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Serving two masters - the work as healthcare providers and retail employees in community pharmacies in Sweden
No full textBackground: In Sweden, approximately 11,000 employees in community pharmacies dispense 91 million prescriptions annually and assist 370,000 customers daily. Pharmacists are healthcare professionals, yet their work is embedded in a commercial retail environment, following the 2009 deregulation of the Swedish pharmacy market. International and Swedish literature identifies a persistent tension between professional responsibilities, such as medication counseling and safety, and business imperatives, including sales targets and revenue generation. Research internationally and in Sweden identifies tensions between professional responsibilities and business objectives, with reported impacts on increased focus on sales, stress, increased workload, and utilization of pharmacists' expertise. Little is known about the lived experience of Swedish pharmacists, how they navigate this duality in daily practice, and the contextual factors perceived to influence their work. By addressing this gap, knowledge is added about work in market-driven healthcare landscapes.Aim: The thesis aimed to explore community pharmacy work in Sweden at the intersection of healthcare provision and retail business. Three main questions are explored: (I) How do employees perceive and navigate their work in Swedish pharmacies? (II) What are the main aspects in the context that influence community pharmacists' perceptions of their work? (III) What are the implications for future work in pharmacies, based on the current state and pharmacy sector stakeholders' suggestions for change? Three empirical studies are included in the thesis: Study I examined employees' perceptions and practices in well-functioning pharmacies; Study II investigated how pharmacists combine healthcare obligations with commercial demands; and Study III explored stakeholder-proposed changes to pharmacy practice and their potential impact on future work.Method: An exploratory qualitative design was employed, using semi-structured interviews with pharmacists, pharmacy technicians, managers, industry representatives, educators, and policymakers. Forty-two informants were interviewed across the studies, and the interviews were either in person or online. All interviews were conducted in Swedish and transcribed. The data were analyzed using qualitative content analysis or thematic analysis. The studies were subjected to review by the Swedish Ethical Review Authority.Findings: Across the studies, pharmacists described their work as most meaningful when centered on patient care, dispensing, and counselling, reflecting a strong identification with their healthcare role. In Study I, employees in well- functioning pharmacies described high engagement, collegial support, and loyalty to their profession and patients rather than to corporate objectives. Study II identified persistent conflicts between professional and business responsibilities, intensified by time constraints and organizational emphasis on sales targets. Pharmacists managed these conflicts individually through strategies such as compromise, reframing, and stretching mandates, which allowed some alignment of business tasks with professional purpose but did not resolve underlying tensions. Study III found that stakeholders had a multitude of suggestions for changes, including increased staffing, enhanced reimbursement, expanded clinical services, and new offerings. While proposals to reinforce professional work (e.g., paid counselling, extended clinical roles) could strengthen professional autonomy, diversification into non-core services risked diluting professional identity.Conclusion: Swedish community pharmacy practice is characterized by the continual negotiation of healthcare and commercial roles within a context where the constellation of institutional logics seems dominated by state and corporate logics. Pharmacists sustain professional identity and patient-centred work through individual adaptation, yet structural conditions perpetuate conflicts of interest between professional and business priorities. Strengthening reimbursement for core services, expanding integration with primary care, and granting greater professional control over work processes could enhance autonomy and reduce tensions. Conversely, service diversification and technology-driven delivery models should be critically assessed for potential impacts on professional status. This thesis contributes empirical knowledge on the lived experience of pharmacy work and offers insights that could be helpful to align commercial and professional imperatives.List of scientific papersI. Hagsten, K., Eriksson, A., & Palm, K. (2024). Self-propelled Employees - Co-workership in Swedish Community Pharmacies. Nordic Journal of Working Life Studies, 14(1), 47-66.https://doi.org/10.18291/njwls.142122II. Hagsten, K., Eriksson, A., Svensson, I., & Palm, K. (2024). The juggling act of pharmacists in Sweden: A qualitative study on balancing healthcare professionalism and retail employment. BMC Health Services Research, 24(1), 1212.https://doi.org/10.1186/s12913-024-11682-wIII. Hagsten, K., Eriksson, A., Palm, K., & Svensson, I. Ambitions for change: An Institutional logics' perspective on potential changes in Swedish pharmacy practice. [Manuscript]</p
Chemical and genetic screening approaches for the discovery of novel treatments
No full textTo discover novel treatments, a variety of methods are used. In our laboratory we focus on the discovery of novel drug candidates through chemical high- throughput phenotypic screening. After identifying new compounds with therapeutic potential, the characterization of the properties of these drugs as well as elucidate their mechanism of action (MoA) becomes an important task. In addition to identifying novel therapies, and with the help of genome-wide CRISPR- Cas9 screens, we also try to discover mutations that modulate its effects, which can help to identify patients most likely to respond, or resist, to the drug.In Paper I, we conducted a high-throughput image based chemical screen to identify compounds which could upregulate human leukocyte antigen I (HLA-I) on the surface of cancer cells and thus improve the recognition of tumor cells by cytotoxic T cells. In the screen we utilized cells with an inactive IFNy signaling pathway achieved by knocking out STAT1, since mutations in this pathway are one of the main causes of resistance to cancer immunotherapies. We thus explored whether it is possible to upregulate HLA-I expression with drugs independently of the JAK/STAT signaling pathway. The compound library comprised of more than 5.000 chemicals, including medically approved drugs and several agents in advanced preclinical development, targeting several different cell signaling pathways. Unfortunately, we could not identify any significant hit compound, indicating that drug-dependent modulation of HLA-I expression is strictly dependent on intact IFNy signaling.In Paper II, we performed a genome-wide CRISPR screen to identify genetic modulators of the toxicity of RNA Polymerase I (Pol I) inhibitors, which are being explored as novel agents in the treatment of cancer. To do so, we studied the antibiotic Actinomycin D (ActD), which is commonly used in cancer therapy, and the pre-clinical tested small molecule BMH21, both known to inhibit Pol I and induce nucleolar stress. While mutations in genes known to regulate the nucleolar stress checkpoint such as TP53 and RB led to resistance to both compounds, mutations that enhanced PI3K/mTOR signalling lead to an increased sensitivity to Pol I inhibition. Interestingly, we could identify mutations which lead to resistance to one drug but sensitivity to the other, suggesting that the drugs have distinct effects on the cells despite both being used as Pol I inhibitors. Overall, our research provides an overview on genetic modulators of nucleolar stress inducing compounds and could therefore help to identify patients who could benefit the most from Pol I targeted therapies based on their tumor genetics.In Paper III, we discovered a novel molecule with antiviral properties by conducting a high-throughput phenotypic screen using a pseudotype virus expressing the SARS-CoV-2 spike protein. Subsequence experiments using the molecule, which we named virapinib, demonstrated its ability to limit an infection by SARS-CoV-2 as well as other viruses, such as mpox and tick-borne encephalitis virus (TBEV). Additional mechanistic studies showed that virapinib inhibits macropinocytosis, limiting the entry for viruses using this route of infection of host cells. Virapinib presented no significant toxic effect on the host cells which further highlights its potential as an alternative treatment to prevent viral infections.List of scientific papersI. Myriam Barz*, Bartlomiej Porebski*, Pranauti Panshikar, Maria Häggbladd, Daniela Hühn, Oscar Fernandez-Capetillo. 2023. 'A chemical screen underscores the essential role of STAT1- dependent IFNy signaling to regulate HLA-I expression in cancer cells'. microPublication Biology. https://doi.org/10.17912/micropub.biology.000697.II. Myriam Barz*, Alba Corman*, Maria Häggbladd, Alicia González- Serrano, Louise Lidemalm, Matilde Murga, Daniela Hühn, Oscar Fernandez-Capetillo. 2025. 'The PI3K/mTOR axis modulates the response to nucleolar stress'. [Manuscript]III. Bartlomiej Porebski, Wanda Christ, Alba Corman, Martin Haraldsson, Myriam Barz, Louise Lidemalm, Maria Häggbladd, Juliana Ilmain, Shane C Wright, Matilde Murga, Jan Schlegel, Malin Jarvius, Maris Lapins, Erdinc Sezgin, Gira Bhabha, Volker M Lauschke, Jordi Carreras-Puigvert, Miguel Lafarga, Jonas Klingström, Daniela Hühn, Oscar Fernandez-Capetillo. 2024. 'Discovery of a novel inhibitor of macropinocytosis with antiviral activity' Mol Ther. 2024 Jul 2:S1525-0016(24)00455-6. https://doi.org/10.1016/j.ymthe.2024.06.038*These authors contributed equally</p
Evaluating neuroblastoma and paraganglioma cancer heterogeneity and cell of origin through single cell transcriptomics
No full textNeuroblastoma is a cancer that arises in the adrenal medulla and sympathetic chain. Paraganglioma is a cancer that arises in the adrenal and extra-adrenal chromaffin cells. Neuroblastoma is a pediatric cancer with an average age at diagnosis of 18 months of age. Paraganglioma is most often present in adults, with an average age at diagnosis of 55 years of age. Neuroblastoma is highly metastatic, with almost 80% of high-risk cases having metastasize at diagnosis. Only 10 to 30% of paraganglioma metastasize.In paper I we aimed to explore inter- and intra- tumor heterogeneity in human neuroblastoma. Particularly we investigated a cohort of high- and low-risk neuroblastoma samples to understand cancer cellular identities and their relationship with risk and age stratification. In paper II we aimed to characterize a postnatal progenitor-like population of cells in the healthy adrenal gland and its relationship with paraganglioma tumors. In paper III we aimed to explore inter- and intra- tumor heterogeneity in a cohort of neuroblastomas and paragangliomas. We looked to identify transcriptional similarities between these tumors and the healthy adrenal gland and between neuroblastoma and paraganglioma. In paper IV we aimed to examine transcriptional states, tumor microenvironment and epigenetic landscapes in neuroblastoma.To this effect we used single cell/nuclei trancriptomics, bulk transcriptomics, spatial transcriptomics, and multiOmics. In addition, we performed stainings and lineage tracing.In paper I we found that NB samples of different age-groups and risk stratification contained different contribution of cells. High-risk NB samples had a significantly higher proportion of progenitor-like undifferentiated cells, whereas low-risk samples consisted mostly of noradrenergic cells. We found that gene signatures for noradrenergic clusters are significantly upregulated in low-risk patients. In paper II, we identified 2 VHL-related paraganglioma tumors with Schawn-cell-like cells carrying an inferred 3p deletion. The same deletion was found in neuroendocrine cells from the same sample. However, the neuroendocrine cells carried additional copy number alterations. This suggests that in rare cases Schawn-cell-like stroma cells could potentially act as cell of origin of PPGL. In paper III we found a subpopulation of cells in malignant PPGL resembling cycling neuroblasts. This suggests neuroblasts may be influencing clinical progression in paraganglioma. We explore further this finding by running a deconvolution in a bulk transcriptomics dataset enriched with metastatic samples. We observed that metastatic samples had higher proportion of cycling neuroblasts when compared to non-metastatic samples. In paper IV we projected neuroblastoma cells onto a developmental trajectory reference. We identified 7 states that contributed to 2 classes, mesenchymal/neural crest, and sympathoadrenal committed. The 2 classes are linked by an intermediate bridge/connecting state. The bridge state was associated with high risk poorly differentiated neuroblastoma. We used MultiOmics sequencing to obtain information of gene expression and chromatin accessibility. We found that transcription factor E2F7 influences cell transitions and promotes NB malignancy through reinforcing the bridge state. We used spatial transcriptomics to deconvolve the developmental states of the reference into the tumor spatial spot. We quantified the distance between each tumor state-spot. We observed that bridge tumor spots were closer to cancer associated fibroblasts and tumor associated macrophages.In conclusion, we explore cell states underlying a broad cohort of paraganglioma and neuroblastoma tumors and its relationship with the healthy adrenal gland. We identify progenitor-like population of cells that embryonically and postnatal could be influencing tumorigenesis in paraganglioma and neuroblastoma. Understanding the molecular mechanisms underlying PPGL and NB pathogenesis and progression has significant implications. The identification and validation of biomarkers is critical for diagnostic and targeted therapies.List of scientific papersI. Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors O. C. Bedoya-Reina*, W. Li*, M. Arceo, M. Plescher, P. Bulova, H. Pui, M. Kaucka, P. Kharchenko, T. Martinson, J. Holmberg, I. Adameyko, Q. Deng, C. Larsson, C. C. Juhlin, P. Kogner, S. Schlisio Nature communications (2021), 12(1), 5309. https://doi.org/10.1038/s41467-021-24870-7II. Sustentacular glia-like cells as postnatal chromaffin progenitors and tumor cells of origin in a subset of VHL-related paragangliomas. P. Bulova*, P. Cui*, M. Arceo, J. Zhu, W. Li, M. Plescher, V. Poltorachenko, K. Stripling, C. Santangeli, M. E. Kastriti, C. Larsson, C. C. Juhlin, M. Mints and S. Schlisio [Manuscript preprint] https://doi.org/10.21203/rs.3.rs-6907400/v1III. Cells resembling embryonic cycling neuroblasts as potential driver of malignant paraganglioma. M. Arceo*, J. Zhu*, W. Li, K. Stripling, V. Poltorachenko, K. S. Hose, P. Kogner, A. Stenman, C. Larsson, C. C. Juhlin, M. Mints and S. Schlisio [Manuscript]IV. Single-cell MultiOmics and spatial transcriptomics demonstrate neuroblastoma developmental plasticity. Y. Zhu, D. Lou, P. Chen, G. Li, D. Usoskin, J. Pan, F. Li, S. Huang, C. Hess, R. Tang, X. Hu, J. Yu, M. Arceo, R. R. de Krijger, A. Tischler, S. Schlisio, P. Ernfors, Y. Hu, J. Wang Developmental Cell (2025) https://doi.org/10.1016/j.devcel.2025.04.013(*) equal contributions</p
Advancing precision medicine in pancreatic cancer through bioinformatics-assisted genomic profiling and clinical stratification
No full textPancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies, characterized by late diagnosis, pronounced molecular heterogeneity, and limited responsiveness to current treatments. 0The unifying theme is the integration of molecular, clinical, and epidemiological insights to better understand PDAC's pathogenesis and to guide more effective, individualized approaches for prevention, early intervention, and treatment.In studies I and IV, tumor and matched control samples from 14 and 39 PDAC patients, respectively, were processed under SWEDAC-certified workflows at the Department of Clinical Pathology and Cytology, Karolinska University Hospital. Blocks were reviewed by the pathologist with blocks containing >20% tumor cells used for DNA extraction. Sequencing was preformed; data was subsequently processed using a clinical decision support systems (CDSS). Reports predicting drug efficacy, resistance, and toxicity, oncogenic relevance using the OncoScore algorithm, and assesses variant impact with an evidence-weighted functional impact scoring system. Pharmacogenomic toxicity predictions were cross- validated against the PharmGKB database and FDA adverse event reporting system. In study I, no therapeutic recommendations were made, and the study was a retrospective study to assess the feasibility of implementing personalized cancer medicine in routine clinical practice. However, study IV produced off-label recommendations which were recommended as second-line therapy.Study II investigated predictors of malignant transformation in intraductal papillary mucinous neoplasms (IPMNs), a recognized PDAC precursor. In a retrospective cohort of surgically resected IPMNs (152 patients between 2008- 2015), main pancreatic duct dilation 26 mm, jaundice, and elevated CA19-9 were independently associated with high-grade dysplasia (HGD) or invasive cancer. These findings identify preoperative clinical features that may aid earlier intervention in high-risk patients.Study III examined the association between new-onset diabetes mellitus (NODM), anti-diabetic medications, and pancreatic cancer risk in a nested case-control design within the UK Health Improvement Network (1996-2010). New-onset T2DM and rising glycated hemoglobin (HbA1c) levels were independent risk factors for pancreatic cancer. Risk varied by medication, with the highest observed among insulin users, followed by sulphonylureas, and a weaker association seen with metformin use.All four studies are linked by their shared focus on improving the early detection, risk stratification, and personalized management of pancreatic ductal adenocarcinoma (PDAC). Precision oncology approaches, using next-generation sequencing offer potential to identify actionable alterations, predict treatment efficacy and toxicity, and demonstrated potential for integration into routine care within a 2-week timeframe. Specific preoperative features can identify IPMN patients at high risk for advanced dysplasia, and metabolic factors such as NODM and worsening glycemic control are independent pancreatic cancer risk factors. Together, these findings inform strategies for PDAC risk assessment, early intervention, and potential integration of precision oncology into clinical care, while emphasizing the need for critical evaluation of emerging molecular tools.List of scientific papersI. Malgerud L, Lindberg J, Wirta V, Gustafsson-Liljefors M, Karimi M, Moro CF, Stecker K, Picker A, Huelsewig C, Stein M, Bohnert R, Del Chiaro M, Haas SL, Heuchel RL, Permert J, Maeurer MJ, Brock S, Verbeke CS, Engstrand L, Jackson DB, Grönberg H, Löhr JM. Bioinformatory-assisted analysis of next-generation sequencing data for precision medicine in pancreatic cancer. Mol Oncol. 2017;11(10):1413-29. https://doi.org/10.1002/1878-0261.12108II. Ateeb Z, Valente R, Pozzi-Mucelli RM, Malgerud L, Schlieper Y, Rangelova E, Fernandez-Moro C, Löhr JM, Arnelo U, Del Chiaro M. Main pancreatic duct dilation greater than 6 mm and elevated preoperative CA19-9 levels are associated with an increased risk of high-grade dysplasia and cancer in IPMN patients. Langenbecks Arch Surg. 2019;404(1):31-37. https://doi.org/10.1007/s00423-018-1740-8III. Lu Y, García-Rodríguez LA, Malgerud L, González-Pérez A, Martín- Pérez M, Lagergren J, Bexelius TS. New-onset type 2 diabetes, elevated HbA1c, anti-diabetic medications, and risk of pancreatic cancer. Br J Cancer. 2015 Nov 17;113(11):1607-1614. https://doi.org/10.1038/bjc.2015.353IV. Malgerud L*, Kordes M*, Frödin J-E, Yachnin J, Fernandez Moro C, Ghazi S, Pozzi Mucelli R, Kartalis N, Ghorbani P, Del Chiaro M, Wirta V, Björnstedt M, Liljefors MG, Lohr J-M. Consistency of a clinical decision support system with molecular tumour board recommendations for tumour sequencing-guided treatment of pancreatic cancer: a prospective observational study. ESMO Gastrointestinal Oncology. 2024;1(1):100070. https://doi.org/10.1016/j.esmogo.2024.100070 *Equal contributions as first authors</p
Knowledge and attitudes of medical students regarding human papilloma virus infection and vaccine : cross-sectional study from Jordan
No full textBackground: As of the present moment, Jordan is yet to incorporate cervical cancer screening in its cancer control program nor advocates for vaccines. This paper aims to examines the perceptions and attitudes of medical students towards HPV and its vaccine. Methods: We conducted a cross-examination of HPV knowledge and vaccine uptake among medical students across the period between January and March 2024. Participants completed a questionnaire developed and validated by the existing literature. The questionnaire was composed of 4 domains pertaining to sociodemographic, knowledge of HPV, knowledge of HPV vaccine, and attitudes. Medical students were conveniently sampled from Jordan’s six public medical schools. Predictors to self-vaccinate, recommending vaccination to friends/family, and recommending vaccination to patients were examined using a binary logistic regression model. All analyses were conducted on R version (4.3.3).ResultsA total of 473 medical students were included in the final analysis. On a scale of 12 and 8, mean HPV and vaccine knowledge scores were 5.4 ± 3.1 and 2.9 ± 1.9, respectively. Knowledge of HPV and its vaccine were significantly higher among females, students in their clinical years, and those with self-perceived understanding of HPV (all p Conclusion: The study implies that the overall awareness and attitudes regarding HPV and its vaccine is alarmingly poor among medical students. Moreover, there exists a gender difference in the knowledge and attitudes favoring females. Concerned policy makers and institutions should strive to improve vaccine awareness and uptake through informational, behavioral, and environmental interventions. Moreover, medical students should be well equipped to tackle HPV vaccine hesitancy through curricular reforms, targeted training, and increased exposure to public vaccine promotional efforts.</p
Advancing assessments of endocrine disruptors using adverse outcome pathways and novel methodologies
No full textProtecting human and environmental health from adverse effects of endocrine disruptors (EDs) is a high priority in the EU. These substances cause a range of adverse effects, such as reproductive toxicity, neurotoxicity, metabolic disruption, and cancer. If an organism is exposed during a developmental life stage, the effects may also be permanent. Assessing if a substance has endocrine disrupting properties is a lengthy and complex process that requires considerable amounts of animal data. There is a demand to phase-out animal testing in the EU and, simultaneously, there is growing use of alternative methods, like in silico, in chemico, and in vitro methods. Hence, there is a need, and an opportunity, to move toward ED assessments based on mechanistic data from alternative methods. However, there is a lack of methodology to connect these types of novel and complex data to adverse outcomes for use in ED assessments.The aim of my doctoral project was to develop and explore methodologies for the assessment of endocrine disruptors based on mechanistic data. The Adverse Outcome Pathway (AOP) framework was crucial to achieve this and was used across all subprojects of the thesis. I explored many complex aspects of the AOP framework, including development and application of AOP network and quantitative AOPs (qAOPs). Literature-based, computational, and experimental approaches were utilized, as well as combinations of these.In Study I, I developed a data-driven approach to generate AOP networks. This approach combines a systematic approach to identifying relevant AOPs in the AOP-Wiki with a computational approach to process and filter AOP-Wiki data. The output could then be imported into a software for visualization and analysis of networks.In Study II, I conducted and compared a standard ED assessment according to current guidance, to a mechanism-based assessment without in vivo data. A thyroid-related AOP network was utilized for identifying relevant search terms and for mapping collected data to identify a potential Mode of Action. This case study was performed using perfluorooctane sulfonic acid (PFOS) as a model substance, investigating its potential for thyroid disruption and developmental neurotoxicity.In Study III, RNA-sequencing of zebrafish embryos exposed to either cadmium (Cd) or 3,3',4,4',5-pentachlorobiphenyl (PCB126) was performed to investigate how transcriptomics data can be coupled to an AOP network. Multiple different data analysis approaches were explored, and their potential connection to an estrogen, androgen, thyroid, and steroidogenesis (EATS) related AOP network was evaluated. Ultimately, I developed and compared a data-driven and an expert-driven approach to connect Gene Ontology (GO) terms from enrichment analysis to key events (KEs) in the network.In Study IV, I developed an approach to quantify a Key Event Relationship (KER) based on data from published literature, and applied this approach on a KER linking decreased circulating testosterone levels to decreased sperm count. The approach consists of two parts, (1) A structured search strategy, study reliability assessment, and standardized data extraction to collect and assess data for quantification, and (2) a statistical modelling approach to make the best use of the collected data.Through the development and application of AOP networks (Study I and III) I identified several opportunities for improving AOP development and functionality of the AOP-Wiki. The issues identified hinder topological analysis and application of data-driven approaches to connect mechanistic data to the network. In Study II, based on the standard ED assessment, I concluded that PFOS fulfils the scientific criteria as an ED based on thyroid disruption and developmental neurotoxicity. On the other hand, in the mechanism-based assessment, I could only identify endocrine activity and not endocrine-mediated adversity. There was a lack of quantitative understanding of the AOPs in the network, which was essential to inferring adversity based on mechanistic data. Study III revealed that both cadmium and PCB126 potentially have endocrine disrupting properties. Endocrine activity, and adversity likely mediated by EATS or non- EATS modalities, were observed. The data-driven approach to connect transcriptomics data to the AOP network yielded very few results, while the expert-driven approach provided many more connections. Gene expression measurements followed by enrichment analysis may be fit for connecting data to intermediate and late KEs, but not for early KEs and molecular initiating events (MIEs). In Study IV, the quantified KER can be used to predict decreased sperm count based on a decrease in circulating testosterone levels, including some uncertainty in the circulating testosterone levels. The model can potentially be used to reduce or replace animal experiments if coupled to e.g., in vitro testosterone synthesis experiments or physiologically based kinetic (PBK) models.To conclude, I have developed and applied novel risk assessment methodologies to maximize the use of mechanistic data for ED assessment. Both opportunities and challenges with these approaches have been explored, and future research needs have been identified. Moreover, endocrine disrupting properties of chemicals not yet classified as EDs (perfluorooctane sulfonic acid , cadmium, and 3,3',4,4',5- pentachlorobiphenyl) were investigated. Altogether, these results pave the way toward non-animal mechanism-based assessment of EDs and improved protection of human health.List of scientific papersI. Wiklund L, Caccia S, Pipal M, Nymark P, Beronius A. Development of a data-driven approach to Adverse Outcome Pathway network generation: a case study on the EATS-modalities. Front Toxicol. 2023 May 9; 5:1183824. https://doi.org/10.3389/ftox.2023.1183824II. Wiklund L, Pipal M, Weiss J, Beronius A. Exploring a mechanism-based approach for the identification of endocrine disruptors using Adverse Outcome Pathways (AOPs) and New Approach Methodologies (NAMs): A perfluorooctane sulfonic acid case study. Toxicology. 2024 May; 504:153794. https://doi.org/10.1016/j.tox.2024.153794III. Wiklund L, Wincent E, Beronius A. Using transcriptomics data and Adverse Outcome Pathway networks to explore endocrine disrupting properties of Cadmium and PCB-126. Environ Int. 2025 Mar; 197:109352. https://doi.org/10.1016/j.envint.2025.109352IV. Wiklund L, Ristovska M, Moe J, Beronius, A. Quantification of the Key Event Relationship "Decreased circulating testosterone leading to impaired spermatogenesis" based on data from peer-reviewed studies. [Manuscript]</p
The view of persons with and without dementia : important aspects of home care service
No full textAim: The overall aim was to explore and describe what older persons, both with and without dementia value and consider important when receiving home care services. Additionally, the thesis aimed to enhance the knowledge of how persons with dementia perceive being treated with dignity and respect in home care services over time and to compare these perceptions with those persons without dementia receiving similar home care services.Method: The included studies (n=3) were conducted within home care service facilities in Sweden. Participants included older persons, both with and without dementia in their medical record, who were receiving support and care from home care services. Studies I and II employed a qualitative design, with the data collected through semi-structured interviews and analysed using qualitative content analysis.Study III, a longitudinal study with a quantitative design, was based on national survey data from the Swedish National Board of Health and Welfare. Each year, the survey What do Older Persons Think about Care for Older invites all older persons aged 65 years or older who received care from Swedish care for older to participate. Data from 2016–2018 were analysed using descriptive statistics and ordinal logistic regression models.Findings: Study I explored the perspectives of 16 older persons without a dementia diagnosis on the values they considered important within home care services. Two main themes emerged: the need for support as autonomous persons and the need for support as relational beings. Participants reported that these values were only partially fulfilled by the services they received, and their well-being was negatively impacted when staff failed to uphold them. Key fundamental values identified included feeling safe, maintaining autonomy, exercising control and independence, and fostering relationships.In study II one overarching theme that emerged from 14 persons with dementia emphasised the importance of receiving support as unique and capable human beings. They expressed that, despite their dementia diagnoses, it remained essential to be recognised as persons with abilities, even when they required support.Study III found that persons with a dementia diagnosis had significantly lower odds ranging from 3% to 10% of expressing satisfaction with enquiries related to dignity and respect compared to those without dementia. From 2016 to 2018, satisfaction levels declined for both groups. Additionally, dissatisfaction was higher among females, persons with poor self-rated health, and those receiving more hours of home care services.Conclusion: The findings from Studies I, II, and III highlight that older persons, with and without dementia, have care needs closely aligned with the psychosocial dimensions identified in Kitwood’s Model of psychosocial needs; identity, inclusion, attachment, comfort, and meaningful occupation. When these needs are supported, dignity, autonomy, and well-being are strengthened; when neglected, vulnerability and exclusion increase. Structural changes are needed to align policy ambitions with the realities of care, including support for psychosocial needs, investment in staff competence, and continuity in care relationships key factors in achieving truly person-centred care in the care for older.List of scientific papersI. Olsen, M., Udo, C., Dahlberg, L., & Boström, A. M. (2022). Older persons' views on important values in Swedish home care service: A semi-structured interview study. Journal of Multidisciplinary Healthcare, 15, 967-977. https://doi.org/10.2147/JMDH.S347886II. Olsen, M., Udo, C., Boström, A. M., & Hammar, L. M. (2021). Important aspects of home care service: An interview study of persons with dementia. Dementia, 20(5), 1649–1663. https://doi.org/10.1177/1471301220964393III. Hammar, L. M., Alam, M., Olsen, M., Swall, A., & Boström, A. M. (2021). Being treated with respect and dignity? Perceptions of home care service among persons with dementia. Journal of the American Medical Directors Association, 22(3), 656-662. https://doi.org/10.1016/j.jamda.2020.07.002</p
Type 1 diabetes during pregnancy, birth, and breastfeeding
No full textBackgroundManaging Type 1 diabetes (T1D) during pregnancy remains a clinical challenge due to the increased risks of complications for both mother and child, making the well-documented benefits of breastfeeding especially important in this context. To reduce the risk of complications, evidence-based care is essential throughout the perinatal period. In Sweden, perinatal care for pregnant women with T1D is managed by decentralised, hospital-specific guidelines without evaluation of the perinatal outcomes over the past two decades. Breastfeeding also plays a vital role in perinatal care; therefore, antenatal colostrum expression is recommended for women with T1D to support the early provision of exclusive colostrum. However, the composition of antenatal colostrum in women with T1D has not been previously explored.Aim This thesis aims to improve care for pregnant women with T1D and their newborns by studying care provision in terms of guidelines, colostrum composition, and maternal and neonatal outcomes.MethodStudy 1 was a descriptive study aimed at comparing all the Swedish guidelines for the management of T1D during pregnancy and birth in terms of the degree of consensus among them. The second aim was to measure adherence to three of these guidelines in use at four hospitals and to describe the pregnancy and labour outcomes in relation to the level of adherence.Study 2 was a prospective cohort study that aimed to investigate and compare the macronutrient content in colostrum collected from women with and without T1D during gestational weeks 36 to 40 and postpartum days one to five. The study also aimed to compare the colostrum contents between women with and without T1D. A secondary aim was to compare the colostrum content from postpartum day one with colostrum from all the other timepoints and with formula.Study 3 was a retrospective cohort study using the Swedish Medical Birth Register to explore the odds of adverse neonatal outcomes in newborns of mothers with T1D compared to those of mothers without T1D during the years 2010-2022.Study 4 was a retrospective cohort study that utilized the Swedish Medical Birth Register to explore the odds of adverse maternal outcomes in women with T1D compared to women without T1D during the years 2010-2022.ResultsNo complete consensus was identified across the 30 hospital guidelines. Adherence to the guidelines with a rate of 270% was found to be low. A high adherence to the birth guidelines was significantly more common when the birth was induced. When pregnancy or birth guidelines were followed with low adherence non-instrumental vaginal births occurred more often.The colostrum content, specifically in terms of fat, carbohydrates, protein, and kilocalories, varied between the time points. Colostrum differed in protein in antenatal colostrum between women with and without T1D. Colostrum from postpartum day one was more similar to antenatal colostrum than colostrum from days two to five, and compared with formula.Neonates born to mothers with T1D had significantly increased odds of adverse neonatal outcomes, such as stillbirth, congenital malformations, premature birth, being born large for gestational age, and neonatal death.Women with T1D were generally taller and more often classified as overweight or obese, with higher rates of chronic kidney disease, chronic hypertension, smoking, and having been born in a Nordic country compared to women without T1D. T1D was significantly associated with increased odds of adverse maternal outcomes such as caesarean section, shoulder dystocia, postpartum haemorrhage, and endometritis.ConclusionDeveloping an evidence-based national guideline for preconception and perinatal care with high adherence, incorporating a recommendation to supplement fed newborns with antenatal colostrum, could help improve health outcomes for pregnant women with T1D and their newborns.List of scientific papersI. Goldberg A, Ursing C, Ekéus C, Wiberg-Itzel E. Swedish guidelines for type 1 diabetes and pregnancy outcomes: A nationwide descriptive study of consensus and adherence. Prim Care Diabetes. 2021;15(6):1040-51.https://doi.org/10.1016/j.pcd.2021.08.003II. Goldberg A, Pettersson H, Ekéus C, Ursing C, Wiberg-Itzel E, Tingström J. Comparison Between Antenatal and Postnatal Colostrum From Women With and Without Type 1 Diabetes. J Hum Lact. 2025;41(2):254-62.https://doi.org/10.1177/08903344251318285III. Goldberg A, Wiberg-Itzel E, Tingström J, Ekeus C. Neonatal Outcomes Among Neonates of Women With and Without Type 1 Diabetes in Sweden From 2010 to 2022. Acta Paediatr. 2025.https://doi.org/10.1111/apa.70230IV. Goldberg A, Wiberg-Itzel E, Tingström J, Ekeus C. Maternal outcomes among women with and without Type 1 Diabetes in Sweden. [Submitted]</p
Cell free DNA fragmentation in health and disease
No full textCell death is an important part of life. Cells have turnover rates that vary with function, environmental stressors, and disease state. Low turnover rates of long-lived differentiated cells such as cardiomyocytes of the heart and neurons of the brain ensure tissue architecture, while high turnover rates are necessary for other cell types to meet physiological demands. For example, erythrocytes and intestinal epithelial cells turnover rapidly to maintain oxygen-carrying capacity and efficient nutrient absorption, respectively. Low turnover rates can also protect against mutation accumulation that can lead to tissue damage and disease in cells that proliferate. Estimating cell death can give us a lens into normal human physiology as well as offer a means to diagnose illness and better monitor patients undergoing treatment.</p
The association between vital signs at hospital admission and adverse outcomes in patients with COVID-19 : a retrospective cohort study
No full textBackground: Vital sign measurements at hospital admission are used to identify patients at risk for adverse events. However, how vital signs at admission are related to adverse outcomes among COVID-19 patients is not fully characterized.Objectives: To characterize vital signs at admission and their associations with intensive care unit/intermediate care unit (ICU/IMCU) admission and in-hospital mortality in adult patients with COVID-19.Methods: This retrospective cohort study included 2,826 adults admitted with COVID-19 to Karolinska University Hospitals, Stockholm, Sweden, between 2 March 2020 and 1 June 2021. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between vital signs at admission and ICU/IMCU admission and in-hospital mortality.ResultsThe median age was 62.2 years, and 62.1% were men. Each unit increase in respiratory rate (HR 1.03, 95% CI 1.02–1.05), heart rate (HR 1.01, 95% CI 1.00–1.02), temperature (HR 1.21, 95% CI 1.11–1.32), and each unit decrease in saturation (HR 1.05, 95% CI 1.04–1.06) were associated with ICU/IMCU admission. Respiratory rate (HR 1.04, 95% CI 1.02–1.07) and saturation (HR 1.04, 95% CI 1.02–1.06) were also associated with in-hospital mortality. These associations persisted across pandemic waves.Conclusion: Respiratory rate and lower saturation at admission were associated with increased ICU/IMCU admission and in-hospital mortality. Our findings suggest that greater emphasis on respiratory rate and oxygen saturation in early warning scores—such as the revised Sequential Organ Failure Assessment (SOFA) score and other sepsis prediction models, to improve risk stratification of viral sepsis, especially in patients with COVID-19.</p