Androgens Modulate the Immune Profile in a Mouse Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is associated with a low-grade inflammation, but it is unknown how hyperandrogenism, the hallmark of PCOS, affects the immune system. Using a PCOS-like mouse model, it is demonstrated that hyperandrogenism affects immune cell populations in reproductive, metabolic, and immunological tissues differently in a site-specific manner. Co-treatment with an androgen receptor antagonist prevents most of these alterations, demonstrating that these effects are mediated through androgen receptor activation. Dihydrotestosterone (DHT)-exposed mice displayed a drastically reduced eosinophil population in the uterus and visceral adipose tissue (VAT). A higher frequency of natural killer (NK) cells and elevated levels of IFN-γ and TNF-α are seen in uteri of androgen-exposed mice, while NK cells in VAT and spleen displayed a higher expression level of CD69, a marker of activation or tissue residency. Distinct alterations of macrophages in the uterus, ovaries, and VAT are also found in DHT-exposed mice and can potentially be linked to PCOS-like traits of the model. Indeed, androgen-exposed mice are insulin-resistant, albeit unaltered fat mass. Collectively, it is demonstrated that hyperandrogenism causes tissue-specific alterations of immune cells in reproductive organs and VAT, which can have considerable implications on tissue function and contribute to the reduced fertility and metabolic comorbidities associated with PCOS.

Alpha 7 Nicotinic Acetylcholine Receptor Agonist PHA 568487 Reduces Acute Inflammation but Does Not Affect Cardiac Function or Myocardial Infarct Size in the Permanent Occlusion Model.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematologic parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h or at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

Effects of proactive healthcare on pain, physical and activities of daily living functioning in vulnerable older adults with chronic pain: a pragmatic clinical trial with one- and two-year follow-up.

PURPOSE: To investigate the changes in pain, physical and activities of daily living (ADL) functioning in vulnerable older adults with chronic pain after proactive primary care intervention. METHODS: This study was embedded in a prospective, pragmatic, matched-control multicenter trial at 19 primary care practices in Sweden, with proactive medical and social care (Intervention Group, IG, n = 134) in comparison with usual care (Control Group, CG, n = 121). Patients with chronic pain, defined as pain experienced longer than 3 months, were included in this subgroup analysis. Data on pain aspects, physical and ADL functioning were collected in the questionnaires at baseline, one- and two-year follow-up (FU-1 and FU-2). Data on prescribed pain medications was collected by local health authorities. RESULTS: Mean age was 83.0 ± 4.7 years with almost equal representation of both genders. From baseline until FU-2, there were no significant within-group or between-group changes in pain intensity. Small adjustments of pain medication prescriptions were made in both groups. Compared to FU-1, the functional changes were more measurable at FU-2 as fewer participants had impaired physical functioning in IG (48.4%) in comparison to CG (62.6%, p = 0.027, Effect Size φ = 0.14). Higher scores of ADL-staircase (more dependent) were found in both groups (p < 0.01, Effect Size r = 0.24 in CG and r = 0.16 in IG). CONCLUSION: Vulnerable older adults with chronic pain seemed to remain physical and ADL functioning after proactive primary care intervention, but they may need tailored strategies of pain management to improve therapeutic effects. TRIAL REGISTRATION: ClinicalTrials.gov 170608, ID: NCT03180606.

The use and application of intensive care unit diaries: An instrumental multiple case study.

AIMS AND OBJECTIVES: The study aim was to explore the use of an Intensive Care Unit (ICU) diary within four different ICUs units in Sweden and thereby contribute to practice guidelines regarding the structure, content and use of an ICU diary. BACKGROUND: ICU diaries are used to aid psychological recovery among critical care patients, but differences remain in diary writing both within and across countries. Few studies have focused on the combined views and experiences of ICU patients, family members and nursing staff about the use of ICU diaries. DESIGN: An instrumental multiple case study design was employed. METHODS: Three focus groups interviews were carried out with 8 former patients and their family members (n = 5) from the research settings. Individual interviews were carried out with 2 patients, a family member and a nurse respectively. Observations, field notes, documentary analysis and conversations with nursing staff were also conducted. Consolidated criteria for reporting qualitative research (COREQ) was followed. RESULTS: The qualitative findings firstly consisted of a matrix and descriptive text of the four ICU contexts and current practices. This highlighted that there were similarities regarding the aims and objectives of the diaries. However, differences existed across the case study sites about how the ICU diary was developed and implemented. Namely, the use of photographs and when to commence a diary. Second, a thematic analysis of the qualitative data regarding patients' and family members' use of the ICU diary, resulted in four themes: i) the diary was used to take in and fully understand the situation; ii) the diary was an opportunity to assimilate warm, personalised and human care; iii) the diary was used to manage existential issues; and iv) the diary was a tool in daily activities. CONCLUSIONS: Analysis of the instrumental case study data led to the identification of core areas for inclusion in ICU diary practice guidelines.

Thanks for hearing me: key elements of primary care according to older patients.

Objective: When organising healthcare and planning for research to improve healthcare, it is important to include the patients' own perceptions. Therefore, the aim was to explore older patients' views on what is important concerning their current care and possible future interventions in a primary care setting.Design: A qualitative design with individual interviews was used. Analysis through latent content analysis.Setting: Seven Swedish primary care centres.Subjects: Patients (n 30) aged >75 years, connected to elder care teams in primary healthcare.Results: Three categories, consisting of 14 sub-categories in total, were found, namely: Care characterised by easy access, continuity and engaged staff builds security; Everyday life and Plans in late life. The overarching latent theme Person-centred care with easy access, continuity and engaged staff gave a deeper meaning to the content of the categories and sub-categories.Conclusion: It is important to organise primary care for older people through conditions which meet up with their specific needs. Our study highlights the importance of elder care teams facilitating the contact with healthcare, ensuring continuity and creating conditions for a person-centred care. There were variations regarding preferences about training and different views on conversations about end-of-life, which strengthens the need for individualisation and personal knowledge. This study also exemplifies qualitative individual interviews as an approach to reach older people to be part of a study design and give input to an upcoming research intervention, as the interviews contribute with important information of value in the planning of the Swedish intervention trial Secure and Focused Primary Care for Older pEople (SAFE).

In this qualitative interview study, the three categories Care characterised by easy access, continuity and engaged staff builds security; Everyday life and Plans in late life with underlying sub-categories describe the older patients' views on what is important in their current care and possible future interventions in a Swedish primary care setting.The latent theme 'Person-centred care with easy access, continuity and engaged staff' was formed to give a deeper meaning to the content of the categories and sub-categories.Having a permanent care contact with a responsible nurse in an elder care team and a personal doctor (most often a general practitioner) over time seems important for vulnerable older patients with high risk of hospitalisation.The study suggests qualitative individual interviews as an approach to increase older peoples' participation in future clinical complex study designs.

A Bispecific, Tetravalent Antibody Targeting Inflammatory and Pruritogenic Pathways in Atopic Dermatitis.

Inhibition of IL-4/IL-13 signaling has dramatically improved the treatment of atopic dermatitis (AD). However, in many patients, clinical responses are slow to develop and remain modest. Indeed, some symptoms of AD are dependent on IL-31, which is only partially reduced by IL-4/IL-13 inhibition. Thus, there is an unmet need for AD treatments that concomitantly block IL-4/IL-13 and IL-31 pathways. We engineered NM26-2198, a bispecific tetravalent antibody designed to accomplish this task. In reporter cell lines, NM26-2198 concomitantly inhibited IL-4/IL-13 and IL-31 signaling with a potency comparable with that of the combination of an anti-IL-4Rα antibody (dupilumab) and an anti-IL-31 antibody (BMS-981164). In human PBMCs, NM26-2198 inhibited IL-4-induced upregulation of CD23, demonstrating functional binding to FcγRII (CD32). NM26-2198 also inhibited the secretion of the AD biomarker thymus and activation-regulated chemokine (TARC) in blood samples from healthy human donors. In male cynomolgus monkeys, NM26-2198 exhibited favorable pharmacokinetics and significantly inhibited IL-31-induced scratching at a dose of 30 mg/kg. In a repeat-dose, good laboratory practice toxicology study in cynomolgus monkeys, no adverse effects of NM26-2198 were observed at a weekly dose of 125 mg/kg. Together, these results justify the clinical investigation of NM26-2198 as a treatment for moderate-to-severe AD.

Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche.

Immunotherapies with antibody-drug-conjugates (ADC) and CAR-T cells, targeted at tumor surface antigens (surfaceome), currently revolutionize clinical oncology. However, target identification warrants a better understanding of the surfaceome and how it is modulated by the tumor microenvironment. Here, we decode the surfaceome and endocytome and its remodeling by hypoxic stress in glioblastoma (GBM), the most common and aggressive brain tumor in adults. We employed a comprehensive approach for global and dynamic profiling of the surfaceome and endocytosed (endocytome) proteins and their regulation by hypoxia in patient-derived GBM cultures. We found a heterogeneous surface-endocytome profile and a divergent response to hypoxia across GBM cultures. We provide a quantitative ranking of more than 600 surface resident and endocytosed proteins, and their regulation by hypoxia, serving as a resource to the cancer research community. As proof-of-concept, the established target antigen CD44 was identified as a commonly and abundantly expressed surface protein with high endocytic activity. Among hypoxia induced proteins, we reveal CXADR, CD47, CD81, BSG, and FXYD6 as potential targets of the stressed GBM niche. We could validate these findings by immunofluorescence analyses in patient tumors and by increased expression in the hypoxic core of GBM spheroids. Selected candidates were finally confronted by treatment studies, showing their high capacity for internalization and ADC delivery. Importantly, we highlight the limited correlation between transcriptomics and proteomics, emphasizing the critical role of membrane protein enrichment strategies and quantitative mass spectrometry. Our findings provide a comprehensive understanding of the surface-endocytome and its remodeling by hypoxia in GBM as a resource for exploration of targets for immunotherapeutic approaches in GBM.

Orthostatic Hypotension and Cognitive Function in Individuals 85 Years of Age: A Longitudinal Cohort Study in Sweden.

Orthostatic hypotension (OH) is more common in the elderly and associated with increased mortality. However, its implications for 85-year-olds are not known. In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH. Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality. OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.

Lifestyle changes are burdensome with my body broken by pain and obesity: patients' perspectives after pain rehabilitation.

BACKGROUND: Despite the existing evidence regarding the interrelated relationship between pain and obesity, knowledge about patients' perspectives of this relationship is scarce, especially from patients with chronic pain and obesity after completing Interdisciplinary Pain Rehabilitation Program (IPRP). AIMS: This qualitative study expands the understanding of patients' perspectives on how chronic pain and obesity influence each other and how the two conditions affect the ability to make lifestyle changes. METHOD: A purposive sample of patients with Body Mass Index (BMI) ≥ 30 kg/m2 and who had completed an IPRP were recruited for individual semi-structured interviews. The transcribed interviews were analysed using latent content analysis and a pattern of theme and categories was constructed based on the participants' perspectives. RESULTS: Sixteen patients (aged 28-63 years, 11 female, BMI 30-43 kg/m2) shared their experiences of chronic pain, obesity and lifestyle changes after IPRP. The analysis revealed one overall theme (lifestyle changes are burdensome with a body broken by both pain and obesity) and four categories (pain disturbing days and nights worsens weight control, pain-related stress makes lifestyle changes harder, a painful and obese body intertwined with negative emotions and the overlooked impact of obesity on chronic pain). Most participants perceived that their pain negatively impacted their obesity, but they were uncertain whether their obesity negatively impacted their pain. Nevertheless, the participants desired and struggled to make lifestyle changes. CONCLUSION: After IPRP, patients with chronic pain and obesity perceived difficulties with self-management and struggles with lifestyle changes. They experienced a combined burden of the two conditions. Their perspective on the unilateral relationship between pain and obesity differed from the existing evidence. Future tailored IPRPs should integrate nutritional interventions and address the knowledge gaps as well.

Safety culture development in the construction industry: The case of a safety park in Sweden.

The problem of occupational accidents in the construction industry has necessitated a focus on proactive measures such as safety management programs. An example of this is safety parks, i.e. facilities where employees and managers from different construction companies can participate in site-specific activities and train in safety-related matters in a realistic context. Two specific focus areas are often present within these types of safety management programs: hands-on safety training and safety culture development as being within the purview of management. The purpose of this article is to investigate the developers' intentions with the park in relation to safety culture development. Twenty interviews were conducted with experts in the area of health and safety. Results indicate that the safety park can contribute as a mirror for the companies own operations, with new information and knowledge of how work can be performed with safety being prioritized, to developing communication regarding safety-related matters, and finally the stations at the park may initiate a translation process as to how the lessons learned at the park can be applied to the participants' own workplaces. All in all, the activities at the park can be said to be normative in nature, i.e. the developers seemingly have a desire to steer the safety culture development in a certain direction. There is a need for further research focusing on the concept of safety culture in these types of programs and, more broadly, in relation to its intended industry-wide effects.

An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin.

Mesothelin (MSLN) is an attractive immuno-oncology target, but the development of MSLN-targeting therapies has been impeded by tumor shedding of soluble MSLN (sMSLN), on-target off-tumor activity, and an immunosuppressive tumor microenvironment. We sought to engineer an antibody-based, MSLN-targeted T-cell engager (αMSLN/αCD3) with enhanced ability to discriminate high MSLN-expressing tumors from normal tissue, and activity in the presence of sMSLN. We also studied the in vivo antitumor efficacy of this molecule (NM28-2746) alone and in combination with the multifunctional checkpoint inhibitor/T-cell co-activator NM21-1480 (αPD-L1/α4-1BB). Cytotoxicity and T-cell activation induced by NM28-2746 were studied in co-cultures of peripheral blood mononuclear cells and cell lines exhibiting different levels of MSLN expression, including in the presence of soluble MSLN. Xenotransplant models of human pancreatic cancer were used to study the inhibition of tumor growth and stimulation of T-cell infiltration into tumors induced by NM28-2746 alone and in combination with NM21-1480. The bivalent αMSLN T-cell engager NM28-2746 potently induced T-cell activation and T-cell mediated cytotoxicity of high MSLN-expressing cells but had much lower potency against low MSLN-expressing cells. A monovalent counterpart of NM28-2746 had much lower ability to discriminate high MSLN-expressing from low MSLN-expressing cells. The bivalent molecule retained this discriminant ability in the presence of high concentrations of sMSLN. In xenograft models, NM28-2746 exhibited significant tumor suppressing activity, which was significantly enhanced by combination therapy with NM21-1480. NM28-2746, alone or in combination with NM21-1480, may overcome shortcomings of previous MSLN-targeted immuno-oncology drugs, exhibiting enhanced discrimination of high MSLN-expressing cell activity in the presence of sMSLN.

Children's independent mobility during dark hours: a scoping review.

Introduction: Independent mobility is every child's right and has implications for their health, wellbeing, and development. This scoping review addresses children's needs and experiences of light conditions in their everyday outdoor life. The review examines peer-reviewed scientific literature that analyses associations between different light conditions and children's independent mobility (CIM) during dark hours. Methods: By formulating a Boolean search string, including terms related to children independent mobility, light and outdoor environment, five scientific databases were searched. The search resulted in 67 eligible papers that were analyzed through an inductive, thematic analysis. Results: Four overarching themes representing the researched topics of the effects of light conditions with importance for CIM during dark hours were identified: (1) physical activity (PA) and active travel, (2) outdoor activities and place use, (3) safety perception, and (4) outdoor risks. The findings highlight that darkness constitutes a major obstacle for CIM, and that fear of darkness is common among children. It restricts the degree of CIM and influences children's safety perception as well as how they navigate through public places outdoors. The findings show that the type and design of outdoor settings during dark hours and children's familiarity with places during daytime could play a role in the degree of CIM after dark. The presence of outdoor lighting is related to children's increased PA and active travel, and outdoor lighting seems to also influence children's place use and interaction with the environment. The presence and extent of outdoor lighting and lighting quality may play a role in children's safety perception, which in turn can influence CIM. Discussion: The findings suggest that promoting CIM during dark hours might not only contribute to the accumulation of children's PA, confidence, and skills, but also support mental health. The understanding of children's perspectives on the quality of outdoor lighting needs to be deepened to support CIM. Highlighting the child perspective would aid the development of current recommendations for outdoor lighting and the implementation of the Agenda 2030 of ensuring healthy lives and promoting wellbeing for all at all ages, and making cities inclusive, safe, resilient and sustainable throughout the day and seasons.

Design of antibody variable fragments with reduced reactivity to preexisting anti-drug antibodies.

Upon reformatting of an antibody to single-chain variable fragment format, a region in the former variable/constant domain interface of the heavy chain becomes accessible for preexisting (PE) anti-drug antibody (ADA) binding. The region exposed because of this reformatting contains a previously hidden hydrophobic patch. In this study, mutations are introduced in this region to reduce PE ADA reactivity and concomitantly reduce the hydrophobic patch. To enhance our understanding of the importance of individual residues in this region with respect to PE ADA reactivity, a total of 50 molecules for each of two antibodies against different tumor-associated antigens were designed, produced, and characterized by an arsenal of biophysical methods. The aim was to identify suitable mutations that reduce, or completely eliminate, PE ADA reactivity to variable fragments, without compromising biophysical and pharmacodynamic properties. Computational methods were used to pinpoint key residues to mutate and to evaluate designed molecules in silico, in order to reduce the number of molecules to produce and characterize experimentally. Mutation of two threonine residues, Thr101 and Thr146 in the variable heavy domain, proved to be critical to eliminate PE ADA reactivity. This may have important implications in optimizing early drug development for antibody fragment-based therapeutics.

The importance of structural, situational, and psychological factors for involving hunters in the adaptive flyway management of geese.

Adaptive flyway management of superabundant geese is emerging as a strategy to reduce damage to agricultural crops and other ecosystem disservices, while also ensuring sustainable use and conservation objectives. Given the calls for intensified hunting as part of flyway management in Europe, we need to increase the understanding of structural, situational, and psychological factors important for goose hunting among hunters. Our survey data, retrieved in southern Sweden, showed a higher potential to intensify hunting among goose hunters than other hunters. In response to hypothetical policy instruments (including regulations, collaborative, and others), hunters declared a minor increase in their intention to hunt geese, with the greatest expected increase among goose hunters should the hunting season be extended. Situational factors (e.g., access to hunting grounds) were associated with goose hunting (frequency, bag size, and intention to increase hunting). In addition, controlled motivation (derived from external pressures or to avoid guilt) and more importantly autonomous motivation (due to hunting being enjoyable or valuable) were along with goose hunter identity positively associated with goose hunting. Hunters' involvement in flyway management may be encouraged by using policy instruments to remove situational barriers and facilitate their autonomous motivation.

Exploring safety culture research in the construction industry.

BACKGROUND: Despite numerous regulatory initiatives to improve health and safety in the construction industry, it still ranks as one of the most accident-prone industries worldwide. A dedicated focus on safety culture has been suggested as a complement to laws, regulations and management systems. OBJECTIVE: This article explores safety culture research conducted in the construction industry, with the aim to provide insight into the specific themes that tend to be in focus as well as what theoretical and methodological approaches that tend to be favored. METHODS: Searches in scientific databases were conducted twice. In a first attempt, searches resulted in 54 hits but only two articles fit the scope of the study. A revision of the search phrase resulted in 124 hits. Ultimately, 17 articles fit the scope of the study and were included. The content of the articles was analyzed and sorted thematically. RESULTS: The results show that four themes are prevalent in the existing literature: 1) unique challenges entail a need for situated applications, 2) models developed to operationalize safety culture, 3) measuring safety culture, and 4) safety management and leadership as key factors. CONCLUSION: Although research focusing on the construction industry has come to favor certain study designs and definitions of safety culture, further research may be enriched by broadening the theoretical and methodological perspectives. Specifically, researchers should conduct more in-depth qualitative studies that take the complexity of the industry into account, including the interpersonal relations between the actors involved.

Understanding and overcoming obstacles in adaptive management.

Adaptive management (AM) is widely promoted to improve management of natural resources, yet its implementation is challenging. We show that obstacles to the implementation of AM are related not only to the AM process per se but also to external factors such as ecosystem properties and governance systems. To overcome obstacles, there is a need to build capacities within the AM process by ensuring adequate resources, management tools, collaboration, and learning. Additionally, building capacities in the legal and institutional frames can enable the necessary flexibility in the governance system. Furthermore, in systems experiencing profound changes in wildlife populations, building such capacities may be even more critical as more flexibility will be needed to cope with increased uncertainty and changed environmental conditions.

Frail community-dwelling older persons' everyday lives and their experiences of rehabilitation - a qualitative study.

BACKGROUND: The number of older persons with frailty is increasing, and rehabilitation to improve the consequences of frailty are important for both the individual and society. However, the perspective of older persons themselves in research and planning of interventions is scarce. AIM: The aim of this study was to describe frail older persons' everyday lives and their experiences and views of rehabilitation. MATERIAL AND METHODS: Twenty older persons were interviewed, and analyses were performed using a qualitative content analysis method. RESULTS: The two main categories were 'Frailty impacts everyday lifé and 'Experiences and perceptions of rehabilitation'. The participants described that they had to adapt their everyday lives in line with their health conditions. They all used strategies and were dependent on support in their activities of daily living. Their social network had decreased. All participants strived to stay active and independent, and wanted rehabilitation and support from professionals, experiencing decreased access to rehabilitation. CONCLUSIONS AND SIGNIFICANCE: Frail older persons are a vulnerable group who often need support in everyday life. There is room for improvement when it comes to helping frail older persons to stay active and facilitate participation in both individual and group interventions.

Cognitive impairment in daily life (CID): A double-faced instrument to detect changes and impairments in activities of daily living for people with suspected cognitive impairment.

BACKGROUND: Assessment of cognitive function and its consequences for activities of daily living is an important part of a dementia evaluation. To describe patients' functional impairment accurately, a feasible instrument is needed. The Cognitive Impairment in Daily Life (CID) is an instrument developed with that purpose. AIM: To describe and compare self- and proxy-reported difficulties in everyday life in patients undergoing a dementia investigation, measured by CID. A secondary aim was to compare the results between those who were diagnosed with dementia versus those without dementia. METHOD: Self- and proxy-reported data using CID in 77 cases in dementia investigations. Of those, 32 were diagnosed with dementia and were compared to those without dementia (n = 45). Descriptive statistics. RESULTS: When comparing self-reported and proxy-reported activity problems, most activities differed significantly. Proxies reported more difficulties than patients did. When comparing no dementia and dementia groups, significant differences were shown regarding initiative, planning and performance but not for memory and attention estimated by the patient themselves. Proxies differed significantly from patients in all tasks. CONCLUSION: Overall, proxies reported that patients had more difficulties than patients reported themselves. The CID seems to be usable in dementia investigations and the results highlight the importance of involving both patients and relatives.

Building a precision medicine infrastructure at a national level: The Swedish experience.

Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.