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1.	Cearns, Micah, et al. (författare) Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach - CORRIGENDUM. 2022 Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 221:2 Tidskriftsartikel (refereegranskat)
2.	Herrera-Rivero, Marisol, et al. (författare) Exploring the genetics of lithium response in bipolar disorders. 2023 Ingår i: Research square. Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
3.	Herrera-Rivero, Marisol, et al. (författare) Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder. 2023 Ingår i: Research square. Annan publikation (övrigt vetenskapligt/konstnärligt)abstract The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
4.	Locke, Adam E, et al. (författare) Genetic studies of body mass index yield new insights for obesity biology. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401 Tidskriftsartikel (refereegranskat)abstract Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
5.	Middeldorp, Christel M., et al. (författare) The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects 2019 Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300 Tidskriftsartikel (refereegranskat)abstract The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
6.	Amare, Azmeraw, et al. (författare) Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder. 2023 Ingår i: Research square. - : Research Square Platform LLC. Tidskriftsartikel (refereegranskat)abstract Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<��.
7.	Amare, Azmeraw T, et al. (författare) Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. 2023 Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261 Tidskriftsartikel (refereegranskat)abstract Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
8.	Amare, Azmeraw T, et al. (författare) Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study. 2018 Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74 Tidskriftsartikel (refereegranskat)abstract Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
9.	Andersson, Henrik, et al. (författare) Ethics education to support ethical competence learning in healthcare : an integrative systematic review 2022 Ingår i: BMC Medical Ethics. - : BioMed Central. - 1472-6939. ; 23 Forskningsöversikt (refereegranskat)abstract Background: Ethical problems in everyday healthcare work emerge for many reasons and constitute threats to ethi- cal values. If these threats are not managed appropriately, there is a risk that the patient may be inflicted with moral harm or injury, while healthcare professionals are at risk of feeling moral distress. Therefore, it is essential to support the learning and development of ethical competencies among healthcare professionals and students. The aim of this study was to explore the available literature regarding ethics education that promotes ethical competence learning for healthcare professionals and students undergoing training in healthcare professions.Methods: In this integrative systematic review, literature was searched within the PubMed, CINAHL, and PsycInfo databases using the search terms ‘health personnel’, ‘students’, ‘ethics’, ‘moral’, ‘simulation’, and ‘teaching’. In total, 40 arti- cles were selected for review. These articles included professionals from various healthcare professions and students who trained in these professions as subjects. The articles described participation in various forms of ethics education. Data were extracted and synthesised using thematic analysis.Results: The review identified the need for support to make ethical competence learning possible, which in the long run was considered to promote the ability to manage ethical problems. Ethical competence learning was found to be helpful to healthcare professionals and students in drawing attention to ethical problems that they were not previ- ously aware of. Dealing with ethical problems is primarily about reasoning about what is right and in the patient’s best interests, along with making decisions about what needs to be done in a specific situation.Conclusions: The review identified different designs and course content for ethics education to support ethical competence learning. The findings could be used to develop healthcare professionals’ and students’ readiness and capabilities to recognise as well as to respond appropriately to ethically problematic work situations.
10.	Andersson, Åsa, et al. (författare) Adverse events in nursing : a retrospective study of reports of patient and relative experiences 2015 Ingår i: International Nursing Review. - : International Council of Nurses. - 0020-8132 .- 1466-7657. ; 62:3, s. 377-385 Tidskriftsartikel (refereegranskat)abstract Patient safety is an important global issue. While it is well known that patients can suffer from adverse events in nursing care, there is a lack of knowledge as to how they experience them. The aim was to examine adverse events in nursing care as they are experienced by patients and relatives. This was a retrospective study taking both a qualitative and quantitative approach. It was based on data regarding 242 adverse events in nursing care, as reported by patients and relatives to Sweden's Medical Responsibility Board, content analysis was used to analys the reports. Patients' and relatives' experiences were analysed into four categories of adverse events, as concerning participation, clinical judgement, nursing intervention and the essentials of care. The reports were classified by the Medical Responsibility Board, without a standardized system. The adverse events reported were few in number and were reported by patients and relatives only. Lack of participation has negative consquences and contributes to adverse events. Adverse events occur through missed care as well as through carer errors. Nurses need to improve their skills that support patient participation. Patient participation needs to be incorporated into nurses' duties. Resources for patients to participate in their own care needs to be a priority underpinning policy-making in health systems. Nursing education systems need to teach students about the value and benefits of involving patients in their care.
11.	Andersson, Åsa, et al. (författare) Factors contributing to serious adverse events in nursing homes 2018 Ingår i: Journal of Clinical Nursing. - : John Wiley & Sons. - 0962-1067 .- 1365-2702. ; 27:1-2, s. e354-e362 Tidskriftsartikel (refereegranskat)abstract AIMS AND OBJECTIVES: The aim of this study was to identify the most common serious adverse events that occurred in nursing homes and their most frequent contributing factors to contribute to improvement of safe nursing care. BACKGROUND: There is a need to improve safe nursing care in nursing homes. Residents are often frail and vulnerable with extensive needs for nursing care. A relatively minor adverse event in nursing care can cause serious injury that could have been preventable. DESIGN: This was a retrospective study, with a total sample of data regarding adverse events (n=173) in nursing homes, concerning nursing care reported by health care providers in Sweden to the Health and Social Care Inspectorate. The reports were analysed with content analysis and the frequencies of the adverse events, and their contributing factors, were described with descriptive statistics. RESULTS: Medication errors, falls, delayed or inappropriate intervention and missed nursing care caused the vast majority (89%) of the serious adverse events. A total of 693 possible contributing factors were identified. The most common contributing factors were 1) lack of competence 2) incomplete, or lack of documentation 3) teamwork failure 4) and inadequate communication. CONCLUSIONS: The contributing factors frequently interacted yet they varied between different groups of serious adverse events. The resident's safety depends on the availability of staff's competence as well as adequate documentation about the resident's condition. Lack of competence was underestimated by health care providers. RELEVANCE TO CLINICAL PRACTICE: Registered Nurses and assistant nurses need to have awareness of contributing factors to adverse events in nursing care. A holistic approach to improve patient safety in nursing homes requires competence of the staff, safe environments as well as resident's and relative's participation. This article is protected by copyright. All rights reserved.
12.	Bolhuis, Koen, et al. (författare) Disentangling Heterogeneity of Childhood Disruptive Behavior Problems Into Dimensions and Subgroups 2017 Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier. - 0890-8567 .- 1527-5418. ; 56:8, s. 678-686 Tidskriftsartikel (refereegranskat)abstract Objective: Irritable and oppositional behaviors are increasingly considered as distinct dimensions of oppositional defiant disorder. However, few studies have explored this multidimensionality across the broader spectrum of disruptive behavior problems (DBPs). This study examined the presence of dimensions and distinct subgroups of childhood DBPs, and the cross-sectional and longitudinal associations between these dimensions.Method: Using factor mixture models (FMMs), the presence of dimensions and subgroups of DBPs was assessed in the Generation R Study at ages 6 (n = 6,209) and 10 (n = 4,724) years. Replications were performed in two population-based cohorts (Netherlands Twin Registry, n = 4,402, and Swedish Twin Study of Child and Adolescent Development, n = 1,089) and a clinical sample (n = 1,933). We used cross-lagged modeling in the Generation R Study to assess cross-sectional and longitudinal associations between dimensions. DBPs were assessed using mother-reported responses to the Child Behavior Checklist.Results: Empirically obtained dimensions of DBPs were oppositional behavior (age 6 years), disobedient behavior, rule-breaking behavior (age 10 years), physical aggression, and irritability (both ages). FMMs suggested that one-class solutions had the best model fit for all dimensions in all three population-based cohorts. Similar results were obtained in the clinical sample. All three dimensions, including irritability, predicted subsequent physical aggression (range, 0.08-0.16).Conclusion: This study showed that childhood DBPs should be regarded as a multidimensional phenotype rather than comprising distinct subgroups. Incorporating multidimensionality will improve diagnostic accuracy and refine treatment. Future studies need to address the biological validity of the DBP dimensions observed in this study; herein lies an important opportunity for neuro-imaging and genetic measures.
13.	Coombes, Brandon J, et al. (författare) Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study. 2021 Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89 Tidskriftsartikel (refereegranskat)abstract Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
14.	Elmqvist, Carina, et al. (författare) Patients' strategies to deal with their situation at an emergency department 2015 Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 29:1, s. 145-151 Tidskriftsartikel (refereegranskat)abstract IntroductionThe care in the emergency department (ED) is often characterised by high standards of efficiency and rapid treatment and the encounter between patient and staff can be described as both short and fragmented. Research within this field has mostly been performed with quantitative measurements and patients are both satisfied and vulnerable in their care at an ED. There is a lack of qualitative studies about patient's strategies to deal with their situation. AimThe aim was to describe patient's strategies for dealing with their situation at an ED. MethodsSecondary analysis has been made of 13 qualitative interviews grounded in a lifeworld perspective. The interviews were analysed by qualitative content analysis. ResultsThe results showed that patients' strategies to deal with the situation at the ED are passive or active. The passive strategy is being patient and the active strategies varied in terms of having hidden tactics, using visible tactics and using families as support. ConclusionThese findings increase the importance of gaining knowledge about these strategies so that the staff at the ED can support the patients so they do not have to use them.
15.	Falk, A. -C, et al. (författare) Barriers in achieving patient participation in the critical care unit 2019 Ingår i: Intensive & Critical Care Nursing. - : Elsevier. - 0964-3397 .- 1532-4036. ; 51, s. 15-19 Tidskriftsartikel (refereegranskat)abstract Objectives: Patient participation in healthcare is important for optimizing treatment outcomes and for ensuring satisfaction with care. Therefore, this study aims to identify barriers to patient participation in the critical care unit, as identified by critical care nurses. Design and settings: Qualitative data were collected in four focus group interviews with 17 nurses from two separate hospitals. The interviews were analyzed using qualitative content analysis. Findings: The results show three main categories: nurse's attitude toward caring, the organization of the critical care unit and the patient's health condition. Conclusion: Barriers for patient participation in the ICU were found and this lead to a power imbalance between patient and nurse. In contrast to other care settings, this imbalance could be a consequence of the critical care organization and its degree of highly specialized care. The clinical application of our results is that these barriers should be considered when implementing patient participation in such a highly technological care situation as a critical care unit. (C) 2018 Elsevier Ltd. All rights reserved.
16.	Frank, Catharina, 1961-, et al. (författare) Ethics rounds in the ambulance service: a qualitative evaluation 2024 Ingår i: BMC Medical Ethics. - : Springer Nature. - 1472-6939. ; 25:1 Tidskriftsartikel (refereegranskat)abstract BackgroundIt is a common ethical challenge for ambulance clinicians to care for patients with impaired decision-making capacities while assessing and determining the degree of decision-making ability and considering ethical values. Ambulance clinicians’ ethical competence seems to be increasingly important in coping with such varied ethical dilemmas. Ethics rounds is a model designed to promote the development of ethical competence among clinicians. While standard in other contexts, to the best of our knowledge, it has not been applied within the ambulance service context. Thus, the aim of this study was to describe ambulance clinicians’ experiences of participating in ethics rounds.MethodsThis was a qualitative descriptive study, evaluating an intervention. Data were collected through sixteen interviews with ambulance clinicians who had participated in an intervention involving ethics rounds. The analysis was performed by use of content analysis.ResultsTwo themes describe the participants’ experiences: (1) Reflecting freely within a given framework, and (2) Being surprised by new insights. The following categories form the basis of the themes; 1a) Gentle guidance by the facilitator, 1b) A comprehensible structure, 2a) New awareness in the face of ethical problems, and 2b) Shared learning through dialogue.ConclusionIncorporating structured ethics rounds seems to create a continuous development in ethical competence that may improve the quality of care in the ambulance service. Structured guidance and facilitated group reflections offer ambulance clinicians opportunities for both personal and professional development. An important prerequisite for the development of ethical competence is a well-educated facilitator. Consequently, this type of ethics rounds may be considered a useful pedagogical model for the development of ethical competence in the ambulance service.
17.	Frank, Catharina, 1961-, et al. (författare) Healthcare professionals’ perceptions of their work with patients of working age with heart failure 2018 Ingår i: Nordic journal of nursing research. - : SAGE Publications Ltd. - 2057-1585 .- 2057-1593. ; 38:3, s. 160-166 Tidskriftsartikel (refereegranskat)abstract There is a lack of knowledge about healthcare professionals’ perspectives on rehabilitation in relation to heart failure. Still, collaboration between different professionals can impact patients. The purpose of this study was to describe healthcare professionals’ perceptions of their work with patients of working age with heart failure. The sample population consisted of six nurses, one physiotherapist and one cardiologist. One individual interview and two focus-group interviews were conducted. The interviews were analyzed using qualitative content analysis. Three descriptive categories were constructed: ‘the impact of heart failure on patients’ life situations’, ‘heart failure service’, and ‘patients’ process of returning to work’. To support patients, healthcare professionals need to find ways to combine patients’ personal needs with protocol-driven care. © The Author(s) 2017.
18.	Frank, Catharina, 1961-, et al. (författare) Older patients’ autonomy when cared for at emergency departments 2022 Ingår i: Nursing Ethics. - : Sage Publications. - 0969-7330 .- 1477-0989. ; 29:5, s. 1266-1279 Tidskriftsartikel (refereegranskat)abstract Background: Older patients in emergency care often have complex needs and may have limited ability to make their voices heard. Hence, there are ethical challenges for healthcare professionals in establishing a trustful relationship to determine the patient’s preferences and then decide and act based on these pref- erences. With this comes further challenges regarding how the patient’s autonomy can be protected and promoted.Aim: To describe nurses’ experiences of dealing with older patients’ autonomy when cared for in emergency departments (EDs).Research design: This study adopted reflective lifeworld theory and a phenomenological design. Participants and research context: A total of 13 open-ended interviews were performed with nurses working at two EDs in Sweden.Ethical considerations: The study was reviewed by the Ethical Advisory Board in South East Sweden and conducted according to the Declaration of Helsinki. All participants gave consent.Findings: Nurses’ experiences of dealing with older patients’ autonomy in EDs are characterized by moving in a conflicting uphill struggle, indicating obscure thoughts on how patient autonomy can be protected in an ethically challenging context. The phenomenon is further described with its meaning constituents: ‘Being hampered by prioritization under stress’, ‘Balancing paternalism and patient autonomy’, ‘Making decisions without consent in the patient’s best interests’ and ‘Being trapped by notions of legitimate care needs’.Conclusion: Stressful work conditions and lacking organizational strategies in EDs contribute to nurses maintaining unjustified paternalistic care, regardless of the patient’s ability and medical condition, and questioning who has legitimacy for participating in decisions about care. The nurses’ protection and pro- motion of older patients’ autonomy is dependent on the opportunity, ability and willingness to create a patient relationship where the patient’s voice and preferences are valued as important. Consequently, strategies are needed to improve patient autonomy in EDs based on the idea of ‘relational autonomy’.
19.	Frank, Catharina, et al. (författare) Patient participation in emergency care : A pheonomenographic analysis of caregivers´conception. 2009 Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 18:18, s. 2555-2562 Tidskriftsartikel (refereegranskat)
20.	Frank, Catharina, 1961-, et al. (författare) Patient participation in emergency care- A phenomenographic study based on patients' lived experience 2009 Ingår i: International emergency nursing. - : Elsevier. - 1755-599X .- 1878-013X. ; 17:1, s. 15-22 Tidskriftsartikel (refereegranskat)abstract International guidelines promote patient participation in health care. When patients participate in their care they experience greater satisfaction. Studies have shown that patients in emergency departments express dissatisfaction with their care, and it was therefore important to study how patients understand and conceptualize their participation. The aim of this study was to describe patients’ qualitatively different conceptions of patient participation in their care in an emergency department. Based on a lifeworld perspective, nine interviews were performed with patients in an emergency department. The phenomenographic analysis shows that participation by patients means contact with the emergency department staff in three categories of conceptions: being acknowledged; struggling to become involved; and having a clear space. The different conceptions of patient participation give us a deeper understanding of how patients may experience their care, and this result may provide a foundation for developing nursing practice and the quality of health care in line with international guidelines.
21.	Frank, Catharina, et al. (författare) Patient participation in the emergency department : an evaluation using a specific instrument to measure patient participation (PPED 2011 Ingår i: Journal of Advanced Nursing. - : Blackwell publishing. - 0309-2402 .- 1365-2648. ; 67:4, s. 728-735 Tidskriftsartikel (refereegranskat)abstract Aim: This study aimed at evaluating patient participation from the perspective of patients who received care in emergency departments, with a separate examination of the relationship between participation and age, sex, education and priority level.Background: International and national guidelines encourage patient participation. High patient participation is required to ensure a high quality of care. No studies evaluating patient participation at an emergency department have been published.Methods: An evaluating study, with the Patient Participation Emergency Department questionnaire, was conducted at emergency departments in Sweden. A consecutive sample of 356 patients participated. Data was collected in 2008: participants were 49% women and with an average age of 56 years. The statistical methods used were Student’s t-test, one-way ANOVA and Spearman correlation.Results: The results revealed that patients experienced good requirement such as time and information for participation. Mutual participation demonstrated a reasonable level but patient participation is low in two dimensions (Fight for participation, Participation in getting basic needs satisfied). Young and well‑educated patients fought more to participate in their care and gained less attention for basic needs than older and less well‑educated patients.Conclusions: Patient participation in a mutual care situation between patients and healthcare professionals requires further improvement to ensure that patients are satisfied and do not have to struggle and fight in order to participate in their care.
22.	Frank, Catharina, 1961-, et al. (författare) Questionnarie for patient participation in emergency departments : development and psychometric testing 2011 Ingår i: Journal of Advanced Nursing. - : Blackwell Publishing Ltd. - 0309-2402 .- 1365-2648. ; 67:3, s. 643-651 Tidskriftsartikel (refereegranskat)abstract Aim The aim of the study was to develop and test the psychometric properties of a patient participation questionnaire in emergency departments. Background Patient participation is an important indicator of quality of healthcare. International and national health care policy guidelines promote patient participation. While patients cared for in emergency departments generally express dissatisfaction with their care, a review of the literature fails to reveal any scientifically tested research instruments for assessing patient participation from the perspective of patients. Methods A methodological study was conducted involving a convenience sample of 356 patients recently cared for in emergency departments in Sweden. Data was collected in 2008 and the analyses performed were tested for construct and criterion validity and also homogeneity and stability reliability. Results A 17- item questionnaire was developed. Two separate factor analyses revealed a distinct four- factor solution which was labelled: fight for participation, requirement for participation, mutual participation and participating in getting basic needs satisfied. Criterion validity presented showed 9 out of 20 correlations above 0.30 and of those 3 moderate correlations of 0.62, 0.63 and 0.70. Cronbach’s alpha coefficient ranged from 0.63 - 0.84 and test- retest varied between 0.59 and 0.93. Conclusion The results signify evidence of acceptable validity and reliability and the questionnaire makes it possible to evaluate patient participation in ED caring situations. In addition it produces data which is useable by a diverse range of healthcare professionals.
23.	Frank, Catharina, et al. (författare) Social insurance administrative officers’ perceptions of their assignment and problematic issues in their work with heart failure clients in the sick-leave and rehabilitation process 2015 Ingår i: Nordic Social Work Research. - 2156-857X .- 2156-8588. ; 5:2, s. 173-188 Tidskriftsartikel (refereegranskat)abstract This article explores social insurance administrative officers’ (AOs’) perceptions of the sick-leave process for heart failure clients. The work situation and the sick-leave process for people with heart failure tend to be complex and problematic. The problems are often caused by a lack of understanding from professionals, such as social insurance AOs. The study draws on two focus group interviews with social insurance AOs from two different social insurance agencies. The interviews were guided by an open approach, and analysis was performed on the interviews’ manifest content through a qualitative content analysis. The findings demonstrate that the AOs were concerned about the clients’ ability to return to work, but they were hindered in fulfilling their duties through insufficient collaboration with physicians and unclear sickness certificates. There seems to be a gap between the AOs’ assignment and their ability to make well-founded decisions about their clients’ ability to work. This can have consequences for the individual who lives with heart failure. In the sociopolitical agenda of Sweden, this can have consequences for the development of collaboration between AOs and the medical experts who provide the foundations for decisions about work ability of the client with heart failure.
24.	Frank, Catharina, 1961-, et al. (författare) Staff strategies for dealing with care situations at an emergency department 2020 Ingår i: Scandinavian Journal of Caring Sciences. - : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 34:4, s. 1038-1044 Tidskriftsartikel (refereegranskat)abstract IntroductionOvercrowding is a common international problem at Emergency Departments often due to those patients get recommendations or referrals from other health professionals to seek care at the emergency department. Crowding brings with it an amount of adverse consequences for both patients and staff, and knowledge about staff’s strategies of dealing with this caring situation is limited.AimThe aim of the present study was thus to describe staffs’ strategies to deal with the caring situations at an emergency department.MethodSecondary analysis has been made of 18 qualitative interviews grounded in a lifeworld perspective. The interviews were analysed by qualitative content analysis.FindingsThe results showed that the staff at the ED worked in twofold directions using both proactive and reactive strategies in order to deal with the care situation when caring for patients at ED. The proactive strategy is optimising conditions, controlling patient flow and being boundary. The reactive strategy is about customising the conversation and holding an open approach.ConclusionIn conclusion, the proactive strategy is to make what you decided for unseen circumstances. The reactive strategy is then about less anticipation of the encounter, waiting for the patient to act and react to it.ImplicationThe result can have implications with respect to developing and improving care at crowded Emergency departments. Knowledge about strategies creates a fundament for developing visible sustainable structure for patient flow in making work patient safety for patients, staff and organisation.
25.	Frank, Catharina, 1961- (författare) Tillfället gör delaktighet : Patienters och vårdares erfarenheter av patientdelaktighet på akutmottagning. En deskriptiv, metodutvecklande och utvärderande studie 2010 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Aim: The overall aim of the present thesis was to examine, develop and evaluate patient participation in emergency department (ED) for promoting the relief of suffering for patients in care relations, from the perspective of patients and caregivers.Method: The explorative studies (I, II) were based on reflective lifeworld approach and analyzed by phenomenographic method. Data were collected from interviews by patients (9) and caregivers (11) about their conception of patient participation in ED. The methodological study (III) performed analyses and were tested for content, construct and criterion validity as well as homogeneity and stability reliability. The sample for study (III, IV) consisted of 356 patients consecutively cared for in EDs in Sweden. In the evaluating study (IV) the questionnaire Patient Participation Emergency Department (PPED) was used. The statistical methods handled were Student’s t-test, one-way ANOVA and Spearman correlation.Findings: The patients’ conception of patient participation means: being acknowledged; struggling to become involved; and having a clear space (I). The caregivers’ conceptions of patient participation can be divided into three different descriptive categories: Caregivers offer the opportunity for participation, Patients demand participation and Mutual participation (II). A 17- item questionnaire was developed. Two separate factor analyses revealed a distinct four- factor solution which was labelled: Fight for participation, Requirement for participation, Mutual participation and Participating in getting basic needs satisfied. Criterion validity presented showed 9 out of 20 correlations equal or above 0.30. Cronbach’s alpha coefficient ranged from 0.63 - 0.84 and test- retest varied between 0.59 and 0.93(III).The results show that patient participation is low in two dimensions (Fight for participation, Participation in getting basic needs satisfied), reasonable in one dimension (Mutual participation), and high in one dimension, Requirement for participation (IV).Conclusions: Participation does occur on occasion when the circumstances are right despite international and national guidelines that lay down the need for patient participation. Patient participation in EDs is perceived when patients are in contact with caregivers and there is space for collaboration in situations of consistency. However, patient participation cannot be offered in a one-sided caring action. In collaboration patient participation contributes to the relief of suffering in the process of health and patients participate when they are allowed to be the point of departure for caring. However, the results point to a lack of strategy for patient participation and for increased patient participation to take place improvements in external organization requirements are required. The results indicate an amplified clarity in how patient participation can be understood for EDs, in education and community and a scientific tested instrument has made it possible to evaluate patient participation.
26.	Gustavell, Tina, et al. (författare) Symptoms and self-care following pancreaticoduodenectomy : Perspectives from patients and healthcare professionals - Foundation for an interactive ICT application 2017 Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 26, s. 36-41 Tidskriftsartikel (refereegranskat)abstract PurposePoor prognosis and a problematic recovery period after pancreaticoduodenectomy means that patients may benefit from early detection of symptoms and support for self-management. Interactive Information and Communication Technology tools can be used for this purpose, but the content needs to be relevant to patients as well as healthcare professionals. To facilitate development of the content of an application for this purpose, the aim of this study was to explore common symptoms and self-care in the first six months after pancreaticoduodenectomy, as identified by patients and healthcare professionals.MethodData were collected through individual interviews with patients (n = 14), along with two focus group interviews and one individual interview with healthcare professionals (n = 10). Data were analysed using qualitative content analysis.ResultsCommon symptoms after surgery were those related to eating, bowel function and emotional wellbeing, along with fatigue and pain. Some self-care activities and advice were mentioned in the interviews. The patients often experienced a lack of advice on self-care at discharge.ConclusionsThe results render knowledge of the symptoms it is important to be aware of and to assess regularly after pancreaticoduodenectomy. The results also contribute to knowledge about specific self-care related to these symptoms, even though it was not extensively described, and further research is needed to define evidence-based self-care advice.
27.	Haugg, Amelie, et al. (författare) Can we predict real-time fMRI neurofeedback learning success from pretraining brain activity? 2020 Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 41:14, s. 3839-3854 Tidskriftsartikel (refereegranskat)abstract Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large inter-individual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pretraining functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pretraining activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain-based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.
28.	Haugg, Amelie, et al. (författare) Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis. 2021 Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 237 Tidskriftsartikel (refereegranskat)abstract Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing.
29.	Hou, Liping, et al. (författare) Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. 2016 Ingår i: Lancet (London, England). - 1474-547X. ; 387:10023, s. 1085-1093 Tidskriftsartikel (refereegranskat)abstract Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.
30.	Hou, Liping, et al. (författare) Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder. 2016 Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94 Tidskriftsartikel (refereegranskat)abstract Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
31.	Hälleberg Nyman, Maria, 1968-, et al. (författare) Patients' Perspective on Participation in Care With or Without the Support of a Smartphone App During Radiotherapy for Prostate Cancer : Qualitative Study 2017 Ingår i: JMIR mhealth and uhealth. - : JMIR Publications. - 2291-5222. ; 5:7 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Patients with prostate cancer are often cared for as outpatients during radiotherapy, which can be an aggravating circumstance for patient participation. There is a need to evaluate whether an interactive smartphone app could enable participation in care, specifically during treatment for prostate cancer. The interactive app (Interaktor) used in this study is developed in codesign with patients and health care professionals; it includes daily reports of symptoms, a risk assessment model, evidence-based self-care advice, along with the provision of immediate access to clinicians.OBJECTIVE: The aim of this study was to explore how patients with prostate cancer perceived their participation with or without the support of the smartphone app during radiotherapy.METHODS: A total of 28 prostate cancer patients receiving adjuvant radiotherapy were interviewed about their perceived participation in their own care. All the patients interviewed in this study participated in an intervention study where the control group received standard care that comprised having access to a contact nurse to turn to with any concerns during their treatment. In addition to standard care, the patients in the intervention group received the app downloaded in a smartphone. The patients' age ranged between 57 and 77 years; 17 patients used the smartphone app. The interviews were analyzed with directed qualitative content analysis.RESULTS: The four dimensions of patient participation, which include mutual participation, fight for participation, requirement for participation, and participation in getting basic needs satisfied, were confirmed as valid perspectives in the interviews with the patients with prostate cancer, irrespective of whether they used the smartphone app. However, the patients who had used the smartphone app described it as a facilitating factor, especially for mutual participation.CONCLUSIONS: Using innovative ways to communicate with patients, such as an interactive app for symptom management with contact with health care in real time, can successfully help achieve increased patient participation in care.
32.	Jacob, Mina A, et al. (författare) Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults: A Worldwide Meta-analysis: The GOAL-Initiative. 2022 Ingår i: Neurology. - 1526-632X. ; 98:6 Tidskriftsartikel (refereegranskat)abstract There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional healthcare services. To study the global distribution of risk factors, causes and 3-month mortality of young ischemic stroke patients, by performing a patient data meta-analysis form different cohorts worldwide.We did a pooled analysis of individual patient data from cohort studies which included consecutive ischemic stroke patients aged 18-50 years. We studied differences in prevalence of risk factors and causes between different ethnic and racial groups, geographic regions and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression.We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Blacks (hypertension, 52.1%; diabetes, 20.7%) and Asians (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often cause of stroke in high-income countries (HICs; both p<0.001), whereas ''other determined stroke'' and ''undetermined stroke'' were higher in low and middle-income countries (LMICs; both p<0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (OR 2.49; 95% CI 1.42-4.36).The ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial, and regional differences in incidence of ischemic stroke. Our results also visualize the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve healthcare facilities in LMICs.
33.	Jelenkovic, Aline, et al. (författare) Associations between birth size and later height from infancy through adulthood : An individual based pooled analysis of 28 twin cohorts participating in the CODATwins project 2018 Ingår i: Early Human Development. - : Elsevier BV. - 0378-3782 .- 1872-6232. ; 120, s. 53-60 Tidskriftsartikel (refereegranskat)abstract Background: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. Aim: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. Results: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14–4.25 cm and 0.18–0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. Conclusion: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight.
34.	Kalman, Janos L, et al. (författare) Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study. 2019 Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75 Tidskriftsartikel (refereegranskat)abstract Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
35.	Kelsoe, John, et al. (författare) Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study. 2023 Ingår i: Research square. Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
36.	Lewczuk, Piotr, et al. (författare) Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. 2018 Ingår i: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. - : Informa UK Limited. - 1814-1412. ; 19:4, s. 244-328 Tidskriftsartikel (refereegranskat)abstract In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
37.	Ma, Zuheng, et al. (författare) Evidence for Presence and Functional Effects of Kv1.1 Channels in beta-Cells: General Survey and Results from mceph/mceph Mice 2011 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4 Tidskriftsartikel (refereegranskat)abstract Background: Voltage-dependent K+ channels (Kv) mediate repolarisation of beta-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K+ channel in this process is however unclear. We tested for presence of Kv1.1 in different species and tested for a functional role of Kv1.1 by assessing pancreatic islet function in BALB/cByJ (wild-type) and megencephaly (mceph/mceph) mice, the latter having a deletion in the Kv1.1 gene. Methodology/Principal Findings: Kv1.1 expression was detected in islets from wild-type mice, SD rats and humans, and expression of truncated Kv1.1 was detected in mceph/mceph islets. Full-length Kv1.1 protein was present in islets from wildtype mice, but, as expected, not in those from mceph/mceph mice. Kv1.1 expression was localized to the beta-cell population and also to alpha-and delta-cells, with evidence of over-expression of truncated Kv1.1 in mceph/mceph islets. Blood glucose, insulin content, and islet morphology were normal in mceph/mceph mice, but glucose-induced insulin release from batch-incubated islets was (moderately) higher than that from wild-type islets. Reciprocal blocking of Kv1.1 by dendrotoxin-K increased insulin secretion from wild-type but not mceph/mceph islets. Glucose-induced action potential duration, as well as firing frequency, was increased in mceph/mceph mouse beta-cells. This duration effect on action potential in beta-cells from mceph/mceph mice was mimicked by dendrotoxin-K in beta-cells from wild-type mice. Observations concerning the effects of both the mceph mutation, and of dendrotoxin-K, on glucose-induced insulin release were confirmed in pancreatic islets from Kv1.1 null mice. Conclusion/Significance: Kv1.1 channels are expressed in the beta-cells of several species, and these channels can influence glucose-stimulated insulin release.
38.	Ou, Anna H., et al. (författare) Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study 2024 Ingår i: TRANSLATIONAL PSYCHIATRY. - 2158-3188. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
39.	Rantala, Andreas, et al. (författare) Older patients’ perceptions of the Swedish ambulance service : A qualitative exploratory study 2023 Ingår i: Presented at the 4th Global Conference on Emergency Nursing & Trauma Care, Gothenburg, Sweden, November 9-11, 2023. Konferensbidrag (refereegranskat)
40.	Rantala, Andreas, et al. (författare) Older patients’ perceptions of the Swedish ambulance service: A qualitative exploratory study 2023 Ingår i: Australasian Emergency Care. - : Elsevier BV. - 2588-994X .- 2589-1375. Tidskriftsartikel (refereegranskat)abstract BackgroundAs worldwide life expectancy increases, the Swedish Ambulance Service is likely to be affected by the demographic shift towards a larger proportion of older persons. An older population tends to increase the demand for ambulances, indicating a need to illuminate older patients’ perspective. Thus, the aim of this study was to explore older patients’ perceptions of the Swedish Ambulance Service.MethodsThis interview study employed a descriptive qualitative design with a phenomenographic approach in accordance with Dahlgren and Fallsberg.ResultsThree main descriptive categories emerged to describe the underlying conceptions in the interviews; A double-edged encounter, Trust is created by perceived competence, and Safety through accessibility in vulnerable situations.ConclusionOlder patients described trust in ambulance clinicians as a prerequisite for feeling safe enough to share their feelings and allow a bodily examination. However, they also criticized the care provided because they questioned the need for certain actions.
41.	Ried, Janina S., et al. (författare) A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape 2016 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7 Tidskriftsartikel (refereegranskat)abstract Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
42.	Schandl, Anna, et al. (författare) Patient participation in the intensive care unit 2017 Ingår i: Intensive & Critical Care Nursing. - : Elsevier. - 0964-3397 .- 1532-4036. ; 42, s. 105-109 Tidskriftsartikel (refereegranskat)abstract Objective: Patient participation in healthcare is important for optimizing treatment outcomes and for ensuring satisfaction with care. The purpose of the study wasto explore critical care nurses' perceptions of patient participation for critically ill patients. Design and settings: Qualitative data were collected in four separate focus group interviews with 17 nurses from two hospitals. The interviews were analyzed using qualitative content analysis. Findings: Initially, the nurses stated that patient participation in the intensive care unit (ICU) was dependent on the patient's health condition and consciousness. However, during the interviews three descriptive categories emerged from their experience, that is: passive patient participation, one-way communication and nurse/patient interaction. Conclusion: In the ICU, the possibilities for patient participation in nursing care are not only dependent on the patient's health condition but also on the nurse's ability to include patients in various care actions despite physical and/or mental limitations. When the patient is not able to participate, nurses strive to achieve participation through relatives' knowledge and/or other external sources of information. (c) 2017 Elsevier Ltd. All rights reserved.
43.	Semb, Gunvor, et al. (författare) A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management. 2017 Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
44.	Sheppard, Neil C, et al. (författare) Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens. 2014 Ingår i: International Immunology. - : Oxford University Press (OUP). - 1460-2377 .- 0953-8178. ; 26:10, s. 531-538 Tidskriftsartikel (refereegranskat)abstract Polyethyleneimine (PEI) is an organic polycation used extensively as a gene- and DNA vaccine delivery reagent. Although the DNA targeting activity of PEI is well documented, its immune activating activity is not. We recently reported that PEI has robust mucosal adjuvanticity when administered intranasally with glycoprotein antigens. Here we show that PEI has strong immune activating activity after systemic delivery. PEI administered subcutaneously with viral glycoprotein (HIV-1 gp140) enhanced antigen-specific serum IgG production in the context of mixed Th1/Th2-type immunity. PEI elicited higher titers of both antigen binding and neutralizing antibodies than alum in mice and rabbits, and induced an increased proportion of antibodies reactive with native antigen. In an intraperitoneal model, PEI recruited neutrophils followed by monocytes to the site of administration, and enhanced antigen uptake by antigen presenting cells. The Th bias was modulated by PEI activation of the Nlrp3 inflammasome, however its global adjuvanticity was unchanged in Nlrp3-deficient mice. When co-formulated with CpG oligodeoxynucleotides, PEI adjuvant potency was synergistically increased and biased towards a Th1-type immune profile. Taken together these data support the use of PEI as a versatile systemic adjuvant platform with particular utility for induction of secondary structure-reactive antibodies against glycoprotein antigens.
45.	Shungin, Dmitry, et al. (författare) New genetic loci link adipose and insulin biology to body fat distribution. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378 Tidskriftsartikel (refereegranskat)abstract Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
46.	Slettmyr, Anna, et al. (författare) Open visting hours : A part of patient centred care in the intensive care unit? 2022 Ingår i: Intensive & Critical Care Nursing. - : Elsevier. - 0964-3397 .- 1532-4036. ; 71 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
47.	Slettmyr, Anna, 1969-, et al. (författare) The core of patient-participation in the Intensive Care Unit : The patient’s views 2022 Ingår i: Intensive & Critical Care Nursing. - : Elsevier. - 0964-3397 .- 1532-4036. ; 68 Tidskriftsartikel (refereegranskat)abstract Objectives: Patient participation is an established concept in public welfare. However, reports of the phe-nomenon of patient participation during intensive care from the patient’s point of view are scarce.Therefore, the aim of this study was to explore the meaning of patient participation in the intensive careunit from the patient’s perspective.Research design: A qualitative design was used for the purpose of the study with a purposive convenientsample of nine adult patients with memories from their intensive care stay.Method: Data was collected through individual interviews and analysed using a phenomenologicalhermeneutical method.Findings: The results of our study show a variety of meanings and degrees of participation that continu-ously move on a sliding scale from acting as a captain to feelings of being on an isolated island. Patientparticipation varied due to individual cognitive abilities and individual preferences, and the caregiver’sattention altered between the body and the person through the continuum of care.Conclusion: Patient participation during ICU care is more than participation in decision-making processesor direct patient care decisions. An understanding of the concept participation from the individual patientis necessary to support person centred care and the patient’s relatives play an important role in duringthe entire care process.
48.	Sundberg, Kay, et al. (författare) Early detection and management of symptoms using an interactive smartphone application (Interaktor) during radiotherapy for prostate cancer 2017 Ingår i: Supportive Care in Cancer. - : Springer. - 0941-4355 .- 1433-7339. ; 25:7, s. 2195-2204 Tidskriftsartikel (refereegranskat)abstract Purpose: Patients undergoing radiotherapy for prostate cancer suffer from a variety of symptoms which influence health-related quality of life. We have developed an application (Interaktor) for smartphones and tablets for early detection, reporting and management of symptoms, and concerns during treatment for prostate cancer. The study evaluates the effect on symptom burden and quality of life when using the application for real-time symptom assessment and management during radiotherapy for localized prostate cancer.Methods: A non-randomized controlled study was used at two university hospitals in Sweden where 64 patients constituted a control group and 66 patients made up an intervention group. The intervention group was asked to report symptoms via the application daily during the treatment as well as 3 weeks after. The EORTC QLQ-C30 and its module PR25 and the Sense of Coherence questionnaire were administered at three time points in both groups.Results: The intervention group rated significantly lower levels of fatigue and nausea at the end of radiotherapy. Moreover, they had significantly less burden in emotional functioning, insomnia, and urinary-related symptoms at the end of treatment as well as 3 months later compared with the control group. In the multivariate analyses, with education and sense of coherence as covariates, the intervention group still significantly rated emotional functioning (p = 0.007), insomnia (p = 0.017), and urinary-related symptoms (p = 0.008) as better than the control group at T2.Conclusion: Study findings suggest that Interaktor could be an efficient mHealth tool for facilitating supportive care needs during cancer treatment.
49.	Veldwijk, Jorien, et al. (författare) How psychological distance of a study sample in discrete choice experiments affects preference measurement : a colorectal cancer screening case study 2019 Ingår i: Patient Preference and Adherence. - : DOVE MEDICAL PRESS LTD. - 1177-889X. ; 13, s. 273-282 Tidskriftsartikel (refereegranskat)abstract Purpose: The purpose of this study was to investigate to what extent the outcomes of a discrete choice experiment (DCE) differ based on respondents' psychological distance to the decision at hand. Methods: A DCE questionnaire regarding individuals' preferences for genetic screening for colorectal cancer (CRC) within the Dutch national CRC screening program was created. The DCE contained nine D-efficient designed choice tasks and was distributed among two populations that differ in their psychological distance to the decision at hand: 1) a representative sample of the Dutch general population aged 55-65 years, and 2) a sample of Dutch individuals who attended an information appointment regarding colonoscopies following the detection of blood in their stool sample in the CRC screening program. The DCE consisted of four attributes related to the decision whether to participate in genetic screening for CRC: 1) risk of being genetically predisposed, 2) risk of developing CRC, 3) frequency of follow-up colonoscopies, and 4) survival. Direct attribute ranking, dominant decision-making behavior, and relative importance scores (based on panel MIXL) were compared between the two populations. Attribute level estimates were compared with the Swait and Louviere test. Results: The proportion of respondents who both ranked survival as the most important attribute, and showed dominant decision-making behavior for this attribute, was significantly higher in the screened population compared to the general population. The relative importance scores of the attributes significantly differed between populations. Finally, the Swait and Louviere test also revealed significant differences in attribute level estimates in both the populations. Conclusion: The study outcomes differed between populations depending on their psychological distance to the decision. This study shows the importance of adequate sample selection; therefore, it is advocated to increase attention to study sample selection and reporting in DCE studies.
50.	Vogelezang, Suzanne, et al. (författare) Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits. 2020 Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10 Tidskriftsartikel (refereegranskat)abstract The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

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