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Founder populations may be enriched with certain genetic variants of high clinical impact compared to nonfounder populations due to bottleneck events and genetic drift. Using exome sequencing (ES), we quantified the load of pathogenic variants that may be clinically actionable in 6136 apparently healthy adults living in the Lancaster, PA Old Order Amish settlement. We focused on variants in 78 genes deemed clinically actionable by the American College of Medical Genetics and Genomics (ACMG) or Geisinger's MyCode Health Initiative. ES revealed 3191 total variants among these genes including 480 nonsynonymous variants. After quality control and filtering, we applied the ACMG/AMP guidelines for variant interpretation and classified seven variants, across seven genes, as either pathogenic or likely pathogenic. Through genetic drift, all seven variants, are highly enriched in the Amish compared to nonfounder populations. In total, 14.7% of Lancaster Amish individuals carry at least one of these variants, largely explained by the 13% who harbor a copy of a single variant in APOB. Other studies report combined frequencies of pathogenic/likely pathogenic (P/LP) variants in actionable genes between 2.0% and 6.2% in outbred populations. The Amish population harbors fewer actionable variants compared to similarly characterized nonfounder populations but have a higher frequency of each variant identified, offering opportunities for efficient and cost-effective targeted precision medicine.

Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are biomarkers for liver health. Here we report the largest genome‐wide association analysis to date of serum ALT and AST levels in over 388k people of European ancestry from UK biobank and DiscovEHR. Eleven million imputed markers with a minor allele frequency (MAF) ≥ 0.5% were analyzed. Overall, 300 ALT and 336 AST independent genome‐wide significant associations were identified. Among them, 81 ALT and 61 AST associations are reported for the first time. Genome‐wide interaction study identified 9 ALT and 12 AST independent associations significantly modified by body mass index (BMI), including several previously reported potential liver disease therapeutic targets, for example, PNPLA3, HSD17B13, and MARC1. While further work is necessary to understand the effect of ALT and AST‐associated variants on liver disease, the weighted burden of significant BMI‐modified signals is significantly associated with liver disease outcomes. In summary, this study identifies genetic associations which offer an important step forward in understanding the genetic architecture of serum ALT and AST levels. Significant interactions between BMI and genetic loci not only highlight the important role of adiposity in liver damage but also shed light on the genetic etiology of liver disease in obese individuals.

Background:Psychotropic drugs are frequently prescribed to people with dementia in nursing homes although severe adverse events and side effects are common. Less is known about the prevalence and types of psychotropic drug prescription in primary care for people with dementia.Objective:This study examined the prevalence of psychotropic drug prescriptions in primary care among persons with dementia from the year of diagnosis onwards.Methods:A longitudinal observational study using electronic health record (EHR) data was conducted. People with dementia were selected from EHR data of 451 general practices in the Netherlands. Age and gender-adjusted psychotropic drug prescription rates were calculated per 1000 person-years from the year the dementia diagnosis was first recorded in general practice up to 8 years after diagnosis.Results:Data of 15,687 patients were analyzed. The prescription rate of psychotropic drugs (not including antidementia drugs) was 420 per 1000 person-years (95% CI 409; 431) in the first year after the recorded dementia diagnosis, which increased to 801 per 1000 person-years (95% CI 649; 989) in the eighth year. The most frequently prescribed drugs were antidepressants, antipsychotics, and antidementia drugs, followed by anxiolytics, hypnotics, and antiepileptics.Conclusions:After a dementia diagnosis is recorded in general practice, the prevalence of psychotropic drug prescriptions is substantial and increases steadily during the disease trajectory of persons with dementia. Although the (in)appropriateness of prescribing was not assessed, these insights may stimulate primary care clinicians to (re)consider their prescription policy of psychotropics for people with dementia more carefully.

BACKGROUND: the number of persons with dementia from ethnic minority backgrounds is increasing. However, ethnic minority groups use health care services less frequently compared to non-migrants. METHOD: We conducted a scoping review and used the theoretical framework developed by Levesque to provide an overview of the literature concerning access to health care for ethnic minority people with dementia and (in)formal caregivers. Our search strategy identified 28 empirical studies in the period 2008-2019. RESULT: Studies mentioned barriers in (1) the ability to perceive a need for care in terms of health literacy, health beliefs and trust and expectations; (2) the ability to seek care because of personal and social values and the lack of knowledge regarding health care options; (3) lack of person-centered care as barrier to continue with professional health care. Studies also mentioned barriers experienced by professionals in (1) communication with ethnic minorities and knowledge about available resources for professionals; (2) cultural and social factors influencing the professionals' attitudes towards ethnic minorities; (3) the appropriateness of care and lacking competencies to work with people with dementia from ethnic minority groups and informal caregivers. CONCLUSION: Ethnic minority people with dementia and informal caregivers may benefit from improve their abilities to access health care. Health care professionals need to strengthen their competencies in order to facilitate access to health care for this group.

Irredentism is a crucial, yet understudied phenomenon of nationalism. Most scholars emphasise how irredentist thinking and practices function as a geopolitical instrument for inter-state formation, resulting in radical nationalism. This article sheds light instead on the cultural preoccupations underlying irredentist discourses. It focusses on irredentist claims on the Adriatic city of Fiume (Rijeka) among Italian nationalists in the 19th and 20th centuries, emphasising how they were driven by cultural imaginaries of a spiritual borderland for the nation. These imaginaries continued to inform irredentist arguments during the phase of political mobilisation. This sheds light on contemporary European politics, in which irredentist imaginaries are once again shaping nationalist discourses.

Purpose Increasing cohorts of patients present with diabetic cardiomyopathy, and with no targeted options, treatment often rely on generic pharmaceuticals such as β‐blockers. β‐blocker efficacy is heterogenous, with second generation β‐blocker metoprolol selectively inhibiting β1‐AR, while third generation β‐blocker carvedilol has α1‐AR inhibition, antioxidant, and anti‐apoptotic actions alongside nonselective β‐AR inhibition. These additional properties have led to the hypothesis that carvedilol may improve cardiac contractility in the diabetic heart to a greater extent than metoprolol. The present study aimed to compare the efficacy of metoprolol and carvedilol on myocardial function in animal models and cardiac tissue from patients with type 2 diabetes and preserved ejection fraction. Methods Echocardiographic examination of cardiac function and assessment of myocardial function in isolated trabeculae was carried out in patients with and without diabetes undergoing coronary artery bypass grafting (CABG) who were prescribed metoprolol or carvedilol. Equivalent measures were undertaken in Zucker Diabetic Fatty (ZDF) rats following 4 weeks treatment with metoprolol or carvedilol. Results Patients receiving carvedilol compared to metoprolol had no difference in cardiac function, and no difference was apparent in myocardial function between β‐blockers. Both β‐blockers similarly improved myocardial function in diabetic ZDF rats treated for 4 weeks, without significantly affecting in vivo cardiac function. Conclusions Metoprolol and carvedilol were found to have no effect on cardiac function in type 2 diabetes with preserved ejection fraction, and were similarly effective in preventing myocardial dysfunction in ZDF rats., In this manuscript, we present data comparing the effects of carvedilol and metoprolol on in vivo and in vitro cardiac function in both diabetic and non‐diabetic human patients, as well as in a rat model of type 2 diabetes (Zucker Diabetic Fatty rats). Our data demonstrate that both carvedilol and metoprolol are able to improve the contractility of cardiac muscle from diabetic humans and rats, as well as preserving cardiac function in both models. Importantly, we saw no extra improvement in individuals or animals that received carvedilol over those who received metoprolol, suggesting that any improvement in health outcomes provided by carvedilol (as seen in the COMET study) are not derived from differences in the contractile function of the cardiac muscle.

Time Trade‐Off (TTO) usually relies on “iteration,” which is susceptible to bias. Discrete Choice Experiment with duration (or DCETTO) is free of such bias, but respondents find this cognitively more challenging. This paper explores non‐iterative TTO with or without lead time: NI(LT)TTO. In NI(LT)TTO, respondents see a series of independent pairwise choices without iteration (similar to DCETTO), but one of the two scenarios always involves full health for a shorter duration (similar to TTO). We compare three different “types” of NI(LT)TTO relative to DCETTO. Each type is presented in two “modes”: (a) verbally tabulated (as in a DCE) and (b) with visual aids (as in a TTO). The study has 8 survey variants, each with 12 experimental choice tasks and a 13th task with a logically determined answer. Data on the 12 experimental choices from an online survey of 6,618 respondents are modelled, by variant, using conditional logistic regressions. The results indicate that NI(LT)TTO is feasible, but some relatively mild states appear to have implausibly low predicted values, and the range of predicted values is much narrower than in DCETTO. The presentation of NI(LT)TTO tasks needs further improvement.

Background Platelets (PLTs) stored in PLT additive solution (PAS) are associated with fewer allergic reactions than plasma-stored PLTs. However, earlier studies could not provide conclusive evidence on febrile reactions and did not analyze other transfusion reactions separately due to limited sample size. We therefore compared incidences of all transfusion reactions of PAS-B-PLTs, PAS-C-PLTs, and plasma-PLTs. Study design and methods In this observational study, all transfusion reactions reported to the national hemovigilance office of the Netherlands from 2006 to 2015 were included. Results During the study period, a total of 2407 transfusion reactions after PLT transfusions were reported. In that period 553,267 pooled buffy coat-derived PLT units were issued, of which 83,884 were stored in PAS-B, 45,728 in PAS-C, and 423,655 in plasma. Regarding transfusion-related circulatory overload, transfusion-related acute lung injury, and "other reactions" no significant differences were observed between the PLT products. When PAS-B-PLT transfusions were compared to plasma-PLT transfusions, the overall relative risk (RR; 95% confidence interval [CI]) of transfusion reactions was 0.99 (0.88-1.11); for allergic and febrile nonhemolytic transfusion reactions (FNHTRs) it was 0.66 (0.55-0.80) and 1.54 (1.27-1.86), respectively. When PAS-C-PLTs were compared to plasma-PLTs, the RR (95% CI) was 0.56 (0.46-0.68) for all transfusion reactions, 0.38 (0.28-0.52) for allergic reactions, and 0.82 (0.59-1.13) for FNHTRs. When PAS-C-PLTs were compared to PAS-B-PLTs, for all reactions the RR (95% CI) was 0.56 (0.45-0.70) for allergic reactions 0.58 (0.40-0.82), and for FNHTRs 0.53 (0.37-0.75). Conclusions PAS-C-PLTs are associated with fewer transfusion reactions compared to plasma-PLTs and compared to PAS-B-PLTs.

© 2017 The Authors Health Economics Published by John Wiley & Sons Ltd. Value sets for the EQ-5D-5L are required to facilitate its use in estimating quality-adjusted life years. An international protocol has been developed to guide the collection of stated preference data for this purpose and has been used to generate EQ-5D-5L valuation data for England. The aim of this paper is report the innovative methods used for modelling those data to obtain a value set. Nine hundred and ninety-six members of the English general public completed time trade-off (TTO) and discrete choice experiment (DCE) tasks. We estimate models, with and without interactions, using DCE data only, TTO data only, and TTO/DCE data combined. TTO data are interpreted as both left and right censored. Heteroskedasticity and preference heterogeneity between individuals are accounted for. We use Bayesian methods in the econometric analysis. The final model is chosen based on the deviance information criterion (DIC). Censoring and taking account of heteroskedasticity have important effects on parameter estimation. For DCE data only, TTO data only, and DCE/TTO data combined, models with parameters for all dimensions and levels perform best, as judged by the DIC. Taking account of heterogeneity improves fit, and the multinomial model reports the lowest DIC. This paper presents approaches that suit observed characteristics of EQ-5D-5L valuation data and recognise respondents' preference heterogeneity. The methods described are potentially relevant to other value set studies.

BACKGROUND We estimated rates for common plasma-associated transfusion reactions and compared reported rates for various plasma types. STUDY DESIGN AND METHODS We performed a systematic review and meta-analysis of peer-reviewed articles that reported plasma transfusion reaction rates. Random-effects pooled rates were calculated and compared between plasma types. Meta-regression was used to compare various plasma types with regard to their reported plasma transfusion reaction rates. RESULTS Forty-eight studies reported transfusion reaction rates for fresh-frozen plasma (FFP; mixed-sex and male-only), amotosalen INTERCEPT FFP, methylene blue-treated FFP, and solvent/detergent-treated pooled plasma. Random-effects pooled average rates for FFP were: allergic reactions, 92/105 units transfused (95% confidence interval [CI], 46-184/105 units transfused); febrile nonhemolytic transfusion reactions (FNHTRs), 12/105 units transfused (95% CI, 7-22/105 units transfused); transfusion-associated circulatory overload (TACO), 6/105 units transfused (95% CI, 1-30/105 units transfused); transfusion-related acute lung injury (TRALI), 1.8/105 units transfused (95% CI, 1.2-2.7/105 units transfused); and anaphylactic reactions, 0.8/105 units transfused (95% CI, 0-45.7/105 units transfused). Risk differences between plasma types were not significant for allergic reactions, TACO, or anaphylactic reactions. Methylene blue-treated FFP led to fewer FNHTRs than FFP (risk difference = −15.3 FNHTRs/105 units transfused; 95% CI, −24.7 to −7.1 reactions/105 units transfused); and male-only FFP led to fewer cases of TRALI than mixed-sex FFP (risk difference = −0.74 TRALI/105 units transfused; 95% CI, −2.42 to −0.42 injuries/105 units transfused). CONCLUSION Meta-regression demonstrates that the rate of FNHTRs is lower for methylene blue-treated compared with FFP, and the rate of TRALI is lower for male-only than for mixed-sex FFP; whereas no significant differences are observed between plasma types for allergic reactions, TACO, or anaphylactic reactions. Reported transfusion reaction rates suffer from high heterogeneity.

At the site of interpersonal conflict resides the potential for learning. This paper presents psychodynamic theories, empirical research and a fictional case study of psychotherapy group supervision. Supervision is discussed in terms of teaching and learning, triangular relations, and group and organizational perspectives. We examine the interconnectedness of patterns of distress that emerge within dynamic relational systems at the levels of the macro-social, organizational, group and individual. The concepts of equivalence, parallel process and reflection process provide frameworks for this discussion. We explore the constraints and dynamic influence of the organization upon the supervision relationship and the ethical tensions that construct im/possible positions for the supervisor. The case study tells a fictional story of a supervision group situated in an organizational context – a university psychotherapy education programme. A collapse of the group into complementarity, that is into polarized conflicted positions, proffers a vitalizing opportunity for learning. Through the clinical discussion, we reveal how this is contingent on the group's capacity to think together about the meaning of their struggle and to transcend a binary conflict and achieve ‘the third’.

Objective Family caregivers of people with dementia often report high levels of stress and depression, but little is known about those who contemplate suicide or self-harm. This study explores thoughts of suicide, self-harm and death in dementia caregivers and investigates the characteristics that distinguish them from those without such thoughts. Methods Data were collected every 3 months, for 24 months, from 192 family caregivers of people with dementia living in the Netherlands. Caregivers did not have a clinical depression or anxiety disorder at baseline. Suicide-related thoughts were measured with an item from the Mini International Neuropsychiatric Interview, a diagnostic instrument for DSM-IV mental disorders. Fisher exact, analysis of variance or Kruskal–Wallis tests compared the characteristics of caregivers who had contemplated suicide with two comparison groups. Results Within 24 months, 76 caregivers reported symptoms of a potential depression and were further assessed for suicidal thoughts. Nine carers (11.8%, 4.7% of the total sample) reported suicidal thoughts with three of those at multiple points. Caregivers with suicidal thoughts had more severe depressive and anxious symptoms, had a lower sense of competence and mastery, felt less happy and experienced more health problems, less family support and more feelings of loneliness than caregivers who had not. Conclusion Suicidal thoughts are present in dementia caregivers and can persist across the care trajectory. Various psychological and social characteristics significantly distinguish caregivers with suicidal thoughts from those without. More research is needed to enable the identification of high-risk caregivers and provide an evidence base for the development of preventive strategies and interventions. © 2017 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

Randomized trials have shown marked reductions in low‐density lipoprotein cholesterol (LDL‐C), a risk factor for cardiovascular disease (CVD), when evolocumab is administered. We hypothesized that evolocumab added to standard of care (SOC) vs SOC alone is cost‐effective in the treatment of patients with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic CVD (ASCVD) with or without statin intolerance and LDL‐C >100 mg/dL. Using a Markov cohort state transition model, primary and recurrent CVD event rates were predicted considering population‐specific trial‐based mean risk factors and calibrated against observed rates in the real world. The LDL‐C–lowering effect from population‐specific phase 3 randomized studies for evolocumab was used together with estimated LDL‐C–lowering effect on CVD event rates per 38.67‐mg/dL LDL‐C lowering from a statin‐trial meta‐analysis. Costs and utilities were included from published sources. Evolocumab treatment was associated with both increased cost and improved quality‐adjusted life‐years (QALY): HeFH (incremental cost: US$153 289, incremental QALY: 2.02, incremental cost‐effectiveness ratio: US$75 863/QALY); ASCVD (US$158 307, 1.12, US$141 699/QALY); and ASCVD with statin intolerance (US$136 903, 1.36, US$100 309/QALY). Evolocumab met both the American College of Cardiology/American Heart Association (ACC/AHA) and World Health Organization (WHO) thresholds in each population evaluated. Sensitivity and scenario analyses confirmed that model results were robust to changes in model parameters. Among patients with HeFH and ASCVD with or without statin intolerance, evolocumab added to SOC may provide a cost‐effective treatment option for lowering LDL‐C using ACC/AHA intermediate/high value and WHO cost‐effectiveness thresholds. More definitive information on the clinical and economic value of evolocumab will be available from the forthcoming CVD outcomes study.

The clinical consequences of isolated decreased serum immunoglobulin (Ig)M are not sufficiently known. Therefore, it is difficult to determine the clinical policy following such a finding. Only few reported IgM‐deficient patients fulfil the European Society for Immunodeficiencies (ESID) diagnostic criteria for selective IgM deficiency (true sIgMdef), or their diagnosis is uncertain due to insufficient laboratory data (possible sIgMdef). Decreased serum IgM is often incidentally found in asymptomatic adults. The objective of our study was to further characterize true sIgMdef and to compare the European data collected through the ESID Registry community (tertiary centres) to our previously published Dutch cohort (secondary centre). Fifteen centres (12 countries) participated with 98 patients. Patients were excluded if serum IgM was only determined once (n = 14), had normalized (n = 8), or if they also had other immunological abnormalities (n = 15). Ten patients (5 adults) completely fulfilled the ESID criteria for true sIgMdef. Age‐matched cut‐off values varied widely between centres; when using the ESID diagnostic protocol reference values, only six patients (five adults) had true sIgMdef. Because of these small numbers, further analyses were performed in patients with true or possible sIgMdef (13 adults, 48 children). Respiratory infections were commonly reported at presentation (adults 54%, children 60%). Symptomatic adults had lower serum IgM levels (mean 0.27 g/L, 95% CI 0.22‐0.31) than those without symptoms (mean 0.33 g/L, 95% CI 0.30‐0.36; P = 0.02). To be able to explore the clinical consequences of true sIgMdef, we should fully analyse and accurately describe those patients in whom a decreased serum IgM is found.

Time Trade-Off (TTO) usually relies on “iteration”, which is susceptible to bias. Discrete Choice Experiment with duration (or DCETTO) is free of such bias, but respondents find this cognitively more challenging. This paper explores non-iterative TTO with or without lead time: NI(LT)TTO. In NI(LT)TTO respondents see a series of independent pairwise choices without iteration (similar to DCETTO), but one of the two scenarios always involves full health for a shorter duration (similar to TTO). We compare three different “Types” of NI(LT)TTO relative to DCETTO. Each Type is presented in two “Modes”: (a) verbally tabulated (as in a DCE); and (b) with visual aids (as in a TTO). The study has eight survey variants, each with 12 experimental choice tasks and a 13th task with a logically determined answer. Data on the 12 experimental choices from an online survey of 6,618 respondents are modelled, by variant, using conditional logistic regressions. The results indicate that NI(LT)TTO is feasible, but some relatively mild states appear to have implausibly low predicted values, and the range of predicted values is much narrower than in DCETTO. The presentation of NI(LT)TTO tasks needs further improvement.

Determining critical attributes associated with consumer perceived benefit and choice is essential for the fast moving consumer goods industry. The goals of the present study were to develop a lexicon specific to usage process for kitchen cleansers using a novel consumer test and to test usage stage-dependency of the lexicon. Holistic usage process of kitchen cleansers was classified into purchase moment, during use and completion point. For a series of projective interviews, a semantic/language library, a collection of attributes relevant to kitchen cleansers was used as response options. Ethnographic observations/interviews were also incorporated into the consumer test to evoke consumers’ natural usage process. Comparisons of the developed lexicon revealed differences of consumers’ evaluation processes across different usage stages. At the purchase moment, attributes associated with Convenience and Functionality categories were found to be more important, whereas at completion point, attributes associated with Sensory Quality and Sentimental Consequence were more important. Practical Applications In sensory science literature, lexicon development for use in descriptive analysis of sensory characterization has been focused on the sensory attributes of various food products including appearance, taste, aroma, flavor, texture and aftertaste of foods. These are important not only for sensory characterization but also for communication between consumers and the people in industry, who are in charge of product development, quality control, marketing, etc. To improve communication with consumers on household cleaning products, the development of a lexicon describing consumers’ holistic product experiences, as well as investigation of the usage stage-dependency of the developed consumer attributes is required. This article introduces a new method to develop a lexicon representing consumer-relevant product attributes across different product usage stages for commercial kitchen cleanser trigger spray products and provides the lexicon associated with the product benefits of such products.

Many people speak more than two languages. How do languages acquired earlier affect the learnability of additional languages? We show that linguistic distances between speakers’ first (L1) and second (L2) languages and their third (L3) language play a role. Larger distances from the L1 to the L3 and from the L2 to the L3 correlate with lower degrees of L3 learnability. The evidence comes from L3 Dutch speaking proficiency test scores obtained by candidates who speak a diverse set of L1s and L2s. Lexical and morphological distances between the L1s of the learners and Dutch explained 47.7% of the variation in proficiency scores. Lexical and morphological distances between the L2s of the learners and Dutch explained 32.4% of the variation in proficiency scores in multilingual learners. Cross-linguistic differences require language learners to bridge varying linguistic gaps between their L1 and L2 competences and the target language.

Novel approaches of dendritic cell (DC) based cancer immunotherapy aim at harnessing the unique attributes of different DC subsets. Classical monocyte-derived DC vaccines are currently being replaced by either applying primary DCs or specifically targeting antigens and adjuvants to these subsets in vivo. Appropriate DC activation in both strategies is essential for optimal effect. For this purpose TLR agonists are favorable adjuvant choices, with TLR7 triggering being essential for inducing strong Th1 responses. However, mouse CD8α(+) DCs, considered to be the major cross-presenting subset, lack TLR7 expression. Interestingly, this DC subset can respond to TLR7 ligand upon concurrent TLR3 triggering. Nevertheless, the mechanism underlying this synergy remains obscure. We now show that TLR3 ligation results in the production of IFN-α, which rapidly induces the expression of TLR7, resulting in synergistic activation. Moreover, we demonstrate that this mechanism conversely holds for plasmacytoid DCs that respond to TLR3 ligation when TLR7 pathway is mobilized. We further demonstrate that this mechanism of sharpening DC senses is also conserved in human BDCA1(+) DCs and plasmacytoid DCs. These findings have important implications for future clinical trials as it suggests that combinations of TLR ligands should be applied irrespective of initial TLR expression profiles on natural DC subsets for optimal stimulation.

Cardiac-derived stem or progenitor cells (CSCs) have emerged as a possible therapeutic intervention for myocardial infarction, potentially ameliorating the devastating effects caused by inadequate blood flow to the heart. The first human clinical trials using these myocardial-derived cells have recently started, but scientific controversy exists regarding the efficacy and origin of some of these stem cells in preclinical animal models. Systematic review of the current literature on CSCs in ischaemic cardiomyopathy can provide useful additional information on the use of CSCs in preclinical trials. By combining all available data, we can adequately compare the different types of cells being used and possibly identify factors that influence cardiac stem cell therapy in general. This protocol provides a thorough description of the methodology that will be used in our systematic review and meta-analysis of all preclinical animal studies involving cardiac stem cell treatment for ischaemic cardiomyopathy.

Objectives: To assess insomnia and its correlates as part of the Services and Health for Elderly in Long TERm care (SHELTER) study, funded by the 7th Framework Programme of the European Union. Design: Cross-cultural investigation. Setting: Long-term care facilities (LTCFs) in eight European countries (Czech Republic, France, Finland, Germany, England, the Netherlands, Italy) and one non-European country (Israel). Participants: Elderly residents (N = 4,156) of 57 LTCFs. Measurements: Information on insomnia, age, sex, activities of daily living (ADLs), cognitive status, depression, major stressful life events, physical activity, fatigue, pain, and sleep medication use was extracted from the International Resident Assessment Instrument (interRAI)LTCF instrument. Rates of insomnia and its correlates were analyzed. Multivariate logistic regression was used to assess factors associated with insomnia, controlling for demographic variables. Results: The prevalence of insomnia was 24% (range 13–30%), with significant differences between countries (P < .001). More insomnia complaints were reported in older than younger residents (P < .001). Higher rates of insomnia were associated with hypnosedatives and depression in all countries (P < .001) and with stressful life events, fatigue, and pain in most countries (P < .001). No associations were found between insomnia and ADLs, physical activity, or cognitive status. Age, depression, stressful life events, fatigue, pain and hypnosedatives were independent significant predictors of insomnia, controlling for all other variables and for country. Conclusion: Hypnosedatives and depression were strong predictors of insomnia beyond cultural differences. Overall, psychosocial variables were more strongly related to insomnia than functional and mental capacities.

The aim of this review is to provide an overview of detection of cardiac fibrosis with MRI using current standards and novel endogenous MRI techniques. Assessment of cardiac fibrosis is important for diagnosis, prediction of prognosis and follow-up after therapy. During the past years, progress has been made in fibrosis detection using MRI. Cardiac infarct size can be assessed noninvasively with late gadolinium enhancement. Several methods for fibrosis detection using endogenous contrast have been developed, such as native T 1 -mapping, T 1ρ -mapping, Magnetization transfer imaging, and T 2 -mapping. Each of these methods will be described, providing the basic methodology, showing potential applications from applied studies, and discussing the potential and challenges or pitfalls. We will also identify future steps and developments that are needed for bringing these methods to the clinical practice.

Misuse of pharmaceuticals is of increasing drug policy and public health concern. A scoping review was conducted on the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions. The research question was broad: What is known from the existing literature about the diversion of pharmaceuticals for non-medicinal use and for home production of drug solutions? The scoping process centred on the systematic selection, collection, and summarization of extant knowledge within this broad thematic remit. One hundred and thirty-four records were grouped into discrete thematic categories namely: non medicinal use and tampering with pharmaceuticals, oral misuse of codeine cough syrups, homemade drug solutions, and home-produced drug-related harms in the narrative review design. Forms of abuse of codeine cough syrup include mixtures with alcohol or soft drinks ('Purple Drank'), with kratom leaves ('Kratom cocktails'), or chemically altered to extract dextromorphan ('Lemon Drop'). Production of homemade opiates ('Cheornaya', 'Kolyosa', Himiya', 'Braun', 'Krokodil'), methamphetamine ('Vint', 'Pervitin'), methcathinone ('Jeff'), and cathinone ('Boltushka') are described. Displacement patterns between the non-medical use of pharmaceuticals, commercial, and homemade drugs appear dependent on availability of opiates, prescribing practices, supervision of substitution drug dosing, availability of cheap ingredients, policing, and awareness of harms. Adverse health and social consequences relate to the use of unknown and contaminated (end) substances, injecting practices, redosing, medical complications, and death. The review highlights a public health imperative requiring a multidisciplinary approach to quantify potential impact and required integrated policy responses incorporating international regulation, enforcement, health surveillance and service delivery.

Background Brachyspira hyodysenteriae infection in pigs (‘swine dysentery’) leads to decreased feed conversion, growth losses and mortality. Current countermeasures have the downside of antibiotic resistance (antibiotics) and ecotoxicity (zinc oxide). The aim of this study was to evaluate the effect of a novel zinc chelate (Intra Dysovinol (ID)) on clinical signs of swine dysentery and shedding of B hyodysenteriae under field conditions. Methods In a randomised, double-blinded, controlled trial under Good Clinical Practice on two commercial farms, 58 B hyodysenteriae positive pigs from 16 pens received drinking water containing ID, or placebo, during six consecutive days. Faecal quality (consistency, colour, additions) was scored and faeces were analysed for presence of B hyodysenteriae by PCR. ID treatment positively affected faecal quality (consistency) and daily growth rates. Results At the last treatment day, B hyodysenteriae was not detectable in the faeces of any of the ID-treated animals, while all placebo animals remained B hyodysenteriae positive by PCR. All ID-treated animals recovered, while 5 placebo-treated animals died and 12 placebo pigs required additional treatment before the end of the study (up to 14 days after treatment start). Conclusion This non-antibiotic treatment stopped the clinical signs and shedding of B hyodysenteriae in naturally infected pigs.