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Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study

Publisher Copyright: © 2022 The Author(s)Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.Peer reviewe

Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours: a multicentre retrospective observational cohort study

Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabinerelated cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n ¼ 170), continuous infusion 5-FU (n ¼ 22), or bolus 5-FU (n ¼ 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n ¼ 228/200) included chest pain (n ¼ 125), coronary syndrome/ infarction (n ¼ 69), arrhythmia (n ¼ 22), heart failure/cardiomyopathy (n ¼ 7), cardiac arrest (n ¼ 4), and malignant hypertension (n ¼ 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.</p

Celiac disease and Infections

Background: Celiac disease (CD) is a chronic immune-mediated enteropathy affecting about 1% of the population worldwide. CD is triggered by ingestion of gluten in genetically predisposed individuals but additional factors (e.g. infections) are required for the disease to develop. CD also seems to be associated with infectious complications. Aim: The main objective of this thesis was to increase the knowledge about the associations between CD and infections. Methods: Epidemiological and laboratory approaches. Studies I-III used a data set consisting of small intestinal biopsy reports. The biopsies were taken in 1969-2008 and collected in 2006-2008. A total of 29,096 individuals with CD, 13,306 with inflammation and 3,719 with potential CD were identified. Each individual was matched with up to 5 controls from the general population (n= 228,632). Through linkage of the data to the Patient Register study I examined the risk of hospital visits due to respiratory syncytial virus (RSV) in children &lt;2 years prior to onset of CD. Study II used the Patient Register and Cause of Death Register to assess whether CD affects the outcome in sepsis. Study III linked the data to microbiological data bases and the Public Health Agency to estimate risk of invasive pneumococcal disease (IPD) in CD. In study IV children with CD and controls were recruited from Kalmar County Hospital. Complement activation (C3a and sC5b-9) in plasma were analysed after incubation with pneumococci. Results: Study I found that children with CD were more likely than controls to have attended hospital due to RSV infection prior to diagnosis (odds ratio 1.46; 95% confidence interval (CI)=1.02-2.07). CD did not seem to influence survival in sepsis (adjusted hazard ratio (HR) 1.10 95%CI=0.72-1.69) (study II). Study III indicated a 46% risk increase for individuals with CD to acquire IPD (HR 1.46; 95%CI=1.05-2.03) but study IV did not reveal any differences in complement response in regard to CD status (p=0.497and p=0.724), explaining this excess risk. Conclusion: This thesis supports associations between CD and infections preceding and complicating diagnosis. However, CD does not seem to influence the outcome in a severe infection like sepsis and altered complement function is unlikely to be responsible for the excess IPD risk in CD

Social hållbarhet inom stadsutveckling – En kvalitativ studie om motiven till socialt hållbarhetsengagemang inom projektet Älvstaden

Introduktion: Företag i Sverige engagerar sig i allt större utsträckning i social hållbarhet. Forskningen kring varför företag engagerar sig i hållbarhet har visat sig vara tvetydig. Göteborgs Stad har i samband med det ökade fokuset på social hållbarhet startat projektet Älvstaden, med visionen att skapa en hållbar stadöppen för världen. De byggherrar som är delaktiga i projektet ställs inför höga krav att leverera social hållbarhet. Trots kraven är intresset hos företag att medverka i projektet fortsatt stort. Syfte: Genom att undersöka varför byggherrar väljer att engagera sig i social hållbarhet vid stadsutveckling syftar uppsatsen till att finna vilka bakomliggande motiv och drivkrafter som finns till det ökade intresset av social hållbarhet. Metod: Uppsatsen utgår från det hermeneutiska förhållningssättet där en kvalitativ metod har tillämpats. Ansatsen är av abduktivt slag då problemet undersökts både från semistrukturerade intervjuer och redan kända teorier. Slutsatser: Något som konstaterats vara en bidragande faktor till att byggherrar intresserar sig för social hållbarhet är att samhället upplevs som mindre tryggt. Då byggherrars intressenter till stor del består av dess hyresgäster, har mindre trygga områden blivit viktiga att säkra för att tillfredsställa intressenterna och skapa legitimitet. Ett annat viktigt motiv som framkommit är den ekonomiska aspekten, där engagemang i social hållbarhet tenderar att bli lönsamt på lång sikt, och således agerar som motiv till socialt hållbarhetsengagemang. Ytterligare motiv till varför byggherrar engagerar sig socialt är att det skapar innovation och konkurrensfördelar

Emancipações distritais - notas de discussão

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Challenges of Achieving a Green Future and Financial Security - A Multiple Case Study of Swedish Pension Firms' Green Bond Assessment Processes

Deriving from an increased awareness of the devastating effects of global warming consequences, the interest for green bonds is growing at an explosive pace. However, researchers and practitioners have raised concerns about the challenges of assessing green bonds. Responding to a well-defined research gap stemming from identified challenges to assess green bonds, the primary purpose of this study is to explore how Swedish pension firms assess green bonds prior to investment. Given the explorative characteristics of the research, this study is conducted qualitatively through a multiple case study, using interviews to capture unique and similar aspects of five Swedish pension firms. In addition to the scarce literature on green bonds, this study uses the adjacent theoretical foundations of sustainable investing and conventional bond assessment. The institutional logics theory constitutes the theoretical lens through which the study analyses green bond assessments. The study concludes that two primary institutional logics are shaping the pension firms’ assessment processes; a financial and an environmental. Findings show that the overall assessment process contains the same basic structure; however, findings also indicate differences within this basic structure. To the extent of our knowledge, this thesis is first to introduce pension firms’ rationale for their choice of assessment approach when handling identified challenges on the green bond market. Findings further imply a paradox that pension firms encounter, in which they have to choose between pensioners’ financial security and the planet’s survival