KI Open Archive Karolinska Institutet
Not a member yet
10598 research outputs found
Sort by
Rumors and fears about the HPV vaccine : perceptions of adolescent girls in government school in Addis Ababa
No full textCervical cancer remains a significant global public health threat, particularly in low- and middle-income countries, like Ethiopia. The Human Papillomavirus (HPV) vaccination is the most effective tool to prevent HPV transmission and reduce cervical cancer-related mortality, but the vaccine uptake remains suboptimal. The public perception of the HPV vaccine is marked by fear and doubt. Although girls are the primary targets of HPV vaccination, little is known about their perspectives, especially in low- and middle-income countries (LMICs). This study addressed the research question: How do adolescent girls perceive the HPV vaccine, and what factors influence their confidence and uptake? The aim was to explore girls’ perceptions and to identify the challenges and factors that shape girls HPV vaccine confidence and uptake. This is a qualitative study that used eight 30 minutes focus group discussions (FGD) with 9 to 10 girls each for a total of 76 girls aged 12 to 15 from selected schools in Addis Ababa. Three trained researchers facilitated the discussion. From using reflexive thematic analysis (RTA), four key themes were created. The FGDs revealed that rumors, misinformation, and poor communication fueled girls’ fear and limited their engagement in the vaccination campaign. Their decisions were influenced by parents, peers, and prior COVID-19 vaccination experiences, while minimal involvement hindered awareness and informed choices. In conclusion, the study underscored the importance of effective communication and involving girls in vaccination campaigns to reduce misinformation, improve awareness, and increase vaccine uptake.</p
Bridging process mining and clinical epidemiology : a framework for discovering disease trajectories in real-world data
No full textProcess mining bridges data mining and process models by extracting knowledge from event logs to discover, monitor, and improve real-world processes. While widely applied in business and manufacturing, its potential in clinical epidemiology remains underexplored. This doctoral thesis addresses this gap by progressively developing and applying process mining methodology to uncover meaningful disease trajectories in chronic kidney disease using real-world clinical data.We first conducted a systematic review of process mining applications in chronic disease research, revealing that while process mining had matured in healthcare workflow optimisation, its use in population-based epidemiology remained limited. The review identified key methodological gaps and established that integration with statistical methods is essential for moving beyond descriptive visualisation to comparative inference (Paper I). We then assessed the feasibility of applying process mining to a validated epidemiological cohort, confirming that process mining can reliably reconstruct estimated glomerular filtration rate pathways and reveals dynamic, bidirectional disease progression patterns that traditional time-to-event methods overlook (Paper II).With the feasibility confirmed by the previous two studies, we proposed and validated an eight-step framework integrating epidemiological design with data-driven process mining techniques encompassing process discovery, statistical testing, and prediction (Paper III). To address interpretation challenges inherent in complex process maps, we developed HealthProcessAI (Paper IV), a generative AI framework that integrates large language models (LLMs) with existing process mining libraries (PM4PY, bupaR) to automate interpretation and generate clinical reports.Papers V and VI applied the developed methodology to clinical questions. Paper V examines how proton pump inhibitor versus H2 blocker use affects trajectories of chronic kidney disease, cardiovascular events, and death. Process models revealed that proton pump inhibitor users experience faster progression to chronic kidney disease and cardiovascular disease, with chronic kidney disease appearing as an intermediate step linking medication use to cardiovascular outcomes. However, the analysis also demonstrated that the overall effect diminishes when accounting for the competing risk of death, illustrating how process mining makes competing pathways visible in ways that standard time-to-event analysis does not. Paper VI analysed 29,901 adults surviving myocardial infarction or heart failure, stratified by chronic kidney disease severity. The study demonstrated that increasing chronic kidney disease severity was associated with greater care complexity, more frequent accumulation of circulatory diagnoses, and high-risk trajectories involving multiple organ systems, all strongly associated with mortality. These findings reveal not just which comorbidities occur, but how they accumulate in temporal sequence, providing potential targets for early intervention.Together, these studies demonstrate the feasibility and added value of integrating process mining with clinical epidemiology. This approach offers a useful, data-driven methodology for understanding disease dynamics that complements traditional epidemiological methods.List of scientific papersThis PhD thesis is based on the following papers.I. Chen, K., Abtahi, F., Carrero, J. J., Fernandez-Llatas, C. & Seoane, F. Process mining and data mining applications in the domain of chronic diseases: a systematic review. Artif Intell Med. 144, 102645. https://doi.org/10.1016/j.artmed.2023.102645II. Chen K, Abtahi F, Xu H, Fernandez-Llatas C, Carrero JJ, Seoane F. The Assessment of the Association of Proton Pump Inhibitor Usage with Chronic Kidney Disease Progression through a Process Mining Approach. Biomedicines. 2024, 12, 1362. https://doi.org/10.3390/biomedicines12061362III. Chen K, Abtahi F, Carrero JJ, Fernandez-Llatas C, Xu H, Seoane F. Validation of an interactive process mining methodology for clinical epidemiology through a cohort study on chronic kidney disease progression. Sci Rep. 14, 27997 (2024). https://doi.org/10.1038/s41598-024-79704-5IV. Eduardo Illueca-Fernandez, Kaile Chen, Fernando Seoane, Farhad Abtahi. HealthProcessAI: A Technical Framework and Proof-of-Concept for LLM-Enhanced Healthcare Process Mining. [Submitted]V. Chen K, Abtahi F, Fernandez-Llatas C, Xu H, Seoane F. Longitudinal trajectories unravel the complex interplay of medication, cardiovascular events, chronic kidney disease, and mortality. Sci Rep. 15, 35577 (2025). https://doi.org/10.1038/s41598-025-23527-5VI. Chen K, Xu H, Abtahi F, Fernandez-Llatas C, Seoane F, Carrero JJ. Mapping the Complexity of Care in Patients with Myocardial Infarction or Heart Failure living with Chronic Kidney Disease. [Submitted]</p
Traumatic mitral valve injury by low-energy chest trauma : a rare cause of acute heart failure
No full textarticle: Traumatic mitral valve injury by low-energy chest trauma: a rare cause of acute heart failure - Italian Journal of Emergency Medicine 2021 April;10(1):39-41 - Minerva Medica - Journals</p
Post operative nausea and vomiting : The big little problem impact on recovery
No full textPostoperative nausea and vomiting (PONV) remain a common and distressing complication following anaesthesia, affecting approximately 30 % of unselected patients and up to 70 % of individuals at high risk within the first 24 hours postoperatively. Women, particularly young non-smokers, are consistently identified as a high-risk group. Multidimensional instruments, such as the Quality of Recovery 15 (QoR-15) scale, provide valuable insight into recovery and the impact of PONV and post-discharge nausea and vomiting (PDNV) on overall patient wellbeing.This thesis aimed to enhance the prediction and management of PONV in female patients undergoing high-risk surgical procedures. Four interconnected studies explored incidence, risk stratification, non-pharmacological interventions, and patient-reported recovery outcomes.In Study I, 275 women scheduled for breast cancer surgery were included; 33 % experienced PONV and 67% did not. Sixty-one of these patients later received adjuvant chemotherapy. In the non-PONV group, 95 % did not experience chemotherapy-induced nausea and vomiting (CINV), compared with only 38 % among those who had previously suffered from PONV. This suggests that certain individuals may possess an intrinsic resistance to nausea and vomiting.Study II included 183 women from the same cohort. PONV occurred in 35 % and incidence increased in line with the Apfel risk score. Preoperative platelet parameters-including count, mean platelet volume and platelet mass-did not differ significantly between groups, indicating that static platelet measurements are insufficient to predict PONV risk.In Study III, 73 ASA 1-2 women undergoing elective laparoscopic surgery were included. The intervention group received a 200 mL nutritional drink two hours pre-operatively and chewed gum post-operatively. Quality of recovery, measured by QoR-15, sum score was significantly higher in the intervention group at 24 hours (113 + 20 vs 101 + 25, p = 0.026) and 48 hours (123 + 13 vs 111 + 13, p = 0.006), demonstrating the potential of simple non-pharmacological measures to enhance early recovery.In Study IV, 98 women undergoing day-case laparoscopic cholecystectomy were followed for one week. All patients were assessed preoperatively with a modified Apfel score and received prophylaxis according to their risk level.Preoperative median QoR-15 score was 129 (95 % CI 128-132). It declined to 123 (95 % Cl 119-129) immediately post-operatively and to 109 (95 % CI 104-114) on day 1, with no significant differences between Apfel risk score groups. Scores increased on day 2 (median 123; 95 % CI 119-128). On day 2, Apfel risk 1 patients scored 131 (95 % CI 130-137) while risk 4 patients scored 118 (95 % CI 108-126; p= 0.019). QoR-15 continued to increase on day 3 and at one week reaching 129 (95 % CI 125-132) and 135 (95 % CI 132-138) respectively, with no significant risk-group differences. These findings confirm that risk-based prophylaxis combined with multimodal opioid-sparing analgesia supports comparable recovery trajectories across risk categories when applied in female day-case surgery.In conclusion, this work provides insights into the multifactorial nature of PONV in women, emphasising the importance of validated risk assessment, tailored prophylaxis, and the value of simple supportive interventions such as nutritional drinks and chewing gum. It underscores the utility of multidimensional patient-reported outcome measures in assessing postoperative recovery, and highlights the potential influence of genetic and individual variability in susceptibility to nausea. The findings support a patient-centred, evidence-based strategy to reduce the incidence and impact of PONV, improve recovery and guide future research on predictive markers and optimised care pathways in female surgical populations.List of scientific papersI. Is there an association between PONV and chemotherapy- induced nausea and vomiting? Oddby-Muhrbeck E, Öbrink E, Eksborg S, Rotstein S, Lönnqvist PA. Acta Anaesthesiol Scand. 2013 Jul;57(6):749-53. Epub 2013 Jan 3. PMID: 23281590 https://doi.org/10.1111/aas.12053II. Preoperative platelet count and volume could not help predict PONV in women undergoing breast cancer surgery: A prospective cohort study Öbrink E, Eksborg S, Lönnqvist PA, Oddby-Muhrbeck E, Jakobsson JG. Int J Surg. 2015 Jun;18:128-31. Epub 2015 Apr 16. PMID: 25889881 https://doi.org/10.1016/j.ijsu.2015.03.006III. Can simple perioperative measures improve quality of recovery following ambulatory laparoscopic surgery in females? An open prospective randomised cohort study, comparing nutritional preoperative drink and chewing gum during recovery to standard care Öbrink E, Lerstrom J, Hillström C, Oddby E, Jakobsson JG Ann Med Surg (Lond). 2019 Jun 8;44:20-25. PMID: 31289670; PMCID: PMC6593201 https://doi.org/10.1016/j.amsu.2019.05.010IV. Quality of Recovery 15 (QoR15) after cholecystectomy in females receiving Apfel risk score based PONV-prophylaxis is similar between high and low risk score. Öbrink E, Jakobsson JG [Manuscript]</p
Expanding the toolkit for studying 3D genome organisation
No full textThe mammalian genome, despite being confined within a small nuclear space, exhibits a non-random spatial organisation essential for establishing and maintaining cellular function and cell identity. Specifically, chromosomes and even specific genomic loci tend to occupy particular radial positioning (thereafter referred to as "radiality"), which is closely linked to their chromatin state and gene regulation.In this thesis, I present an optimised and streamlined version of the GPSeq protocol. This protocol leverages the controlled diffusion of restriction enzymes to digest chromatin from the nuclear periphery towards the centre and thus enables genome-wide mapping of radiality at unprecedentedly high resolution. Alongside this experimental advancement, I streamlined a user-friendly computation pipeline to support the broader study of radial genome organisation.Thereafter, I applied this methodology to address two key biological questions: 1) how two parental alleles are radially positioned in the nucleus and the functional implications of their positioning and 2) whether cell type-specific radiality profiles exist and their functional relevance.In the investigation of allelic radiality, we applied GPSeq to a hybrid mouse cell line that carries two distinguishable alleles and thus allows allele-specific analysis. I found that autosomal alleles display similar positions along the radial axis. However, upon X inactivation, the two X chromosomes showed striking differences in radiality. Unexpectedly, the inactive X chromosome was located more centrally relative to its active counterpart despite its compact and heterochromatic nature. This finding was validated using a FISH experiment and suggests a novel perspective on the mechanism of X inactivation, in which the inactive chromosome X does not rely on the repressive environment at the nuclear periphery to remain silenced but instead relocates inward, likely to be associated with the nucleolus, another repressive nuclear structure.Building on the prior knowledge on radiality, I further profiled five different cell types to explore cell type-specific radial genome organisation. Intriguingly, these profiles revealed distinct patterns amongst cell types, while cell lines of the same cell type but different origins showed high similarity. Examination of intrinsic genomic features uncovered consistent relationship between radiality and chromosome size, as well as gene density across cell types. Moreover, an exceptionally strong correlation between radiality with GC content was observed in all but one cell type, which showed only a moderate correlation. A gradual and dynamic change was also observed during the differentiation of stem cells into cortical neurons, reflecting the specification of radiality profiles during differentiation. These findings together support the hypothesis that radial genome organisation contributes to establishing cell identity, despite the nearly identical genomic sequences across cell types.</p
Neuromyelitis optica spectrum disorder, and related disorders : epidemiology, imaging biomarkers, and electrophysiology
No full textBackground: Acute myelitis is often associated with central nervous system inflammatory diseases as multiple sclerosis (MS), or with the antibody-driven diseases neuromyelitis optica spectrum disorder (NMOSD, i.e., neuromyelitis optica (NMO)), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Studies on the incidence and long-term outcome of acute myelitis are scarce, and much is still unclear the epidemiology and pathophysiology of NMOSD and MOGAD. Both NMOSD and MOGAD are commonly treated with the immunosuppressive agent rituximab, but only a few reports provide real-world data on efficacy and safety.Enlarged perivascular spaces (EPVS) are fluid-filled lesions on brain MRI, possibly involved in autoimmune CNS processes. Studies on EPVS in NMOSD and MOGAD are few, and comparative studies between neuroinflammatory diseases are lacking.An important and challenging differential diagnosis for acute myelitis is spinal cord infarction (SCI). Motor and sensory evoked potentials (MEP/SEP) test the integrity of spinal cord pathways and have been used in intraoperative monitoring to detect spinal cord ischemia.Objectives: The aim of this thesis was: to estimate the incidence and prevalence of NMO/NMOSD in Sweden (Study I); to explore how patients with NMOSD and MOGAD fare on rituximab in terms of relapse incidence and risk of severe infections (Study II); to describe the incidence and clinical presentation of acute myelitis, as well as functional outcome and relapse risk (Study III); to examen the distribution of EPVS in patients with various neuroinflammatory diseases (Study IV); and to test if evoked potentials can differentiate SCI from acute myelitis (Study V).Methods: Study I, included a cohort of individuals with a diagnostic code in the national patient registry (NPR) for NMO/NMOSD, or with a positive aquaporin-4 antibody (AQP4-IgG) analysis, in Sweden from 1987 to 2013 (n = 294). The 2006 NMO diagnostic criteria was used to identify NMO patients (n = 51), and individuals with AQP4-IgG but a more limited clinical presentation were categorized as NMOSD (n = 41).Study III, a cohort study, included individuals with diagnostic codes in the NPR likely to include acute myelitis in Stockholm County from 2008 to 2018 (n = 2321). A modified version of the 2002 Transverse Myelitis Consortium Working Group criteria, which also allows for partial myelitis, was used to identify patients with acute myelitis (n = 461). Follow-up data was collected for patients not receiving an initial diagnosis of MS or NMOSD. Uni- and multivariate analyses were used to explore factors of poor functional outcome, and factors related to risk of relapse after an idiopathic myelitis.In Studies II and IV, patients with NMOSD and MOGAD at Karolinska University Hospital were included. Study III retrospectively studied a cohort of NMOSD, both AQP4-IgG positive (AQP4+NMOSD) (n = 24) and seronegative (n = 10), as well as MOGAD (n = 8) patients treated with rituximab between 2012 and 2021. Study IV prospectively included all available AQP4+NMOSD (n = 22), seronegative NMOSD (n=8), and MOGAD (n = 10) patients during 2021-2022. Additionally, Study IV included three MS cohorts (n = 146) previously collected as part of other studies and healthy controls (n = 70).Incidence rates for relapse and severe infectious events (SIE) during rituximab treatment, in Study II were compared between groups in a multivariate analysis.In Study IV, all brain MRI examinations (n=256) were performed with the same protocol on the same 3 Tesla MRI machine. Using 3D T1-weighted images, brain volumetry was collected with FreeSurfer, and EPVS count, mean size, and volume was quantified with 3D computational framework with a morphological-based Frangi filter. Multivariable analysis was used to compare EPVS metrics between groups, and Spearmann for testing for correlations across disability level within groups.For Study V, patients with acute myelitis or spinal infarction at Karolinska University Hospital were prospectively included within 30 days of onset and underwent neurophysiological examination of lower limb MEP and SEP. Fisher's exact test was used to compare MEP and SEP findings between groups.Results: In Study I, the incidence of NMO/NMOSD in Sweden, per million person-years, increased from 0.3 between 1987 and 2006 to 0.8 between 2007 and 2013. The prevalence at the end of 2013 was 10.4 per million individuals. Most patients (78%) had relapsing disease with a median time to first relapse of 1.4 years.Study II found that half of all patients relapsed on rituximab. Patients with MOGAD had 3 times higher incidence risk ratio (IRR) for relapses compared to AQP4+NMOSD patients. Conversely, the IRR for SIE was around 5 times higher in AQP4+NMOSD than MOGAD.Study III found acute myelitis to have a stable incidence of 24.9 (95% CI 16.7-33.9) per million person-years in Stockholm between 2008 and 2018. Around 11% had poor function outcome and an increase in risk with age over 50 years, transverse spinal cord lesions, elevated count of polymorphonuclear cells, and elevated CSF/serum albumin ratio. Patients with idiopathic myelitis relapsed in 27% of cases, with increased risk related to findings of oligoclonal bands, transverse spinal cord lesions, and multifocal spinal cord lesions. MS was diagnosed at some point in 48% of acute myelitis patients.Study IV found the highest EPVS burden in MOGAD patients, compared to healthy controls, followed by seronegative NMOSD and MS. The EPVS burden was driven by higher counts in MOGAD and larger EPVS mean size in MS. Disability level was not found to correlate with EPVS counts.Study V found that MEP abnormalities, particularly non-responsive MEP, was more frequent in SCI compared to acute myelitis, and could discriminate SCI from acute myelitis with moderate sensitivity and high specificity. No difference in SEP abnormalities was found between the groups.Conclusions: NMO/NMOSD incidence rates were similar to other predominantly Caucasian countries. The increase in incidence rates during the study period was probably related to increased access to AQP4-IgG analysis and increased awareness of the disease.MOGAD patients are at substantial risk of relapses during rituximab treatment and more effective options are needed. Clinicians should be watchful for infections in AQP4+NMOSD patients.Acute myelitis is a relatively common neurological condition with high risk of having an underlying chronic neuroinflammatory disease (particularly MS). A thorough clinical workup and follow-up are recommended to quickly identify those at risk.EPVS metrics varied over CNS inflammatory diseases suggesting distinct characteristics and demonstrate the utility of automatic EPVS quantification.MEP show promise as a supplementary tool when differentiating SCI from acute myelitis but larger studies are needed to validate the findings and further develop the method.List of scientific papersI. Jonsson DI*, Sveinsson O*, Hakim R, Brundin L. Epidemiology of NMOSD in Sweden from 1987 to 2013: A nationwide population- based study. Neurology. 2019 Jul 9;93(2):e181-e189. https://doi.org/10.1212/WNL.0000000000007746II. Carlsson O, Jonsson DI, Brundin L, Iacobaeus E. Relapses and Serious Infections in Patients with Neuromyelitis Optica Spectrum Disorder Treated with Rituximab: A Swedish Single-Center Study. J Clin Med. 2024 Jan 8;13(2):355. https://doi.org/10.3390/jcm13020355III. Jonsson DI, Sveinsson O, Moeini N, Pivac E, Wirdefeldt K, Brundin L, Iacobaeus E. Incidence, Etiology, and Long-Term Outcome of Acute Myelitis in Stockholm County, Sweden: A Population-Based Study. Neurol Neuroimmunol Neuroinflamm. 2025 Nov;12(6):e200472. https://doi.org/10.1212/NXI.0000000000200472IV. Jonsson DI, Ouellette R, Hagbohm C, Park D, Coello RD, Ganeshan AR, Chamyani N, Ineichen BV, Evertsson B, Valdes Hernandez M, Wardlaw J, Jagodic M, Kockum I, Brundin L, Fink K, Piehl F, Iacobaeus E*, Granberg T*. Enlarged perivascular spaces differ across MOGAD, NMOSD, and MS. *Shared last authorship. [Manuscript]V. Jonsson DI, Gripenland J, Iacobaeus E. The Use of Combined Sensory-Evoked Potentials and Motor-Evoked Potentials for Differential Diagnostics of Spinal Infarction and Acute Myelitis. - A Single Center Pilot Study. [Manuscript]</p
Quality of life and use of hormonal treatment following surgical menopause in BRCA-carriers and ovarian cancer survivors
No full textBackground and objectivesRemoval of both ovaries before natural menopause will induce surgical menopause with a negative impact on short- and long-term health. Bilateral salpingo-oophorectomy before menopause is performed to treat ovarian cancer or, in some cases, as a preventive measure. For women treated for ovarian cancer, postoperative Menopausal Hormone Therapy (MHT) may improve quality of life and long-term health. The extent of MHT use and its safety in terms of overall survival after ovarian cancer treatment in premenopausal women is unclear. Women with a BRCA1/2 pathogenic variant have an inherited risk of developing ovarian cancer and are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at a fertile age. Studies on the sexual and psychological consequences following RRSO are needed to improve guidance and care.The objective was to investigate the proportion of postoperative MHT use in premenopausal women treated with bilateral salpingo-oophorectomy due to ovarian cancer. Second, to prospectively assess sexual function and psychological well-being in women before and after RRSO, as well as to compare with healthy women of the same age. Further, to determine whether serum testosterone levels correlate with sexual functioning and psychological well- being after RRSO. Finally, to evaluate whether postoperative MHT use following bilateral salpingo-oophorectomy due to treatment for ovarian cancer affects overall survival.Methods and Main ResultsStudies I and IV are nationwide retrospective register and population-based cohort studies. In Study I, 664 women in Sweden aged 18-50, who underwent bilateral salpingo-oophorectomy as part of treatment for epithelial ovarian cancer, non-epithelial ovarian cancer, or a borderline ovarian tumor diagnosis from January 2008 to December 2014, were identified in the Swedish Quality Register of Gynecologic Cancer. For study IV, the inclusion criterion was identical but extended until December 2015, and a total of 779 women were identified. Dispensing of MHT was obtained by linkage to the National Prescription Drug Register.In study I, the proportion of women who dispensed MHT post-surgery and factors associated with its use were analyzed. Within the first year after surgery 62 % of the total cohort did not dispense MHT. Among women aged 44 or younger, 54% did not receive MHT within the first year. Factors associated with MHT dispensing included younger age (In Study IV, the safety of postoperative MHT use was evaluated in relation to overall survival using flexible parametric survival models, adjusting for covariates, with separate analyses for epithelial ovarian cancer, non-epithelial ovarian cancer, and borderline ovarian tumors. Among 472 women with epithelial ovarian cancer, there was no difference in 10-year overall survival between the postoperative MHT users and the non-users. For the subgroup with epithelial ovarian cancer and no residual disease at surgery (n=363), overall survival was similar regardless of postoperative MHT use. Borderline ovarian tumors were diagnosed in 239 women, with no survival differences related to MHT use.In studies II and III, 43 women with a known BRCA1/2 pathogenic variant, opting for RRSO at Karolinska University Hospital during 2011-2014, and 73 women of the same age with their ovaries preserved, were included. Sexual function and psychological well-being were assessed using the validated questionnaires Female Sexual Function Index, Hospital Anxiety and Depression Scale, and Psychological General Well-Being Index. Blood samples were collected, and serum testosterone was measured by tandem mass spectrometry. Free Androgen Index was also calculated. Data were collected at two time-points in the RRSO group: before and one year after surgery. The comparison group was assessed only at inclusion.After RRSO, areas of sexual function deteriorated, and anxiety levels decreased, while levels of depression and psychological well-being remained unchanged. Women with RRSO reported higher rates of sexual dysfunction and greater anxiety symptoms as opposed to the comparison group, whereas no differences in symptom levels of depression or well-being were found. Serum testosterone levels were unchanged, and the Free Androgen Index was significantly higher among the comparison group. No correlations were observed between testosterone levels and sexual function or psychological health.ConclusionsThe rate of postoperative MHT dispensing after ovarian cancer surgery in women 50 years or younger was low. Risk-reducing salpingo-oophorectomy was linked to a deterioration in sexual function but did not negatively affect psychological well-being. Following RRSO, more sexual dysfunction was reported than among women with retained ovaries; however, endogenous testosterone levels did not relate to sexual or psychological health. Postoperative MHT did not reduce overall survival, supporting its oncological safety. Postoperative MHT use should be discussed with young ovarian cancer survivors to promote short and long-term health.List of scientific papersI. Hormone replacement in premenopausal women treated with bilateral oophorectomy for ovarian cancer - A nationwide population-based study. von Kartaschew ÅE, Dahm-Kähler P, Rodriguez-Wallberg KA, Holmberg E, Rådestad AF. Gynecol Oncol. 2022 Dec;167(3):476-482. https://doi.org/10.1016/j.ygyno.2022.09.027II. Sexual function following risk-reducing salpingo-oophorectomy: a prospective cohort study. von Kartaschew ÅE, Hirschberg AL, Gemzell-Danielsson K, Flöter Rådestad A. Sex Med. 2024 .Nov 19;12(5):qfae078. https://doi.org/10.1093/sexmed/qfae078III. Psychological quality of life in BRCA1/2- carriers following risk-reducing salpingo-oophorectomy: a preliminary report. Ehlin von Kartaschew Å, Lindén Hirschberg A, Gemzell-Danielsson K, Flöter Rådestad A. Menopause. September 2025; 32(9):p 849-857. https://doi.org/10.1097/gme.0000000000002571IV. Menopausal Hormone Therapy After Ovarian Cancer: A 10-Year Survival Analysis in Premenopausal Women. Åsa Ehlin von Kartaschew, Pernilla Dahm-Kähler, Kenny Rodriguez Wallberg, Erik Holmberg, Angelique Flöter Rådestad [Manuscript]</p
From drugs to climate : associations between external factors and profound hyponatremia
No full textBackground:Hyponatremia is the most common electrolyte disturbance and associated with substantial morbidity and mortality. Despite its clinical relevance, many aspects of hyponatremia's epidemiology, including pharmacological and environmental influences remain challenging for clinicians. This doctoral thesis addresses key knowledge gaps using population-based register data to investigate drug- induced hyponatremia, climate-related risk factors, and the value of an integrated cohort with sodium concentrations in focus.Aims:The overarching goal of this thesis is to improve understanding of hyponatremia by examining its pharmacological and environmental determinants. Specifically, the aims were to:1- Investigate the time-dependent risk of hyponatremia associated with proton pump inhibitors (PPIs).2- Establish and describe the Stockholm Sodium Cohort (SSC), a population- based database for sodium research.3- Assess the association between outdoor temperature and severe hyponatremia.4- Evaluate the risk of profound hyponatremia linked to selective serotonin reuptake inhibitors (SSRIs) and venlafaxine.Methods:All studies used population-based registers. Study 1 obtained data from the National Patient Register on hospitalized patients due to hyponatremia between 2006 and 2014. Studies 2-4 utilized the SSC, a cohort of 1.6 million residents of Stockholm County with at least one recorded serum sodium measurement between 2005 and 2018. Individual-level sodium test results were linked to national registers covering demographics, socioeconomic status, diagnoses, health care contacts, and dispensed medications. Study 1 used a case-control design with over 56,000 individuals to analyze the time-course of hyponatremia after omeprazole/esomeprazole initiation. Study 2 describes the creation and representativeness of the SSC. Study 3 was a retrospective cohort analysis assessing temperature-hyponatremia links using daily temperature data matched to residential area. Study 4 applied a within-individual design including 234,217 new users of SSRIs/venlafaxine to analyze the temporal risk of profound hyponatremia.Results:In Study 1, the adjusted odds ratio (aOR) for hospitalization due to hyponatremia was highest within the first week of PPI treatment (aOR 6.87), declining gradually over five weeks. Ongoing use was associated with a modest risk (aOR 1.10). Study 2 showed that the SSC covered 64% of the regional population and over 90% of patients with major chronic diseases, demonstrating its strong representativeness for clinical and pharmacoepidemiologic research. In Study 3, 51,143 episodes of severe hyponatremia (serum sodium Conclusion:This thesis demonstrates that hyponatremia is strongly associated with both pharmacologic exposures and environmental factors. The findings emphasize that PPIs and serotonergic antidepressants pose the greatest risk shortly after initiation, supporting early and targeted sodium monitoring in high-risk populations, particularly elderly women. Moreover, outdoor temperature is an important factor in severe hyponatremia risk, which is projected to rise substantially with future climate warming. The establishment of the SSC provides a robust and generalizable platform for studying sodium-related conditions on a population level. Together, these studies provide new, clinically actionable insights that may inform drug safety monitoring, geriatric care, and public health responses to climate change.List of scientific papersI. Issa I, Skov J, Falhammar H, Calissendorff J, Lindh JD, Mannheimer B. Time- dependent association between omeprazole and esomeprazole and hospitalization due to hyponatremia. Eur J Clin Pharmacol. 2023 Jan;79(1):71-77. https://doi.org/10.1007/s00228-022-03423-xII. Issa I, Skov J, Falhammar H, Franko MA, Lindh JD, Mannheimer B. Establishment and representativeness of the Stockholm Sodium Cohort: A laboratorial and pharmacoepidemiologic database covering 1.6 million individuals in the Stockholm County. Ann Epidemiol. 2024 Mar;91:1-7. https://doi.org/10.1016/j.annepidem.2024.01.005III. Issa I, Skov J, Falhammar H, Lindh JD, Mannheimer B. The Association of Outdoor Temperature with Severe Hyponatremia. J Am Soc Nephrol. 2025 Mar 1;36(3):435-440. doi: 10.1681/ASN.0000000519.https://doi.org/10.1681/ASN.0000000519IV. Issa I, Skov J, Falhammar H, Roos M, Lindh JD, Mannheimer B. The association of selective serotonin reuptake inhibitors and venlafaxine with profound hyponatremia. Eur J Endocrinol. 2025 Jun 30;193(1):179-187. https://doi.org/10.1093/ejendo/lvaf140</p
Decision makers’ perceptions on implementing welfare technology in Swedish municipal elder care: a qualitative study
No full textBackground Welfare technology is often depicted as a potential solution for managing the increasing challenges on elder care services, which is expected to rise due to demographic changes. In this study, we explore local decision-makers’ perceptions on implementing welfare technologies in Swedish municipal elder care. Methods Four politicians and twelve local government officials were interviewed, and reflexive thematic analysis was utilized. Results Our findings suggest that welfare technology is portrayed as a sustainable long-term solution, governed by bureaucratic structures. Successful implementation requires shared responsibility among various stakeholders but also moving in-between resistance and acceptance among staff and older people. Furthermore, welfare technology was viewed to reduce staff burdens and increase independence and participation for older people. Conclusions Welfare technology is viewed positively by local decision-makers as a long-term solution to challenges associated with funding and staff shortages in elder care. It is expected to reduce the burden on staff and increase independence and participation for older people. However, bureaucratic challenges must be addressed to enhance the quality of elder care.</p
Prosocial learning and decision-making in alcohol use disorder
No full textBackground:Alcohol Use Disorder (AUD) is one of the most prevalent and burdensome psychiatric conditions worldwide. Despite evidence-based treatments, clinical outcomes remain modest, and many patients continue to suffer. One overlooked factor may be interpersonal functioning. While previous research has largely focused on clinical symptoms such as craving and withdrawal, less is known about how prosocial behavior-acts intended to benefit others-relate to the development, maintenance, and treatment of AUD.Aims:The overarching goal of this thesis was to investigate prosocial behavior in relevance to AUD using a multimodal approach. Specifically, it aimed to:(1) examine prosocial learning and decision-making in individuals with AUD (Studies I-II), (2) test whether intranasal oxytocin could modulate prosocial decision-making and preferences in AUD (Study III), and (3) evaluate whether individual differences in prosocial and antisocial behavior predict future substance use and psychiatric symptoms in youth and adult clinical populations (Studies IV and V).Methods:The thesis includes five empirical studies involving clinical, experimental, and longitudinal designs.· Studies I-II assessed altruism, fairness, trust, third-party punishment and social reward learning using behavioral economic tasks and reinforcement learning paradigms in large samples of individuals with AUD and matched healthy controls (N=500 total).· Study III was a double-blind, placebo-controlled clinical trial (N=206) evaluating the causal effects of intranasal oxytocin on prosocial decision- making and preferences.· Study IV used nationwide longitudinal data (N=3,817 adolescents) to examine whether antisocial and prosocial behaviors at age 15-16 predicted substance use at age 17-18.· Study V used a 1-year prospective cohort of adults with psychiatric diagnoses (N=4,484) to investigate how different subtypes of prosociality predicted later psychiatric symptom trajectories.Results:· Study I showed that individuals with AUD consistently exhibited lower levels of altruism, fairness, and reciprocal trust across both lab and online samples. These effects were not explained by recent drinking or comorbid psychiatric symptoms, but were linked to attentional focus and moral reasoning indicating trait-like deficits in core prosocial domains.· Study Il found that social reward learning-learning how one's actions benefit others-was intact in AUD, suggesting that reduced prosociality reflects a motivational deficit rather than a learning impairment.· Study III showed that intranasal oxytocin did reduce prosocial decision- making in AUD, in particular for those with an individualistic disposition. However, oxytocin increased prosocial preferences-especially among individuals lower emotional empathy and lower attachment anxiety- suggesting that oxytocin may influence social motivation in terms of preferences, even if it does not translate directly into behavior.· Study IV showed that antisocial traits in terms conduct problems and criminal behavior and redued institutional trust were strong and independent predictors of later substance use.· Study V revealed that specific subtypes of prosociality differentially predicted psychiatric trajectories: anonymous helping was protective against future AUD symptoms, whereas public and emotional helping were associated with greater risk for SUD and anxiety, respectively.Conclusions:This thesis demonstrates that prosocial behavior in AUD is not a unitary construct but varies in its manifestations, mechanisms, and predictive value. Reductions in prosocial decision-making appear to be stable, trait-like vulnerabilities rather than transient effects of alcohol use. Although the oxytocin system seems to play a role in explaining reduced prosociality in AUD, individual differences in emotional processes is crucial to predict the effect of administering oxytocin endogenously. Moreover, different subtypes of prosociality-particularly anonymous versus public and emotionally driven helping-carry distinct implications for psychiatric risk and resilience. Together, these findings suggest that social functioning in AUD is best understood not as a general deficit, but as a nuanced and dynamic domain that differs between individuals with the same patient group. Future research should investigate individual differences in social behavior by applying computational approaches to objectively characterize the underlying causal mechanisms and subsequently design corresponding personalized treatments.Clinical and Research Implications:The results underscore the potential of incorporating objective social behavioral measures into clinical assessment and treatment planning for AUD. Interventions should be developed for targeting social motivation. Pharmacological interventions such as oxytocin may serve as useful adjuncts in modulating social motivation in subgroups of AUD with low emotional responding , though further research is needed. Finally, the predictive role of specific prosocial behaviors in psychiatric outcomes highlights the potential value of early social interventions to prevent later substance use and emotional distress.List of scientific papersI. Jangard, S., Lindström, B., Khemiri, L., Pärnamets, P., Jayaram- Lindström, N., & Olsson, A. (2022). Alcohol use disorder displays trait- related reductions in prosocial decision making. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 7(9), 925-934. https://www.biologicalpsychiatrycnni.org/article/S2451- 9022(22)00118-5/https://doi.org/10.1016/j.bpsc.2022.05.002II. Jangard, S., Lindström, B., Khemiri, L., Jayaram-Lindström, N., & Olsson, A. (2025). Dissociating social reward learning and behavior in alcohol disorder. Translational Psychiatry, 15(1), 30. https://www.nature.com/articles/s41398-025-03236-3https://doi.org/10.1038/s41398-025-03236-3III. Jangard S., Guterstam, J., Gustavsson, E., Asperholm., M., Helldén, J., Olsson, A., & Jayaram-Lindström, N. The Impact of Oxytocin on Prosocial Decision Making and Preferences in Males with Alcohol Use Disorder [Manuscript]IV. Jangard, S., Olsson, A., Molero, Y., Jayaram-Lindström, N., & Raninen, J. (2025). Antisocial and prosocial behaviors as predictors of subsequent substance use in adolescence. Addictive Behaviors, 166, 108308. https://www.sciencedirect.com/science/article/pii/S0306460325000 632https://doi.org/10.1016/j.addbeh.2025.108308V. Jangard, S., Vieira, J. B., Garke, M. Å., Ojala, O., Månsson, N.T., K., Sörman, K., El Alaoui, S., Hedman-Lagerlöf, M., Rozental, A., Forsström, D., Lundin, J., Shahnavaz, S., Lundgren, T., Olsson, A., & Jayaram-Lindström, N. Situation-specific Prosocial Behaviors Predict Substance Use and Anxiety Symptoms in Psychiatric Disorders [Manuscript]</p