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1.
  • Alfvén, Tobias, et al. (författare)
  • Agenda 2030 och målen för en hållbar utveckling angår oss alla
  • 2020
  • Ingår i: Läkartidningen. - 0023-7205. ; 117
  • Tidskriftsartikel (refereegranskat)abstract
    • The 2030 Agenda for Sustainable Development and its seventeen Sustainable Development Goals were adopted by the United Nations General Assembly in 2015. It is a bold agenda for global social, environmental and economic development, with human health as a central theme. Even though substantial improvements in health have been achieved during the last decades, every year over 5 million children die, mostly from preventable causes, and 300 000 women die in conjunction with childbirth. Premature deaths from non-communicable diseases are increasing, and our ability to treat infections is under threat through widespread anti-microbial resistance. Climate change is recognized as the biggest threat to health in our time. When the world now starts to plan for how society and our health systems should be reorganized after the COVID-19 pandemic the 2030 Agenda could and should play a central role. In this context, Agenda 2030 provides an ambitious roadmap for development, with its emphasis on collaboration across borders and disciplines. The agenda is achievable but reaching its goals will require strong commitment at all levels and societal change on a large scale.
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2.
  • Alfvén, Tobias, et al. (författare)
  • Agenda 2030 och målen för en hållbar utveckling angår oss alla [The 2030 Agenda for Sustainable Development - an important opportunity to improve global health]
  • 2020
  • Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 117
  • Forskningsöversikt (refereegranskat)abstract
    • The 2030 Agenda for Sustainable Development and its seventeen Sustainable Development Goals were adopted by the United Nations General Assembly in 2015. It is a bold agenda for global social, environmental and economic development, with human health as a central theme. Even though substantial improvements in health have been achieved during the last decades, every year over 5 million children die, mostly from preventable causes, and 300 000 women die in conjunction with childbirth. Premature deaths from non-communicable diseases are increasing, and our ability to treat infections is under threat through widespread anti-microbial resistance. Climate change is recognized as the biggest threat to health in our time. When the world now starts to plan for how society and our health systems should be reorganized after the COVID-19 pandemic the 2030 Agenda could and should play a central role. In this context, Agenda 2030 provides an ambitious roadmap for development, with its emphasis on collaboration across borders and disciplines. The agenda is achievable but reaching its goals will require strong commitment at all levels and societal change on a large scale.
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3.
  • Axelsson, Mette, et al. (författare)
  • Mat vid diabetes. : En systematisk översikt med utvärdering av effekter samt hälsoekonomiska och etiska aspekter.
  • 2022
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • SlutsatserTyp 1- och typ 2-diabetes Det finns ett samband mellan att äta medelhavskost och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det finns ett samband mellan att äta en större andel2 fibrer eller baljväxter och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel nötter och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet) samt lägre risk att insjukna i hjärt- och kärlsjukdom (låg tillförlitlighet). Det finns ett samband mellan att dricka mer2 kaffe och lägre risk att dö i förtid oavsett orsak och lägre risk att dö i förtid i kranskärlssjukdom (måttlig tillförlitlighet) samt möjligen en lägre risk att dö i förtid i hjärt- och kärlsjukdom (låg tillförlitlighet). Det råder generell brist på studier med lång uppföljningstid som jämför inverkan av olika slags kostråd på överlevnad, diabeteskomplikationer, diabetesremission3, livskvalitet och biverkningar. Tillförlitligheten av befintliga resultat är dessutom mycket låg för de flesta koster, kostbehandlingar, livsmedel och näringsämnen som har utvärderats. Effekter på hälsa och relaterade mått kan i dessa fall inte bedömas.2. Begreppet ”större andel” eller ”mer” avser inte nödvändigtvis att äta eller dricka mer totalt utan att öka mängden av ett visst livsmedel genom att byta ut annan mat eller dryck.Typ 2-diabetes Det kan finnas ett samband mellan att äta en större andel mättat fett och högre risk för att dö i förtid av hjärt- och kärlsjukdom (låg tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel enkelomättat fett och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet). En behandling med en initial period av kraftigt minskat energiintag med hjälp av lågenergipulver (VLED) med efterföljande övergång till mat för viktstabilitet jämfört med vanlig kostbehandling har gynnsamma effekter på livskvalitet (enligt EQ-5D), långtidsblodsocker (HbA1c) och vikt upp till 12 månader (måttlig tillförlitlighet)4. Vidare kan metoder där VLED ingår ha gynnsamma effekter på diabetesremission5 och midjeomfång upp till 12 månader (låg tillförlitlighet) och långtidsblodsocker (HbA1c) upp till 24 månader (låg tillförlitlighet). Intensiv livsstilsbehandling därlågfettkost kombineras med fysisk aktivitet och minskat energiintag har gynnsamma effekter jämfört med vanlig kostbehandling på långtidsblodsocker (HbA1c), vikt, kroppsmasseindex (BMI), midjeomfång och vissa blodfetter upp till 12 månader (måttlig tillförlitlighet)3. Viktminskningen kan kvarstå upp till omkring 10 år (låg tillförlitlighet). Behandlingen kan leda till bättre fysisk livskvalitet upp till 8 år (låg tillförlitlighet) medan effektskillnaden i psykisk livskvalitet under samma tid kan vara obefintlig eller försumbar (låg tillförlitlighet). Jämförelsen påvisar ingen förändrad risk att dö i förtid oavsett orsak eller att dö eller insjukna av kardiovaskulära orsaker efter omkring 10 år (låg tillförlitlighet). I det hälsoekonomiska perspektivet är intensiv livsstilsbehandling mer resurskrävande än vanlig kostbehandling, och beräkningar visar små eller inga vinster i kvalitetsjusterade levnadsår (QALYs) på individnivå. Energirestriktion i samband med intensiv livsstilsbehandling med ketogen kost eller med högproteinkost (20 E%) i kombination med fysisk aktivitet jämfört med vanlig kostbehandling kan ge en viktminskning upp till 11 månader (låg tillförlitlighet) men det saknas studier som kan visa om vikten kan bibehållas på längre sikt. Det saknas studier som undersökt kliniskt viktiga utfall som dödlighet, kardiovaskulära sjukdomar, livskvalitet och diabetesremission.3. Gäller endast vid typ 2-diabetes.4. Utgår från individer med en medelkroppsvikt på cirka 100 kg och medel-HbA1c på 60 mmol/mol.5. Resultaten för utfallet diabetesremission (att uppnå normala blodsockervärden) gäller när en diabetesdiagnos sattes för mindre än 6 år sedan eller för mindre än 3 år sedan. Definitionen för diabetesremission var ett HbA1c på mindre än 48 mmol/mol och att samtidigt vara fri från blodsockersänkande läkemedel.Graviditetsdiabetes Det saknas studier om kost vid graviditetsdiabetes med tillräcklig tillförlitlighet för att kunna bedöma effekterna.
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4.
  • Ekman, Anna-Theresia, et al. (författare)
  • Prevalence of children under five with disabilities in Sierra Leone in 2017: Insights from a population-based multiple indicator cluster survey
  • 2023
  • Ingår i: Disability and Health Journal. - : ELSEVIER SCIENCE INC. - 1936-6574 .- 1876-7583. ; 16:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Children with disabilities have been low on the agenda of child health, including in Sierra Leone, and there are still many gaps in our knowledge and understanding of the issue.Objective: To estimate the prevalence of children with disabilities in Sierra Leone using functional difficulty as a proxy and to understand the factors associated with disabilities among children two to four years living in Sierra Leone.Methods: We used cross-sectional data from the Sierra Leone 2017 Multiple Indicator Cluster Survey. Disability was defined using a functional difficulty definition with additional thresholds used to define children with severe functional difficulty and multiple disabilities. Logistic regression models estimated odds ratios (ORs) of childhood disability and how they were associated with socioeconomic factors and living conditions.Results: Prevalence of children with disabilities was 6.6% (95% confidence interval (CI) 5.8-7.6%) and there was a high risk of comorbidity between different functional difficulties. Children with disabilities were less likely to be girls (adjusted odds ratio (AOR) 0.8 (CI 0.7-1.0) and older (AOR 0.3 (CI 0.2-0.4)), but more prone to be stunted (AOR 1.4 (CI 1.1-1.7)) and have younger caregivers (AOR 1.3 (CI 0.7-2.3)).Conclusion: The prevalence of disabilities in young Sierra Leonean children was comparable to other countries in West and Central Africa when using the same measure of disability. Preventive as well as early detection and intervention efforts are recommended to be integrated with other programs, e.g vaccinations, nutrition, and poverty reducing programs.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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5.
  • Krebs, Alice, et al. (författare)
  • The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods
  • 2020
  • Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 94:7, s. 2435-2461
  • Tidskriftsartikel (refereegranskat)abstract
    • Hazard assessment, based on new approach methods (NAM), requires the use of batteries of assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information to be usable for integrated hazard assessment, strategic project decisions and/or for regulatory purposes. The EU-ToxRisk project developed a strategy to provide regulatorily valid data, and exemplified this using a panel of > 20 assays (with > 50 individual endpoints), each exposed to 19 well-known test compounds (e.g. rotenone, colchicine, mercury, paracetamol, rifampicine, paraquat, taxol). Examples of strategy implementation are provided for all aspects required to ensure data validity: (i) documentation of test methods in a publicly accessible database; (ii) deposition of standard operating procedures (SOP) at the European Union DB-ALM repository; (iii) test readiness scoring accoding to defined criteria; (iv) disclosure of the pipeline for data processing; (v) link of uncertainty measures and metadata to the data; (vi) definition of test chemicals, their handling and their behavior in test media; (vii) specification of the test purpose and overall evaluation plans. Moreover, data generation was exemplified by providing results from 25 reporter assays. A complete evaluation of the entire test battery will be described elsewhere. A major learning from the retrospective analysis of this large testing project was the need for thorough definitions of the above strategy aspects, ideally in form of a study pre-registration, to allow adequate interpretation of the data and to ensure overall scientific/toxicological validity.
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6.
  • Tegel, Hanna, et al. (författare)
  • High throughput generation of a resource of the human secretome in mammalian cells
  • 2020
  • Ingår i: New Biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 58, s. 45-54
  • Tidskriftsartikel (refereegranskat)abstract
    • The proteins secreted by human tissues and blood cells, the secretome, are important both for the basic understanding of human biology and for identification of potential targets for future diagnosis and therapy. Here, a high-throughput mammalian cell factory is presented that was established to create a resource of recombinant full-length proteins covering the majority of those annotated as 'secreted' in humans. The full-length DNA sequences of each of the predicted secreted proteins were generated by gene synthesis, the constructs were transfected into Chinese hamster ovary (CHO) cells and the recombinant proteins were produced, purified and analyzed. Almost 1,300 proteins were successfully generated and proteins predicted to be secreted into the blood were produced with a success rate of 65%, while the success rates for the other categories of secreted proteins were somewhat lower giving an overall one-pass success rate of ca. 58%. The proteins were used to generate targeted proteomics assays and several of the proteins were shown to be active in a phenotypic assay involving pancreatic beta-cell dedifferentiation. Many of the proteins that failed during production in CHO cells could be rescued in human embryonic kidney (HEK 293) cells suggesting that a cell factory of human origin can be an attractive alternative for production in mammalian cells. In conclusion, a high-throughput protein production and purification system has been successfully established to create a unique resource of the human secretome.
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7.
  • Thalén, Niklas, et al. (författare)
  • Tuning of CHO secretional machinery improve activity of secreted therapeutic sulfatase 150-fold
  • 2024
  • Ingår i: Metabolic engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 81, s. 157-166
  • Tidskriftsartikel (refereegranskat)abstract
    • Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. The recombinant production of such sulfatases suffers greatly from both low product activity and yield, further limiting accessibility for patient groups. To mitigate the low product activity, we have investigated cellular properties through computational evaluation of cultures with varying media conditions and comparison of two CHO clones with different levels of one active sulfatase variant. Transcriptome analysis identified 18 genes in secretory pathways correlating with increased sulfatase production. Experimental validation by upregulation of a set of three key genes improved the specific enzymatic activity at varying degree up to 150-fold in another sulfatase variant, broadcasting general production benefits. We also identified a correlation between product mRNA levels and sulfatase activity that generated an increase in sulfatase activity when expressed with a weaker promoter. Furthermore, we suggest that our proposed workflow for resolving bottlenecks in cellular machineries, to be useful for improvements of cell factories for other biologics as well.
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8.
  • Aberg, Fredrik, et al. (författare)
  • A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease
  • 2021
  • Ingår i: HEPATOLOGY COMMUNICATIONS. - : John Wiley & Sons. - 2471-254X. ; 5:6, s. 1021-1035
  • Tidskriftsartikel (refereegranskat)abstract
    • The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.
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9.
  • Almgren, Matilda, et al. (författare)
  • Fatigue after heart transplantation - a possible barrier to self-efficacy
  • 2021
  • Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 35:4, s. 1301-1308
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale Recovery after heart transplantation is challenging and many heart recipients struggle with various transplant-related symptoms, side-effects of immunosuppressive medications and mental challenges. Fatigue has been reported to be one of the most common and distressing symptoms after heart transplantation and might therefore constitute a barrier to self-efficacy, which acts as a moderator of self-management. Aim To explore the prevalence of fatigue and its relationship to self-efficacy among heart recipients 1-5 years after transplantation. Research method An explorative cross-sectional design, including 79 heart recipients due for follow-up 1-5 years after transplantation. Three different self-assessment instruments were employed; The Multidimensional Fatigue Inventory-19, Self-efficacy for managing chronic disease 6-Item Scale and The Postoperative Recovery Profile. Ethical approval The study was approved by the Regional Ethics Board of Lund (Dnr. 2014/670-14/10) with supplementary approval from the Swedish Ethical Review Authority (Dnr. 2019-02769). Results The reported levels of fatigue for the whole group were moderate in all dimensions of the Multidimensional Fatigue Inventory-19, with highest ratings in the General Fatigue sub-scale. Those most fatigued were the groups younger than 50 years; pretransplant treatment with Mechanical Circulatory Support; not recovered or had not returned to work. Self-efficacy was associated with the sub-dimensions Mental Fatigue (rho = -0 center dot.649) and Reduced Motivation (rho = -0 center dot 617), which explained 40 center dot 1% of the variance when controlled for age and gender. Study limitations The small sample size constitutes a limitation. Conclusions The moderate levels of fatigue reported indicate that it is not a widespread problem. However, for those suffering from severe fatigue it is a troublesome symptom that affects the recovery process and their ability to return to work. Efforts should be made to identify those troubled by fatigue to enable sufficient self-management support.
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10.
  • Almgren, Matilda, et al. (författare)
  • Self-efficacy, recovery and psychological wellbeing one to five years after heart transplantation: a Swedish cross-sectional study
  • 2021
  • Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 20:1, s. 34-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Self-efficacy refers to a person ' s confidence in carrying out treatment-related activities and constitutes the foundation of self-management as well as long-term follow-up after heart transplantation. Exploring the heart recipients ' experiences by means of self-report instruments provides healthcare professionals with valuable information on how to supply self-management support after heart transplantation. Aims The aim was to explore self-efficacy in relation to the self-reported level of recovery and psychological wellbeing, among adult heart recipients, one to 5 years after transplantation. Methods This cross-sectional study includes 79 heart recipients, due for follow-up one to 5 years after transplantation. Three different self-assessment instruments were employed: the self-efficacy for managing chronic disease 6-item scale; the postoperative recovery profile; and the psychological general wellbeing instrument. Results The reported level of self-efficacy was high (median 8.3, maximum score 10). Significantly higher self-efficacy was seen among those who had returned to work (P = 0.003) and those without pre-transplant mechanical circulatory support (P = 0.033). In total, 65.5% (n = 52) reported being reasonably recovered, while 18.8% (n = 12) were not recovered. The median total psychological general wellbeing score was 108 (P-25 = 24,P-75 = 117), suggesting overall good psychological wellbeing in the whole group of heart recipients. Conclusion The heart transplant recipients in our study had an overall high level of self-efficacy. Low self-efficacy was found among those with a low self-reported level of recovery, pre-transplant treatment with mechanical circulatory support or who had not returned to work. This is important information for transplant professionals when helping heart recipients to balance their expectations about recovery.
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