| 1. |
- Bergthorsdottir, Ragnhildur, 1971, et al.
(author)
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Increased risk of hospitalization, intensive care and death due to covid-19 in patients with adrenal insufficiency : a Swedish nationwide study
- 2024
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In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 295:3, s. 322-330
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Journal article (peer-reviewed)abstract
- Background: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown.Methods: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis.Results: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28).Conclusion: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.
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| 2. |
- Bobjer, Johannes, et al.
(author)
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Location of retroperitoneal lymph node metastases in upper tract urothelial carcinoma : results from a prospective lymph node mapping study
- 2023
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In: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 57, s. 37-44
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Journal article (peer-reviewed)abstract
- Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC).Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND).Design, setting, and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node–positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates.Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used.Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates.Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited.Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.
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| 3. |
- Einarsdottir, Margret, et al.
(author)
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Impact of chronic oral glucocorticoid treatment on mortality in patients with COVID-19: analysis of a population-based cohort.
- 2024
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In: BMJ Open. - 2044-6055. ; 14:3
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Journal article (peer-reviewed)abstract
- While glucocorticoid (GC) treatment initiated for COVID-19 reduces mortality, it is unclear whether GC treatment prior to COVID-19 affects mortality. Long-term GC use raises infection and thromboembolic risks. We investigated if patients with oral GC use prior to COVID-19 had increased mortality overall and by selected causes.Population-based observational cohort study.Population-based register data in Sweden.All patients infected with COVID-19 in Sweden from January 2020 to November 2021 (n=1 200 153).Any prior oral GC use was defined as ≥1GC prescription during 12 months before index. High exposure was defined as ≥2GC prescriptions with a cumulative prednisolone dose ≥750mg or equivalent during 6 months before index. GC users were compared with COVID-19 patients who had not received GCs within 12 months before index. We used Cox proportional hazard models and 1:2 propensity score matching to estimate HRs and 95% CIs, controlling for the same confounders in all analyses.3378 deaths occurred in subjects with any prior GC exposure (n=48806; 6.9%) and 14850 among non-exposed (n=1 151 347; 1.3%). Both high (HR 1.98, 95% CI 1.87 to 2.09) and any exposure (1.58, 1.52 to 1.65) to GCs were associated with overall death. Deaths from pulmonary embolism, sepsis and COVID-19 were associated with high GC exposure and, similarly but weaker, with any exposure. High exposure to GCs was associated with increased deaths caused by stroke and myocardial infarction.Patients on oral GC treatment prior to COVID-19 have increased mortality, particularly from pulmonary embolism, sepsis and COVID-19.
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| 4. |
- Ekström, Magnus, et al.
(author)
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Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.
- 2024
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In: Respiratory research. - : BioMed Central (BMC). - 1465-993X .- 1465-9921. ; 25:1
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Journal article (peer-reviewed)abstract
- Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population.Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64years. Breathlessness (modified Medical Research Council [mMRC]≥2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease.We included 25,948 people aged 57.5±[SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI≥30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers.Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.
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| 5. |
- Nyberg, Oskar, et al.
(author)
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Characterizing antibiotics in LCA-a review of current practices and proposed novel approaches for including resistance
- 2021
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In: The International Journal of Life Cycle Assessment. - : Springer Science and Business Media LLC. - 0948-3349 .- 1614-7502. ; 26, s. 1816-1831
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Journal article (peer-reviewed)abstract
- Purpose: With antibiotic resistance (ABR) portrayed as an increasing burden to human health, this study reviews how and to what extent toxicological impacts from antibiotic use are included in LCAs and supplement this with two novel approaches to include ABR, a consequence of antibiotic use, into the LCA framework.Methods: We review available LCA studies that deal with toxicological aspects of antibiotics to evaluate how these impacts from antibiotics have been characterized. Then, we present two novel approaches for including ABR-related impacts in life cycle impact assessments (LCIAs). The first approach characterizes the potential for ABR enrichment in the environmental compartment as a mid-point indicator, based on minimum selective concentrations for pathogenic bacteria. The second approach attributes human health impacts as an endpoint indictor, using quantitative relationships between the use of antibiotics and human well-being.Results and discussion: Our findings show that no LCA study to date have accounted for impacts related to ABR. In response, we show that our novel mid-point indicator approach could address this by allowing ABR impacts to be characterized for environmental compartments. We also establish cause-effect pathways between antibiotic use, ABR, and human well-being that generate results which are comparable with USEtox and most endpoint impact assessment approaches for human toxicology.Conclusions: Our proposed methods show that currently overlooked impacts from ABR enrichment in the environment could be captured within the LCA framework as a robust characterization methodology built around the established impact model USEtox. Substantial amounts of currently unavailable data are, however, needed to calculate emissions of antibiotics into the environment, to develop minimum selective concentrations for non-pathogenic bacteria, and to quantify potential human health impacts from AB use.
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| 6. |
- Nyberg, Oskar, et al.
(author)
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Ecotoxicological HC20-values and their statistical distribution : A nonlinear weighted regression applied to thousands of chemicals
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Other publication (other academic/artistic)abstract
- Ecotoxicological effect data which form the basis of evaluations of ecological impacts from chemical emissions are incomplete, and completely absent for some chemicals, which result in risks being overlooked. Where data are available, they tend to be heterogeneous and accompanied with large uncertainties. In the present research we curate ecotoxicological data from openly available sources and present a methodology for quantifying the variability in toxicity for chemicals and evaluate its implications for environmental assessment frameworks, such as life cycle assessments.The data collection resulted in a database detailing 118,131 curated records that span 1,736 species and 3,692 chemicals suitable for calculating the concentration response slope factors corresponding to the slope on the SSD curve at the 20% response level of organisms exposed to a chemical (CRFHC20). From these data we are able to calculate values and 95% percentile distributions of the CRFHC20 for 2,350 and 1,117 chemicals respectively. Pesticides is the most data rich category of chemicals, yet has the largest variability attached to the CRFHC20.We show that the variance among toxicity estimates for the same species and chemical can be used in weighted nonlinear model fitting to generate an uncertainty range attached to a CRFHC20 value, allowing for uncertainties related to ecotoxicological impact characterization in environmental frameworks to be estimated. Data scarcity is an omnipresent issue when it comes to characterizing toxicity of chemicals, where only 63.7 % of all chemicals with effect data records have enough data to calculate a CRFHC20 value, and 30.3 % have enough data to fit a weighted nonlinear least squares model. Our recommendation is to incorporate toxicological variance in estimations of ecotoxicity impacts and life cycle impact assessment categories, to reduce ambiguity and allow for verification when comparing ecotoxicological impacts.
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| 7. |
- Nyberg, Oskar, et al.
(author)
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Identifying mismatches in the classification of toxic emissions and potentials to gap-fill characterization factors in agricultural LCAs
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Other publication (other academic/artistic)abstract
- Life Cycle Assessment (LCA) is vital for evaluating environmental impacts throughout the value chain of a product, including toxicity in freshwater ecosystems and human health. Several methodologies to characterize toxicity of chemicals have emerged over time, generating an increasing number of characterized chemicals. Yet, evaluating toxicological impacts in agri-food LCA studies poses significant challenges. LCA data inventories are dynamic, lack uniformity, and may not encompass all relevant chemical attributes. Additionally, widely-used LCA software tools often lack completeness checks of available characterizations, potentially resulting in underestimations of toxicity impacts within value chains.Our study evaluates agri-food LCA studies, revealing significant underestimations of toxicological impacts due to missing characterization factors, especially concerning pesticide usage, highlighting the need for robust toxicological characterizations to support certification.We also explore the use of computational quantitative structure-activity relationship models to predict missing toxicological characterizations. However, challenges arise from these predictions, offering less reliable results due to complex toxic mechanisms and limited empirical data availability. We also scrutinize the limitations of applying generic characterization factors for pesticide groups.We propose criteria for LCA software developers to minimize the underestimation of toxicological impacts and boost transparency in studies and recommend to include completeness checks, avoiding generic characterization factors, and flagging chemicals without corresponding characterization factors.
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| 8. |
- Nyberg, Oskar, 1985-, et al.
(author)
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Poultry manure fertilization of Egyptian aquaculture ponds brings more cons than pros
- 2024
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In: Aquaculture. - 0044-8486 .- 1873-5622. ; 590
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Journal article (peer-reviewed)abstract
- Aquaculture is a crucial sector for Egyptian food production, providing a cheap source of animal protein while securing income and employment for a substantial part Egypt's population. Nile tilapia (Oreochromis niloticus) is the most commonly produced fish, usually farmed in earthen ponds around the Northern Delta Lakes. A common practice among farms is to fertilize ponds with chicken manure (CM) in order to increase nutrient levels and promote phytoplankton, consumed by the fish. However, with reports of use of antibiotics in Egypt's poultry sector, and that CM contains residues of antibiotics, antibiotic resistant pathogens and antibiotic resistance genes (ARGs) are production benefits large enough to compensate a potential health hazard?Using production data from 501 aquaculture farms and fish pond sediment from 28 ponds we evaluated potential benefits in yields and profitability for farms using CM for fertilization, and used qPCRs to screen sediments for three antibiotic resistance genes coding for resistance to the most commonly used antibiotics in the poultry sector. The analysis showed no significant benefits to fish yields or profitability in farms where CM was applied, but a risk of significantly increased nutrient loads. Meanwhile, we detected increased abundances of tetA and tetW resistance genes in fish pond sediment where CM was applied. With the risk of disseminating ARGs and causing eutrophication of local waterways, we recommend that Egyptian tilapia pond farmers refrain from using CM and adopt best management practices for increasing farm profitability in order to to reduce environmental and health hazards.
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| 9. |
- Nyberg, Oskar, 1985-
(author)
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Protecting food with poison : Exploring ecotoxicity of agrochemicals and pharmaceuticals
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Chemicals are being emitted into the environment through human activities, such as agriculture or animal husbandry. Emissions can either occur intentionally, as pesticide application of crops, or inadvertently, such as pharmaceutical residues in wastewater effluents. Chicken manure (CM) is occasionally used as a cheap fertilizer in aquaculture pond farms to increase the productivity and the profitability. Depending on local regulation and production strategy, animal manures can contain substantial amounts of antibiotics (AB) and other pharmaceuticals used for raising animals. The benefits of this practice, however, have not been clearly established in relation to the potential adverse consequences. By analysing production data from Egyptian fish farms in Study I, I show that CM fertilization promotes eutrophication, without corresponding to increased fish yields or clear benefits for the producers. Study I support arguments to cease CM fertilization in Egyptian aquaculture if the goal is to increase fish yields or profitability. Additionally, I employ a qPCR assay to show that CM fertilization correlates with increased abundance of antibiotic resistance genes (ARGs) in pond sediment. AB emitted to the environment can induce resistance development in bacteria and promote selection of resistant genotypes. Study II aim to capture the effects of AB emitted throughout the value chain of agri-food products, and life cycle assessment (LCA) is investigated for this purpose. LCA is a framework developed to assess environmental impacts throughout the value chain of products. In Study II, I present an approach to quantify potential AB resistance enrichment in the environment within LCA. I also discuss a mass-balance approach to capture the relationship between regional AB use and regional human health impacts, in order to capture the full range of potential impacts caused by emissions of AB. Characterizations of potential toxic effects of chemicals in LCA are generally drawn from species sensitivity distribution models that aim to describe an ecosystem-wide response to chemical emission. While this provides insights into the toxicity of a chemical, predictions of the “true” ecosystem wide effects will always be shrouded by uncertainty, depending on the availability and quality of data. Detailed knowledge on adverse effects and potential hazard chemicals impose are required for stakeholders at both global and local scales to make informed decisions on how to regulate the use and emissions of chemicals. Study IV identify LCA studies where toxicological impacts are evaluated and chemicals in the inventory are classified towards ecotoxicological impact, but ecotoxicological characterizations are missing, which leads to underestimating the ecotoxicological impact. To enhance the precision of ecotoxicological effect assessments for chemicals, Study III gathers an extensive toxicological dataset and present a method to assess the uncertainty associated with ecotoxicological effect calculations. The proposed method opens up for exploring uncertainty in ecotoxicological effect calculations, but data availability is limiting the number of chemicals that can be assessed for ecotoxicological effect and uncertainty. To gap-fill information on toxic effect of chemicals, Study IV explores quantitative structure-activity relationship (QSAR) models to predict ecotoxicological effect of chemicals. However, mechanistic understanding of toxic mode of action is not provided by these models. Thus, the accuracy and validity of predicted toxicological effect data are not yet established. Since current LCA software lacks functionality to aggregate uncertainties throughout assessments, the use of predicted toxicological data is discouraged.This thesis presents some of the many challenges we face when assessing toxicological impacts from chemicals emitted to the environment, and provides methods and recommendations how to better evaluate impacts and uncertainties in toxicological characterization of chemicals.
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| 10. |
- Ragnarsson, Oskar, 1971, et al.
(author)
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Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission
- 2017
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 82, s. 117-125
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Journal article (peer-reviewed)abstract
- Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 commis matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p < 0.001) and in the right inferior occipital gyrus (p < 0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p = 0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p < 0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p < 0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function.
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