Search

Political leaders play a crucial role in shaping societal perceptions and citizens’ expectations of gender roles. Through their self-presentation on social media, political leaders have the power to either reinforce or challenge existing gender stereotypes, thereby influencing how citizens perceive and interpret gender norms. However, research on how women and men politicians present themselves on social media is scarce. This comparative study contributes to remedying this research gap by content analysing the official Facebook and Instagram pages of 18 political leaders during the 2021 national election campaigns in Germany and Norway. In contrast to earlier research on gendered presentations of politicians in the news, we did not find strong evidence of gendered self-presentations in either country, neither in terms of personalisation nor in terms of gender issue ownership. This could be because gender roles in Germany and Norway have become more fluid, or because the successful politicians we have analysed have been successful due to their ability to “walk the double bind” of needing to conform to both masculine and feminine gender expectations. Our study calls for more comparative research into this field, including studies of lower profile politicians and politicians in countries with lower degrees of gender equality.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic bronchitis, emphysema and vascular remodelling. The disease is associated with hypoxia, inflammation and oxidative stress. Lung fibroblasts are important cells in remodelling processes in COPD, as main producers of extracellular matrix proteins but also in synthesis of growth factors and inflammatory mediators. Methods In this study we aimed to investigate if there are differences in how primary distal lung fibroblasts obtained from COPD patients and healthy subjects respond to hypoxia (1% O2) and pro-fibrotic stimuli with TGF-β1 (10 ng/mL). Genes and proteins associated with oxidative stress, endoplasmic reticulum stress, remodelling and inflammation were analysed with RT-qPCR and ELISA. Results Hypoxia induced differences in expression of genes involved in oxidative stress (SOD3 and HIF-1α), ER stress (IRE1, PARK and ATF6), apoptosis (c-Jun and Bcl2) and remodelling (5HTR2B, Collagen7 and VEGFR2) in lung fibroblasts from COPD subjects compared to control subjects, where COPD fibroblasts were in general less responsive. The release of VEGF-C was increased after hypoxia, whereas TGF-β significantly reduced the VEGF response to hypoxia and the release of HGF. COPD fibroblasts had a higher release of IL-6, IL-8, MCP-1 and PGE2 compared to lung fibroblasts from control subjects. The release of inflammatory mediators was less affected by hypoxia, whereas TGFβ1 induced differences in inflammatory profile between fibroblasts from COPD and control subjects. Conclusion These results suggest that there is an alteration of gene regulation of various stress responses and remodelling associated mediator release that is related to COPD and hypoxia, where fibroblasts from COPD patients have a deficient response.

IntroductionParkinson's Disease affects over 8.5 million people and there are currently no medications approved to treat underlying disease. Clinical trials for disease modifying therapies (DMT) are hampered by a lack of sufficiently sensitive measures to detect treatment effect. Reliable digital assessments of motor function allow for frequent at-home measurements that may be able to sensitively detect disease progression.MethodsHere, we estimate the test-retest reliability of a suite of at-home motor measures derived from raw triaxial accelerometry data collected from 44 participants (21 with confirmed PD) and use the estimates to simulate digital measures in DMT trials. We consider three schedules of assessments and fit linear mixed models to the simulated data to determine whether a treatment effect can be detected.ResultsWe find at-home measures vary in reliability; many have ICCs as high as or higher than MDS-UPDRS part III total score. Compared with quarterly in-clinic assessments, frequent at-home measures reduce the sample size needed to detect a 30% reduction in disease progression from over 300 per study arm to 150 or less than 100 for bursts and evenly spaced at-home assessments, respectively. The results regarding superiority of at-home assessments for detecting change over time are robust to relaxing assumptions regarding the responsiveness to disease progression and variability in progression rates.DiscussionOverall, at-home measures have a favorable reliability profile for sensitive detection of treatment effects in DMT trials. Future work is needed to better understand the causes of variability in PD progression and identify the most appropriate statistical methods for effect detection.

Measuring pain self-efficacy is suggested as relevant in patients with musculoskeletal disorders (MSDs) in a primary care setting. However, there is no pain self-efficacy questionnaire (PSEQ) available in Swedish. The aim of this study was to translate and culturally adapt PSEQ-2 to Swedish and evaluate reliability and validity in a population of patients with MSDs.

Social media has contributed to the spread of populist political communication, yet we still lack systematic knowledge of the contextual factors affecting its use. In this study, we investigated how and to what degree platforms (Facebook, Instagram, Twitter) and party characteristics (populist vs. non-populist parties; political ideology) affected the use of populist communication by Norwegian political parties on social media during the 2021 national election campaign. Based on a tripartite conceptualisation of populist communication consisting of people-centrism, anti-elitism, and the exclusion of out-groups, we conducted a standardised content analysis of the official social media accounts of nine parties and their party leaders. Populist communication was overall rather rare, being most widespread on Facebook and least widespread on Twitter. Which parties used populist communication the most depended on the platform, and it was not always the populist Progress Party [Fremskrittspartiet] that communicated in the most populist manner. Parties located towards the fringes of the political party spectrum used more populist communication. Anti-elitism was more widespread among left-wing parties, and almost exclusively the right-wing Progress Party excluded out-groups.

Martin Garcia-Ryde,1 Nicole MD van der Burg,1 Carin E Larsson,1 Anna-Karin Larsson-Callerfelt,2 Gunilla Westergren-Thorsson,2 Leif Bjermer,1 Ellen Tufvesson1 1Department of Clinical Sciences Lund, Respiratory Medicine, Allergology and Palliative Medicine, Lund University, Lund, Sweden; 2Department of Experimental Medical Science, Lung Biology, Lund University, Lund, SwedenCorrespondence: Ellen Tufvesson, Department of Clinical Sciences Lund, Respiratory Medicine, Allergology and Palliative Medicine, Lund University, BMC, D12, 221 84, Lund, Sweden, Email Ellen.Tufvesson@med.lu.seBackground and aim: Cigarette smoking is the most common cause of chronic obstructive pulmonary disease (COPD) but more mechanistic studies are needed. Cigarette smoke extract (CSE) can elicit a strong response in many COPD-related cell types, but no studies have been performed in lung fibroblasts. Therefore, we aimed to investigate the effect of CSE on gene expression in lung fibroblasts from healthy and COPD subjects.Patients and methods: Primary lung fibroblasts, derived from six healthy and six COPD subjects (all current or ex-smokers), were either unstimulated (baseline) or stimulated with 30% CSE for 4 h prior to RNA isolation. The mRNA expression levels were measured using the NanoString nCounter Human Fibrosis V2 panel (760 genes). Pathway enrichment was assessed for unique gene ontology terms of healthy and COPD.Results: At baseline, a difference in the expression of 17 genes was found in healthy and COPD subjects. Differential expression of genes after CSE stimulation resulted in significantly less changes in COPD lung fibroblasts (70 genes) than in healthy (207 genes), with 51 genes changed in both. COPD maintained low NOTCH signaling throughout and upregulated JUN > 80%, indicating an increase in apoptosis. Healthy downregulated the Mitogen-activated protein kinase (MAPK) signaling cascade, including a ≥ 50% reduction in FGF2, CRK, TGFBR1 and MEF2A. Healthy also downregulated KAT6A and genes related to cell proliferation, all together indicating possible cell senescence signaling.Conclusion: Overall, COPD lung fibroblasts responded to CSE stimulation with a very different and deficient expression profile compared to healthy. Highlighting that stimulated healthy cells are not an appropriate substitute for COPD cells which is important when investigating the mechanisms of COPD.Plain Language Summary: We investigated, for the first time, the effect of cigarette smoke extract (CSE) on gene expression in lung fibroblasts from healthy subjects and subjects with COPD. We found that fibroblasts from subjects with COPD respond very differently than from healthy subjects by changing fewer gene expressions after CSE. Pathway enrichment suggested that fibroblasts from subjects with COPD respond to CSE by affecting genes involved in apoptosis pathways, while fibroblasts from healthy subjects respond by affecting genes involved in cell senescence. This study highlights the importance of assessing stimulated COPD cells in mechanistic studies.Keywords: COPD, lung fibroblast, gene expression, cigarette smoke extract, GO term, signaling pathways

Abstract Background The two-way partial AUC has been recently proposed as a way to directly quantify partial area under the ROC curve with simultaneous restrictions on the sensitivity and specificity ranges of diagnostic tests or classifiers. The metric, as originally implemented in the tpAUC R package, is estimated using a nonparametric estimator based on a trimmed Mann-Whitney U-statistic, which becomes computationally expensive in large sample sizes. (Its computational complexity is of order $$O(n_x n_y)$$ O ( n x n y ) , where $$n_x$$ n x and $$n_y$$ n y represent the number of positive and negative cases, respectively). This is problematic since the statistical methodology for comparing estimates generated from alternative diagnostic tests/classifiers relies on bootstrapping resampling and requires repeated computations of the estimator on a large number of bootstrap samples. Methods By leveraging the graphical and probabilistic representations of the AUC, partial AUCs, and two-way partial AUC, we derive a novel estimator for the two-way partial AUC, which can be directly computed from the output of any software able to compute AUC and partial AUCs. We implemented our estimator using the computationally efficient pROC R package, which leverages a nonparametric approach using the trapezoidal rule for the computation of AUC and partial AUC scores. (Its computational complexity is of order $$O(n \log n)$$ O ( n log n ) , where $$n = n_x + n_y$$ n = n x + n y .). We compare the empirical bias and computation time of the proposed estimator against the original estimator provided in the tpAUC package in a series of simulation studies and on two real datasets. Results Our estimator tended to be less biased than the original estimator based on the trimmed Mann-Whitney U-statistic across all experiments (and showed considerably less bias in the experiments based on small sample sizes). But, most importantly, because the computational complexity of the proposed estimator is of order $$O(n \log n)$$ O ( n log n ) , rather than $$O(n_x n_y)$$ O ( n x n y ) , it is much faster to compute when sample sizes are large. Conclusions The proposed estimator provides an improvement for the computation of two-way partial AUC, and allows the comparison of diagnostic tests/machine learning classifiers in large datasets where repeated computations of the original estimator on bootstrap samples become too expensive to compute.

Ritah Bakesiima,1,2 Kristina Gemzell-Danielsson,2,3 Jolly Beyeza-Kashesya,4 Amanda Cleeve,2,3,5 Elin C Larsson,2,3,6 Rose Chalo Nabirye7 1Department of Obstetrics and Gynaecology, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 2Department of Women’s and Children’s Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden; 3WHO Collaborating Centre, Division of Women’s Health, Karolinska University Hospital, Stockholm, Sweden; 4Department of Obstetrics and Gynaecology, Mulago Specialised Women and Neonatal Hospital, Kampala, Uganda; 5Department of Women´s Health, South General Hospital, Stockholm, Sweden; 6Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; 7Department of Nursing, Faculty of Health Sciences, Busitema University, Mbale, UgandaCorrespondence: Ritah Bakesiima, Department of Obstetrics and Gynaecology, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda, Email esmie.ritah@gmail.comBackground: Contraceptive adherence is the current and consistent use of a contraceptive method as prescribed by a health worker or family planning provider so as to prevent pregnancy. Globally, adherence is lowest among adolescents. This has greatly contributed to the high burden of adolescent pregnancies. Adherence and reasons for discontinuation among refugee adolescents are poorly understood. The aim of this study was to determine the rates and predictors of adherence to modern contraceptives among female refugee adolescents in northern Uganda.Methods: This was a prospective single cohort study, nested into a randomised controlled trial (RCT) assessing the effect of peer counselling on acceptance of modern contraceptives. The RCT was conducted among female refugee adolescents in Palabek refugee settlement, northern Uganda. The study involved 272 new starters of modern contraceptives who were followed up for six months from May 2019 to January 2020. The outcome was measured at one, three, and six months after receiving a contraceptive method, and the predictors of adherence were determined using Generalised Estimating Equations (GEE). Data were analysed using STATA version 14.0.Results: Adherence rates were low and reduced over time. By the end of the six months, only 44% of the participants were using a contraceptive method. Participants using long-acting reversible contraceptives (LARC) were more likely to adhere compared to those who were using short-acting reversible contraceptives (SARC) (OR: 3.37, 95% CI: 1.914– 5.937, p< 0.001).Conclusion: Adherence to modern contraceptives was low, leaving adolescents at risk of unintended pregnancies. Participants using LARC were more likely to adhere than those using SARC. Interventions addressing fear of side effects and partner prohibition should be studied and implemented to enable adherence to modern contraceptives.Keywords: contraceptive adherence, contraceptive discontinuation, adolescents, refugees, teenage pregnancy

Marie Dahlen Granrud,1 Vigdis Abrahamsen Grøndahl,2 Ann Karin Helgesen,2 Carina Bååth,2,3 Cecilia Olsson,3,4 Maria Tillfors,5 Christina Melin-Johansson,6 Jane Österlind,7 Maria Larsson,3 Reidun Hov,8 Tuva Sandsdalen9 1Department of Social Sciences and Guidance, Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, Elverum, Norway; 2Department of Nursing, Health and Laboratory Science, Faculty of Health, Welfare and Organization, Østfold University College, Halden, Norway; 3Department of Health Sciences, Faculty of Health Science and Technology, Karlstad University, Karlstad, Sweden; 4Department of Bachelor Education in Nursing, Lovisenberg Diaconal University College, Oslo, Norway; 5Department of Social and Psychological Sciences, Faculty of Arts and Social Sciences, Karlstad University, Karlstad, Sweden; 6Department of Health Sciences, Mid Sweden University, Östersund, Sweden; 7Department of Health Care Sciences, Marie Cederschiöld University, Stockholm, Sweden; 8Centre of Development of Institutional and Home Care Services, Innland (Hedmark), Hamar Municipality, Norway; 9Department of Health and Nursing Sciences, Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, Elverum, NorwayCorrespondence: Marie Dahlen Granrud, Department of Social Sciences and Guidance, Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, Elverum, Norway, Tel +47 62 43 02 68, Email marie.granrud@inn.noPurpose: The provision of high-quality palliative care is challenging, especially during a pandemic like COVID-19. The latter entailed major consequences for health care systems and health care personnel (HCP) in both specialist and community health care services, in Norway and worldwide. The aim of this study was to explore how the HCP perceived the quality of palliative care in nursing homes, medical care units, and intensive care units during the COVID-19 pandemic.Methods: This study had a cross-sectional design. A total of 290 HCP from Norway participated in the study (RR = 25.8%) between October and December 2021. The questionnaire comprised items concerning respondents’ demographics and quality of care, the latter measured by the short form of the Quality from the Patient’s Perspective—Palliative Care instrument, adapted for HCP. The STROBE checklist was used.Results: This study shows that the HCP scored subjective importance as higher in all dimensions, items and single items than their perception of the actual care received. This could indicate a need for improvement in all areas. Information about medication, opportunity to participate in decisions about medical and nursing care and continuity regarding receiving help from the same physician and nurse are examples of areas for improvement.Conclusion: Study results indicate that HCP from nursing homes, medical care units, and intensive care units perceived that quality of palliative care provided was not in line with what they perceived to be important for the patient. This indicate that it was challenging to provide high-quality palliative care during the COVID-19 pandemic.Keywords: COVID-19 pandemic, health care personnel perspective, palliative care, quality of care

Abstract Background Exercise has various health benefits for people with Parkinson’s disease (PD). However, implementing exercise into daily life and long-term adherence remain challenging. To increase a sustainable engagement with physical activity of people with PD, interventions that are motivating, accessible, and scalable are needed. We primarily aim to investigate whether a smartphone app (STEPWISE app) can increase physical activity (i.e., step count) in people with PD over one year. Our second aim is to investigate the potential effects of the intervention on physical fitness, and motor- and non-motor function. Our third aim is to explore whether there is a dose-response relationship between volume of physical activity and our secondary endpoints. Methods STEPWISE is a double-blind, randomized controlled trial. We aim to include 452 Dutch people with PD who can walk independently (Hoehn & Yahr stages 1–3) and who do not take more than 7,000 steps per day prior to inclusion. Physical activity levels are measured as step counts on the participant’s own smartphone and scaled as percentage of each participant’s baseline. Participants are randomly assigned to an active control group with an increase of 5–20% (active controls) or any of the three intervention arms with increases of 25–100% (intermediate dose), 50–200% (large dose), or 100–400% (very large dose). The primary endpoint is change in step count as measured by the STEPWISE smartphone app from baseline to 52 weeks. For our primary aim, we will evaluate the between-group difference in average daily step count change from baseline to 52 weeks. For our second aim, measures of physical fitness, and motor- and non-motor function are included. For our third aim, we will associate 52-week changes in step count with 52-week changes in secondary outcomes. Discussion This trial evaluates the potential of a smartphone-based intervention to increase activity levels in people with PD. We envision that motivational apps will increase adherence to physical activity recommendations and could permit conduct of remote clinical trials of exercise for people with PD or those at risk of PD. Trial registration ClinicalTrials.gov; NCT04848077; 19/04/2021. Clinicaltrials.gov/ct2/show/NCT04848077.

Thomas Wagner,1,2 Jakob Lauritsen,1 Mikkel Bandak,1 Linda Aagaard Rasmussen,3 Johannes Bakker,4 Hanna Birkbak Hovaldt,4 Heidi Larsson,4 Ib Jarle Christensen,1 Birgitte Grønkær Toft,2 Mads Agerbæk,5 Lars Dysager,6 Michael Kreiberg,1 Josephine Julie Rosenvilde,1 Birte Engvad,7 Daniel M Berney,8 Gedske Daugaard1 1Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 3Research Unit for General Practice, Aarhus, Denmark; 4The Danish Clinical Quality Program – National Clinical Registries (RKKP), Aarhus, Odense and Copenhagen, Denmark; 5Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; 6Department of Oncology, Odense University Hospital, Odense, Denmark; 7Department of Pathology, Odense University Hospital, Odense, Denmark; 8Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UKCorrespondence: Thomas Wagner, Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark, Tel +45 35459682, Email thomas.wagner.nielsen@regionh.dkPurpose: The Danish Testicular Cancer (DaTeCa) database aims to monitor and improve quality of care for testicular cancer patients. Relapse data registered in the DaTeCa database rely on manual registration. Currently, some safeguarding against missing registrations is attempted by a non-validated register-based algorithm. However, this algorithm is inaccurate and entails time-consuming medical record reviews. We aimed (1) to validate relapse data as registered in the DaTeCa database, and (2) to develop and validate an improved register-based algorithm identifying patients diagnosed with relapse of clinical stage I testicular cancer.Patients and Methods: Patients registered in the DaTeCa database with clinical stage I testicular cancer from 2013 to 2018 were included. Medical record information on relapse data served as a gold standard. A pre-specified algorithm to identify relapse was tested and optimized on a random sample of 250 patients. Indicators of relapse were obtained from pathology codes in the Danish National Pathology Register and from diagnosis and procedure codes in the Danish National Patient Register. We applied the final algorithm to the remaining study population to validate its performance.Results: Of the 1377 included patients, 284 patients relapsed according to the gold standard during a median follow-up time of 5.9 years. The completeness of relapse data registered in the DaTeCa database was 97.2% (95% confidence interval (CI): 95.2– 99.1). The algorithm achieved a sensitivity of 99.6% (95% CI: 98.7– 100), a specificity of 98.9% (95% CI: 98.2– 99.6), and a positive predictive value of 95.9% (95% CI: 93.4– 98.4) in the validation cohort (n = 1127, 233 relapses).Conclusion: The registration of relapse data in the DaTeCa database is accurate, confirming the database as a reliable source for ongoing clinical quality assessments. Applying the provided algorithm to the DaTeCa database will optimize the accuracy of relapse data further, decrease time-consuming medical record review and contribute to important future clinical research.Keywords: testicular cancer, relapse, algorithm, validation, registries

Synthetic health data have the potential to mitigate privacy concerns when sharing data to support biomedical research and the development of innovative healthcare applications. In this work, the authors introduce a use case oriented benchmarking framework to evaluate data synthesis models through a set of utility and privacy metrics.

Comprehensive profiling of ligand-induced perturbation responses of the MCF10A mammary epithelial cell line provides an exhaustive resource for identification of the molecular basis of cellular phenotypes.

Kjell Larsson,1 Karin Lisspers,2 Björn Ställberg,2 Gunnar Johansson,2 Florian S Gutzwiller,3 Karen Mezzi,3 Bine Kjoeller Bjerregaard,4 Leif Jorgensen,4 Hyewon Koo,5 Christer Janson6 1Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 3Novartis Pharma AG, Basel, Switzerland; 4IQVIA Solutions, Copenhagen, Denmark; 5IQVIA Solutions, Solna, Sweden; 6Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, SwedenCorrespondence: Kjell Larsson, Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SE-171 77, Sweden, Tel +467 0582 0763, Email kjell.larsson@ki.seBackground: Patients with mild chronic obstructive pulmonary disease (COPD) account for more than half of the total COPD population but are often undiagnosed and sparsely studied. This real-world, longitudinal study compared the socioeconomic burden, clinical characteristics and treatment patterns in patients with mild COPD and age- and gender-matched controls.Patients and methods: Our population included mild COPD patients (forced expiratory volume in one second ≥ 80% of predicted value) and reference controls from 52 Swedish primary care centres over 15 years (2000– 2014). We linked electronic medical record (EMR) data to Sweden’s National Health Registries. The outcomes analyzed were socioeconomic status including annual income from work, presence of comorbidities and the use of medications.Results: 844 patients with mild COPD were included in this study and matched with 844 reference controls. Compared with the reference controls, mild COPD patients had a significantly lower annual income from work (mean difference, men: 12,559€ and women: 7143€) and were significantly less likely to be married or employed. The presence of comorbidities, including cardiovascular disease, anxiety and depression (only women) was significantly higher in mild COPD patients. The use of medications, such as proton pump inhibitors, antidepressants, central painkillers and sleep medications, was significantly higher in the mild COPD group.Conclusion: Mild COPD presents a considerable socioeconomic and clinical burden compared with reference controls The findings suggest that COPD constitutes a condition that influences health status even in mild disease clearly demanding an increased need for early detection and treatment.Keywords: chronic obstructive pulmonary disease, socioeconomic status, comorbidities, co-medications, annual income, exacerbation, Sweden

Abstract Introduction Collagenous colitis (CC) is a common cause of chronic diarrhea and is characterized by a subepithelial thickened collagen layer in the colonic mucosa. It shares many of the characteristics found in autoimmune diseases, but no autoantibodies have been identified. In CC, an imbalance in collagen turnover is evident. The purpose of the present study was to investigate whether any collagen-associated autoantibodies or other antibodies such as TPO and ASCA were present, and if levels of total IgE were increased. Methods Sera from women with active CC were analysed with ELISA for detection of autoantibodies against collagen type III and IV (Col III and IV), matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and tenascin-C (TNC). Sera were also analysed for TPO, ASCA and total IgE. Healthy female blood donors served as controls. The cut-off value in the control group was defined as relative units > 97.5th percentile. Results Sixty-six women were included (mean age 60 years; range 31–74, mean disease duration 6 years; range 1–22). No autoantibody was significantly overexpressed in the CC population compared to controls. The mean disease duration was lower (p = 0.03) in the subjects who expressed collagen-associated autoantibodies (3.7 years; range 1–14), compared to those who did not (6.4 years; range 1–22). Treatment with budesonide was not associated with any of these autoantibodies. Conclusion No increased presence of the investigated antibodies could be found in the present study of CC. Neither could antibodies against ASCA or TPO, or elevated levels of IgE, be found. Consequently, no association was found between CC and these proteins, even though this may not be generalizable to other compounds in the collagen layer.

One of the promising opportunities of digital health is its potential to lead to more holistic understandings of diseases by interacting with the daily life of patients and through the collection of large amounts of real-world data. Validating and benchmarking indicators of disease severity in the home setting is difficult, however, given the large number of confounders present in the real world and the challenges in collecting ground truth data in the home. Here we leverage two datasets collected from patients with Parkinson's disease, which couples continuous wrist-worn accelerometer data with frequent symptom reports in the home setting, to develop digital biomarkers of symptom severity. Using these data, we performed a public benchmarking challenge in which participants were asked to build measures of severity across 3 symptoms (on/off medication, dyskinesia, and tremor). 42 teams participated and performance was improved over baseline models for each subchallenge. Additional ensemble modeling across submissions further improved performance, and the top models validated in a subset of patients whose symptoms were observed and rated by trained clinicians.

Lena Lundh,1,2 Kjell Larsson,3 Anders Lindén,4,5 Scott Montgomery,6– 8 Lena Palmberg,3 Hanna Sandelowsky1,2,7 1Academic Primary Health Care Centre, Stockholm County Council, Stockholm, Sweden; 2Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; 3Division of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 4Division for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 5Karolinska Severe COPD Center, Department of Respiratory Medicine and Allergy, Karolinska University Hospital Solna, Stockholm, Sweden; 6Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; 7Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; 8Department of Epidemiology and Public Health, University College London, London, UKCorrespondence: Hanna Sandelowsky, Karolinska Institutet, Department of Medicine, Division of Clinical Epidemiology, Stockholm, SE-171 76, Sweden, Tel +46738902565, Email hanna.sandelowsky@ki.seBackground: To facilitate effective personalized medicine, primary health care needs better methods of assessing and monitoring chronic obstructive pulmonary disease (COPD).Aim: This cohort study aims to investigate how biomarkers relate to clinical characteristics and COPD patients’ subjective needs over time.Methods: Patients (n=750) in different COPD severity according to the GOLD criteria and age- and sex-matched controls (n=750) will be recruited over a period of 5 years from 15 primary health care centers in Region Stockholm, Sweden, and followed for 10 years in the first instance. Data on patients’ subjective needs will be collected via telephone/email, data on clinical/physiological variables (eg, symptoms, exacerbations, comorbidities, medications, smoking habits, lung function) from existing databases that are based on medical records, and data on biomarkers via repeated blood sampling. Quantitative and qualitative methods will be used. Initial results are expected after 2 years (feasibility test), and a larger body of evidence after 5 years.Discussion: The study is expected to provide definitive and clinically useful scientific evidence about how biomarkers relate to clinical variables and patients’ subjective needs. This new evidence will facilitate accurate, and personalized COPD management by the use of valid biomarkers. It will provide useful tools for primary care professionals and may facilitate optimal self-management.Keywords: airway inflammation, COPD, biomarkers, cohort, patients’ needs, personalized medicine, primary care

In several graves from the Mesolithic sites of Skateholm, South Sweden, animal teeth were found. Some of these teeth were used as beads in clothing. The strontium isotope analysis of 11 animal teeth is reported and discussed in comparison with human values from burials at the sites and baseline values from South Sweden. Roughly half of the animal teeth are nonlocal and from different places of origin. The beads themselves appear to carry symbolic information that may be related to the physical or social attributes of the wearer. This study involved a detailed investigation of the use-wear around the perforation and its relation to the local and nonlocal origin of the teeth.

Background: Smartphones can generate objective measures of Parkinson’s disease (PD) and supplement traditional in-person rating scales. However, smartphone use in clinical trials has been limited. Objective: This study aimed to determine the feasibility of introducing a smartphone research application into a PD clinical trial and to evaluate the resulting measures. Methods: A smartphone application was introduced part-way into a phase 3 randomized clinical trial of inosine. The application included finger tapping, gait, and cognition tests, and participants were asked to complete an assessment battery at home and in clinic alongside the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Results: Of 236 eligible participants in the parent study, 88 (37%) consented to participate, and 59 (27 randomized to inosine and 32 to placebo) completed a baseline smartphone assessment. These 59 participants collectively completed 1,292 batteries of assessments. The proportion of participants who completed at least one smartphone assessment was 61% at 3, 54% at 6, and 35% at 12 months. Finger tapping speed correlated weakly with the part III motor portion (r = −0.16, left hand; r = −0.04, right hand) and total (r = −0.14) MDS-UPDRS. Gait speed correlated better with the same measures (r = −0.25, part III motor; r = −0.34, total). Over 6 months, finger tapping speed, gait speed, and memory scores did not differ between those randomized to active drug or placebo. Conclusions: Introducing a smartphone application midway into a phase 3 clinical trial was challenging. Measures of bradykinesia and gait speed correlated modestly with traditional outcomes and were consistent with the study’s overall findings, which found no benefit of the active drug.

Kjell Larsson,1 Ann Ekberg-Jansson,2 Caroline Stridsman,3 Malin Hanno,4 Lowie EGW Vanfleteren5,6 1Integrative Toxicology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden; 4Boehringer Ingelheim AB, Stockholm, Sweden; 5COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, 413 45, Sweden; 6Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 413 45, SwedenCorrespondence: Kjell LarssonIntegrative Toxicology, National Institute of Environmental Medicine, IMM, Karolinska Institutet, Stockholm, SE-171 77 Tel +46 70 582 07 63Email kjell.larsson@ki.seIntroduction: Swedish guidelines adhere to the international GOLD document regarding management of chronic obstructive pulmonary disease (COPD). Based on data from the Swedish National Airway Register (SNAR) the aim was to evaluate adherence to guidelines of pharmacological treatment of COPD in Swedish primary and secondary care.Methods: During a period of 18 months, data on symptoms (CAT, mMRC), lung function, exacerbation history and pharmacological treatment from 15,595 COPD patients from 853 primary care and 125 secondary care clinics were collected from SNAR. Patients with a co-diagnosis of asthma were excluded. Patients were divided into four treatment groups: no pharmacological treatment, short-acting bronchodilators alone, long-acting bronchodilators alone and ICS alone or in combination with bronchodilators.Results: Of the patients, 29% were in GOLD group A, 58% in group B, 2% in group C and 11% in group D. CAT score was ≥ 10 and mMRC score was below 2 in 30.9% of the patients and mMRC score was ≥ 2 and CAT score < 10 in 4.2% of the patients. In 61.4% of the patients, no exacerbation was registered during the last year. Long-acting bronchodilators were prescribed for 78% and ICS for 46% of all patients. In groups A, B, C and D, respectively, 21%, 11%, 11% and 5% did not receive any inhaler therapy; 67%, 81%, 81% and 90% received long-acting bronchodilators; 33%, 46%, 55% and 71% received any ICS containing therapy and 19%, 34%, 39% and 61% received triple therapy.Discussion: Data from the SNAR indicate that only a minority of COPD patients were untreated. There was a liberal use of ICS containing drug combinations in subjects who do not have an indication for ICS. A considerable proportion of subjects at high risk of exacerbations did not receive ICS treatment.Keywords: chronic obstructive pulmonary disease, COPD, glucocorticoids, registry

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis-regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation.

Björn Ställberg,1 Karin Lisspers,1 Kjell Larsson,2 Christer Janson,3 Mario Müller,4 Mateusz Łuczko,5 Bine Kjøller Bjerregaard,6 Gerald Bacher,7 Björn Holzhauer,7 Pankaj Goyal,7 Gunnar Johansson1 1Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 2Integrative Toxicology, Karolinska Institutet, Stockholm, Sweden; 3Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 4Department of Data Science and Advanced Analytics, IQVIA, Frankfurt Am Main, Germany; 5Department of Data Science and Advanced Analytics, IQVIA, Warsaw, Poland; 6Department of Real World Evidence Solutions, IQVIA, Copenhagen, Denmark; 7Department of Clinical Development and Analytics, Novartis Pharma AG, Basel, SwitzerlandCorrespondence: Björn StällbergDepartment of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Box 564, Uppsala, SE-75122, SwedenTel +46-070-3149944Email b.stallberg@telia.comPurpose: Chronic obstructive pulmonary disease (COPD) exacerbations can negatively impact disease severity, progression, mortality and lead to hospitalizations. We aimed to develop a model that predicts a patient’s risk of hospitalization due to severe exacerbations (defined as COPD-related hospitalizations) of COPD, using Swedish patient level data.Patients and Methods: Patient level data for 7823 Swedish patients with COPD was collected from electronic medical records (EMRs) and national registries covering healthcare contacts, diagnoses, prescriptions, lab tests, hospitalizations and socioeconomic factors between 2000 and 2013. Models were created using machine-learning methods to predict risk of imminent exacerbation causing patient hospitalization due to COPD within the next 10 days. Exacerbations occurring within this period were considered as one event. Model performance was assessed using the Area under the Precision-Recall Curve (AUPRC). To compare performance with previous similar studies, the Area Under Receiver Operating Curve (AUROC) was also reported. The model with the highest mean cross validation AUPRC was selected as the final model and was in a final step trained on the entire training dataset.Results: The most important factors for predicting severe exacerbations were exacerbations in the previous six months and in whole history, number of COPD-related healthcare contacts and comorbidity burden. Validation on test data yielded an AUROC of 0.86 and AUPRC of 0.08, which was high in comparison to previously published attempts to predict COPD exacerbation.Conclusion: Our work suggests that clinically available information on patient history collected via automated retrieval from EMRs and national registries or directly during patient consultation can form the basis for future clinical tools to predict risk of severe COPD exacerbations.Keywords: COPD, machine learning, exacerbation, hospitalization

Kjell Larsson,1 Christer Janson,2 Karin Lisspers,3 Björn Ställberg,3 Gunnar Johansson,3 Florian S Gutzwiller,4 Karen Mezzi,4 Bine Kjoeller Bjerregaard,5 Leif Jorgensen5 1Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; 2Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 3Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 4Novartis Pharma AG, Global Patient Access, Basel, Switzerland; 5IQVIA Solutions, Real World Evidence Solutions, Copenhagen, DenmarkCorrespondence: Kjell LarssonIntegrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institute, Stockholm, SE-171 77, SwedenTel +467 0582 0763Email kjell.larsson@ki.sePurpose: The aim of this study was to assess the association between exacerbation frequency and clinical and economic outcomes in patients with COPD.Patients and Methods: Electronic medical record data linked to National Health Registries were collected from COPD patients at 52 Swedish primary care centers (2000– 2014). The outcomes analyzed were exacerbation rate, mortality, COPD treatments, lung function and healthcare costs during the follow-up period. Based on the exacerbation rate two years before index date, the patients were initially classified into three groups, either 0, 1 or ≥ 2 exacerbations per year. After the index date, the classification into exacerbation groups was updated each year based on the exacerbation rate during the last year of follow-up. A sensitivity analysis was conducted excluding patients with asthma diagnosis from the analysis.Results: In total 18,586 COPD patients were analyzed. A majority of the patients (60– 70%) who either have had no exacerbation or frequent exacerbations (≥ 2/year) during the pre-index period remained in their group (ie, with 0 or ≥ 2 annual exacerbations) during up to 11 years of follow-up. Compared with having no exacerbation, mortality was higher in patients having 1 (HR; 2.06 [1.93– 2.20]) and ≥ 2 (4.58 [4.33– 4.84]) exacerbations at any time during the follow-up. Lung function decline was more rapid in patients with frequent exacerbations and there was an almost linear relationship between exacerbations frequency and mortality. Total healthcare costs were higher in the frequent exacerbation group (≥ 2/year) than in patients with no or one exacerbation annually (p< 0.0001 for both). The results did not differ from the main analysis after exclusion of patients with a concurrent asthma diagnosis.Conclusion: In addition to faster lung function decline and increased mortality, frequent exacerbations in COPD patients imply a significant economic burden.Keywords: chronic obstructive pulmonary disease, exacerbations, mortality, lung function, healthcare cost, Sweden

Abstract Consumer wearables and sensors are a rich source of data about patients’ daily disease and symptom burden, particularly in the case of movement disorders like Parkinson’s disease (PD). However, interpreting these complex data into so-called digital biomarkers requires complicated analytical approaches, and validating these biomarkers requires sufficient data and unbiased evaluation methods. Here we describe the use of crowdsourcing to specifically evaluate and benchmark features derived from accelerometer and gyroscope data in two different datasets to predict the presence of PD and severity of three PD symptoms: tremor, dyskinesia, and bradykinesia. Forty teams from around the world submitted features, and achieved drastically improved predictive performance for PD status (best AUROC = 0.87), as well as tremor- (best AUPR = 0.75), dyskinesia- (best AUPR = 0.48) and bradykinesia-severity (best AUPR = 0.95).

Benjamin Lebwohl,1,2 Emma Larsson,3 Jonas Söderling,4 Bjorn Roelstraete,4 Joseph A Murray,5 Peter HR Green,1 Jonas F Ludvigsson1,4,6 1Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA; 2Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; 3Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; 4Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; 5Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 6Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, SwedenCorrespondence: Jonas F LudvigssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, PO Box 281, Stockholm, SE-17177, SwedenTel +46-19-6021000Email jonasludvigsson@yahoo.comBackground: Patients with celiac disease (CeD) are at increased risk of certain viral infections and of pneumococcal pneumonia, raising concerns that they may be susceptible to severe coronavirus disease 2019 (Covid-19). We aimed to quantify the association between CeD and severe outcomes related to Covid-19.Methods: We performed a population-based cohort study, identifying individuals with CeD in Sweden, as defined by small intestinal villus atrophy diagnosed at all (n=28) Swedish pathology departments during the years spanning 1969– 2017, and alive on February 1, 2020. We compared these patients to controls matched by sex, age, county, and calendar period. We performed Cox proportional hazards with follow-up through July 31, 2020, assessing risk of 1) hospital admission with a primary diagnosis of laboratory-confirmed Covid-19 (co-primary outcome); and 2) severe disease as defined by admission to intensive care unit and/or death attributed to Covid-19 (co-primary outcome).Results: Among patients with CeD (n=40,963) and controls (n=183,892), the risk of hospital admission for Covid-19 was 2.9 and 2.2 per 1000 person-years respectively. After adjusting for comorbidities, the risk of hospitalization for Covid-19 was not significantly increased in patients with CeD (HR 1.10; 95% CI 0.80– 1.50), nor was the risk of severe Covid-19 increased (HR 0.97; 95% CI 0.59– 1.59). Results were similarly null when we compared CeD patients to their non-CeD siblings with regard to these outcomes. Among all patients with CeD and controls hospitalized with a diagnosis of Covid-19 (n=58 and n=202, respectively), there was no significant difference in mortality (HR for CeD compared to controls 0.96; 95% CI 0.46– 2.02).Conclusion: In this population-based study, CeD was not associated with an increased risk of hospitalization for Covid-19 or intensive care unit and/or death attributed to Covid-19.Keywords: Covid-19, celiac disease, epidemiology, infection, SARS-CoV-2

Abstract Objective The expanding power and accessibility of personal technology provide an opportunity to reduce burdens and costs of traditional clinical site‐centric therapeutic trials in Parkinson’s disease and generate novel insights. The value of this approach has never been more evident than during the current COVID‐19 pandemic. We sought to (1) establish and implement the infrastructure for longitudinal, virtual follow‐up of clinical trial participants, (2) compare changes in smartphone‐based assessments, online patient‐reported outcomes, and remote expert assessments, and (3) explore novel digital markers of Parkinson’s disease disability and progression. Methods Participants from two recently completed phase III clinical trials of inosine and isradipine enrolled in Assessing Tele‐Health Outcomes in Multiyear Extensions of Parkinson’s Disease trials (AT‐HOME PD), a two‐year virtual cohort study. After providing electronic informed consent, individuals complete annual video visits with a movement disorder specialist, smartphone‐based assessments of motor function and socialization, and patient‐reported outcomes online. Results From the two clinical trials, 226 individuals from 42 states in the United States and Canada enrolled. Of these, 181 (80%) have successfully downloaded the study’s smartphone application and 161 (71%) have completed patient‐reported outcomes on the online platform. Interpretation It is feasible to conduct a large‐scale, international virtual observational study following the completion of participation in brick‐and‐mortar clinical trials in Parkinson’s disease. This study, which brings research to participants, will compare established clinical endpoints with novel digital biomarkers and thereby inform the longitudinal follow‐up of clinical trial participants and design of future clinical trials.

Measurement(s) body movement coordination trait • Movement Disorder Society Unified Parkinson’s Disease Rating Scale Questionnaire • Medication • motor coordination/balance trait • sleep pattern • MDS-UPDRS Tasks and Simulated Activities of Daily Living (in-clinic) • Activity of Daily Living Technology Type(s) Accelerometer • body movement/behavior method • Clinical Observation • smartphone • Subject Diary Factor Type(s) age of patient • gender of patient • timing of medication intake Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13574279

Measurement(s) body movement coordination trait • Movement Disorder Society Unified Parkinson’s Disease Rating Scale Questionnaire • Medication • motor coordination/balance trait • sleep pattern • MDS-UPDRS Tasks and Simulated Activities of Daily Living (in-clinic) • Activity of Daily Living Technology Type(s) Accelerometer • body movement/behavior method • Clinical Observation • smartphone • Subject Diary Factor Type(s) age of patient • gender of patient • timing of medication intake Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13342055

Emma Larsson,1 Mala Mawkin,1 Simon D Taylor-Robinson,1 Peter Harrington,2 Hastings Gondwe,3 Chris Watson,2,4 Joseph Gallagher,2 Mark Ledwidge,2 Griphin Baxter Chirambo,5,6 John O’Donoghue2,6,7 1Imperial College London, South Kensington, London SW7 2BX, UK; 2gHealth Research Group, University College Dublin, Dublin, Ireland; 3St John’s Hospital, Mzuzu, Malawi; 4Wellcome-Wolfson Institute for Experimental Medicine, Queens University Belfast, Belfast, Northern Ireland; 5Mzuzu University, Mzuzu, Malawi; 6Malawi eHealth Research Centre, University College Cork, Cork, Ireland; 7ASSERT Research Centre, University College Cork, Cork, IrelandCorrespondence: John O’DonoghueASSERT Research Centre, University College Cork, College Road, Cork T12 K8AF, IrelandTel +353 21 420 5616Email john.odonoghue@ucc.ieIntroduction: Safe, reliable, and effective healthcare systems are essential for all nations to ensure the health and wellbeing of their citizens. However, this is not always achievable with clinical therapies constantly evolving, resulting in a domino effect of structural, policy and training changes. For low- and middle-income countries (LMICs), implementing change is restricted. It is essential that innovative and realistic solutions are developed, so that effective change can be realised in LMICs.Materials and Methods: In this report of a global health conference held in July 2019, six perspectives are presented which aim to generate long-term positive change in Malaŵi. Perspective 1: Pneumonia – the BIOTOPE study (BIOmarkers TO diagnose PnEumonia) sought to determine the aetiology of pneumonia in children presenting in primary care. It assessed blood-based markers of bacterial infection as part of a rapid diagnostic approach to better utilise existing resources in Malaŵi. Perspective 2: Cardiovascular – the CARDIA project (CARdiac Dysfunction in Africa) was established to assess clinical and biochemical phenotypes of diabetic patients in Malaŵi. Perspective 3: Asthma – an observational study was conducted to implement a health system strengthening initiative for asthma. The use of locally adapted formularies and protocols with ongoing online mentoring through expert partnerships provided an opportunity to sustainably build capacity. Perspective 4: Sustainable Partnerships – establishing the Malaŵi electronic Health (eHealth) Research Centre, an international hub to develop education, research and innovation for long-term collaboration. Perspective 5: Part-Time PhD Studies – undertaking a part-time PhD within a LMIC provides logistic challenges, but also a number of opportunities for observational research. Perspective 6: Medical electives – an undergraduate elective allows real exposure to global health and facilitates life-long collaborations at an early stage in a medical career.Conclusion: Malaŵi is an under-doctored and resource-poor country. North-South partnerships in Malaŵi should be strengthened with particular emphasis on healthcare innovations, such as eHealth, which allow healthcare problems to be highlighted early while preventative measures are still possible.Keywords: eHealth, mHealth, non-communicable diseases, respiratory disease, cardiovascular disease, diabetes