The effect of the apolipoprotein E phenotype on plasma lipids is not influenced by environmental variability: results of a Dutch twin study

We tested the influence of the apolipoprotein E (apoE) polymorphism on the intrapair differences in the levels of plasma cholesterol, plasma triglycerides, low density lipoprotein-cholesterol, apoB and apoE in monozygotic (MZ) twins, and estimated whether or not there was a interaction between the apoE polymorphism and environmental factors. In 65 MZ twin pairs, the intrapair differences in the measured lipoprotein parameters were similar in the different apoE phenotype classes. This indicates that the effect of the apoE polymorphism is not influenced by environmental variability between the MZ pair members and accordingly identifies the APOE gene as a "level" gene. © 1993 Springer-Verlag

A guided, internet-based stress management intervention for university students with high levels of stress:Feasibility and acceptability study

BackgroundTransitioning to adulthood and challenges in university life can result in increased stress levels among university students. Chronic and severe stress is associated with deleterious psychological and physiological effects. Digital interventions could succeed in approaching and helping university students who might be at risk; however, the experiences of students with internet-based stress management interventions are insufficiently understood.ObjectiveThis study aims to explore the feasibility; acceptability; and changes in perceived stress, depressive symptoms, and quality of life from baseline to posttest assessment of a 5-session, internet-based stress management intervention guided by an e-coach, developed for university students experiencing high levels of stress.MethodsA single-arm study was conducted. Students were recruited from different channels, mainly from a web survey. Students were eligible if they (1) scored ≥20 on the Perceived Stress Scale-10, (2) were aged ≥18 years, and (3) were studying at one of the participating universities. Feasibility and acceptability of the intervention were investigated using several indications, including satisfaction (Client Satisfaction Questionnaire-8) and usability (System Usability Scale-10). We also investigated the indicators of intervention adherence using use metrics (eg, the number of completed sessions). Our secondary goal was to explore the changes in perceived stress (Perceived Stress Scale-10), depressive symptoms (Patient Health Questionnaire-9), and quality of life (EQ-5D-5L scale) from baseline to posttest assessment. In addition, we conducted semistructured interviews with intervention completers and noncompleters to understand user experiences in depth. For all primary outcomes, descriptive statistics were calculated. Changes from baseline to posttest assessment were examined using 2-tailed paired sample t tests or the Wilcoxon signed rank test. Qualitative data were analyzed using thematic analysis.ResultsOf 436 eligible students, 307 (70.4%) students started using the intervention. Overall, 25.7% (79/307) completed the core sessions (ie, sessions 1-3) and posttest assessment. A substantial proportion of the students (228/307, 74.3%) did not complete the core sessions or the posttest assessment. Students who completed the core sessions reported high satisfaction (mean 25.78, SD 3.30) and high usability of the intervention (mean 86.01, SD 10.25). Moreover, this group showed large reductions in perceived stress (Cohen d=0.80) and moderate improvements in depression score (Cohen d=0.47) and quality of life (Cohen d=-0.35) from baseline to posttest assessment. Qualitative findings highlight that several personal and intervention-related factors play a role in user experience.ConclusionsThe internet-based stress management intervention seems to be feasible, acceptable, and possibly effective for some university students with elevated stress levels. However, given the high dropout rate and qualitative findings, several adjustments in the content and features of the intervention are needed to maximize the user experience and the impact of the intervention.Trial Registration: Netherlands Trial Register 8686; https://onderzoekmetmensen.nl/nl/trial/20889.International Registered Report Identifier (IRRID): RR2-10.1016/j.invent.2021.100369.</p

Harmful communication behaviors in cancer care:A systematic review of patients and family caregivers perspectives

ObjectiveIssues regarding clinician communication remain an important source of complaints within healthcare. This systematic review aims to determine cancer patients' and their family caregivers' views on which clinicians' communication behaviors can harm (i.e. eliciting negative feelings/consequences for patients/family caregivers).MethodsWe searched for all types of peer-reviewed studies that determined adult (≥18 years) cancer patients' and/or family caregivers' perspectives on which clinicians' communication behaviors can harm in several databases (PubMed, Embase, Web of Science, Cochrane Library, Emcare, PsycINFO and Academic Search Premier), supplemented by expert-consultation. Studies were screened using the Artificial intelligence screening tool of ASReview and data was analyzed using Thematic Analysis. To assess the quality of the studies the Qualsyst critical appraisal tool was used.ResultsA total of 47 studies were included. Four main themes of harmful communication behaviors were identified: (1) Lack of tailored information provision (e.g. giving too little or too much/specific information) (2) Lack of tailored decision making (ranging from; patient exclusion, to the patients' responsibility, and/or haste) (3) Lack of feeling seen and heard (seen as a disease, not as a human being; not listened to concerns and emotions) (4) Lack of feeling held and remembered (forgotten agreements; lack of care continuity).ConclusionsOur results reveal an overview of patients' and family caregivers' perspectives on which clinicians' communication behaviors can harm. Harm could be prevented when information and decision involvement are tailored and patients' and family caregivers' needs to feel seen, heard, held and remembered are met

Non-dispensing pharmacist integrated in the primary care team:Effect on the quality of physician's prescribing, a non-randomised comparative study

BackgroundEspecially in elderly with polypharmacy, medication can do harm. Clinical pharmacists integrated in primary care teams might improve quality of pharmaceutical care.ObjectiveTo assess the effect of non-dispensing clinical pharmacists integrated in primary care teams on general practitioners' prescribing quality.SettingThis study was conducted in 25 primary care practices in the Netherlands.MethodsNon-randomised, controlled, multi-centre, complex intervention study with pre-post comparison. First, we identified potential prescribing quality indicators from the literature and assessed their feasibility, validity, acceptability, reliability and sensitivity to change. Also, an expert panel assessed the indicators' health impact. Next, using the final set of indicators, we measured the quality of prescribing in practices where non-dispensing pharmacists were integrated in the team (intervention group) compared to usual care (two control groups). Data were extracted anonymously from the healthcare records. Comparisons were made using mixed models correcting for potential confounders.Main outcome measureQuality of prescribing, measured with prescribing quality indicators.ResultsOf 388 eligible indicators reported in the literature we selected 8. In addition, two more indicators relevant for Dutch general practice were formulated by an expert panel. Scores on all 10 indicators improved in the intervention group after introduction of the non-dispensing pharmacist. However, when compared to control groups, prescribing quality improved solely on the indicator measuring monitoring of the renal function in patients using antihypertensive medication: relative risk of a monitored renal function in the intervention group compared to usual care: 1.03 (95% CI 1.01-1.05, p-value 0.010) and compared to usual care plus: 1.04 (1.01-1.06, p-value 0.004).ConclusionThis study did not demonstrate a consistent effect of the introduction of non-dispensing clinical pharmacists in the primary care team on the quality of physician's prescribing. This study is part of the POINT-study, which was registered at The Netherlands National Trial Register with trial registration number NTR-4389

Non-dispensing pharmacists integrated into general practices as a new interprofessional model: a qualitative evaluation of general practitioners’ experiences and views

Background: A new interprofessional model incorporating non-dispensing pharmacists in general practice teams can improve the quality of pharmaceutical care. However, results of the model are dependent on the context. Understanding when, why and how the model works may increase chances of successful broader implementation in other general practices. Earlier theories suggested that the results of the model are achieved by bringing pharmacotherapeutic knowledge into general practices. This mechanism may not be enough for successful implementation of the model. We wanted to understand better how establishing new interprofessional models in existing healthcare organisations takes place. Methods: An interview study, with a realist informed evaluation was conducted. This qualitative study was part of the Pharmacotherapy Optimisation through Integration of a Non-dispensing pharmacist in primary care Teams (POINT) project. We invited the general practitioners of the 9 general practices who (had) worked closely with a non-dispensing pharmacist for an interview. Interview data were analysed through discussions about the coding with the research team where themes were developed over time. Results: We interviewed 2 general practitioners in each general practice (18 interviews in total). In a context where general practitioners acknowledge the need for improvement and are willing to work with a non-dispensing pharmacist as a new team member, the following mechanisms are triggered. Non-dispensing pharmacists add new knowledge to current general practice. Through everyday talk (discursive actions) both general practitioners and non-dispensing pharmacists evolve in what they consider appropriate, legitimate and imaginable in their work situations. They align their professional identities. Conclusions: Not only the addition of new knowledge of non-dispensing pharmacist to the general practice team is crucial for the success of this interprofessional healthcare model, but also alignment of the general practitioners’ and non-dispensing pharmacists’ professional identities. This is essentially different from traditional pharmaceutical care models, in which pharmacists and GPs work in separate organisations. To induce the process of identity alignment, general practitioners need to acknowledge the need to improve the quality of pharmaceutical care interprofessionally. By acknowledging the aspect of interprofessionality, both general practitioners and non-dispensing pharmacists will explore and reflect on what they consider appropriate, legitimate and imaginable in carrying out their professional roles. Trial registration: The POINT project was pre-registered in The Netherlands National Trial Register, with Trial registration number NTR-4389

Mini viral RNAs act as innate immune agonists during influenza virus infection

We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant 090532/Z/09/Z) for the generation of adapter-ligated mvRNA sequencing data. This work was supported by the Wellcome Trust grant 098721/Z/12/Z, the joint Wellcome Trust and Royal Society grant 206579/Z/17/Z and a Netherlands Organization for Scientific Research (NWO) grant 825.11.029 to A.J.W.t.V.; EPA Cephalosporin Junior Research Fellowship to D.L.V.B.; support by the Intramural Research Program of NIAID, NIH, to E.d.W.; Research Grants Council of the Hong Kong Special Administrative Region, China, project no. T11-705/14N and a Croucher Senior Research Fellowship to L.L.M.P.; and Medical Research Council (MRC) programme grants MR/K000241/1 and MR/R009945/1 to E.F. and studentship to J.C.L.The molecular processes that determine the outcome of influenza virus infection in humans are multifactorial and involve a complex interplay between host, viral and bacterial factors1. However, it is generally accepted that a strong innate immune dysregulation known as ‘cytokine storm’ contributes to the pathology of infections with the 1918 H1N1 pandemic or the highly pathogenic avian influenza viruses of the H5N1 subtype2,3,4. The RNA sensor retinoic acid-inducible gene I (RIG-I) plays an important role in sensing viral infection and initiating a signalling cascade that leads to interferon expression5. Here, we show that short aberrant RNAs (mini viral RNAs (mvRNAs)), produced by the viral RNA polymerase during the replication of the viral RNA genome, bind to and activate RIG-I and lead to the expression of interferon-β. We find that erroneous polymerase activity, dysregulation of viral RNA replication or the presence of avian-specific amino acids underlie mvRNA generation and cytokine expression in mammalian cells. By deep sequencing RNA samples from the lungs of ferrets infected with influenza viruses, we show that mvRNAs are generated during infection in vivo. We propose that mvRNAs act as the main agonists of RIG-I during influenza virus infection.PostprintPeer reviewe

From chemical gardens to chemobrionics

Chemical gardens in laboratory chemistries ranging from silicates to polyoxometalates, in applications ranging from corrosion products to the hydration of Portland cement, and in natural settings ranging from hydrothermal vents in the ocean depths to brinicles beneath sea ice. In many chemical-garden experiments, the structure forms as a solid seed of a soluble ionic compound dissolves in a solution containing another reactive ion. In general any alkali silicate solution can be used due to their high solubility at high pH. The cation should not precipitate with the counterion of the metal salt used as seed. A main property of seed chemical-garden experiments is that initially, when the fluid is not moving under buoyancy or osmosis, the delivery of the inner reactant is diffusion controlled. Another experimental technique that isolates one aspect of chemical-garden formation is to produce precipitation membranes between different aqueous solutions by introducing the two solutions on either side of an inert carrier matrix. Chemical gardens may be grown upon injection of solutions into a so-called Hele-Shaw cell, a quasi-two-dimensional reactor consisting in two parallel plates separated by a small gap

Dutch trauma system performance: are injured patients treated at the right place?

Background: The goal of trauma systems is to match patient care needs to the capabilities of the receiving centre. Severely injured patients have shown better outcomes if treated in a major trauma centre (MTC). We aimed to evaluate patient distribution in the Dutch trauma system. Furthermore, we sought to identify factors associated with the undertriage and transport of severely injured patients (Injury Severity Score (ISS) >15) to the MTC by emergency medical services (EMS).Methods: Data on all acute trauma admissions in the Netherlands (2015-2016) were extracted from the Dutch national trauma registry. An ambulance driving time model was applied to calculate MTC transport times and transport times of ISS >15 patients to the closest MTC and non-MTC. A multivariable logistic regression analysis was performed to identify factors associated with ISS >15 patients' EMS undertriage to an MTC.Results: Of the annual average of 78,123 acute trauma admissions, 4.9% had an ISS >15. The nonseverely injured patients were predominantly treated at non-MTCs (79.2%), and 65.4% of patients with an ISS >15 received primary MTC care. This rate varied across the eleven Dutch trauma networks (36.8%-88.4%) and was correlated with the transport times to an MTC (Pearson correlation -0.753, p=0.007). The trauma networks also differed in the rates of secondary transfers of ISS >15 patients to MTC hospitals (7.8% 59.3%) and definitive MTC care (43.6% - 93.2%). Factors associated with EMS undertriage of ISS >15 patients to the MTC were female sex, older age, severe thoracic and abdominal injury, and longer additional EMS transport times.Conclusions: Approximately one-third of all severely injured patients in the Netherlands are not initially treated at an MTC. Special attention needs to be directed to identifying patient groups with a high risk of undertriage. Furthermore, resources to overcome longer transport times to an MTC, including the availability of ambulance and helicopter services, may improve direct MTC care and result in a decrease in the variation of the undertriage of severely injured patients to MTCs among the Dutch trauma networks. Furthermore, attention needs to be directed to improving primary triage guidelines and instituting uniform interfacility transfer agreements. (C) 2021 Elsevier Ltd. All rights reserved.Trauma Surger

The Dutch nationwide trauma registry: The value of capturing all acute trauma admissions

Introduction: Twenty years ago the Dutch trauma care system was reformed by the designating 11 level one Regional trauma centres (RTCs) to organise trauma care. The RTCs set up the Dutch National Trauma Registry (DNTR) to evaluate epidemiology, patient distribution, resource use and quality of care. In this study we describe the DNTR, the incidence and main characteristics of Dutch acutely admitted trauma patients, and evaluate the value of including all acute trauma admissions compared to more stringent criteria applied by the national trauma registries of the United Kingdom and Germany. Methods: The DNTR includes all injured patients treated at the ED within 48 hours after trauma and consecutively followed by direct admission, transfers to another hospital or death at the ED. DNTR data on admission years 2007-2018 were extracted to describe the maturation of the registry. Data from 2018 was used to describe the incidence rate and patient characteristics. Inclusion criteria of the Trauma Audit and Research (TARN) and the Deutsche Gesellschaft für Unfallchirurgie (DGU) were applied on 2018 DNTR data. Results: Since its start in 2007 a total of 865,460 trauma cases have been registered in the DNTR. Hospital participation increased from 64% to 98%. In 2018, a total of 77,529 patients were included, the median age was 64 years, 50% males. Severely injured patients with an ISS≥16, accounted for 6% of all admissions, of which 70% was treated at designated RTCs. Patients with an ISS≤ 15were treated at non-RTCs in 80% of cases. Application of DGU or TARN inclusion criteria, resulted in inclusion of respectively 5% and 32% of the DNTR patients. Particularly children, elderly and patients admitted at non-RTCs are left out. Moreover, 50% of ISS≥16 and 68% of the fatal cases did not meet DGU inclusion criteria Conclusion: The DNTR has evolved into a comprehensive well-structured nationwide population-based trauma register. With 80,000 inclusions annually, the DNTR has become one of the largest trauma databases in Europe The registries strength lies in the broad inclusion criteria which enables studies on the burden of injury and the quality and efficiency of the entire trauma care system, encompassing all trauma‐receiving hospitals