. Prescribers did not obtain baseline laboratory values within 1 week before or after the time of TSOAC initiation for a majority of study patients. At the time of TSOAC initiation, two patients had abnormally elevated alanine aminotransferase, six had elevated total bilirubin, and 43 had low haemoglobin. A majority (61%) of study patients were prescribed an appropriate TSOAC dose based upon their indication and renal function; however, dosing accuracy could not be determined for all patients as baseline serum creatinine was not obtained by prescribers for 148 patients (37%) at the time of prescribing. TSOACs were dosed inappropriately according to baseline serum creatinine in six patients, and two patients receiving treatment for venous thromboembolism were maintained on a high dose of rivaroxaban for an inappropriate duration. A total of 157 (40%) patients were available by phone and agreed to answer questions regarding their current TSOAC use. Twenty-four patients (23%) reported taking rivaroxaban inappropriately without food, and six patients (14%) endorsed inappropriate storage of dabigatran. Ten patients (6%) reported missing at least one TSOAC dose per week, and 25 (16%) described minor bleeding with their TSOAC., What Is New and Conclusion: Inappropriate prescribing, monitoring and administration of TSOACs occurred frequently in patients not formally enrolled in an anticoagulation monitoring programme. These results indicate a need for more thorough patient education at the time of TSOAC initiation, as well as improved prescriber education regarding recommended TSOAC dosing and monitoring., (© 2015 John Wiley & Sons Ltd.)

Background: Advance care planning (acp) is an important process in health care today. How to prospectively identify potential local barriers and facilitators to uptake of acp across a complex, multi-sector, publicly funded health care system and how to develop specific mitigating strategies have not been well characterized., Methods: We surveyed a convenience sample of clinical and administrative health care opinion leaders across the province of Alberta to characterize system-specific barriers and facilitators to uptake of acp. The survey was based on published literature about the barriers to and facilitators of acp and on the Michie Theoretical Domains Framework., Results: Of 88 surveys, 51 (58%) were returned. The survey identified system-specific barriers that could challenge uptake of acp. The factors were categorized into four main domains. Three examples of individual system-specific barriers were "insufficient public engagement and misunderstanding," "conflict among different provincial health service initiatives," and "lack of infrastructure." Local system-specific barriers and facilitators were subsequently explored through a semi-structured informal discussion group involving key informants. The group identified approaches to mitigate specific barriers., Conclusions: Uptake of acp is a priority for many health care systems, but bringing about change in multi-sector health care systems is complex. Identifying system-specific barriers and facilitators to the uptake of innovation are important elements of successful knowledge translation. We developed and successfully used a simple and inexpensive process to identify local system-specific barriers and enablers to uptake of acp, and to identify specific mitigating strategies.

Unlabelled: Acute, severe hypovolemia is a medical emergency. Traditional vital sign parameters allow no optimal triage. High predictive power of finger plethysmography-based stroke volume (SV) and pulse pressure (PP) was recently suggested. To assess the performance of the PP and SV parameters, lower body negative pressure of -40 mmHg, than -60 mmHg - corresponding to moderate and severe central hypovolemia - was applied in 22 healthy males (age 35 ± 7 years). Slow breathing induced fluctuations in the above indices, characterized by stroke volume variability (SVV), and pulse pressure variability (PPV), were assessed. Responses in heart rate (HR) and shock index (SI) were also studied. Discriminative capacity of these parameters was characterized by the area under the ROC (receiver operating characteristic) curves (AUC)., Results: In comparison of baseline to severe central hypovolemia SV, PP, HR, and SI showed good discriminating capacity (AUC 99%, 88%, 87%, and 93%, respectively). The discriminating capacity of SVV and PPV was poor (77% and 70%, respectively). In comparison of moderate and severe hypovolemia, the discriminating capacity of the studied parameters was uniformly limited., Conclusions: Plethysmography-based SV and PP parameters can be used to detect acute severe volume loss. Sensitive parameters discriminating moderate and severe central hypovolemia are still lacking.

Registries have provided a wealth of information on the clinical and disease characteristics of patients living with pulmonary arterial hypertension (PAH) since the 1980s. Certain PAH demographics, such as the prevalence of various PAH subgroups and preponderance of female patients, appear to have remained stable over time. Contemporary registry data indicate that the average age of patients diagnosed with PAH has increased, at least in the Western world. Older patients with PAH are more likely to be diagnosed with a more advanced stage of the disease, have lower exercise capacity and present with multiple comorbidities. They also have worse survival compared with younger patients. Within the PAH population, there is also a subset of patients with a lower diffusing capacity of the lung for carbon monoxide who are generally older and display more severe disease characteristics. This review discusses the implications that the increased age of the PAH population at diagnosis has on the treatment and management of the disease, as well as the need for earlier and improved diagnosis in these patients., (©ERS 2014.)