General practitioners' and community pharmacists' beliefs and practices on opioids for non-malignant pain.

BACKGROUND: In Europe, opioid use has surged, largely due to prescriptions for chronic non-malignant pain (CNMP). General practitioners (GPs) and community pharmacists (CPs) play a major role in opioid prescribing for non-malignant pain. Exploring their personal beliefs and practices might reveal underlying mechanisms to identify measures that could halt the further escalation of opioid use. METHODS: Guided by the health belief model, a survey was designed and distributed nationwide to examine the practices and beliefs of GPs and CPs in the domains: threats, benefits, barriers and self-efficacy. The results of GPs and CPs were compared at the statement level using chi-square analysis. RESULTS: Of 214 GPs and 212 CPs who completed the survey, the majority agreed that too many opioids are used in the treatment of chronic non-malignant pain (66.8% GPs and 66.5% CPs). Furthermore, they were concerned about the addictive potential of opioids (83.1% GPs and 71.7% CPs). In general, both professions have concerns about opioid use. GPs report a slightly higher degree of self-efficacy and perceive fewer benefits from opioids in treating CNMP. GPs and CPs valued the recommended measures to reduce opioid prescribing, yet less than half actively implement these strategies in their clinics. CONCLUSION: GPs and CPs believe that opioids are being used too frequently to treat CNMP. However, both professions lack the actions to improve opioid-related care. GPs and CPs require education, collaboration and tools to implement guidelines on non-malignant pain and opioids. SIGNIFICANCE: This study, guided by the health belief model, reveals that general practitioners and community pharmacists have serious concerns about opioid use in chronic non-malignant pain. Despite shared concerns, both professions differ in their beliefs about opioid benefits and perceived self-efficacy. Both professions have in common that they value recommended measures to reduce opioid prescribing. Also, they both struggle to implement strategies, emphasizing the urgent need for education, collaboration and tools to align practices with guidelines on non-malignant pain and opioids.

[A patient with Alice in Wonderland syndrome]. / Een patiënt met het Alice in Wonderland-syndroom.

We present the case of a 65-year-old man who was referred to the old-age department of our psychiatric hospital because of a depressed mood and inactivity. During his stay he exhibited a variety of peculiar visual perceptions and bodily experiences. We concluded that he suffered from a severe depressive disorder, as well as from symptoms that fitted largely into the clinical pattern of the Alice in Wonderland syndrome. In this case report we discuss the symptoms, etiology, and treatment options.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Inflammatory bowel disease and risk of adenocarcinoma and neuroendocrine tumors in the small bowel.

BACKGROUND: Uncertainty prevails about the magnitude of excess risk of small bowel cancer in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: To quantify the risk of small bowel adenocarcinoma and neuroendocrine tumors in patients with ulcerative colitis (UC) and Crohn's disease (CD), we undertook a population-based cohort study of all patients with IBD diagnosed in Norway and Sweden from 1987 to 2016. Patients were followed through linkage to national registers. We calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) of small bowel adenocarcinomas and neuroendocrine tumors for patients with CD and UC. We excluded the first year of follow-up to reduce reverse causality. RESULTS: Among 142 008 patients with a median follow-up of 10.0 years, we identified 66 adenocarcinomas and 57 neuroendocrine tumors in the small bowel. The SIR of small bowel adenocarcinoma was 8.3 (95% CI 5.9-11.3) in CD and 2.0 (95% CI 1.2-3.1) in UC. The incidence rates of adenocarcinomas were highest in CD with stricturing disease and extent limited to the small bowel, at 14.7 (95% CI 8.2-24.2) and 15.8 (95% CI 8.4-27.0) per 100 000 person-years, respectively. The SIR of neuroendocrine tumors was 2.5 (95% CI 1.5-3.9) in CD and 2.0 (95% CI 1.4-2.8) in UC. CONCLUSIONS: Patients with CD experienced an eightfold increased risk of small bowel adenocarcinomas, patients with both UC and CD experienced an about twofold increased risk of neuroendocrine tumors, and patients with UC experienced a twofold increased risk of small bowel adenocarcinoma. The small absolute excess cancer risk suggests that active surveillance to diagnose small intestinal cancer early is unlikely to be cost-effective.

Online computer or therapist-guided cognitive behavioral therapy in university students with anxiety and/or depression: study protocol of a randomised controlled trial.

INTRODUCTION: Emerging adulthood is a phase in life that is associated with an increased risk to develop a variety of mental health disorders including anxiety and depression. However, less than 25% of university students receive professional help for their mental health reports. Internet-based cognitive behavioural therapy (iCBT) may entail useful interventions in a format that is attractive for university students. The aim of this study protocol is to test the effectiveness of a therapist-guided versus a computer-guided transdiagnostic iCBT programme with a main focus on anxiety and depression. METHODS AND ANALYSIS: University students with anxiety and/or depressive symptoms will be randomised to a (1) 7-week iCBT programme (excluding booster session) with therapist feedback, (2) the identical iCBT programme with computer feedback only or (3) care as usual. Participants in the care as usual condition are informed and referred to conventional care services and encouraged to seek the help they need. Primary outcome variables are self-reported levels of anxiety as measured with the General Anxiety Disorder-7 and self-reported levels of depression as measured with the Patient Health Questionnaire-9. Secondary outcomes include treatment adherence, client satisfaction, medical service use, substance use, quality of life and academic achievement. Assessments will take place at baseline (t1), midtreatment (t2), post-treatment (t3), at 6 months (t4) and 12 months (t5) postbaseline. Social anxiety and perfectionism are included as potentially important predictors of treatment outcome. Power calculations are based on a 3 (group) × 3 (measurement: pretreatment, midtreatment and post-treatment) interaction, resulting in an aimed sample of 276 participants. Data will be analysed based on intention-to-treat and per protocol samples using mixed linear models. ETHICS AND DISSEMINATION: The current study was approved by the Medical Ethics Review Committee (METC) of the Academic Medical Centre, Amsterdam, The Netherlands (number: NL64929.018.18). Results of this trial will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NL7328.

[Somatoparaphrenia in a patient with schizophrenia and addiction problems: 'That arm is not mine, doctor']. / Somatoparafrenie bij een patiënt met schizofrenie en verslavingsproblematiek: 'Die arm is niet van mij, dokter'.

Somatoparaphrenia is a disorder of body perception, usually on the left side. One or both limbs are seen as foreign or as belonging to somebody else. In the literature this rare phenomenon has been described in patients with brain damage, usually due to an infarction or other lesion to the right parietal lobe. We describe a patient with schizophrenia and addiction problems who believed that his left forearm was not his, but rather belonged to a Spanish girl. An EEG and an MRI of the brain showed no abnormalities. Despite years of antipsychotic treatment, the delusion persisted. To rule out neurological causes we recommend auxiliary investigations in all patients with somatoparaphrenia. No evidence-based treatments are known for this monothematic delusion in the context of schizophrenia.

Emergency upscaling of video consultation during the COVID-19 pandemic: Contrasting user experience with data insights from the electronic health record in a large academic hospital.

BACKGROUND: Video consultation (VC) has been scaled up at our academic centre attempting to facilitate and accommodate patient-provider interaction in times of social distancing during the recent and ongoing COVID-19 pandemic. OBJECTIVES: This study evaluates qualitative outcomes with data insights from the electronic health record, to contrast satisfaction outcomes with the actual use of VC. METHODS: Healthcare providers and patients using VC during the COVID-19 pandemic at a large academic centre in the Netherlands were surveyed for user satisfaction and experiences with VC. In addition, quantitative technical assessment was performed using data related to VC from the EHR record. RESULTS: In total, 1,027/4,443 patients and 87/166 healthcare providers completed their online questionnaire. Users rated the use of VC during a pandemic with an average score of 8.3/10 and 7.6/10 respectively. Both groups believed the use of VC was a good solution to continue the provision of healthcare during this pandemic. The use of VC increased from 92 in March 2020 to 837 in April 2020. CONCLUSION: This study strongly signals that VC is an important modality in futureproofing outpatient care during and beyond pandemic times. Further development in end-user technology is needed for EHR integrated VC solutions. Guidelines needs to be developed advising both patients and healthcare providers. Such guidelines should not solely focus on technical implementation and troubleshooting, but must also consider important aspects such as digital health literacy, patient and provider authentication, privacy and ethics.

Coded diagnoses from general practice electronic health records are a feasible and valid alternative to self-report to define diabetes cases in research.

AIMS: To examine the feasibility and validity of obtaining International Classification of Primary Care (ICPC)-coded diagnoses of diabetes mellitus (DM) from general practice electronic health records for case definition in epidemiological studies, as alternatives to self-reported DM. METHODS: The Netherlands Epidemiology of Obesity study is a population-based cohort study of 6671 persons aged 45-65 years at baseline, included between 2008-2012. Data from electronic health records were collected between 2012-2014. We defined a reference standard using diagnoses, prescriptions and consultation notes and investigated its agreement with ICPC-coded diagnoses of DM and self-reported DM. RESULTS: After a median follow-up of 1.8 years, data from 6442 (97%) participants were collected. With the reference standard, 506 participants (79/1000 person-years) were classified with prevalent DM at baseline and 131 participants (11/1000 person-years) were classified with incident DM during follow-up. The agreement of prevalent DM between self-report and the reference standard was 98% (kappa 0.86), the agreement between ICPC-coded diagnoses and the reference standard was 99% (kappa 0.95). The agreement of incident DM between ICPC-coded diagnoses and the reference standard was >99% (kappa 0.92). CONCLUSIONS: ICPC-coded diagnoses of DM from general practice electronic health records are a feasible and valid alternative to self-reported diagnoses of DM.

[Optical illusions and the work of M.C. Escher]. / Optische illusies en het werk van M.C. Escher.

BACKGROUND: The name Maurits Escher is inextricably linked with the notion of 'optical illusion', a type of illusion evoked by his 'impossible figures'. Despite the sober style in which he realised these figures, they go on to mesmerise generations of art lovers. It is unclear what causes this, and whether other factors than aesthetic ones are involved.
AIM: To gain insight into the genesis of optical illusions in Escher's work, and in the role of the perceptual system in that process.
METHOD: An explorative literature search in PubMed, Science.gov, Google Scholar, and the historical literature.
RESULTS: Since 'impossible figures' cannot be found in our natural environment, and therefore have a high novelty factor to the brain, they inevitably draw our attention. The reason that we remain captivated, is at least partly associated with the fact that the hippocampus and parahippocampal place area come into conflict with each other, and (in vain) accept the challenge to find a 'best fit'.
CONCLUSION: Fundamental research may benefit from Escher's 'impossible figures' to fathom the rules of our visual grammar. The optical illusions they evoke moreover constitute an ongoing source of inspiration for other artists, architects, and film makers.

Vortioxetine Prevents Lipopolysaccharide-Induced Memory Impairment Without Inhibiting the Initial Inflammatory Cascade.

Vortioxetine is a novel multimodal antidepressant that modulates a wide range of neurotransmitters throughout the brain. Preclinical and clinical studies have shown that vortioxetine exerts positive effects on different cognitive domains and neuroprotective effects. Considering the key role of microglial cells in brain plasticity and cognition, we aimed at investigating the effects of pretreatment with vortioxetine in modulating behavioral and molecular effects induced by an immune challenge: peripheral injection of lipopolysaccharide (LPS). To this purpose, C57BL/6J male mice were first exposed to a 28-day standard diet or vortioxetine-enriched diet, which was followed by an acute immune challenge with LPS. Sickness symptoms and depressive-like behaviors (anhedonia and memory impairment) were tested 6 and 24 h after exposure to LPS, respectively. Moreover, the expressions of markers of immune activation and M1/M2 markers of microglia polarization were measured in the dorsal and ventral parts of the hippocampus. The pretreatment with vortioxetine did not affect both LPS-induced sickness behavior and anhedonia but prevented the deficit in the recognition memory induced by the immune challenge. At the transcriptional level, chronic exposure to vortioxetine did not prevent LPS-induced upregulation of proinflammatory cytokines 6 h after the immune challenge but rather seemed to potentiate the immune response to the challenge also by affecting the levels of expression of markers of microglia M1 phenotype, like cluster of differentiation (CD)14 and CD86, in an area-dependent manner. However, at the same time point, LPS injection significantly increased the expression of the M2 polarization inducer, interleukin 4, only in the hippocampus of animals chronically exposed to vortioxetine. These results demonstrate that a chronic administration of vortioxetine specifically prevents LPS-induced memory impairment, without affecting acute sickness behavior and anhedonia, and suggest that hippocampal microglia may represent a cellular target of this novel antidepressant medication. Moreover, we provide a useful model to further explore the molecular mechanisms specifically underlying cognitive impairments following an immune challenge.

Lymnaea stagnalis as model for translational neuroscience research: From pond to bench.

The purpose of this review is to illustrate how a reductionistic, but sophisticated, approach based on the use of a simple model system such as the pond snail Lymnaea stagnalis (L. stagnalis), might be useful to address fundamental questions in learning and memory. L. stagnalis, as a model, provides an interesting platform to investigate the dialog between the synapse and the nucleus and vice versa during memory and learning. More importantly, the "molecular actors" of the memory dialogue are well-conserved both across phylogenetic groups and learning paradigms, involving single- or multi-trials, aversion or reward, operant or classical conditioning. At the same time, this model could help to study how, where and when the memory dialog is impaired in stressful conditions and during aging and neurodegeneration in humans and thus offers new insights and targets in order to develop innovative therapies and technology for the treatment of a range of neurological and neurodegenerative disorders.

Genomic analysis of a novel nontoxigenic Corynebacterium diphtheriae strain isolated from a cancer patient.

The genome of a novel nontoxigenic Corynebacterium diphtheriae, strain 5015, isolated from a patient with adenoid cystic carcinoma was sequenced and compared with 117 publically available genomes. This strain is phylogenetically distinct and lacks virulence genes encoding the toxin, BigA and Sdr-like adhesins. Strain 5015 possesses spaD-type and spaH-type pilus gene clusters with a loss of some gene functions, and 31 unique genes that need molecular characterization to understand their potential role in virulence characteristics.

Codon Usage Heterogeneity in the Multipartite Prokaryote Genome: Selection-Based Coding Bias Associated with Gene Location, Expression Level, and Ancestry.

Prokaryotes represent an ancestral lineage in the tree of life and constitute optimal resources for investigating the evolution of genomes in unicellular organisms. Many bacterial species possess multipartite genomes offering opportunities to study functional variations among replicons, how and where new genes integrate into a genome, and how genetic information within a lineage becomes encoded and evolves. To analyze these issues, we focused on the model soil bacterium Sinorhizobium meliloti, which harbors a chromosome, a chromid (pSymB), a megaplasmid (pSymA), and, in many strains, one or more accessory plasmids. The analysis of several genomes, together with 1.4 Mb of accessory plasmid DNA that we purified and sequenced, revealed clearly different functional profiles associated with each genomic entity. pSymA, in particular, exhibited remarkable interstrain variation and a high density of singletons (unique, exclusive genes) featuring functionalities and modal codon usages that were very similar to those of the plasmidome. All this evidence reinforces the idea of a close relationship between pSymA and the plasmidome. Correspondence analyses revealed that adaptation of codon usages to the translational machinery increased from plasmidome to pSymA to pSymB to chromosome, corresponding as such to the ancestry of each replicon in the lineage. We demonstrated that chromosomal core genes gradually adapted to the translational machinery, reminiscent of observations in several bacterial taxa for genes with high expression levels. Such findings indicate a previously undiscovered codon usage adaptation associated with the chromosomal core information that likely operates to improve bacterial fitness. We present a comprehensive model illustrating the central findings described here, discussed in the context of the changes occurring during the evolution of a multipartite prokaryote genome.IMPORTANCE Bacterial genomes usually include many thousands of genes which are expressed with diverse spatial-temporal patterns and intensities. A well-known evidence is that highly expressed genes, such as the ribosomal and other translation-related proteins (RTRPs), have accommodated their codon usage to optimize translation efficiency and accuracy. Using a bioinformatic approach, we identify core-genes sets with different ancestries, and demonstrate that selection processes that optimize codon usage are not restricted to RTRPs but extended at a genome-wide scale. Such findings highlight, for the first time, a previously undiscovered adaptation strategy associated with the chromosomal-core information. Contrasted with the translationally more adapted genes, singletons (i.e., exclusive genes, including those of the plasmidome) appear as the gene pool with the less-ameliorated codon usage in the lineage. A comprehensive summary describing the inter- and intra-replicon heterogeneity of codon usages in a complex prokaryote genome is presented.

Musical hallucinations and their relation with epilepsy.

Musical hallucinations are poorly understood phenomena. Their relation with epilepsy was first described over a century ago, but never systematically explored. We, therefore, reviewed the literature, and assessed all descriptions of musical hallucinations attributed to epileptic activity. Our search yielded 191 articles, which together describe 983 unique patients, with 24 detailed descriptions of musical hallucinations related to epilepsy. We also describe six of our own patients. Based on the phenomenological descriptions and neurophysiological data, we distinguish four subgroups of epilepsy-related musical hallucination, comprising auras/ictal, inter-ictal and post-ictal phenomena, and phenomena related to brain stimulation. The case descriptions suggest that musical hallucinations in epilepsy can be conceptualised as lying on a continuum with other auditory hallucinations, including verbal auditory hallucinations, and-notably-tinnitus. To account for the underlying mechanism we propose a Bayesian model involving top-down and bottom-up prediction errors within the auditory network that incorporates findings from EEG and MEG studies. An analysis of phenomenological characteristics, pharmacological triggers, and treatment effects suggests wider ramifications for understanding musical hallucinations. We, therefore, conclude that musical hallucinations in epilepsy open a window to understanding these phenomena in a variety of conditions.

Modulation of neuroplasticity-related targets following stress-induced acute escape deficit.

Understanding resilience is a major challenge to improve current pharmacological therapies aimed at complementing psychological-based approaches of stress-related disorders. In particular, resilience is a multi-factorial construct where the complex network of molecular events that drive the process still needs to be resolved. Here, we exploit the acute escape deficit model, an animal model based on exposure to acute unavoidable stress followed by an escape test, to define vulnerable and resilient phenotypes in rats. Hippocampus and prefrontal cortex (PFC), two of the brain areas most involved in the stress response, were analysed for gene expression at two different time points (3 and 24 h) after the escape test. Total Brain-Derived Neurotrophic Factor (BDNF) was highly responsive in the PFC at 24-h after the escape test, while expression of BDNF transcript IV increased in the hippocampus of resistant animals 3 h post-test. Expression of memory enhancers like Neuronal PAS Domain Protein 4 (Npas4) and Activity-regulated cytoskeleton-associated protein (Arc) decreased in a time- and region-dependent fashion in both behavioural phenotypes. Also, the memory inhibitor Protein Phosphatase 1 (Ppp1ca) was increased in the hippocampus of resilient rats at 3 h post-test. Given the importance of neurotrophic factors and synaptic plasticity-related genes for the development of appropriate coping strategies, our data contribute to an additional step forward in the comprehension of the psychobiology of stress and resiliency.

Incidence of sight-threatening diabetic retinopathy in people with Type 2 diabetes mellitus and numbers needed to screen: a systematic review.

AIM: To investigate the incidence of sight-threatening diabetic retinopathy in Type 2 diabetes mellitus. BACKGROUND: In most countries, yearly or biennial screening intervals for diabetic retinopathy in people with Type 2 diabetes are recommended. Fewer screening sessions reduce the effort required of people with Type 2 diabetes and reduce healthcare costs. METHODS: We conducted a search of PubMed, Embase, Web of Science and the COCHRANE Library for studies published betweeen 1 January 2000 and 1 January 2017. Eligible studies were those that included general populations of >100 people with Type 2 diabetes mellitus. Additional study population criteria were absence of moderate diabetic retinopathy or more severe diabetic retinopathy at last screening session and at least two gradable retinal screening sessions. Outcomes of interest in the included studies were moderate and severe non-proliferative diabetic retinopathy (R2), proliferative diabetic retinopathy (R3) or maculopathy (M1), collectively known as sight-threatening or referable diabetic retinopathy. RESULTS: A total of 17 studies were included. In people with Type 2 diabetes without or with only mild diabetic retinopathy at baseline, the average incidence rates of sight-threatening diabetic retinopathy were ~1 per 100 person-years and ~8 per 100 person-years, respectively. The average numbers needed to screen to detect one case of sight-threatening diabetic retinopathy were 175 and 19 in people without and with mild retinopathy at last screening, respectively. CONCLUSION: In people with Type 2 diabetes without retinopathy at last screening, the incidence of severe sight-threatening retinopathy at the subsequent screening session was low. In people with mild retinopathy, progression to sight-threatening diabetic retinopathy was nearly 10-fold higher. This review supports lengthening of the screening interval of patients with Type 2 diabetes without retinopathy at last screening session.

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus.

The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease-oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow-up: strategies in care planning, self-management and medication-related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self-management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.

[Brua and psychiatry: A pilot study among Dutch-Antillean patients in the Netherlands]. / Brua en psychiatrie: een pilotstudie onder patiënten in Nederland afkomstig van de voormalige Nederlandse Antillen.

BACKGROUND: Individuals native to Aruba, Bonaire, and Curaçao, the abc islands of the former Netherlands Antilles, often attribute their complaints to brua, although they seldom discuss this with health professionals. This may have a negative influence on the therapeutic relationship and diagnostic processes.
AIM: To explore the role of brua in the illness perception of psychiatric patients in the Netherlands who were originally from the abc islands.
METHOD: A random sample of patients under treatment at Parnassia Psychiatric Institute in The Hague were interviewed with the aid of a semi-structured questionnaire.
RESULTS: Of the 18 psychiatric patients interviewed, 10 (56%) believed in brua, and 3 (17%) considered it the cause of their disease. Although none of the interviewees admitted to an active involvement in brua, 8 (44%) had been in touch with a traditional healer and 9 (50%) possessed artifacts meant to provide protection against evil. Regarding the usefulness of discussing brua with health professionals, opinions were divided.
CONCLUSION: Psychiatric patients in the Netherlands native to the abc islands are all knowledgeable of brua, with more than half of them believing in it. Despite the fear and shame that people often experience, making brua fit for discussion in clinical practice would improve the relationship between health professional and patient, yielding further opportunities for diagnosis and treatment.

Circulating serum miR-223-3p and miR-16-5p as possible biomarkers of early rheumatoid arthritis.

Small non-coding RNAs have emerged as possible biomarkers for various diseases including autoimmune diseases. A number of studies have demonstrated that the expression of specific microRNAs (miRNAs) is dysregulated in rheumatoid arthritis (RA). So far, all studies on miRNAs in RA patients have been performed using either microarray or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Compared to RT-qPCR and microarray analyses, next-generation sequencing (NGS) allows the genome-wide analysis of small RNAs and the differentiation between miRNAs that differ by a single nucleotide. The application of NGS to the analysis of small RNAs circulating in sera of RA patients has not been reported. This study provides a global overview of the circulating small RNAs in the sera of RA patients and healthy subjects and identifies differences between these groups using NGS. Several classes of small RNAs, including hY RNA-derived fragments, tRNA-derived fragments and miRNAs, were determined. Differentially expressed individual small RNAs were verified by RT-qPCR. The levels of two miRNAs, miR-223-3p and miR-16-5p, were significantly lower in the sera from early RA patients than in those from established RA patients and healthy controls. In contrast, the serum level of miR-16-5p was higher in patients with established RA than in healthy control samples. These miRNAs may not only serve as biomarkers, but may also shed more light on the pathophysiology of RA.

The frail older person does not exist: development of frailty profiles with latent class analysis.

BACKGROUND: A fundamental issue in elderly care is targeting those older people at risk and in need of care interventions. Frailty is widely used to capture variations in health risks but there is no general consensus on the conceptualization of frailty. Indeed, there is considerable heterogeneity in the group of older people characterized as frail. This research identifies frailty profiles based on the physical, psychological, social and cognitive domains of functioning and the severity of the problems within these domains. METHODS: This research was a secondary data-analysis of older persons derived from The Older Person and Informal Caregiver Minimum Dataset. Selected respondents were 60 years and older (n = 43,704; 59.6% female). The following variables were included: self-reported health, cognitive functioning, social functioning, mental health, morbidity status, and functional limitations. Using latent class analysis, the population was divided in subpopulations that were subsequently discussed in a focus group with older people for further validation. RESULTS: We distinguished six frailty profiles: relatively healthy; mild physically frail; psychologically frail; severe physically frail; medically frail and multi-frail. The relatively healthy had limited problems across all domains. In three profiles older people mostly had singular problems in either the physical or psychological domain and the severity of the problems differed. Two remaining profiles were multidimensional with a combination of problems that extended to the social and cognitive domains. CONCLUSIONS: Our research provides an empirical base for meaningful frailty profiles. The profiles showed specific patterns underlying the problems in different domains of functioning. The heterogeneous population of frail older people has differing needs and faces different health issues that should be considered to tailor care interventions. Evaluation research of these interventions should acknowledge the heterogeneity of frailty by profiling.