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Abstract Background In order to estimate the prevalence and understand the spread of SARS-CoV-2 in Sweden, the Public Health Agency of Sweden, with support from the Swedish Armed Forces, conducted a series of point prevalence surveys between March and December 2020. Methods Sampling material and instructions on how to perform self-sampling of the upper respiratory tract were delivered to the homes of the participants. Samples were analysed by real-time PCR, and the participants completed questionnaires regarding symptoms. Findings The first survey in the Stockholm region in March 2020 included 707 participants and showed a SARS-CoV-2 prevalence of 2.5%. The following five surveys, performed on a national level, with between 2461 and 2983 participants, showed SARS-CoV-2 prevalences of 0.9% (April), 0.3% (May), 0.0% (August), 0.0% (September), and 0.7% (December). All positive cases who responded to questionnaires reported experiencing symptoms that occurred from 2 weeks before the date of sampling up to and including the date of sampling. Interpretation None of the individuals shown to be PCR-positive were asymptomatic at the time of sampling or in the 14 days prior to sampling. This is in contrast to many other surveys in which a substantial proportion of positive cases have been reported to be asymptomatic. Our surveys demonstrate a decreasing ratio between notified cases and the observed prevalence throughout the year, in line with increasing testing capacity and the consecutive inclusion of all symptomatic individuals in the case definition for testing.

This paper analyses disfluencies and ungrammatical expressions in the speech of 11-13-year-old Finnish-speaking boys with ASD (N = 5) and with neurotypical development (N = 6). The ASD data were from authentic group therapy sessions and neurotypical data from teacher-led group discussions. The proportion of disfluencies and ungrammatical expressions was greater in the speech of participants with ASD (26.4%) than in the control group (15.5%). Furthermore, a qualitative difference was noted: The ASD group produced long, complex disfluent turns with word searches, self-repairs, false starts, fillers, prolongations, inconsistent syntactic structures and grammatical errors, whereas in the control group, the disfluencies were mainly fillers and sound prolongations. The disfluencies and ungrammatical expressions occurring in the ASD participants' interactions also caused comprehension problems.

The testing effect, defined as the positive effect of "retrieval practice" (i.e., self-testing) on long-term memory retention relative to other ways to support learning, is a robust empirical phenomenon. Despite substantial scientific evidence for the testing effect, less is known about its effectiveness in relation to individual differences in cognitive ability. In the present study, we examine whether the effect of retrieval practice is beneficial independent of cognitive ability using behavioral and brain imaging data. In a within-subject design, upper-secondary students learned Swahili-Swedish word pairs through retrieval practice and study. The testing effects were assessed at a direct test and for a subsample after 1- and 4-weeks retention intervals, respectively. Another subsample performed the 1-week retention test during functional MRI (fMRI). Memory retention was analyzed in relation to an educationally relevant composite score dividing participants into low, intermediate, and high cognitive-ability groups. We provide behavioral evidence that the testing effect is independent of cognitive ability. The fMRI findings confirmed a general effectiveness of retrieval practice by showing that brain regions associated with successful retrieval of conceptual representations and semantic processing were more strongly engaged after retrieval practice in all cognitive-ability groups. It is argued that the advantages of retrieval practice should be conveyed to all teachers and students.

Purpose: Longitudinal patient-partnered experiences may promote medical student empathy, but evaluation of such programs is limited. The aim of this study was to compare areas of learning among first-year medical students randomized to a patient-centered track (PCT) or traditional track (TT) longitudinal clinical experience. Methods: PCT students (n = 24) were paired with 2 patients and a physician to participate in their patients’ care across multiple settings. TT students (n = 56) were paired with a physician preceptor and participated in caring for a variety of patients in a single setting. This qualitative study used a phenomenological approach to template analysis, examining and comparing student reflective essays for areas of learning. Results: Three domains of learning emerged: 1) Focus of learning (biomedical, patient-centered); 2) Roles and relationships (clinical skills, relationship-building, teaching from preceptor and patients); and 3) Context of care (health systems science, interprofessional care). PCT students described patient-centered learning, relationship-building, and patients’ role as teachers. In contrast, TT students emphasized biomedical learning, clinical skills development, and teaching from physician preceptors. Conclusions: Longitudinal patient-partnered clinical experiences provide rich opportunities for preclinical students to cultivate empathy and develop patient-centered values.

Abstract Background In order to reduce work-related upper limb disorders, the Swedish Work Environment Authority introduced an occupational health surveillance targeting hand-intensive work. A process model, aimed at supporting the employers as well as the occupational health service provider (i.e., ergonomist) in the work process with the occupational health surveillance, was developed. The objective of this qualitative study was to explore ergonomists’ experiences of the execution of occupational health surveillance for hand-intensive work when following the novel process model as well as factors influencing the execution. Methods Semi-structured individual interviews were conducted with ten ergonomists on one occasion regarding their experience of following the work process. Qualitative content analysis with an inductive approach was used for analyzing the data. Results The ergonomists’ experiences were summarized in one theme “A joint roadmap supporting a participatory process” and two categories “Clear structure provided by the components” and “The process influenced by collaboration and context”. The ergonomists valued being guided by the systematics of the model, which provided structure and clarity in their work. Factors affecting the execution were related to communication deficiencies and uncertainties regarding expectations between different roles and functions (e.g., ergonomists and contact person, lack of information to workers). Additional factors, for instance, companies’ routines and the ergonomist’s intra-organizational support, such as access to IT-resources, could also affect the process. Conclusions The findings reveal that this process model facilitates the ergonomists’ work and cooperation with a client company. However, the process model needs to be developed and accompanied by a guideline with information related to the process, including e.g., description of a start-up meeting and of the roles/functions of the involved parties.

Abstract Background Longitudinal, real-world data on the management of metastatic breast cancer is increasingly relevant to understand breast cancer care in routine clinical practice. Yet such data are scarce, particularly beyond second- and third-line treatment strategies. This study, therefore, examined both the long-term treatment patterns and overall survival (OS) in a regional Swedish cohort of female patients with metastatic breast cancer stratified by subtype in routine clinical practice during a recent eight-year period and correlation to current treatment guidelines. Methods Consecutive female patients with metastatic breast cancer clinically managed at Uppsala University Hospital, Uppsala, Sweden, during 2009–2016 and followed until the end of September, 2017 (n = 370) were included and, where possible, classified as having one of five, intrinsic subtypes: Luminal A; Luminal B; human epidermal growth factor receptor 2-positive (HER2+)/ estrogen receptor-positive (ER+); HER2+/estrogen receptor-negative (ER-); or triple negative breast cancer (TNBC). Treatment patterns and OS were estimated by subtype using time-to-event methods. Results A total of 352/370 patients with metastatic breast cancer (mean age 67.6 years) could be subtyped: 118 (34%) were Luminal A, 119 (34%) Luminal B, 31 (8%) HER2+/ER-, 38 (11%) HER2+/Luminal, and 46 (13%) TNBC. The median number of metastatic treatment lines was 3. Most patients were on active treatment during follow-up (80% of the observation period), except for patients with TNBC who were on treatment for 60% of the observation time. Overall, 67% of patients died whilst on treatment. Among all patients (n = 370), median OS was 32.5 months (95% CI = 28.2–35.7). The 5-year survival rate was highest for HER2+/Luminal (46%) patients, followed by Luminal B (29%), Luminal A (28%), HER2+/ER- (21%), and TNBC (7%). Increasing age and number of metastatic sites also predicted worse survival. Conclusions Metastatic breast cancer patients in Sweden, irrespective of subtype, generally receive active treatment until time of death. Survival varies considerably across subtypes and is also associated with patient characteristics. Regardless of differences in treatment patterns for Luminal A and B patients, long-term OS was the same.

Abstract Aim To describe newly graduated registered nurses’ (NGRNs’) experiences of encountering stress in emergency departments (EDs) during the COVID‐19 pandemic. Design A qualitative descriptive study. Methods Data from 14 in‐depth interviews with NGRNs working in an ED for 3‐36 months after graduation was analysed by the means of qualitative content analysis as described by Graneheim and Lundman. Interviews were conducted from March to November 2020 covering the first two waves of the pandemic. Results Data revealed three categories and nine subcategories comprised in the theme Battling extraordinary situations and conflicting emotions. Empowered by acknowledging themselves as important caregivers during the pandemic NGRNs struggle against limitations and exert themselves beyond their known limit. External stressors due to work overload in combination with understaffing force NGRNs into the role of the experienced nurse prematurely and internal stressors derives from part taking in less qualitative care.

Hanna Sandelowsky,1– 3 Christer Janson,4 Fredrik Wiklund,5 Gunilla Telg,6 Sofie de Fine Licht,6 Björn Ställberg7 1Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden; 2Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Solna, Sweden; 3Academic Primary Health Care Centre, Region Stockholm, Stockholm, Sweden; 4Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 5Statisticon AB, Uppsala, Sweden; 6AstraZeneca Nordic, Stockholm, Sweden; 7Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, SwedenCorrespondence: Hanna Sandelowsky, Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, Tel +46738902565, Email hannasandelowsky@gmail.comObjective: The Swedish guidelines recommend that patients with chronic obstructive pulmonary disease (COPD) on maintenance treatment are monitored annually, and within six weeks after an exacerbation. We describe the patterns of COPD-related visits in Sweden, both regular follow-up and post-exacerbation visits.Methods: Patients (> 40 years) with a first-time COPD diagnosis between 2006 and 2017 were identified in primary care medical records and linked to hospital contacts and administered drug data. The index date was defined as the first collection of inhaled COPD maintenance treatment after the diagnosis. Regular COPD visits within 15-months after the index, and post-exacerbation visits for COPD within six weeks and 15-months after an exacerbation were estimated using the cumulative incidence function adjusted for competing risk. Visits without a ICD code for COPD were not included in the analyses.Results: A total of 19,857 patients (mean age 69 years, 57% females) were included. The overall probability of having a regular follow-up visit for COPD within 15 months post-index was 39.1%. In total, 15,095 (76%) patients experienced at least one COPD exacerbation during the observation period. Among them, the probability of having a post-exacerbation visit was 7.0% within six weeks and 29.7% within 15-months. Patients without a regular COPD follow-up visit claimed significantly more oral corticosteroids (25.6% vs 15.6%), more respiratory antibiotics (39.1% vs 23.1%), and less maintenance treatment (10.9% vs 16.5%).Conclusion: Only 39% of COPD patients attended a regular follow-up visit within 15-months from the COPD diagnosis and one-third had a post-exacerbation visit. The adherence to guideline recommendations need to be improved.Keywords: COPD, follow-up visit, exacerbation, guidelines

Multiple myeloma is a heterogeneous hematological disease that originates from the bone marrow and is characterized by the monoclonal expansion of malignant plasma cells. Despite novel therapies, multiple myeloma remains clinically challenging. A common feature among patients with poor prognosis is the increased activity of the epigenetic silencer EZH2, which is the catalytic subunit of the PRC2. Interestingly, the recruitment of PRC2 lacks sequence specificity and, to date, the molecular mechanisms that define which genomic locations are destined for PRC2-mediated silencing remain unknown. The presence of a long non-coding RNA (lncRNA)-binding pocket on EZH2 suggests that lncRNA could potentially mediate PRC2 recruitment to specific genomic regions. Here, we coupled RNA immunoprecipitation sequencing, RNA-sequencing and chromatin immunoprecipitation-sequencing analysis of human multiple myeloma primary cells and cell lines to identify potential lncRNA partners to EZH2. We found that the lncRNA plasmacytoma variant translocation 1 (PVT1) directly interacts with EZH2 and is overexpressed in patients with a poor prognosis. Moreover, genes predicted to be targets of PVT1 exhibited H3K27me3 enrichment and were associated with pro-apoptotic and tumor suppressor functions. In fact, PVT1 inhibition independently promotes the expression of the PRC2 target genes ZBTB7C, RNF144A and CCDC136. Altogether, our work suggests that PVT1 is an interacting partner in PRC2-mediated silencing of tumor suppressor and pro-apoptotic genes in multiple myeloma, making it a highly interesting potential therapeutic target.

Background Short-acting β2-agonist (SABA) overuse has been associated with an increased risk of exacerbations in asthma; however, less is known about SABA use in COPD. Our aim was to describe SABA use and investigate potential associations between high SABA use and the risk of future exacerbations and mortality in COPD. Methods This observational study identified COPD patients in primary care medical records in Sweden. Data were linked to the National Patient Registry, the Prescribed Drug Registry and the Cause of Death Registry. The index date was 12 months after the date of COPD diagnosis. During a 12-month prior to index baseline period, information on SABA use was collected. Patients were followed with respect to exacerbations and mortality for 12 months post index. Results Of the 19 794 COPD patients included (mean age 69.1 years, 53.3% females), 15.5% and 7.0% had collected ≥3 or ≥6 SABA canisters during the baseline period, respectively. A higher level of SABA use (≥6 canisters) was independently associated with a higher risk of both moderate and severe exacerbations (hazard ratio (HR) 1.28 (95% CI 1.17‒1.40) and 1.76 (95% CI 1.50‒2.06), respectively) during follow-up. In total, 673 (3.4%) patients died during the 12-month follow-up period. An independent association was found between high SABA use and overall mortality (HR 1.60, 95% CI 1.07‒2.39). This association, however, was not found in patients using inhaled corticosteroids as maintenance treatment. Conclusion In COPD patients in Sweden, high SABA use is relatively common and associated with a higher risk of exacerbations and all-cause mortality.

Immunotherapy is revolutionizing cancer therapy. The rapid development of new immunotherapeutic strategies to treat solid tumors is posing new challenges for preclinical research, demanding novel in vitro methods to test treatments. Such methods should meet specific requirements, such as enabling the evaluation of immune cell responses like cytotoxicity or cytokine release, and infiltration into the tumor microenvironment using cancer models representative of the original disease. They should allow high-throughput and high-content analysis, to evaluate the efficacy of treatments and understand immune-evasion processes to facilitate development of new therapeutic targets. Ideally, they should be suitable for personalized immunotherapy testing, providing information for patient stratification. Consequently, the application of in vitro 3-dimensional (3D) cell culture models, such as tumor spheroids and organoids, is rapidly expanding in the immunotherapeutic field, coupled with the development of novel imaging-based techniques and -omic analysis. In this paper, we review the recent advances in the development of in vitro 3D platforms applied to natural killer (NK) cell-based cancer immunotherapy studies, highlighting the benefits and limitations of the current methods, and discuss new concepts and future directions of the field.

ObjectiveThis study aimed to investigate directional influences in the association between adiposity and physical activity (PA) from pre-puberty to early adulthood.MethodsIn the Calex-study, height, weight, body fat and leisure-time physical activity (LTPA) were measured at age11.2-years, 13.2-years and 18.3-years in 396 Finnish girls. Body fat was measured by dual-energy X-ray absorptiometry, calculating fat mass index (FMI) as total fat mass in kilograms divided by height in meters squared. LTPA level was evaluated using a physical activity questionnaire. In the European Youth Heart Study (EYHS), height, weight and habitual PA were measured at age 9.6-years, 15.7-years and 21.8-years in 399 Danish boys and girls. Habitual PA and sedentary behaviour were assessed with an accelerometer. Directional influences of adiposity and PA were examined using a bivariate cross-lagged path panel model.ResultsThe temporal stability of BMI from pre-puberty to early adulthood was higher than the temporal stability of PA or physical inactivity over the same time period both in girls and boys. In the Calex-study, BMI and FMI at age 11.2-years were both directly associated with LTPA at age 13.2-years (β = 0.167, p = 0.005 and β = 0.167, p = 0.005, respectively), whereas FMI at age 13.2-years showed an inverse association with LTPA at age 18.3-years (β = - 0.187, p = 0.048). However, earlier LTPA level was not associated with subsequent BMI or FMI. In the EYHS, no directional association was found for physical inactivity, light-, moderate-, and vigorous-PA with BMI during the follow-up in girls. In boys, BMI at age 15.7-years was directly associated with moderate PA (β = 0.301, p = 0.017) at age 21.8-years, while vigorous PA at age 15.7-years showed inverse associations with BMI at age 21.8-years (β = - 0.185, p = 0.023).ConclusionOur study indicates that previous fatness level is a much stronger predictor of future fatness than level of leisure-time or habitual physical activity during adolescence. The directional associations between adiposity and physical activity are not clear during adolescence, and may differ between boys and girls depending on pubertal status.

Chemical immobilization of captive European bison (Bison bonasus) is often required for veterinary care, transportation, or husbandry practices playing an important role in conservation breeding and reintroduction of the species. We evaluated the efficiency and physiological effects of an etorphine-acepromazine-xylazine combination with supplemental oxygen in 39 captive European bison. Animals were darted with a combination of 1.4 mg of etorphine, 4.5 mg of acepromazine, and 20 mg of xylazine per 100 kg based on estimated body mass. Arterial blood was sampled on average 20 min after recumbency and again 19 min later and analyzed immediately with a portable i-STAT analyzer. Simultaneously, heart rate, respiratory rate, and rectal temperature were recorded. Intranasal oxygen was started after the first sampling at a flow rate of 10 mL.kg−1.min−1 of estimated body mass until the end of the procedure. The initial mean partial pressure of oxygen (PaO2) was 49.7 mmHg with 32 out of 35 sampled bison presenting with hypoxemia. We observed decreased respiratory rates and pH and mild hypercapnia consistent with a mild respiratory acidosis. After oxygen supplementation hypoxemia was resolved in 21 out of 32 bison, but respiratory acidosis was accentuated. Bison immobilized with a lower initial drug dose required supplementary injections during the procedure. We observed that lower mean rectal temperatures during the immobilization event were significantly associated with longer recovery times. For three bison, minor regurgitation was documented. No mortality or morbidity related to the immobilizations were reported for at least 2 months following the procedure. Based on our findings, we recommend a dose of 0.015 mg.kg−1 etorphine, 0.049 mg.kg−1 acepromazine, and 0.22 mg.kg−1 xylazine. This dose reduced the need for supplemental injections to obtain a sufficient level of immobilization for routine management and husbandry procedures in captive European bison. Nevertheless, this drug combination is associated with development of marked hypoxemia, mild respiratory acidosis, and a small risk of regurgitation. Oxygen supplementation is strongly recommended when using this protocol.

Adverse Outcome Pathways (AOPs) summarize mechanistic understanding of toxicological effects and have, for example, been highlighted as a promising tool to integrate data from novel in vitro and in silico methods into chemical risk assessments. Networks based on AOPs are considered the functional implementation of AOPs, as they are more representative of complex biology. At the same time, there are currently no harmonized approaches to generate AOP networks (AOPNs). Systematic strategies to identify relevant AOPs, and methods to extract and visualize data from the AOP-Wiki, are needed. The aim of this work was to develop a structured search strategy to identify relevant AOPs in the AOP-Wiki, and an automated data-driven workflow to generate AOPNs. The approach was applied on a case study to generate an AOPN focused on the Estrogen, Androgen, Thyroid, and Steroidogenesis (EATS) modalities. A search strategy was developed a priori with search terms based on effect parameters in the ECHA/EFSA Guidance Document on Identification of Endocrine Disruptors. Furthermore, manual curation of the data was performed by screening the contents of each pathway in the AOP-Wiki, excluding irrelevant AOPs. Data were downloaded from the Wiki, and a computational workflow was utilized to automatically process, filter, and format the data for visualization. This study presents an approach to structured searches of AOPs in the AOP-Wiki coupled to an automated data-driven workflow for generating AOPNs. In addition, the case study presented here provides a map of the contents of the AOP-Wiki related to the EATS-modalities, and a basis for further research, for example, on integrating mechanistic data from novel methods and exploring mechanism-based approaches to identify endocrine disruptors (EDs). The computational approach is freely available as an R-script, and currently allows for the (re)-generation and filtering of new AOP networks based on data from the AOP-Wiki and a list of relevant AOPs used for filtering.

IntroductionEngineers’ work has become more complex with increased demands in today’s changing working life. Self-efficacy is essential to successfully adapt to work-related changes and to cope with adverse job demands. However, less is known about aging engineers’ occupational self-efficacy. Therefore, this study explores facilitators and barriers to aging engineers’ occupational self-efficacy beliefs to continue working until expected retirement age. An additional purpose is to explore if any of the aspects described by the engineers are more prominent.MethodsThe study design was exploratory, using mixed methods with a qualitative to quantitative approach. A total of 125 engineers, aged between 45 and 65 years, answered two open-ended survey questions about what positively and negatively affect their occupational self-efficacy beliefs to continue working. First, data was analyzed using an inductive manifest qualitative content analysis. Next, descriptive statistics were performed based on the results of the qualitative study.ResultsThe analyses revealed that health and working conditions that affect health were crucial facilitators and barriers for the aging engineers’ occupational self-efficacy to continue working until expected retirement age. Furthermore, the engineers emphasized competence, motivation from meaningful tasks, family and leisure, and private economy.DiscussionThe aging engineers’ own health seems to be prominent in their self-efficacy regarding a full working life; consequently, support still needs to address issues affecting health.