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1.	Larsson, Kjell (författare) Tätare uppdateringar behövs av riktlinjer vid astma och KOL 2020 Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 117 Tidskriftsartikel (populärvet., debatt m.m.)abstract Rekommendationer för omhändertagande vid astma och kroniskt obstruktiv lungsjukdom (KOL) uppdateras av Läkemedelsverket cirka vart sjunde år och ligger till grund för diagnostik och behandling framför allt i primärvården. Internationella riktlinjer för omhändertagande av astma (Global initiative for asthma, GINA) och KOL (Global initiative for chronic obstructive lung disease, GOLD) uppdateras årligen för att ny kunskap om behandling snabbt ska nå patienterna.De långa intervallen mellan uppdateringarna innebär att rekommendationerna hinner bli inaktuella innan nästa version publiceras, och Sverige hamnar i otakt med internationella riktlinjer. Farmakologisk behandling uppdateras av regionala läkemedelskommittéer, men rekommendationerna skiljer sig i olika delar av landet och stäms ofta inte av mot internationella riktlinjer, vilket leder till ojämlik behandling över landet. Läkemedelsverkets kunskapsstöd Läkemedelsboken innehöll ett kapitel om astma och KOL där man vid behov kunde uppdatera riktlinjer för primärvården, men detta stöd har lagts ned.Vid astma rekommenderar riktlinjerna kortverkande beta-2-agonister vid behov som enda behandling vid lindrig astma (steg 1) samt som tillägg till underhållsbehandling vid svårare sjukdom vid symtomgenombrott [1]. Som alternativ vid svårare astma (steg 3–5) rekommenderas inhalationssteroider i fast kombination med formoterol (steroid + formoterol) vid behov i stället för kortverkande b2-agonister [1]. Vid lindrig astma ger steroid + formoterol vid behov som enda behandling bättre resultat än endast kortverkande beta-2-agonister vid behov [2-5]. Vidare har steroid + formoterol (inhalerat vid behov) lika god exacerbationsförebyggande effekt som regelbunden behandling med inhalationssteroider och kortverkande beta-2-agonister vid behov trots en betydligt lägre kortisonbelastning [3, 5].I juni 2019 uppdaterades GINA:s astmarekommendationer genomgripande [6]. Här rekommenderas steroid + formoterol vid behov vid alla svårighetsgrader av astma. Kortverkande beta-2-agonister (salbutamol, terbutalin) vid behov är struket som förstahandsalternativ. Data indikerar att endast kortverkande beta-2-agonister vid behov faktiskt ökar risken för svåra exacerbationer och astmarelaterad mortalitet. Genom tillägg av inhalationssteroid till en snabb- och långverkande beta-2-agonist reduceras risken signifikant [6]. Vidare rekommenderas steroid + formoterol vid behov som alternativ till regelbunden behandling med inhalationssteroider på steg 2. Riktlinjerna har redan godkänts i flera länder.Vid KOL-behandling är två viktiga mål att lindra symtom och förebygga exacerbationer. Basbehandlingen för att uppnå detta är långverkande antikolinergika. Tillägg av långverkande beta-2-agonist till långverkande antikolinergika ger ytterligare god effekt på symtom, men en mer blygsam tilläggseffekt på exacerbationer [8]. Vid KOL ges inhalationssteroid i syfte att förebygga exacerbation. Hög nivå av eosinofiler i blod förekommer ofta vid KOL. Nyare forskning visar att blodeosinofili varierar hos patienter med KOL. Inhalationssteroider förebygger exacerbationer mer effektivt hos KOL-patienter med eosinofili, och blodeosinofili kan vägleda den förebyggande behandlingen [9-12]. Kontroll av eosinofiler i blod förespråkas i det senaste GOLD-dokumentet inför val av terapi och nydiagnostiserad KOL. Vid KOL och samtidig eosinofili anges inhalationssteroid + långverkande beta-2-agonist som tänkbart förstahandsalternativ i förebyggande syfte [13].Vi anser att behandling av patienter med astma och/eller KOL i Sverige ska baseras på rekommendationer från Läkemedelverket och att de senaste landvinningarna inom området måste återfinnas i riktlinjerna. Läkemedelsverket bör uppdatera riktlinjerna kontinuerligt, helst årligen. Detta kan göras av en mindre grupp experter genom en begränsad arbetsinsats till låg kostnad. Potentiella bindningar eller jävsförhållanden: Samtliga författare har deltagit i expertgrupp och/eller föreläst/haft utbildningsuppdrag hos företag som verkar inom området.
2.	Ludvigsson, Jonas F., 1969-, et al. (författare) Adaptation of the Charlson Comorbidity Index for Register-Based Research in Sweden 2021 Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 13, s. 21-41 Tidskriftsartikel (refereegranskat)abstract Purpose: Comorbidity indices are often used to measure comorbidities in register-based research. We aimed to adapt the Charlson comorbidity index (CCI) to a Swedish setting.Methods: Four versions of the CCI were compared and evaluated by disease-specific experts.Results: We created a cohesive coding system for CCI to 1) harmonize the content between different international classification of disease codes (ICD-7,8,9,10), 2) delete incorrect codes, 3) enhance the distinction between mild, moderate or severe disease (and between diabetes with and without end-organ damage), 4) minimize duplication of codes, and 5) briefly explain the meaning of individual codes in writing.Conclusion: This work may provide an integrated and efficient coding algorithm for CCI to be used in medical register-based research in Sweden.
3.	Torén, Kjell, et al. (författare) Restrictive Spirometric Pattern and Preserved Ratio Impaired Spirometry in a Population 50-64 Years. 2024 Ingår i: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621. Tidskriftsartikel (refereegranskat)abstract RATIONALE: Knowledge regarding prevalence and shared and unique characteristics of Restrictive spirometric pattern (RSP) and Preserved ratio impaired spirometry (PRISm) is lacking for a general population investigated with post-bronchodilator spirometry and computed tomography of the lungs.OBJECTIVES: To investigate shared and unique features for RSP and PRISm.METHODS: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population sample of 28,555 people aged 50 - 64 years (including 14,558 never-smokers) was assessed. The participants answered a questionnaire and underwent computed tomography of the lungs, post-bronchodilator spirometry, and coronary artery calcification score (CACS). Odds ratios (OR) with 95% confidence intervals (CI) were calculated using adjusted logistic regression. RSP was defined as FEV1/FVC≥0.70 and FVC<80%. PRISm was defined as FEV1/FVC≥0.70 and FEV1<80%. A local reference equation was applied.MEASUREMENTS AND RESULTS: The prevalence of RSP and PRISm were 5.1% (95% CI 4.9 - 5.4) and 5.1% (95% CI 4.8 - 5.3), respectively, with similar values seen in never-smokers. For RSP and PRISm, shared features were current smoking, dyspnea, chronic bronchitis, rheumatic disease, diabetes, ischemic heart disease (IHD), bronchial wall thickening, interstitial lung abnormalities (ILA), and bronchiectasis. Emphysema was uniquely linked to PRISm (OR 1.69, 1.36-2.10) vs 1.10 (0.84-1.43) for RSP. CACS≥300 was related to PRISm, but not among among never-smokers.CONCLUSIONS: PRISm and RSP have respiratory, cardiovascular, and metabolic conditions as shared features. Emphysema is only associated with PRISm. Coronary atherosclerosis may be associated with PRISm. Our results indicate that RSP and PRISm may share more features than not. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
4.	Ahlford, Marianne, et al. (författare) Uppsala Underdogs - A Robot Soccer Project 2006 Rapport (populärvet., debatt m.m.)abstract In this paper, we describe the four-legged soccer team Uppsala Underdogs developed by a group of 4th year computer science students at Uppsala University during the fall of 2004. The project is based on the experience from two similar previous projects. This year the emphasis of the project has been on distribution of data and on support for evaluation and reconfiguration of strategies. To support data distribution, a middleware has been developed, which implements a replication algorithm and provides a clean interface for the other software modules (or behaviors). To enable easy reconfiguration of strategies, an automata-based graphical description language has been developed, which can be compiled into code that uses the database and the lower level modules, such as tactics and positioning, to make decisions and control the robot. In addition, a graphical simulator has been developed in which the strategies can be evaluated.
5.	Ahmadi, Zainab, et al. (författare) Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease 2022 Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Background: The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease.Methods: Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure.Results: In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramér's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramér's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes.Conclusion: In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.
6.	Blomberg, Anders, et al. (författare) Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population. 2024 Ingår i: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621. Tidskriftsartikel (refereegranskat)abstract RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure.OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population.METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7.RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCOCONCLUSIONS: In this large population-based study of middle-aged people, CAL and impaired DLCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
7.	Ekström, Karin M, et al. (författare) Konsumentbeteende i handeln : vad säger forskarna? 2012 Annan publikation (övrigt vetenskapligt/konstnärligt)
8.	Ekström, Magnus, et al. (författare) Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women. 2024 Ingår i: Respiratory research. - : BioMed Central (BMC). - 1465-993X .- 1465-9921. ; 25:1 Tidskriftsartikel (refereegranskat)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.
9.	Ekström, Magnus, et al. (författare) Minimal clinically important differences for Dyspnea-12 and MDP scores are similar at 2 weeks and 6 months : follow-up of a longitudinal clinical study 2021 Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 57:3 Tidskriftsartikel (refereegranskat)abstract Chronic breathlessness is a dominating symptom that restricts daily life for many people with cardiorespiratory disease [1]. Different dimensions of the symptom, such as the intensity, sensory qualities and emotional responses, can be assessed using the instruments Dyspnea-12 (D-12) [2] and the Multidimensional Dyspnea Profile (MDP) [3], which share similarities in the underlying constructs of what is measured [4] and have emerged as widely used instruments for multi-dimensional measurement of breathlessness
10.	Ekström, Magnus P., et al. (författare) Minimal Clinically Important Differences and Feasibility of Dyspnea-12 and the Multidimensional Dyspnea Profile in Cardiorespiratory Disease 2020 Ingår i: Journal of Pain and Symptom Management. - : Elsevier. - 0885-3924 .- 1873-6513. ; 60:5, s. 968-975 Tidskriftsartikel (refereegranskat)abstract Context: Breathlessness is a cardinal symptom in cardiorespiratory disease and consists of multiple dimensions that can be measured using the instruments Dyspnea-12 (D12) and the Multidimensional Dyspnea Profile (MDP). Objectives: The objective of the study is to determine the minimal clinically important differences (MCIDs) of all D12 and MDP summary and subdomain scores as well as the instruments' feasibility in patients with cardiorespiratory disease. Methods: Prospective multicenter cohort study of outpatients with diagnosed cardiorespiratory disease and breathlessness in daily life. D12 and MDP were assessed at baseline, after 30-90 minutes and two weeks. MCIDs were calculated using anchor-based and distributional methods for summary and subdomain scores. Feasibility was assessed as rate of missing data, help required, self-reported difficulty, and completion time. Results: A total 182 outpatients (53.3% women) were included; main diagnoses were chronic obstructive pulmonary disease (COPD; 25%), asthma (21%), heart failure (19%), and idiopathic pulmonary fibrosis (19%). Anchor-based MCIDs were for D12 total score 2.83 (95% CI 1.99-3.66); D12 physical 1.81 (1.29-2.34); D12 affective 1.07 (0.64-1.49); MDP A1 unpleasantness 0.82 (0.56-1.08); MDP perception 4.63 (3.21-6.05), and MDP emotional score 2.37 (1.10-3.64). The estimates were consistent with small-to-moderate effect sizes using distributional analysis, and MCIDs were similar between COPD and non-COPD patients. The instruments were generally feasible and quick to use. Conclusion: D12 and MDP are responsive to change and feasible for use for assessing multidimensional breathlessness in outpatients with cardiorespiratory disease. MCIDs were determined for use as endpoints in clinical trials.
11.	Ekström, Magnus Pär, et al. (författare) The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study 2019 Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964 Tidskriftsartikel (refereegranskat)abstract Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
12.	Ekström, Magnus, et al. (författare) Validation of the Swedish Multidimensional Dyspnea Profile (MDP) in outpatients with cardiorespiratory disease 2019 Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 6:1 Tidskriftsartikel (refereegranskat)abstract Introduction Breathlessness is a cardinal symptom in cardiorespiratory disease. An instrument for measuring different aspects of breathlessness was recently developed, the Multidimensional Dyspnea Profile (MDP). This study aimed to validate the MDP in terms of the underlying factor structure, internal consistency, test-retest reliability and concurrent validity in Swedish outpatients with cardiorespiratory disease. Methods Outpatients with stable cardiorespiratory disease and breathlessness in daily life were recruited. Factor structure of MDP was analysed using confirmatory factor analysis; internal consistency was analysed using Cronbach's alpha; and test-retest reliability was analysed using intraclass correlation coefficients (ICCs) for patients with unchanged breathlessness between assessments (baseline, after 30-90 min and 2 weeks). Concurrent validity was evaluated using correlations with validated scales of breathlessness, anxiety, depression and health-related quality of life. Results In total, 182 outpatients with cardiorespiratory disease and breathlessness in daily life were included; 53.3% were women; main diagnoses were chronic obstructive pulmonary disease (24.7%), asthma (21.4%), heart failure (19.2%) and idiopathic pulmonary fibrosis (18.7%). The MDP total, immediate perception and emotional response scores, and individual item scores showed expected factor structure and acceptable measurement properties: internal consistency (Cronbach's alpha, range 0.80-0.93); test-retest reliability at 30-90 min and 2 weeks (ICC, range 0.67-0.91); and concurrent validity. There was no evidence of a learning effect. Findings were similar between diagnoses. Discussion MDP is a valid instrument for multidimensional measurement of breathlessness in Swedish outpatients across cardiorespiratory diseases.
13.	Finnegan, Sarah L., et al. (författare) A common model for the breathlessness experience across cardiorespiratory disease 2021 Ingår i: ERJ Open Research. - Sheffield : European Respiratory Society. - 2312-0541. ; 7:2 Tidskriftsartikel (refereegranskat)abstract Chronic breathlessness occurs across many different conditions, often independently of disease severity. Yet, despite being strongly linked to adverse outcomes, the consideration of chronic breathlessness as a stand-alone therapeutic target remains limited. Here we use data-driven techniques to identify and confirm the stability of underlying features (factors) driving breathlessness across different cardiorespiratory diseases.Questionnaire data on 182 participants with main diagnoses of asthma (21.4%), COPD (24.7%), heart failure (19.2%), idiopathic pulmonary fibrosis (18.7%), other interstitial lung disease (2.7%), and "other diagnoses" (13.2%) were entered into an exploratory factor analysis (EFA). Participants were stratified based on their EFA factor scores. We then examined model stability using 6-month follow-up data and established the most compact set of measures describing the breathlessness experience.In this dataset, we have identified four stable factors that underlie the experience of breathlessness. These factors were assigned the following descriptive labels: 1) body burden, 2) affect/mood, 3) breathing burden and 4) anger/frustration. Stratifying patients by their scores across the four factors revealed two groups corresponding to high and low burden. These two groups were not related to the primary disease diagnosis and remained stable after 6 months.In this work, we identified and confirmed the stability of underlying features of breathlessness. Previous work in this domain has been largely limited to single-diagnosis patient groups without subsequent re-testing of model stability. This work provides further evidence supporting disease independent approaches to assess breathlessness.
14.	Hoffman, Mariana, et al. (författare) Exertional Desaturation During the 6-Minute Walk Test vs Daily Life in People With Fibrotic Interstitial Lung Disease 2024 Ingår i: Chest. - 0012-3692. ; 165:3, s. 632-635 Tidskriftsartikel (refereegranskat)
15.	Holland, Anne E., et al. (författare) Ambulatory oxygen for treatment of exertional hypoxaemia in pulmonary fibrosis (PFOX trial) : A randomised controlled trial 2020 Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:12 Tidskriftsartikel (refereegranskat)abstract Introduction Interstitial lung diseases are characterised by scarring of lung tissue that leads to reduced transfer of oxygen into the blood, decreased exercise capacity and premature death. Ambulatory oxygen therapy may be used to treat exertional oxyhaemoglobin desaturation, but there is little evidence to support its efficacy and there is wide variation in clinical practice. This study aims to compare the clinical efficacy and cost-effectiveness of ambulatory oxygen versus ambulatory air in people with fibrotic interstitial lung disease and exertional desaturation. Methods and analysis A randomised, controlled trial with blinding of participants, clinicians and researchers will be conducted at trial sites in Australia and Sweden. Eligible participants will be randomised 1:1 into two groups. Intervention participants will receive ambulatory oxygen therapy using a portable oxygen concentrator (POC) during daily activities and control participants will use an identical POC modified to deliver air. Outcomes will be assessed at baseline, 3 months and 6 months. The primary outcome is change in physical activity measured by number of steps per day using a physical activity monitor (StepWatch). Secondary outcomes are functional capacity (6-minute walk distance), health-related quality of life (St George Respiratory Questionnaire, EQ-5D-5L and King's Brief Interstitial Lung Disease Questionnaire), breathlessness (Dyspnoea-12), fatigue (Fatigue Severity Scale), anxiety and depression (Hospital Anxiety and Depression Scale), physical activity level (GENEActive), oxygen saturation in daily life, POC usage, and plasma markers of skeletal muscle metabolism, systematic inflammation and oxidative stress. A cost-effectiveness evaluation will also be undertaken. Ethics and dissemination Ethical approval has been granted in Australia by Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/42) with governance approval at all Australian sites, and in Sweden (Lund Dnr: 2019-02963). The results will be published in peer-reviewed scientific journals, presented at conferences and disseminated to consumers in publications for lay audiences. Trial registration number ClinicalTrials.gov Registry (NCT03737409).
16.	Olsson, Max, et al. (författare) Factors important for health-related quality of life in men and women : The population based SCAPIS study 2023 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:11 Tidskriftsartikel (refereegranskat)abstract IntroductionHealth-related quality of life (HRQoL) is essential for human wellbeing, influenced by a complex interplay of factors, and is reported lower in women than men. We aimed to evaluate which factors were the most important for HRQoL in a middle-aged general population.MethodsThis was a cross-sectional, multi-centre study of 29,212 men (48%) and women (52%) aged 50-64 in the general population in Sweden. Physical and mental HRQoL (0-100) was assessed using the Short Form 12 questionnaire, and association was evaluated for 356 variables including demographics, lifestyle, symptoms, physiological measurements, and health conditions. Using machine learning, each variable ' s importance for HRQoL was measured by an importance score, comparable to effect size, and summarised in 54 factors, in men and women separately.ResultsMen and women had similar mean and standard deviation (SD) scores for physical HRQoL (53.4 [SD 8.1] vs 51.4 [9.7]) and mental HRQoL (37.1 [5.0] vs 37.3 [5.4]). The most important factors for physical HRQoL were (importance score) physical activity (40), employment (36), pain (33), sleep (33), and sense of control (26). The most important factors for mental HRQoL were sense of control (18), physical activity (12), depression (12), pain (6), and employment (5).ConclusionsThe factors important for HRQoL identified by this study are likely to be amenable to interventions, and our findings can support prioritising interventions. The identified factors need to be a target even before middle-age to lay the foundation for long and happy lives.
17.	Olsson, Max, et al. (författare) Factors most strongly associated with breathlessness in a population aged 50-64 years 2024 Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 10:2 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Breathlessness is a troublesome and prevalent symptom in the population, but knowledge of related factors is scarce. The aim of this study was to identify the factors most strongly associated with breathlessness in the general population and to describe the shapes of the associations between the main factors and breathlessness.METHODS: A cross-sectional analysis was carried out of the multicentre population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) of adults aged 50 to 64 years. Breathlessness was defined as a modified Medical Research Council breathlessness rating ≥2. The machine learning algorithm extreme gradient boosting (XGBoost) was used to classify participants as either breathless or nonbreathless using 449 factors, including physiological measurements, blood samples, computed tomography cardiac and lung measurements, lifestyle, health conditions and socioeconomics. The strength of the associations between the factors and breathlessness were measured by SHapley Additive exPlanations (SHAP), with higher scores reflecting stronger associations.RESULTS: A total of 28 730 participants (52% women) were included in the study. The strongest associated factors for breathlessness were (in order of magnitude): body mass index ( SHAP score 0.39), forced expiratory volume in 1 s (0.32), physical activity measured by accelerometery (0.27), sleep apnoea (0.22), diffusing lung capacity for carbon monoxide (0.21), self-reported physical activity (0.17), chest pain when hurrying (0.17), high-sensitivity C-reactive protein (0.17), recent weight change (0.14) and cough (0.13).CONCLUSION: This large population-based study of men and women aged 50-64 years identified the main factors related to breathlessness that may be prevented or amenable to public health interventions.
18.	Sundh, Josefin, 1972-, et al. (författare) Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial 2020 Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 21:1 Tidskriftsartikel (refereegranskat)abstract Background: Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking. The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.Methods: The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT. A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only. The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events. Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter. Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year. Outcome data are obtained from medical history and record review during study visits, as well as from national registries.Discussion: BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD. The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.
19.	Sundh, Josefin, 1972-, et al. (författare) Clinical validation of the Swedish version of Dyspnoea-12 instrument in outpatients with cardiorespiratory disease 2019 Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 6:1 Tidskriftsartikel (refereegranskat)abstract Introduction Breathlessness is the cardinal symptom in both cardiac and respiratory diseases, and includes multiple dimensions. The multidimensional instrument Dyspnoea-12 has been developed to assess both physical and affective components of breathlessness. This study aimed to perform a clinical validation of the Swedish version of Dyspnoea-12 in outpatients with cardiorespiratory disease. Methods Stable outpatients with cardiorespiratory disease and self-reported breathlessness in daily life were recruited from five Swedish centres. Assessments of Dyspnoea-12 were performed at baseline, after 30-90 min and after 2 weeks. Factor structure was tested using confirmatory factor analysis and internal consistency using Cronbach's alpha. Test-retest reliability was analysed using intraclass correlation coefficients (ICCs). Concurrent validity at baseline was evaluated by examining correlations with lung function and several instruments for the assessment of symptoms and health status. Results In total, 182 patients were included: with the mean age of 69 years and 53% women. The main causes of breathlessness were chronic obstructive pulmonary disease (COPD; 25%), asthma (21%), heart failure (19%) and idiopathic pulmonary fibrosis (19%). Factor analysis confirmed the expected underlying two-component structure with two subdomains. The Dyspnoea-12 total score, physical subdomain score and affective subdomain scores showed high internal consistency (Cronbach's alpha 0.94, 0.84 and 0.80, respectively) and acceptable reliability after 2 weeks (ICC total scores 0.81, 0.79 and 0.73). Dyspnoea-12 showed concurrent validity with the instruments modified Medical Research Council scale, COPD Assessment Test, European Quality of Life-Five Dimensions-Five levels, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and with forced expiratory volume in 1 s in percentage of predicted value. The results were consistent across different cardiorespiratory conditions. Conclusion The Dyspnoea-12 is a valid instrument for multidimensional assessment of breathlessness in Swedish patients with cardiorespiratory diseases.
20.	Teni, F. S., et al. (författare) Variations in Patients' Overall Assessment of Their Health Across and Within Disease Groups Using the EQ-5D Questionnaire: Protocol for a Longitudinal Study in the Swedish National Quality Registers 2021 Ingår i: Jmir Research Protocols. - Toronto, ON, Canada : JMIR Publications Inc.. - 1929-0748. ; 10:8 Tidskriftsartikel (refereegranskat)abstract Background: EQ-5D is one of the most commonly used questionnaires to measure health-related quality of life. It is included in many of the Swedish National Quality Registers (NQRs). EQ-5D health states are usually summarized using "values" obtained from members of the general public, a majority of whom are healthy. However, an alternative, which remains to be studied in detail, is the potential to use patients' self-reported overall health on the visual analog scale (VAS) as a means of capturing experience-based perspective. Objective: The aim of this study is to assess EQ VAS as a valuation method with an experience-based perspective through comparison of its performance across and within patient groups, and with that of the general population in Sweden. Methods: Data on nearly 700,000 patients from 12 NQRs covering a variety of diseases/conditions and nearly 50,000 individuals from the general population will be analyzed. The EQ-5D-3L data from the 12 registers and EQ-5D-5L data from 2 registers will be used in the analyses. Longitudinal studies of patient-reported outcomes among different patient groups will be conducted in the period from baseline to 1-year follow-up. Descriptive statistics and analyses comparing EQ-5D dimensions and observed self-assessed EQ VAS values across and within patient groups will be performed. Comparisons of the change in health state and observed EQ VAS values at 1-year follow-up will also be undertaken. Regression models will be used to assess whether EQ-5D dimensions predict observed EQ VAS values to investigate patient value sets in each patient group. These will be compared across the patient groups and with the existing Swedish experience-based VAS and time trade-off value sets obtained from the general population. Results: Data retrieval started in May 2019 and data of patients in the 12 NQRs and from the survey conducted among the general population have been retrieved. Data analysis is ongoing on the retrieved data. Conclusions: This research project will provide information on the differences across and within patient groups in terms of self-reported health status through EQ VAS and comparison with the general population. The findings of the study will contribute to the literature by exploring the potential of self-assessed EQ VAS values to develop value sets using an experience-based perspective.
21.	Abdelmenan, Semira, et al. (författare) The Social Stratification of Availability, Affordability, and Consumption of Food in Families with Preschoolers in Addis Ababa : The EAT Addis Study in Ethiopia 2020 Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 12:10 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to understand the quality of diet being consumed among families in Addis Ababa, and to what extent social stratification and perceptions of availability and affordability affect healthy food consumption. Data were collected from 5467 households in a face-to-face interview with mothers/caretakers and analyzed using mixed effect logistic regression models. All family food groups, except fish were perceived to be available by more than 90% of the participants. The food groups cereals/nuts/seeds, other vegetables, and legumes were considered highly affordable (80%) and were the most consumed (>75%). Households with the least educated mothers and those in the lowest wealth quintile had the lowest perception of affordability and also consumption. Consumption of foods rich in micronutrients and animal sources were significantly higher among households with higher perceived affordability, the highest wealth quintile, and with mothers who had better education. Households in Addis Ababa were generally seen to have a monotonous diet, despite the high perceived availability of different food groups within the food environment. There is a considerable difference in consumption of nutrient-rich foods across social strata, hence the cities food policies need to account for social differences in order to improve the nutritional status of the community.
22.	Adeloye, Davies, et al. (författare) Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade 2021 Ingår i: Journal of Global Health. - : International Global Health Society. - 2047-2986 .- 2047-2978. ; 11, s. 15003-15003 Tidskriftsartikel (refereegranskat)abstract Background: The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD. Methods: We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities. Results: 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity. Conclusions: The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.
23.	Ahmadi, Zainab, et al. (författare) Does Long-Term Oxygen Therapy 24 H/day Improve Survival Compared To 15 H/day In Hypoxemic Chronic Obstructive Pulmonary Disease? 2016 Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 193 Tidskriftsartikel (refereegranskat)
24.	Ahmadi, Zainab, et al. (författare) End-of-life care in oxygen-dependent COPD and cancer: a national population-based study. 2015 Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 46:4, s. 1190-1193 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
25.	Ahmadi, Zainab, et al. (författare) End-of-life care in oxygen-dependent ILD compared with lung cancer : a national population-based study 2016 Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 71:6, s. 510-516 Tidskriftsartikel (refereegranskat)abstract Rationale: Advanced fibrosing interstitial lung disease (ILD) is often progressive and associated with a high burden of symptoms and poor prognosis. Little is known about the symptom prevalence and access to palliative care services at end of life (EOL).Objectives: Compare prevalence of symptoms and palliative treatments between patients dying with oxygen-dependent ILD and patients dying of lung cancer.Methods: Nationwide registry-based cohort study of patients with oxygen-dependent ILD and patients with lung cancer who died between 1 January 2011 and 14 October 2013. Prevalence of symptoms and treatments during the last seven days of life were compared using data in Swedish Registry of Palliative Care.Measurements and main results: 285 patients with ILD and 10 822 with lung cancer were included. In ILD, death was more likely to be 'unexpected' (15% vs 4%), less likely to occur in a palliative care setting (17% vs 40%) and EOL discussions with the patients (41% vs 59%) were less common than in lung cancer. Patients with ILD suffered more from breathlessness (75% vs 42%) while patients with lung cancer had more pain (51% vs 73%) (p<0.005 for all comparisons). Patients with ILD had more unrelieved breathlessness, pain and anxiety. The survival time from initiation of oxygen therapy in ILD was a median 8.4 months (IQR 3.4-19.2 months).Conclusions: Patients with ILD receive poorer access to specialist EOL care services and experience more breathlessness than patients with lung cancer. This study highlights the need of better EOL care in oxygen-dependent ILD.
26.	Ahmadi, Zainab, et al. (författare) Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease : a population-based prospective study 2014 Ingår i: Respiratory Research. - : BioMed Central. - 1465-9921 .- 1465-993X. ; 15:1, s. 30- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO2) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown. The aim of this study was to estimate the association between PaCO2 and mortality in oxygen-dependent COPD. METHODS: National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint. The association between PaCO2 while breathing air, PaCO2 (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO2), World Health Organization performance status, body mass index, comorbidity, and medications. RESULTS: Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation. No patient was lost to follow-up. PaCO2 (air) independently predicted adjusted mortality (p < 0.001). The association with mortality was U-shaped, with the lowest mortality at approximately PaCO2 (air) 6.5 kPa and increased mortality at PaCO2 (air) below 5.0 kPa and above 7.0 kPa. CONCLUSION: In oxygen-dependent COPD, PaCO2 (air) is an independent prognostic factor with a U-shaped association with mortality.
27.	Ahmadi, Zainab, et al. (författare) Is chronic breathlessness less recognised and treated compared with chronic pain? A case-based randomised controlled trial 2018 Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 52:3 Tidskriftsartikel (refereegranskat)
28.	Ahmadi, Zainab, et al. (författare) Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease 2016 Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 11:9 Tidskriftsartikel (refereegranskat)abstract Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed.
29.	Ahmadi, Zainab, et al. (författare) Palliative oxygen for chronic breathlessness : What new evidence? 2017 Ingår i: Current Opinion in Supportive and Palliative Care. - 1751-4258. ; 11:3, s. 159-164 Forskningsöversikt (refereegranskat)abstract Purpose of review Supplemental oxygen improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxaemia, but the effect of oxygen therapy in mild or moderate hypoxaemia to reduce symptomatic chronic breathlessness remains unclear. This review provides an overview of recent evidence about the role of oxygen therapy for the relief of chronic breathlessness in advanced illness. Recent findings In COPD, a recent Cochrane review strengthens earlier findings regarding the positive effect of supplemental oxygen compared with air during exercise test in the training setting. The novel analysis of effect of oxygen therapy on quality of life (QoL) showed no clear effect. Short-burst oxygen therapy given before exercise had no effect and should not be used. Summary Supplemental oxygen during exercise has been shown to reduce breathlessness in patients with COPD who have no or mild hypoxaemia, but it is not clear whether the reduction in breathlessness shown in the laboratory setting translates into a clinically important benefit. Further studies are needed to establish this.
30.	Ahmadi, Zainab, et al. (författare) Prescription of opioids for breathlessness in end-stage COPD : A national population-based study 2016 Ingår i: International Journal of COPD. - 1176-9106. ; 11:1, s. 2651-2657 Tidskriftsartikel (refereegranskat)abstract Background: Low-dose opioids can relieve breathlessness but may be underused in late-stage COPD due to fear of complications, contributing to poor symptom control. Objectives: We aimed to study the period prevalence and indications of opioids actually prescribed in people with end-stage COPD. Methods: The study was a longitudinal, population-based study of patients starting long-term oxygen therapy (LTOT) for COPD between October 1, 2005 and June 30, 2009 in Sweden. A random sample (n=2,000) of their dispensed opioid prescriptions was obtained from the national Prescribed Drugs Register from 91 days before starting LTOT until the first of LTOT withdrawal, death, or study end (December 31, 2009). We analyzed medication type, dispensed quantity, date of dispensing, and indications categorized as pain, breathlessness, other, or unknown. Results: In total, 2,249 COPD patients (59% women) were included. During a median follow-up of 1.1 (interquartile range 0.6–2.0) years, 1,034 patients (46%) were dispensed ≥1 opioid prescription (N=13,722 prescriptions). The most frequently prescribed opioids were tramadol (23%), oxycodone (23%), morphine (16%), and codeine (16%). Average dispensed quantity was 9.3 (interquartile range 3.7–16.7) defined daily doses per prescription. In the random sample, the most commonly stated indication was pain (97%), with only 2% for breathlessness and 1% for other reasons. Conclusion: Despite evidence that supported the use of opioids for the relief of breathlessness predating this study, opioids are rarely prescribed to relieve breathlessness in oxygen-dependent COPD, potentially contributing to less-than-optimal symptom control. This study creates a baseline against which to compare future changes in morphine prescribing in this setting.
31.	Ahmadi, Zainab, et al. (författare) Smoking and home oxygen therapy : a review and consensus statement from a multidisciplinary Swedish taskforce 2024 Ingår i: European Respiratory Review. - : European Respiratory Society. - 0905-9180 .- 1600-0617. ; 33:171 Forskningsöversikt (refereegranskat)abstract Background: Home oxygen therapy (HOT) improves survival in patients with hypoxaemic chronic respiratory disease. Most patients evaluated for HOT are former or active smokers. Oxygen accelerates combustion and smoking may increase the risk of burn injuries and fire hazards; therefore, it is considered a contraindication for HOT in many countries. However, there is variability in the practices and policies regarding this matter. This multidisciplinary Swedish taskforce aimed to review the potential benefits and risks of smoking in relation to HOT, including medical, practical, legal and ethical considerations.Methods: The taskforce of the Swedish Respiratory Society comprises 15 members across respiratory medicine, nursing, medical law and ethics. HOT effectiveness and adverse risks related to smoking, as well as practical, legal and ethical considerations, were reviewed, resulting in five general questions and four PICO (population–intervention–comparator–outcome) questions. The strength of each recommendation was rated according to the GRADE (grading of recommendation assessment, development and evaluation) methodology.Results: General questions about the practical, legal and ethical aspects of HOT were discussed and summarised in the document. The PICO questions resulted in recommendations about assessment, management and follow-up of smoking when considering HOT, if HOT should be offered to people that meet the eligibility criteria but who continue to smoke, if a specific length of time of smoking cessation should be considered before assessing eligibility for HOT, and identification of areas for further research.Conclusions: Multiple factors need to be considered in the benefit/risk evaluation of HOT in active smokers. A systematic approach is suggested to guide healthcare professionals in evaluating HOT in relation to smoking.
32.	Ahuja, Sat pal, et al. (författare) Glutathione S-transferase µ(GST) modifies activities of proteases and levels of cystatin C secreted by mouse retinal explants 2004 Ingår i: Investigative Ophthalmology & Visual Science. - 1552-5783. ; 45, s. 352-352 Konferensbidrag (refereegranskat)abstract Purpose: In one form of human autosomal recessive retinitis pigmentosa and in retinal degeneration (rd1) mouse, mutation occurs in the genes encoding ß subunit of rod photoreceptor cGMP phosphodiesterase. Therefore, rd1 mutant mouse is an appropriate model for human inherited retinal degeneration studies. Retinal explants are successfully cultured in serum free chemically defined R16 medium to evaluate effects of various rescue factors and retinal conditioned medium (RCM) for secreted molecules like proteases and their inhibitors. Cysteine protease inhibitor cystatin C has recently been identified in rodent neuroretina and RPE. RCM of explants treated with GST were analyzed for proteases and cystatin C to explain, in part, mode of action of GST in protection of degenerating retina. Methods: Postnatal day 2 (PN2) and PN7 control (wt) and rd1 were cultured with (10 ng / ml GST) and without GST in R16 medium, respectively, for 26 and 21 days in vitro (div). Retinal extracts (RE) and RCM were analyzed by fluorometry using casein green fluorescent labeled with BODIPY–FL (Molecular Probes) for total proteases; Z–Phe–Arg–NMec or Z–Arg–Arg–NMec for cysteine proteases and by ELISA for cystatin C, respectively, for levels and secretion of proteases and cystatin C. The protein content of RE was measured. Results: Protein content (µg) of RE from wt and rd1 retinal extracts respectively increased and decreased with age. Cystatin C (ng/ml RCM) content in wt and rd1 RE increased with age (was always higher in wt) up to PN14 and then decreased but was higher than that at PN2. Progressive secretion of cystatin C by PN2 explants was lower than that by PN7 explants; and that by rd1 PN2 and PN7 explants was initially lower up to in vitro age of PN19 and subsequently it was higher than that by wt explants. Secretion of total cystatin C by PN2 and PN7 wt and rd1 explants was similar and was increased by GST. During initial stage of culture total protease activity ({Delta} F / 100 µl RCM) in RCM of rd1 PN2 and PN7 explants was higher and was decreased in GST treated explants. Conclusions: Cystatin C content and secretion by wt RE is always higher and that of proteases is lower than that of rd1. Treatment with GST increases content of cystatin C and consequently decreases that of proteases especially cysteine proteases.
33.	Ahuja, Sat pal, et al. (författare) Physiopathology of retinal degeneration in rd1 mouse model of retinitis pigmentosa : TGF-Β1, proteinases and oxidative stress mechanisms 2009 Ingår i: Retinal Degeneration: Causes, Diagnosis and Treatment. - 9781607410072 ; , s. 1-41 Bokkapitel (refereegranskat)abstract The rd1 (retinal degeneration) mouse retina shows degeneration homologous to a form of retinitis pigmentosa with a rapid loss of rod photoreceptors and deficiency of retinal blood vessels. Due to Pde6brd1 gene mutation, β subunit of phosphodiesterase (PDE) of rd1 retina has an inactive PDE which elevates cGMP and Ca2+ ions level. In vitro retinal explants provide a system close to the in vivo situation, so both approaches were used to compare the status of oxidative stress, transforming growth factor-β1 (TGF-β1), sialylation, galactosylation of proteoglycans, and different proteinases-endogenous inhibitors systems participating in extracellular matrix (ECM) remodeling/degeneration and programmed cell death (PCD)/apoptosis in wt and rd1 mouse retinas. Proteins and desialylated sulfated glucosaminoglycan parts of proteoglycans in ECM of rd1 retina were, respectively, decreased and increased due to enhanced activities of proteinases. Desialylation increases the susceptibility of cells to phoagocytosis/apoptosis, decreased neurogenesis and faulty guidance cues for synaptogenesis. In vivo activities of total proteinases, matrix metalloproteinase-9 (MMP-9) and cathepsin B were increased in rd1 retina on postnatal day 14 (PN14), -21 and -28, due to relatively lower levels of tissue inhibitor of MMPs (TIMP-1) and cystatin C, respectively. This corresponded with increased in vitro secretion of these proteinases by rd1 retina. Cells including end-feet of Mueller cells in degenerating rd1 retina showed intense immunolabeling for MMP-9, MMP-2/TIMP-1, TIMP-2 and cathepsin B/cystatin C, and proteinases pool was increased by Mueller cells. Intense immunolabeling of ganglion cell (RGC) layer for cathepsin B and of inner-plexiform layer of both PN2/PN7 rd1 and wt retinas indicated importance of cathepsin B in synaptogenesis and PCD of RGC. Increased levels of TGF-β1 in vitro transiently increased the secretion of MMPs and cathepsins activities by wt explants which activate TGF-β1 and remodel the ECM for angiogenesis and ontogenetic PCD. Whereas, lower level of TGF-β1 and persistently higher activities of MMPs and cathepsins in rd1 retinas and conditioned medium, suggested that proteinases degraded TGF-β1 and ECM and caused retinal degeneration. Lower activities of glutathione-S-transferase and glutathione-peroxidase in rd1 retina contribute to oxidative stress which damages membranes and increased the expression, release/secretion of proteinases relative to their endogenous inhibitors. Participation of oxidative stress in rd1 retinal degeneration was further confirmed from the partial protection of rd1 photoreceptors by in vitro and/or in vivo supplementation with glutathione-S-transferase or a combination of antioxidants namely lutein, zeaxanthin, α-lipoic acid and reduced-L-glutathione. Treatment with combination(s) of broad spectrum proteinase inhibitor(s) and antioxidants needs investigation.
34.	Ahuja, Sat pal, et al. (författare) rd1 Mouse retina shows an imbalance in the activity of cysteine protease cathepsins and their endogenous inhibitor cystatin C. 2008 Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 49:3, s. 1089-1096 Tidskriftsartikel (refereegranskat)abstract PURPOSE: To compare in vivo levels, spatial localization, and in vitro secretion of cysteine protease cathepsins and cystatin C (cysC) in the retinal degeneration 1 (rd1) mouse model of retinitis pigmentosa and control (wt) mouse retinas. METHODS: The spatial localization, protein contents, cysC levels and cathepsin-B, -S, and -L activities in wt and rd1 retinas at postnatal (PN) days 2, 7, 14, 21, and 28 were analyzed by immunostaining, spectrophotometry, ELISA, and fluorescence spectrophotometry. The in vitro secretion of cysC and cysteine proteases by PN7 retinal explants into the conditioned medium (RCM) was quantified. RESULTS: The pigment epithelium, photoreceptors, and inner retinal and ganglion cell layers of both wt and rd1 retinas showed cysC and cathepsin-B labeling. CysC immunostaining was extensive in the optic nerve head fibers. The rd1 explants secreted higher amounts of cysteine protease into the RCM. The protein content in wt and rd1 retinal extracts increased up to PN14, then decreased in rd1 but not in wt. In rd1 extracts at PN14 to -28, cathepsin activity was higher and increased with age, but the cysC level was higher and constant. The ratios of cathepsin activity to cysC (cathepsin-L at PN2 and total, -B, and -L at PN14 to -28) were higher in rd1 extracts. CONCLUSIONS: Similar localization of both cathepsin-B and cysC in wt and rd1 retinas along with lower proteins and higher cathepsin activity in rd1 retinal extracts and RCM are consistent with their localization in extracellular matrix and a role in physiopathologic remodeling in wt and rd1 retinas.
35.	Ahuja, Sat pal, et al. (författare) rd1 Mouse Retina Shows Imbalance in Cellular Distribution and Levels of TIMP-1/MMP-9, TIMP-2/MMP-2 and Sulfated Glycosaminoglycans. 2006 Ingår i: Ophthalmic Research. - : S. Karger AG. - 1423-0259 .- 0030-3747. ; 38:3, s. 125-136 Tidskriftsartikel (refereegranskat)abstract Background: The rd1 mouse retina displays fast degeneration of photoreceptors resulting in a depletion of almost all rod photoreceptors by postnatal day 21 (PN21). To evaluate the role of proteinases in the pathophysiology of this animal model of retinitis pigmentosa, C3H rd1 and congenic wild-type (wt) mice retinas were analyzed. Material and Methods: The cellular localization and levels of proteins, matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), total sulfated glycosaminoglycans (sGAG) and nature of saccharides in roll and wt retinal extracts were compared. Results: MMP-2/TIMP-2 and MMP-9/TIMP-1 were predominantly localized in the interphotoreceptor matrix (IPM) of both genotypes, but MMP-2/TIMP-2 also appeared in the Muller cell fibers of rd1 retina. In rd1 retinal extracts the levels of total proteins were lower and those of active MMP-9, MMP-2, TIMP-1 and total sGAG were higher than those of wt extracts. Despite an increase in TIMP-1, active MMP-9/MMP-2 were disproportionately elevated in rd1 compared to wt retina. With increasing age, MMPs in wt retinas were decreased but were increased in rd1. The sialylation of proteoglycans in PN2 and PN7 rd1 retinas was lower, and galactosylation was higher than that in wt retinas. Conclusions: MMP-9/ MMP-2 and TIMP-1/TIMP-2 are associated with IPM, possibly after secretion by retinal pigmented epithelial cells. In degenerating rd1 retina, MMP-2/TIMP-2 are associated with the Muller cell fibers, which apparently play a central role in modifying the balance between MMPs and TIMPs. Elevated sGAG and proteolysis due to an imbalance in the levels of TIMPs and active MMP-9/MMP-2 in rd1 retina possibly contribute to retinal degeneration in the rd1 mouse.
36.	Akbarshahi, Hamid, et al. (författare) No gender-related bias in COPD diagnosis and treatment in Sweden : a randomised, controlled, case-based trial 2020 Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:4 Tidskriftsartikel (refereegranskat)abstract Introduction: COPD is a major cause of morbidity and mortality. The prevalence, morbidity and mortality of COPD among females have increased. Previous studies indicate a possible gender bias in the diagnosis and management of COPD. The present study aims to determine if there is gender bias in the management of COPD in Sweden.Methods: This was a double-blind, randomised (1:1), controlled, parallel-group, web-based trial using the hypothetical case scenario of a former smoker (40 pack-years and quit smoking 3 years ago) who was male or female. The participants were blind to the randomisation and the purpose of the trial. The case progressively revealed more information with associated questions on how the physician would manage the patient. Study participants chose from a list of tests and treatments at each step of the case scenario.Results: In total, 134 physicians were randomised to a male (n=62) or a female (n=72) case. There was no difference in initial diagnosis (61 (98%) male cases and 70 (97%) female cases diagnosed with COPD) and planned diagnostic procedures between the male and female cases. Spirometry was chosen by all the physicians as one of the requested diagnostic tests. The management of the hypothetical COPD case did not differ by sex of the responding physician.Conclusion: In Sweden, diagnosis and management of a hypothetical patient with COPD did not differ by the gender of the patient or physician.
37.	Alsanius, Beatrix W, et al. (författare) Optimizing horticulture for urban agriculture 2020 Ingår i: Achieving sustainable urban agriculture. - 9781786763167 ; , s. 1-57 Bokkapitel (refereegranskat)
38.	Angelov, Angel G., et al. (författare) Four-decision tests for stochastic dominance, with an application to environmental psychophysics 2019 Ingår i: Journal of mathematical psychology (Print). - : Elsevier. - 0022-2496 .- 1096-0880. ; 93 Tidskriftsartikel (refereegranskat)abstract If the survival function of a random variable X lies to the right of the survival function of a random variable Y, then X is said to stochastically dominate Y. Inferring stochastic dominance is particularly complicated because comparing survival functions raises four possible hypotheses: identical survival functions, dominance of X over Y, dominance of Y over X, or crossing survival functions. In this paper, we suggest four-decision tests for stochastic dominance suitable for paired samples. The tests are permutation-based and do not rely on distributional assumptions. One-sided Cramér–von Mises and Kolmogorov–Smirnov statistics are employed but the general idea may be utilized with other test statistics. The power to detect dominance and the different types of wrong decisions are investigated in an extensive simulation study. The proposed tests are applied to data from an experiment concerning the individual’s willingness to pay for a given environmental improvement.
39.	Angelov, Angel G., et al. (författare) Maximum likelihood estimation for survey data with informative interval censoring 2019 Ingår i: AStA Advances in Statistical Analysis. - : Springer. - 1863-8171 .- 1863-818X. ; 103:2, s. 217-236 Tidskriftsartikel (refereegranskat)abstract Interval-censored data may arise in questionnaire surveys when, instead of being asked to provide an exact value, respondents are free to answer with any interval without having pre-specified ranges. In this context, the assumption of noninformative censoring is violated, and thus, the standard methods for interval-censored data are not appropriate. This paper explores two schemes for data collection and deals with the problem of estimation of the underlying distribution function, assuming that it belongs to a parametric family. The consistency and asymptotic normality of a proposed maximum likelihood estimator are proven. A bootstrap procedure that can be used for constructing confidence intervals is considered, and its asymptotic validity is shown. A simulation study investigates the performance of the suggested methods.
40.	Angelov, Angel G., 1983- (författare) Methods for interval-censored data and testing for stochastic dominance 2018 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract This thesis includes four papers: the first three of them are concerned with methods for interval-censored data, while the forth paper is devoted to testing for stochastic dominance.In many studies, the variable of interest is observed to lie within an interval instead of being observed exactly, i.e., each observation is an interval and not a single value. This type of data is known as interval-censored. It may arise in questionnaire-based studies when the respondent gives an answer in the form of an interval without having pre-specified ranges. Such data are called self-selected interval data. In this context, the assumption of noninformative censoring is not fulfilled, and therefore the existing methods for interval-censored data are not necessarily applicable.A problem of interest is to estimate the underlying distribution function. There are two main approaches to this problem: (i) parametric estimation, which assumes a particular functional form of the distribution, and (ii) nonparametric estimation, which does not rely on any distributional assumptions. In Paper A, a nonparametric maximum likelihood estimator for self-selected interval data is proposed and its consistency is shown. Paper B suggests a parametric maximum likelihood estimator. The consistency and asymptotic normality of the estimator are proven.Another interesting problem is to infer whether two samples arise from identical distributions. In Paper C, nonparametric two-sample tests suitable for self-selected interval data are suggested and their properties are investigated through simulations.Paper D concerns testing for stochastic dominance with uncensored data. The paper explores a testing problem which involves four hypotheses, that is, based on observations of two random variables X and Y, one wants to discriminate between four possibilities: identical survival functions, stochastic dominance of X over Y, stochastic dominance of Y over X, or crossing survival functions. Permutation-based tests suitable for two independent samples and for paired samples are proposed. The tests are applied to data from an experiment concerning the individual's willingness to pay for a given environmental improvement.
41.	Angelov, Angel G., et al. (författare) Nonparametric estimation for self-selected interval data collected through a two-stage approach 2017 Ingår i: Metrika (Heidelberg). - : Springer. - 0026-1335 .- 1435-926X. ; 80:4, s. 377-399 Tidskriftsartikel (refereegranskat)abstract Self-selected interval data arise in questionnaire surveys when respondents are free to answer with any interval without having pre-specified ranges. This type of data is a special case of interval-censored data in which the assumption of noninformative censoring is violated, and thus the standard methods for interval-censored data (e.g. Turnbull's estimator) are not appropriate because they can produce biased results. Based on a certain sampling scheme, this paper suggests a nonparametric maximum likelihood estimator of the underlying distribution function. The consistency of the estimator is proven under general assumptions, and an iterative procedure for finding the estimate is proposed. The performance of the method is investigated in a simulation study.
42.	Angelov, Angel G., et al. (författare) Quantile regression with interval-censored data in questionnaire-based studies 2024 Ingår i: Computational statistics (Zeitschrift). - : Springer Berlin/Heidelberg. - 0943-4062 .- 1613-9658. ; 39:2, s. 583-603 Tidskriftsartikel (refereegranskat)abstract Interval-censored data can arise in questionnaire-based studies when the respondent gives an answer in the form of an interval without having pre-specified ranges. Such data are called self-selected interval data. In this case, the assumption of independent censoring is not fulfilled, and therefore the ordinary methods for interval-censored data are not suitable. This paper explores a quantile regression model for self-selected interval data and suggests an estimator based on estimating equations. The consistency of the estimator is shown. Bootstrap procedures for constructing confidence intervals are considered. A simulation study indicates satisfactory performance of the proposed methods. An application to data concerning price estimates is presented.
43.	Angelov, Angel G., et al. (författare) Testing for stochastic dominance : Procedures with four hypotheses Annan publikation (övrigt vetenskapligt/konstnärligt)
44.	Angelov, Angel G., et al. (författare) Tests of stochastic dominance with repeated measurements data 2023 Ingår i: AStA Advances in Statistical Analysis. - : Springer. - 1863-8171 .- 1863-818X. ; 107:3, s. 443-467 Tidskriftsartikel (refereegranskat)abstract The paper explores a testing problem which involves four hypotheses, that is, based on observations of two random variables X and Y, we wish to discriminate between four possibilities: identical survival functions, stochastic dominance of X over Y, stochastic dominance of Y over X, or crossing survival functions. Four-decision testing procedures for repeated measurements data are proposed. The tests are based on a permutation approach and do not rely on distributional assumptions. One-sided versions of the Cramér–von Mises, Anderson–Darling, and Kolmogorov–Smirnov statistics are utilized. The consistency of the tests is proven. A simulation study shows good power properties and control of false-detection errors. The suggested tests are applied to data from a psychophysical experiment.
45.	Aspenberg, Magnus, et al. (författare) On the asymptotics of the scenery flow 2015 Ingår i: Discrete and Continuous Dynamical Systems. Series A. - : American Institute of Mathematical Sciences (AIMS). - 1553-5231. ; 35:7, s. 2797-2815 Tidskriftsartikel (refereegranskat)abstract We study the asymptotics of the scenery flow. We give corrected versions with proofs of a certain lemma by Hochman, and study some related phenomena.
46.	Aucoin, Rachelle, et al. (författare) Impact of trigeminal and/or olfactory nerve stimulation on measures of inspiratory neural drive : Implications for breathlessness 2023 Ingår i: Respiratory Physiology and Neurobiology. - : Elsevier BV. - 1569-9048. ; 311 Forskningsöversikt (refereegranskat)abstract The perception of breathlessness is mechanistically linked to the awareness of increased inspiratory neural drive (IND). Stimulation of upper airway cold receptors on the trigeminal nerve (TGN) with TGN agonists such as menthol or cool air to the face/nose has been hypothesized to reduce breathlessness by decreasing IND. The aim of this systematic scoping review was to identify and summarize the results of studies in animals and humans reporting on the impact of TGN stimulation or blockade on measures of IND. Thirty-one studies were identified, including 19 in laboratory animals and 12 in human participants. Studies in laboratory animals consistently reported that as TGN activity increased, measures of IND decreased (e.g., phrenic nerve activity). In humans, stimulation of the TGN with a stream of cool air to the face/nose decreased the sensitivity of the ventilatory chemoreflex response to hypercapnia. Otherwise, TGN stimulation with menthol or cool air to the face/note had no effect on measures of IND in humans. This review provides new insight into a potential neural mechanism of breathlessness relief with selected TGN agonists.
47.	Aucoin, Rachelle, et al. (författare) Impact of trigeminal nerve and/or olfactory nerve stimulation on activity of human brain regions involved in the perception of breathlessness 2023 Ingår i: Respiratory Physiology and Neurobiology. - : Elsevier BV. - 1569-9048. ; 311 Forskningsöversikt (refereegranskat)abstract Breathlessness is a centrally processed symptom, as evidenced by activation of distinct brain regions such as the insular cortex and amygdala, during the anticipation and/or perception of breathlessness. Inhaled L-menthol or blowing cool air to the face/nose, both selective trigeminal nerve (TGN) stimulants, relieve breathlessness without concurrent improvements in physiological outcomes (e.g., breathing pattern), suggesting a possible but hitherto unexplored central mechanism of action. Four databases were searched to identify published reports supporting a link between TGN stimulation and activation of brain regions involved in the anticipation and/or perception of breathlessness. The collective results of the 29 studies demonstrated that TGN stimulation activated 12 brain regions widely implicated in the anticipation and/or perception of breathlessness, including the insular cortex and amygdala. Inhaled L-menthol or cool air to the face activated 75% and 33% of these 12 brain regions, respectively. Our findings support the hypothesis that TGN stimulation contributes to breathlessness relief by altering the activity of brain regions involved in its central neural processing.
48.	Axelsson, Robert, et al. (författare) The Challenge of Transdisciplinary Research : A Case Study of Learning by Evaluation for Sustainable Transport Infrastructures 2020 Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 12:17, s. 1-24 Tidskriftsartikel (refereegranskat)abstract While transdisciplinary (TD) research is desired in order to solve real world sustainability issues, this may be challenging for both academic and non-academic participants. Supporting learning through evaluation, we analyzed a project aiming at sustainable transport infrastructures. After developing a TD research framework as a benchmark, two external independent evaluators interviewed all project researchers, representatives for end-users, and donors. The evaluators compared results with the framework, and evaluators and participants critically reflected on the results together. There were three inconsistencies relative to the framework: (1) limited understanding of TD research among project management, end-users, and most of the researchers; (2) no structured learning process among end-users; instead, they expressed very diverse opinions about what they expected from the project; (3) project leaders had limited understanding of the special challenges of TD research, did not fully understand the status of the project's social system, and thus did not act as facilitators of the required collaborative learning process. Non-academic participants saw themselves as customers and not as partners in the knowledge production process. We conclude that TD problem-solving research requires much time and needs facilitation and training. A preparatory phase with a lower level of funding would be helpful in preparing for TD processes.
49.	Aydemir, Umut, et al. (författare) In situ assembly of an injectable cardiac stimulator 2024 Ingår i: Nature Communications. - 2041-1723. ; 15 Tidskriftsartikel (refereegranskat)abstract Without intervention, cardiac arrhythmias pose a risk of fatality. However, timely intervention can be challenging in environments where transporting a large, heavy defibrillator is impractical, or emergency surgery to implant cardiac stimulation devices is not feasible. Here, we introduce an injectable cardiac stimulator, a syringe loaded with a nanoparticle solution comprising a conductive polymer and a monomer that, upon injection, forms a conductive structure around the heart for cardiac stimulation. Following treatment, the electrode is cleared from the body, eliminating the need for surgical extraction. The mixture adheres to the beating heart in vivo without disrupting its normal rhythm. The electrofunctionalized injectable cardiac stimulator demonstrates a tissue-compatible Young’s modulus of 21 kPa and a high conductivity of 55 S/cm. The injected electrode facilitates electrocardiogram measurements, regulates heartbeat in vivo, and rectifies arrhythmia. Conductive functionality is maintained for five consecutive days, and no toxicity is observed at the organism, organ, or cellular levels.
50.	Backman, Helena, et al. (författare) Interpretative implications of not adjusting for race : a switch to the global lung function initiative global spirometry equations 2024 Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 209:1, s. 10-12 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)

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