| 1. |
- Alanärä, Anders, et al.
(författare)
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Utsättning av djur för jakt och fiske
- 2021
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Bok (populärvet., debatt m.m.)abstract
- SLUs vetenskapliga råd för djurskydd har fått i uppdrag av Jordbruksverket att sammanställa aktuell forskning kring utsättning av djur för jakt och fiske samt att belysa eventuella kunskapsluckor på området. Uppdraget omfattar gräsand, rapphöna, fasan och laxfiskar. Bruket att föda upp fåglar och fiskar för utsättning i syfte att gynna jakt och fiske ifrågasätts inte sällan av etiska skäl, men den diskussionen ligger utanför fokus för denna rapport. Utsättning av fågel och fisk är en antropogen verksamhet som, till skillnad från många andra typer av mänsklig påverkan, syftar till att gynna arterna i fråga. Det kan handla om naturvårdsinsatser, att återinföra försvunna arter eller att på andra sätt berika ekosystemet, inte sällan med ökade möjligheter till jakt eller fiske som slutändamål. Ofta förbereds och åtföljs utsättningar av habitatförbättrande åtgärder som inte endast gynnar de utsatta individerna och deras artfränder, utan även har positiva konsekvenser för biologisk mångfald och ekosystemet i stort. I utarbetandet av regelverket knutet till utsättning av fågel och fisk är det viktigt att även beakta de positiva föresatserna och de konsekvenser som verksamheten kan medföra. Annars riskerar man att engagemang och incitament förloras, till men för biologisk mångfald och en rik och levande landsbygd.
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| 2. |
- Andersson, Hanna, et al.
(författare)
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Natur på skolgården för lärande, hälsa och hållbarhet
- 2024. - 2024
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Rapport (populärvet., debatt m.m.)abstract
- Gröna och artrika utemiljöer främjar barns och ungas välbefinnande och kunskap, bådegenom hälsofördelar kopplade till biologisk mångfald och genom att skapa förutsättningarför lek och lärande om natur och miljöfrågor. Skolgården skulle kunna bidra till allt detta,men är idag i hög grad en outnyttjad plats för biologisk mångfald och klimatanpassningav städer. I denna policy brief presenteras huvudsakliga motiv och möjliga åtgärder för attutveckla gröna miljöer och biologisk mångfald på skolgårdar och förskolegårdar.
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| 3. |
- Askenmalm, Fredrika
(författare)
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Hur mjölk i tanken blir kronor på banken : Bondförnuftets rationalitet
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lantbrukare har under senare år ofta hörts framföra klagomål om att den administrativa bördan blivit allt tyngre vad gäller rapportering och ansökningar som ska göras till olika myndigheter. Tidigare forskning framställer det som att den administrativa bördan skulle kunna utsträckas till att också gälla redovisning, så som bokföring, kalkylering och budgetering. Detta då det beskrivs som att lantbrukare varken förstår eller använder redovisning för att sköta sitt lantbruk. Tidigare forskning tycks dock bortse från att lantbrukare ofta tillämpar en annan form av logik än den som förutsätts gälla inom redovisningsforskning. Det verkar också förutsättas att lantbrukarna ska kunna förstå och använda den redovisningsterminologi som finns inom forskningsvärlden trots att lantbrukarna ofta saknar utbildning inom redovisning. Mot denna bakgrund undersöker denna avhandling hur lantbrukare förstår och använder redovisning.Avhandlingen bygger på det grundläggande teoretiska perspektivet att se redovisning som ett språk för att på detta sätt förklara lantbrukarnas förståelse av redovisning. Avhandlingen bygger vidare på familjeföretagsforskning, speciellt socioemotional wealth (SEW), och beslutsteori för att förklara lantbrukarnas användning av redovisningsinformation.Den empiriska studien är inspirerad av grundad teori. Det empiriska materialet utgörs främst av intervjuer med mjölkbönder i Jönköpings län. Även intervjuer med rådgivare och bankmän och vissa sekundärdata har utgjort underlag för avhandlingen.Resultatet av undersökningen visar att lantbrukare har större kunskaper vad gäller redovisning än vad tidigare forskning indikerat. Delvis kan detta förklaras av att lantbrukare använder en annan terminologi än vad som vanligtvis används inom redovisningsforskning när de beskriver redovisning. Mjölkföretag drivs vanligen som familjeföretag och denna avhandling visar på en mycket stark familjeförankring i dessa företag. Det innebär att mjölkföretag ibland (speciellt vad gäller fastigheten) prioriterar annat än finansiella mål, vilket ofta kopplas samman med en intuitiv beslutsstil. Inom redovisning förutsätts generellt att finansiella mål är eftersträvansvärda. Lantbrukarnas sätt att se på redovisning påverkar också hur den används. Även om de förstår och använder redovisning är det inte säkert att den används på det mest vinstmaximerande sättet. I stället kan SEW vara det som prioriteras. Användning av redovisning anpassas efter den situation lantbrukaren befinner sig i. Vissa delar av redovisningen ses och förstås som speglingar av verkligheten eller som framåtriktade ledtrådar. När lantbrukare förstår redovisningen på så vis, uppfattas den som användbar för beslutsfattande. Andra delar av redovisningen ses som regelföljande, eller ibland till och med som helt frikopplad från själva verksamheten. Detta gäller framför allt redovisning till Skatteverket och Jordbruksverket. Dessa redovisningar används inte för beslut, men de är ändå rationellt utformade för att uppnå bästa möjliga utfall (skatteutjämning eller jordbruksstöd).
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| 4. |
- Backman, Helena, et al.
(författare)
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Decreased COPD prevalence in Sweden after decades of decrease in smoking
- 2020
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCOPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009.MethodsTwo large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009–2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion.ResultsBased on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009–2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking.ConclusionsThe prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.
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| 5. |
- Backman, Helena, et al.
(författare)
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FEV1 decline in relation to blood eosinophils and neutrophils in a population-based asthma cohort
- 2020
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Ingår i: World Allergy Organization Journal. - : Elsevier. - 1939-4551. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies.Objective: The aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort.Methods: In 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline.Results: The mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses.Conclusions and clinical relevance: Besides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.
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| 6. |
- Backman, Helena, et al.
(författare)
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Risk factors for severe asthma among adults with asthma
- 2020
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:Suppl 64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Severe asthma is a considerable challenge for patients, health care professionals and society, but there are few long-term studies on risk factors for severe asthma.Aim: To identify baseline risk factors of severe asthma in a longitudinal adult asthma cohort study.Methods: An adult asthma cohort was identified in 1986-2001 by clinical examinations of population samples within the OLIN studies in northern Sweden. The examinations included structured interviews, spirometry with reversibility testing, skin prick testing and metacholine challenge. The cohort was followed up in 2012-2014 when n=1006 participated (mean age 59y). Adjusted Risk Ratios (RR) for baseline factors as risk factors for GINA defined severe asthma (SA) at follow-up (n=51) were estimated by Poisson regression.Results: Older age, impaired lung function, increased reversibility and hyperreactivity, asthmatic wheeze, persistent wheeze, nighttime awakenings due to respiratory symptoms, and dyspnea were significant baseline risk factors for SA. Allergic sensitization, smoking, occupational groups or BMI did not predict SA. When adjusted for age, sex and smoking, post-bronchodilator FEV1/FVC<0.7, both present at baseline (RR 4.2, 95%CI 1.8-9.9) and developed during follow-up (2.9, 1.6-5.3), increased the risk. Also FEV1<80% at baseline associated with SA (2.9, 1.6-5.2). Triggers for respiratory symptoms at baseline such as tobacco smoke (2.1, 1.2-3.7) and physical activity (3.5, 1.5-81) associated with SA at follow-up, while pollen and furry animals did not.Conclusion: Among adults with asthma, impaired lung function, wheeze, dyspnea and nighttime awakenings due to respiratory symptoms are important long-term risk factors for severe asthma.
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| 7. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 8. |
- Ghanipour, Lana, et al.
(författare)
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Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer : A phase I and III open label randomized controlled registry-based clinical trial protocol
- 2024
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:3
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Tidskriftsartikel (refereegranskat)abstract
- Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15–30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.
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| 9. |
- Gummesson, Anders, 1973, et al.
(författare)
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Longitudinal plasma protein profiling of newly diagnosed type 2 diabetes
- 2021
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Ingår i: EBioMedicine. - : Elsevier B.V.. - 2352-3964. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comprehensive proteomics profiling may offer new insights into the dysregulated metabolic milieu of type 2 diabetes, and in the future, serve as a useful tool for personalized medicine. This calls for a better understanding of circulating protein patterns at the early stage of type 2 diabetes as well as the dynamics of protein patterns during changes in metabolic status. Methods: To elucidate the systemic alterations in early-stage diabetes and to investigate the effects on the proteome during metabolic improvement, we measured 974 circulating proteins in 52 newly diagnosed, treatment-naïve type 2 diabetes subjects at baseline and after 1 and 3 months of guideline-based diabetes treatment, while comparing their protein profiles to that of 94 subjects without diabetes. Findings: Early stage type 2 diabetes was associated with distinct protein patterns, reflecting key metabolic syndrome features including insulin resistance, adiposity, hyperglycemia and liver steatosis. The protein profiles at baseline were attenuated during guideline-based diabetes treatment and several plasma proteins associated with metformin medication independently of metabolic variables, such as circulating EPCAM. Interpretation: The results advance our knowledge about the biochemical manifestations of type 2 diabetes and suggest that comprehensive protein profiling may serve as a useful tool for metabolic phenotyping and for elucidating the biological effects of diabetes treatments. Funding: This work was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, the Erling Persson Foundation, the Knut and Alice Wallenberg Foundation, and the Swedish state under the agreement between the Swedish government and the county councils (ALF-agreement).
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| 10. |
- Jansson, Caroline, et al.
(författare)
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Retinoic acid promotes differentiation of WiT49- but not of CCG99-11 Wilms tumour cells
- 2023
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Ingår i: Cancer Reports. - 2573-8348. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most children with Wilms tumour are successfully treated with multidrug chemotherapy and surgery. These treatments cause severe side effects for the patients, an issue that needs to be addressed by exploring other treatment options with less or no side effects. One option is to complement current therapies with agents that could potentially induce tumour cell differentiation, for example retinoic acid (RA). Aims: To facilitate quick assessment of an agent's effect on Wilms tumour differentiation by a rapid in vitro model system. Methods and Results: Here WiT49 and CCG99-11 Wilms tumour cells were treated with 10 μM RA for 72 h or 9 days. Cultured cells were scraped off from Petri dishes, pelleted and embedded in paraffin in the same way as clinical tumour specimens are preserved. Cell morphology and differentiation were evaluated by analyses of haematoxylin eosin (H&E) and immunohistochemical stainings. Based on H&E, WT1 and CKAE1/3 stainings, RA treatment induced further epithelial differentiation of WiT49 cells, whereas there was no sign of induced maturation in CCG99-11 cells. Ki67 staining showed that RA inhibited cell proliferation in both cell lines. Conclusions: Our study shows that in vitro culturing of WiT49 and CCG99-11 cells, followed by pelleting and paraffin embedding of cell pellets, could aid in a quick evaluation of potential differentiating agents against Wilms tumour. In addition, our results strengthen previous results that retinoic acid could be a potential complement to regular Wilms tumour treatment.
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| 11. |
- Jansson, Karin Hassan, 1966-, et al.
(författare)
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Ortsbeskrivningar
- 2020
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Ingår i: Fantastiska verb. - Uppsala : Swedish Science Press. - 9789198450934 ; , s. 47-71
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Jansson, Sven-Arne, et al.
(författare)
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Life-years lost due to asthma and COPD
- 2020
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:Suppl 64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Quality-adjusted life-years (QALYs) is commonly used in health-economic evaluations. QALY-weights combine health status and time into one measure.Aims: To investigate the association between multimorbidity and QALY-weights among adults with asthma and COPD.Methods: Within the OLIN-studies in northern Sweden, a random sample was invited to a postal questionnaire survey. A random sample of 1016 responders was invited to clinical examinations and interviews in 2009 (737 participated, ages 21-86 years), of which 605 completed the health-related quality of life (HRQL) questionnaire SF-36. QALY-weights were derived from the SF-36 data using the SF-6D tool via the standard gamble method. The SF-6D scores are equivalent to QALY-weights with low values representing poor health and the score one representing perfect health.Results: Of the 605 participants, 74 had current asthma, 81 had COPD (FEV1/FVC<0.7), 66 had heart disease, 30 had diabetes, 30 had rheumatic disease, and 160 had hypertension. There was an association between an increasing number of morbid conditions and lower QALY-weights (p<0.001). The mean QALY-weight tended to be lower among subjects with asthma compared to COPD, 0.77 and 0.81, respectively (p=0.078). Subjects with COPD and two or more non-respiratory conditions had significantly lower QALY-weights compared to subjects with COPD alone (0.75 vs.0.83, p=0.016). No significant difference in QALY-weights was found among asthmatics with versus without other non-respiratory conditions.Conclusions: Subjects with asthma tended to have lower QALY-weights compared to subjects with COPD. Having two or more non-respiratory conditions affected the QALY-weight negatively among subjects with COPD but not among subjects with asthma.
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| 13. |
- Jansson, Sven-Arne, et al.
(författare)
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Severe asthma is related to high societal costs and decreased health related quality of life
- 2020
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 162
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to estimate the societal costs and the key cost drivers for patients with severe asthma in Sweden. In addition, health-related quality of life (HRQOL) and morbidity of patients with severe asthma is described. Methods: The study population comprised adults with severe asthma recruited from a large asthma cohort within the Obstructive Lung Disease in Northern Sweden (OLIN) studies. During 2017, patients were interviewed quarterly over telephone regarding their resource utilization and productivity losses. Results: Estimated mean annual asthma-related costs per patient with severe asthma amounted to (sic)6,500, of which approximately (sic)2400 and (sic)4100 were direct and indirect costs, respectively. The main cost drivers for direct costs were hospitalizations followed by drugs: approximately (sic)1000 and (sic)800, respectively. Patients on treatment with regular oral corticosteroids (OCS) had greater direct costs compared with those without regular OCS treatment. Co-morbid conditions were common and the costs were substantial also for co-morbid conditions, with a total cost of approximately (sic)4200. The OCS group had significantly lower HRQOL compared to the non-OCS group. Conclusions: The societal costs due to severe asthma were substantial. Costs for co-morbid conditions contributed substantially to both direct and indirect costs. The direct costs were significantly higher in the maintenance OCS-group compared to the non-maintenance OCS-group. These results indicate a need for improved management and treatment regimens for patients with severe asthma.
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| 14. |
- Karlsson Sundbaum, Johanna, et al.
(författare)
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Severe COVID-19 among patients with asthma and COPD: a report from the Swedish National Airway Register
- 2021
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Ingår i: Therapeutic Advances in Respiratory Disease. - : SAGE Publications. - 1753-4658 .- 1753-4666. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with obstructive lung diseases may be at risk of hospitalization and/or death due to COVID-19. Aim: To estimate the frequency of severe COVID-19, and COVID-19-related mortality in a well-defined large population of patients with asthma and chronic inflammatory lung disease (COPD). Further to assess the frequency of asthma and COPD as registered comorbidities at discharge from hospital, and in death certificates. Methods: At the start of the pandemic, the Swedish National Airway Register (SNAR) included 271,404 patients with a physician diagnosis of asthma and/or COPD. In September 2020, after the first COVID-19 wave in Sweden, the database was linked with the National Patient Register (NPR), the Swedish Intensive Care Register and the Swedish Cause of Death Register, which all provide data about COVID-19 based on International Classification of Diseases (ICD-10) codes. Severe COVID-19 was defined as hospitalization and/or intensive care or death due to COVID-19. Results: Among patients in SNAR, 0.5% with asthma, and 1.2% with COPD were identified with severe COVID-19. Among patients < 18 years with asthma, only 0.02% were severely infected. Of hospitalized adults, 14% with asthma and 29% with COPD died. Further, of patients in SNAR, 56% with asthma and 81% with COPD were also registered in the NPR, while on death certificates the agreement was lower (asthma 24% and COPD 71%). Conclusion: The frequency of severe COVID-19 in asthma and COPD was relative low. Mortality for those hospitalized was double as high in COPD compared to asthma. Comorbid asthma and COPD were not always identified among patients with severe COVID-19.
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| 15. |
- Karlsson Sundbaum, Johanna, et al.
(författare)
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Uncontrolled asthma predicts severe COVID-19: a report from the Swedish National Airway Register.
- 2022
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Ingår i: Therapeutic advances in respiratory disease. - : SAGE Publications. - 1753-4666 .- 1753-4658. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Severe asthma increases the risk of severe COVID-19 outcomes such as hospitalization and death. However, more studies are needed to understand the association between asthma and severe COVID-19.A cohort of 150,430 adult asthma patients were identified in the Swedish National Airway Register (SNAR) from 2013 to December 2020. Data on body mass index, smoking habits, lung function, and asthma control test (ACT) were obtained from SNAR, and uncontrolled asthma was defined as ACT ⩽19. Patients with severe COVID-19 were identified following hospitalization or in death certificates based on ICD-10 codes U07.1 and U07.2. The Swedish Prescribed Drug register was used to identify comorbidities and data from Statistics Sweden for educational level. Multivariate logistic regression analyses were used to estimate associations with severe COVID-19.Severe COVID-19 was identified in 1067 patients (0.7%). Older age (OR=1.04, 95% CI=1.03-1.04), male sex (1.42, 1.25-1.61), overweight (1.56, 1.27-1.91), obesity (2.12, 1.73-2.60), high-dose inhaled corticosteroids in combination with long-acting β-agonists (1.40, 1.22-1.60), dispensed oral corticosteroids ⩾2 (1.48, 1.25-1.75), uncontrolled asthma (1.64, 1.35-2.00), cardiovascular disease (1.20, 1.03-1.40), depression (1.47, 1.28-1.68), and diabetes (1.52, 1.29-1.78) were associated with severe COVID-19, while current smoking was inversely associated (0.63, 0.47-0.85). When comparing patients who died from COVID-19 with those discharged alive from hospital until 31 December 2020, older age, male sex, and current smoking were associated with COVID-19 death.Patients with uncontrolled asthma and high disease burden, including increased asthma medication intensity, should be identified as risk patients for severe COVID-19. Furthermore, current smoking is strongly associated with COVID-19 death in asthma.
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| 16. |
- Kvedaraite, Egle, et al.
(författare)
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Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA+CD142−/low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA+CD142−/low fibroblasts foster monocyte transition to CCR2+CD206+ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2+CD206+ cells from co-cultures have a phenotype similar to intestinal CCR2+CD206+ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.
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| 17. |
- Larsson, Kjell, et al.
(författare)
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Adherence to treatment recommendations for chronic obstructive pulmonary disease-results from the Swedish national airway register
- 2021
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : DovePress. - 1176-9106 .- 1178-2005. ; 16, s. 909-918
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Swedish guidelines adhere to the international GOLD document regarding management of chronic obstructive pulmonary disease (COPD). Based on data from the Swedish National Airway Register (SNAR) the aim was to evaluate adherence to guidelines of pharmacological treatment of COPD in Swedish primary and secondary care.Methods: During a period of 18 months, data on symptoms (CAT, mMRC), lung function, exacerbation history and pharmacological treatment from 15,595 COPD patients from 853 primary care and 125 secondary care clinics were collected from SNAR. Patients with a co-diagnosis of asthma were excluded. Patients were divided into four treatment groups: no pharmacological treatment, short-acting bronchodilators alone, long-acting bronchodilators alone and ICS alone or in combination with bronchodilators.Results: Of the patients, 29% were in GOLD group A, 58% in group B, 2% in group C and 11% in group D. CAT score was ≥10 and mMRC score was below 2 in 30.9% of the patients and mMRC score was ≥2 and CAT score <10 in 4.2% of the patients. In 61.4% of the patients, no exacerbation was registered during the last year. Long-acting bronchodilators were prescribed for 78% and ICS for 46% of all patients. In groups A, B, C and D, respectively, 21%, 11%, 11% and 5% did not receive any inhaler therapy; 67%, 81%, 81% and 90% received long-acting bronchodilators; 33%, 46%, 55% and 71% received any ICS containing therapy and 19%, 34%, 39% and 61% received triple therapy.Discussion: Data from the SNAR indicate that only a minority of COPD patients were untreated. There was a liberal use of ICS containing drug combinations in subjects who do not have an indication for ICS. A considerable proportion of subjects at high risk of exacerbations did not receive ICS treatment.
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| 18. |
- Peña-Martínez, Pablo, et al.
(författare)
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Interleukin 4 promotes phagocytosis of murine leukemia cells counteracted by CD47 upregulation
- 2022
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 107:4, s. 816-824
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Tidskriftsartikel (refereegranskat)abstract
- Cytokines are key regulators of tumor immune surveillance by controlling immune cell activity. Here, we investigated whether interleukin 4 (IL4) has antileukemic activity via immune-mediated mechanisms in an in vivo murine model of acute myeloid leukemia driven by the MLL-AF9 fusion gene. Although IL4 strongly inhibited leukemia development in immunocompetent mice, the effect was diminished in immune-deficient recipient mice, demonstrating that the antileukemic effect of IL4 in vivo is dependent on the host immune system. Using flow cytometric analysis and immunohistochemistry, we revealed that the antileukemic effect of IL4 coincided with an expansion of F4/80+ macrophages in the bone marrow and spleen. To elucidate whether this macrophage expansion was responsible for the antileukemic effect, we depleted macrophages in vivo with clodronate liposomes. Macrophage depletion eliminated the antileukemic effect of IL4, showing that macrophages mediated the IL4-induced killing of leukemia cells. In addition, IL4 enhanced murine macrophage-mediated phagocytosis of leukemia cells in vitro. Global transcriptomic analysis of macrophages revealed an enrichment of signatures associated with alternatively activated macrophages and increased phagocytosis upon IL4 stimulation. Notably, IL4 concurrently induced Stat6-dependent upregulation of CD47 on leukemia cells, which suppressed macrophage activity. Consistent with this finding, combining CD47 blockade with IL4 stimulation enhanced macrophage-mediated phagocytosis of leukemia cells. Thus, IL4 has two counteracting roles in regulating phagocytosis in mice; enhancing macrophage-mediated killing of leukemia cells, but also inducing CD47 expression that protects target cells from excessive phagocytosis. Taken together, our data suggest that combined strategies that activate macrophages and block CD47 have therapeutic potential in acute myeloid leukemia.
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| 19. |
- Rastegar, Bahar, et al.
(författare)
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Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution
- 2023
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 29:14, s. 2668-2677
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: While patients with intermediate-risk (IR) Wilms tumors now have an overall survival (OS) rate of almost 90%, those affected by high-stage tumors with diffuse anaplasia have an OS of only around 50%. We here identify key events in the pathogenesis of diffuse anaplasia by mapping cancer cell evolution over anatomic space in Wilms tumors.EXPERIMENTAL DESIGN: We spatially mapped subclonal landscapes in a retrospective cohort of 20 Wilms tumors using high-resolution copy-number profiling and TP53 mutation analysis followed by clonal deconvolution and phylogenetic reconstruction. Tumor whole-mount sections (WMS) were utilized to characterize the distribution of subclones across anatomically distinct tumor compartments.RESULTS: Compared with non-diffuse anaplasia Wilms tumors, tumors with diffuse anaplasia showed a significantly higher number of genetically distinct tumor cell subpopulations and more complex phylogenetic trees, including high levels of phylogenetic species richness, divergence, and irregularity. All regions with classical anaplasia showed TP53 alterations. TP53 mutations were frequently followed by saltatory evolution and parallel loss of the remaining wild-type (WT) allele in different regions. Morphologic features of anaplasia increased with copy-number aberration (CNA) burden and regressive features. Compartments demarcated by fibrous septae or necrosis/regression were frequently (73%) associated with the emergence of new clonal CNAs, although clonal sweeps were rare within these compartments.CONCLUSIONS: Wilms tumors with diffuse anaplasia display significantly more complex phylogenies compared with non-diffuse anaplasia Wilms tumors, including features of saltatory and parallel evolution. The subclonal landscape of individual tumors was constrained by anatomic compartments, which should be considered when sampling tissue for precision diagnostics.
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| 20. |
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| 21. |
- Stridsman, Caroline, et al.
(författare)
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The first years of the Swedish National Airway register
- 2020
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Ingår i: European Respiratory Journal. - : ERS Publications. - 0903-1936 .- 1399-3003. ; 56:Suppl 64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Swedish National Airway Register (SNAR) was initiated to improve and ensure quality of care for patients with asthma and COPD.Aim: To describe the register design of SNAR and unique patients between the years of 2014 until 2019.Methods: SNAR has been ongoing since 2013 and includes patients with asthma (both children and adults) and COPD from primary and secondary care (both in- and outpatients). Data about healthcare provider, symptoms, comorbidities, additional investigations (i.e. spirometry) and prescribed treatment is registered. The registrations are performed manually by healthcare professionals, or directly transmitted from medical records to a web-based platform.Results: In 2019, 853 primary care clinics, 125 secondary care clinics (whereof 62 pediatric clinics) and 24 inpatient wards were linked to the register. Data was directly transmitted from medical records of about 80% of the clinics, and manually by 20%. The register includes in total 205833 unique patients with asthma and 80372 with COPD. Registrations of new patients and follow-up visits in 2019 applied 73788 patients with asthma (58% women, mean age 44yr) whereof 10190 were <11yr and 6248 were 12-17yr, 33276 with COPD (57% women, mean age 73yr), and 5013 with both asthma and COPD (ACO) (61% women, mean age 71yr). In COPD, the proportion of patients in GOLD 1-4 were; GOLD1 15%, GOLD2 55%, GOLD3 25% GOLD4 5%. During 2019, 1506 registered patients with asthma and 3791 with COPD died.Conclusion: The SNAR has cumulatively registered over 280000 individuals and provides a unique insight into the care of patients with asthma and COPD in Sweden.
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| 22. |
- Stridsman, Caroline, et al.
(författare)
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The Swedish National Airway Register (SNAR): development, design and utility to date
- 2020
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Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Swedish National Airway Register (SNAR) was initiated in 2013 to ensure and improve the quality of care for patients with asthma and COPD. Aim: To describe the development and design of SNAR, and to study the 2019 data to evaluate its potential utility related to improvement of quality of care. Methods: SNAR includes data from patients with asthma (both children and adults) and COPD from primary, secondary and tertiary care, and also, for COPD inpatient care. Data on diagnostic investigations (e.g. spirometry, blood sample, skin prick test), symptom-scores, comorbidities and prescribed treatments are registered. The registrations are entered manually by healthcare professionals, or directly transferred from electronic medical records to a web-based platform. Results: In 2019, 1000 clinics participated and data were directly transferred by about 88% of them. The register included data on 205,833 patients with asthma and 80,372 with COPD (of these, 5% had both diagnoses). Registrations of new patients and follow-up visits from primary and secondary/tertiary care in 2019 were completed for 75,707 patients with asthma (11,818 children <12 yr, 6545 adolescents 12-17 yr, and 57,344 adults >17 yr) and 38,117 with COPD. Depending on age and disease group, 43-77% had performed spirometry, 36-65% Asthma Control Test, and 60% COPD Assessment Test. The prevalence of current smoking was about 2% in adolescents, 10% in adults with asthma, and 34% in COPD. For these, smoking cessation support was offered to 27%, 38% and 51%, respectively. Overall, limited data were available on investigation of allergy, 6-min walk test, patient education and written treatment plans. Regarding asthma, sex-differences in disease management were evident. Conclusion: SNAR has cumulatively registered data from over 270,000 individuals, and the register is important for patients, caregivers, authorities, politicians and researchers to evaluate the effect of treatment and to ensure high and equal quality of care nationwide.
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| 23. |
- Uno, Kaname, et al.
(författare)
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A Gradual Transition Toward Anaplasia in Wilms Tumor Through Tolerance to Genetic Damage
- 2024
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Ingår i: Modern Pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. - 1530-0285. ; 37:1, s. 100382-100382
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Wilms tumor (WT) in general have excellent survival, but the prognosis of patients belonging to the subgroup of WT with diffuse anaplasia (DA) is poor due to frequent resistance to chemotherapy. We hypothesized that DA WT cells might undergo changes, such as acquiring a persistent tolerance to DNA damage and copy number aberrations (CNAs), which could eventually lead to their resistance to chemotherapy treatment. Tissue sections from chemotherapy-treated DA WTs (n = 12) were compared with chemotherapy-treated nonanaplastic WTs (n = 15) in a tissue microarray system, enabling analysis of 769 tumor regions. All regions were scored for anaplastic features and immunohistochemistry was used to quantify p53 expression, proliferation index (Ki67), and DNA double-strand breaks (γH2AX). CNAs were assessed by array-based genotyping and TP53 mutations using targeted sequencing. Proliferation index and the frequency of DNA double-strand breaks (γH2AX dot expression) increased with higher anaplasia scores. Almost all (95.6%) areas with full-scale anaplasia had TP53 mutations or loss of heterozygosity, along with an increased amount of CNAs. Interestingly, areas with wild-type TP53 with loss of heterozygosity and only one feature of anaplasia (anaplasia score 1) also had significantly higher proliferation indices, more DNA double-strand breaks, and more CNAs than regions without any anaplastic features (score 0); such areas may be preanaplastic cell populations under selective pressure for TP53 mutations. In conclusion, we suggest that chemoresistance of DA WTs may be partly explained by a high proliferative capability of anaplastic cells, which also have a high burden of double-stranded DNA breaks and CNAs, and that there is a gradual emergence of anaplasia in WT.
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| 24. |
- Valind, Anders, et al.
(författare)
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Macrophage infiltration promotes regrowth in MYCN-amplified neuroblastoma after chemotherapy
- 2023
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Ingår i: OncoImmunology. - 2162-4011 .- 2162-402X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite aggressive treatment, the 5-year event-free survival rate for children with high-risk neuroblastoma is <50%. While most high-risk neuroblastoma patients initially respond to treatment, often with complete clinical remission, many eventually relapse with therapy-resistant tumors. Novel therapeutic alternatives that prevent the recurrence of therapy-resistant tumors are urgently needed. To understand the adaptation of neuroblastoma under therapy, we analyzed the transcriptomic landscape in 46 clinical tumor samples collected before (PRE) or after (POST) treatment from 22 neuroblastoma patients. RNA sequencing revealed that many of the top-upregulated biological processes in POST MYCN amplified (MNA +) tumors compared to PRE MNA + tumors were immune-related, and there was a significant increase in numerous genes associated with macrophages. The infiltration of macrophages was corroborated by immunohistochemistry and spatial digital protein profiling. Moreover, POST MNA + tumor cells were more immunogenic compared to PRE MNA + tumor cells. To find support for the macrophage-induced outgrowth of certain subpopulations of immunogenic tumor cells following treatment, we examined the genetic landscape in multiple clinical PRE and POST tumor samples from nine neuroblastoma patients revealing a significant correlation between an increased amount of copy number aberrations (CNA) and macrophage infiltration in POST MNA + tumor samples. Using an in vivo neuroblastoma patient-derived xenograft (PDX) chemotherapy model, we further show that inhibition of macrophage recruitment with anti-CSF1R treatment prevents the regrowth of MNA + tumors following chemotherapy. Taken together, our work supports a therapeutic strategy for fighting the relapse of MNA + neuroblastoma by targeting the immune microenvironment.
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| 25. |
- Vanfleteren, Lowie, et al.
(författare)
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Room for improvement for smoking cessation support in asthma and COPD - a perspective from the Swedish National Airway Register
- 2020
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Ingår i: European Respiratory Journal. - : ERS Publications. - 0903-1936 .- 1399-3003. ; 56:Suppl 64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The prevalence of smoking has decreased in the general population and is nowadays around 7% in Sweden. The Swedish National Airway Register (SNAR) gives a unique opportunity to study obstructive lung diseases and related factors such as smoking habits.Aim: To provide a survey of data registered in SNAR and to report the prevalence of smoking and offered smoking cessation support among patients with asthma and COPD.Methods: In 2019, registrations of new patients and follow-up visits from primary and secondary care included 3845 adolescents with asthma (aged 12-17yr), 43721 adults with asthma, and 29945 with COPD with complete data about smoking habits. Smoking cessation support was defined as offered nicotine replacement therapy or motivational interviewing. The registrations were performed manually by healthcare professionals, or directly transmitted from medical records to a web-based platform.Results: The proportion of current smokers was 1.7% among adolescents with asthma (girls 2.4% vs. boys 1.1% p=0.003), 12.3% among adults with asthma (women 12.9% vs. men 11.3%, p<0.001) and 36.7% in COPD (women 37.9% vs. men 35.0%, p<0.001). Smoking cessation support was offered to 26.5% of the adolescents with asthma (girls 31.0% vs. boys 19.2%, p=0.440), 38.7% of the adults with asthma (women 39.3% vs. men 37.7%, p=0.260), and to 49.6% of those with COPD (women 49.3% vs. men 50.0%, p=0.430).Conclusion: In Sweden, a substantial proportion of patients with diagnosed asthma or COPD continue to smoke, with room for improvment for smoking cessation support.
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| 26. |
- Yasui, Hiroaki, et al.
(författare)
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A dynamic mutational landscape associated with an inter-regionally diverse immune response in malignant rhabdoid tumour
- 2020
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 252:1, s. 22-28
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Tidskriftsartikel (refereegranskat)abstract
- Malignant rhabdoid tumour (MRT) is a childhood neoplasm of high malignancy characterised by biallelic mutation and/or loss of the epigenetic master regulator SMARCB1, accompanied by no or few other oncogenic drivers. In spite of their generally low mutational burden, an intratumoural T-cell response has been reported in a subset of MRTs, indicating that immune checkpoint inhibition may be considered a viable therapy option for some patients. We assess here the evolution over time and space of predicted neoantigens and indicators of immune checkpoint status in two MRT patients who progressed under treatment. Both patients showed an accumulation of novel clonal and subclonal mutations, including predicted neoantigens, in metastases compared to their inferred ancestral clones in the primary tumours. The first patient had peritoneal metastases from an MRT of the liver. Clonal deconvolution revealed polyclonal seeding from the primary tumour to a single metastatic site, followed by a local subclonal burst of mutations. The second patient had a renal MRT with multiple pulmonary metastases, each of which could be traced back to a single genetically unique founder cell, with formation of novel subclones in two metastases. Both patients showed a regionally heterogeneous landscape of predicted neoantigens and of tumour-infiltrating lymphocytes expressing CD8 and PD1. In both patients, some tumour regions fulfilled established criteria for PD-L1 positivity (> 1% of tumour cells), while others did not. This suggests that even in a tumour type like MRT, with a single driver mutation, there can be heterogeneity in neoantigen repertoire, immune response, and biomarkers for checkpoint blockade among sampled locations. This must be taken into account when assessing progressed MRT patients for checkpoint inhibition therapy.
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