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1.
  • Aslam, Tayyba N., et al. (författare)
  • A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure
  • 2023
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 67:10, s. 1383-1394
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
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2.
  • Barbateskovic, Marija, et al. (författare)
  • A new tool to assess Clinical Diversity In Meta-analyses (CDIM) of interventions
  • 2021
  • Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356 .- 1878-5921. ; 135, s. 29-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. Study design and setting: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. Results: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. Conclusion: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.
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3.
  • Jonmarker, Sandra, et al. (författare)
  • A retrospective multicenter cohort study of the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19
  • 2023
  • Ingår i: Thrombosis Journal. - 1477-9560. ; 21, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19.METHOD: This retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients' minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations.RESULTS: In total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients' minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism.CONCLUSIONS: Measuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results.TRIAL REGISTRATION: The study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.
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4.
  • Cronhjort, Mikael, PhD, 1965-, et al. (författare)
  • Avstånd med olika metriker
  • 2021
  • Ingår i: Nämnaren. - Göteborg : Nationellt Centrum för Matematikutbildning. - 0348-2723. ; :1, s. 44-50
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Författarna beskriver en lektion om avståndsberäkningar med olika metrikersom de tror att kan vara inspirerande både för elever och matematiklärare pågymnasiet. Lektionen utvecklades i ett samarbete mellan fem lärare underKleindagarna i januari 2020. 
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5.
  • Cronhjort, Mikael, et al. (författare)
  • Can Peer Instruction in calculus improve student learning? 
  • 2013
  • Ingår i: Proceedings of the 9th International CDIO Conference<em></em>. - Cambridge, Massachusetts, USA : CDIO.
  • Konferensbidrag (refereegranskat)abstract
    • We report on an experiment in which we used Peer Instruction instead of traditional lectures in a Calculus course for beginning engineering students at KTH Royal Institute of Technology. In order to enable evaluation in a controlled experiment setting, we kept the rest of the course – text book, tutorials and examination – unchanged. The student’s pre-knowledge was measured by a diagnostic test, and their post-knowledge was measured by the written exam of the course. Our data indicate that the Peer Instruction group learned more than the control group, who had traditional lectures. In questionnaires at the beginning of the course and at the end, we asked for the students’ perceptions of Peer Instruction as teaching method and if they had found it useful as a tool for learning calculus. The answers show that the students appreciated being more active and motivated with Peer Instruction, but also that they found the method challenging and somewhat frustrating. A major problem was that the textbook was difficult to read in advance.
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6.
  • Cronhjort, Mikael, et al. (författare)
  • Improved engagement and learning in flipped-classroom calculus
  • 2018
  • Ingår i: Teaching Mathematics and its Applications. - : Oxford University Press. - 0268-3679 .- 1471-6976. ; 37:3, s. 113-121
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on an effort tomeasure the effect of replacing traditional lecture-based teachingin calculus with a flipped-classroom approach.We base the comparison between the twoteaching models on data fromthree sources: (a) a Calculus BaselineTest, designed specificallyfor this purpose and given as pre-test and post-test; (b) a survey measuring studentengagement; and (c) student achievement on the final exam. On the Calculus BaselineTest, we found that the normalized gain was 13% higher in the flipped-classroom group.Similarly, the flipped-classroom group scored significantly higher on the engagementsurvey. Also, the students of the flipped-classroom group performedmuch better than expectedon the final exam of the course, with a substantial decrease in failure rate.
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7.
  • Cronhjort, Mikael, 1965-, et al. (författare)
  • STUDENT PERSPECTIVES ON FLIPPED CLASSROOMS INENGINEERING EDUCATION
  • 2016
  • Ingår i: Proceedings of the 12th International CDIO Conference. - : CDIO. ; , s. 1041-1050
  • Konferensbidrag (refereegranskat)abstract
    • We used focus group interviews and the student perspective in order to investigate student perceptions of flipped classroom in engineering education. The learning environment included web-based interactive video films, where students had to answer quizzes in order to continue seeing the films, and interactive in-class sessions with clickers. In general the students had experience of flipped classroom in many courses and subjects, and could compare different implementations in physics, mechanics and calculus. We studied perceived advantages, strengths, drawbacks, or difficulties, and students’ views on learning with flipped classroom. Overall, the students were positive, or in one case indifferent to flipped classroom. They saw many advantages, but they also pointed out difficulties and had many opinions about how a flipped learning environment was best implemented. In the interviews, they also expressed their views on learning and described how they studied. Many used rote learning and surface approaches to learning, but many also had a focus on understanding. Some declared an intention to focus on understanding but still used rote learning. Some students expressed a strategic approach to learning with focus on the examination. Heavy workload and a threatening examination system seem to favor surface approaches to learning also in a flipped classroom learning environment. One of our interviewees had dyslexia and described her experience and special conditions. We conclude by suggesting a list of five key elements for flipped classroom. We think that the interplay between these elements is important, and that they are considerably weaker without the support of the others.
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8.
  • Cronhjort, Maria (författare)
  • Treatment of septic patients : fluids, blood and timing of antibiotics
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Fluid therapy is an important component of the treatment of septic shock. The Surviving Sepsis Campaign recommends early fluid resuscitation with at least 30 ml/kg and there is no recommendation on when to stop giving fluids. Many studies have shown an association between fluid overload and morbidity and mortality. Clinicians base fluid prescription on variables that do not reflect fluid responsiveness. Aim: The overall intention was to explore what scientific support there is for the treatment of septic patients in terms of their fluid management and the timing of antibiotics and to investigate new tools that could help the clinician decide on the amount and timing of blood and other fluids in septic shock. Overview of methods: See image in thesis pdf Summary of research results: The scientific support for how fluid management in patients with septic shock should be performed is poor. • It is safe to adopt a Hb threshold of 7 g/dl in septic ICU patients except in patients with preexisting cardiovascular disease for whom a transfusion threshold of 8 g/dl is suggested. • It is uncertain whether fluid overload is associated with mortality at a median fluid balance of 2.5 l on day three. • It has not been proven that protocolised haemodynamic management improves outcome. • It was possible to use the protocol based on a passive leg raising (PLR) test, but the recruitment rate was low. The weight gain was low in both the PLR and the control groups. • Female patients and patients with surgical sepsis were overrepresented in the group that received antibiotics after more than one hour in the emergency department. We could neither confirm nor exclude a survival benefit from early administration of antibiotics.
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9.
  • Granholm, Anders, et al. (författare)
  • Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial
  • 2022
  • Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48:1, s. 45-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. Methods We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. Results The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. Conclusion We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.
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10.
  • Granholm, Anders, et al. (författare)
  • Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis
  • 2021
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:5, s. 702-710
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.
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11.
  • Granholm, Anders, et al. (författare)
  • Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia
  • 2022
  • Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 580-589
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). Conclusion Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.
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12.
  • Håkansson, Anders, et al. (författare)
  • Cognitive Behavioral Therapy and Acceptance and Commitment Therapy (CBT-ACT) vs. Standard Care After Critical Illness Due to COVID-19 : Protocol for a Pilot Randomized Controlled Trial
  • 2022
  • Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Post-covid syndrome is an emerging condition involving a wide range of symptoms, including high rates of poor mental health. The diagnostic relevance and clinical severity of these symptoms are largely unknown, and evidence for treatment of post-covid mental health symptoms is lacking. This protocol describes a pilot randomized clinical trial, primarily aiming to assess feasibility, participant adherence and satisfaction in a novel phycho-therapeutic intervention on post-covid anxiety and depression symptoms ≥1 year after critically ill COVID-19. Whether the intervention may generate improvements in post-covid depression, anxiety, post-traumatic stress and health-related quality of life (HRQoL) will be addressed in a following larger trial. Methods: A multicenter, investigator-initiated randomized controlled trial (Clinical Trial Identifier number NCT05119608) including Intensive Care Unit (ICU)-treated COVID-19 survivors, who display symptoms of anxiety and/or depression at follow-up 12 months after hospitalization (Hospital Anxiety and Depression Scale ≥8 for depression or anxiety). Eligible individuals are referred to a psychiatrist for structured diagnostic assessment and inclusion in the trial. Participants will be randomized to either a 10-week cognitive behavioral therapy intervention with added acceptance and commitment therapy (CBT-ACT) or standard care (primary care referral). Primary study outcome measure is feasibility and patient adherence, defined as the proportion of participants who consent to randomization and remain in the study including follow-up. Secondary outcome measures include reduced symptoms in the HADS depression/anxiety subscales, post-traumatic symptoms, HRQoL and user satisfaction at 3 months after the intervention. Discussion: This protocol describes a pilot trial to assess feasibility and preliminary effects of a structured psycho-therapeutic intervention to ameliorate mental health in a population severely affected by COVID-19, where evidence for structured psycho-therapy is lacking.
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13.
  • Jonmarker, Sandra, et al. (författare)
  • Effects of 12 mg vs. 6 mg dexamethasone on thromboembolism and bleeding in patients with critical COVID-19-a post hoc analysis of the randomized, blinded COVID STEROID 2 trial
  • 2023
  • Ingår i: Annals of Intensive Care. - : SPRINGER. - 2110-5820. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThromboembolism is more common in patients with critical COVID-19 than in other critically ill patients, and inflammation has been proposed as a possible mechanism. The aim of this study was to investigate if 12 mg vs. 6 mg dexamethasone daily reduced the composite outcome of death or thromboembolism in patients with critical COVID-19.MethodsUsing additional data on thromboembolism and bleeding we did a post hoc analysis of Swedish and Danish intensive care unit patients enrolled in the blinded randomized COVID STEROID 2 trial comparing 12 mg vs. 6 mg dexamethasone daily for up to 10 days. The primary outcome was a composite outcome of death or thromboembolism during intensive care. Secondary outcomes were thromboembolism, major bleeding, and any bleeding during intensive care.ResultsWe included 357 patients. Whilst in intensive care, 53 patients (29%) in the 12 mg group and 53 patients (30%) in the 6 mg group met the primary outcome with an unadjusted absolute risk difference of - 0.5% (95% CI - 10 to 9.5%, p = 1.00) and an adjusted OR of 0.93 (CI 95% 0.58 to 1.49, p = 0.77). We found no firm evidence of differences in any of the secondary outcomes.ConclusionsAmong patients with critical COVID-19, 12 mg vs. 6 mg dexamethasone daily did not result in a statistically significant difference in the composite outcome of death or thromboembolism. However, uncertainty remains due to the limited number of patients.
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14.
  • Mele, Alessandro, et al. (författare)
  • Fluid accumulation and major adverse kidney events in sepsis : a multicenter observational study
  • 2022
  • Ingår i: Annals of Intensive Care. - : Springer Nature. - 2110-5820. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Whether early fluid accumulation is a risk factor for adverse renal outcomes in septic intensive care unit (ICU) patients remains uncertain. We assessed the association between cumulative fluid balance and major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or sustained renal dysfunction, in such patients. Methods We performed a multicenter, retrospective observational study in 1834 septic patients admitted to five ICUs in three hospitals in Stockholm, Sweden. We used logistic regression analysis to assess the association between cumulative fluid balance during the first two days in ICU and subsequent risk of MAKE30, adjusted for demographic factors, comorbidities, baseline creatinine, illness severity variables, haemodynamic characteristics, chloride exposure and nephrotoxic drug exposure. We assessed the strength of significant exposure variables using a relative importance analysis. Results Overall, 519 (28.3%) patients developed MAKE30. Median (IQR) cumulative fluid balance was 5.3 (2.8-8.1) l in the MAKE30 group and 4.1 (1.9-6.8) l in the no MAKE30 group, with non-resuscitation fluids contributing to approximately half of total fluid input in each group. The adjusted odds ratio for MAKE30 was 1.05 (95% CI 1.02-1.09) per litre cumulative fluid balance. On relative importance analysis, the strongest factors regarding MAKE30 were, in decreasing order, baseline creatinine, cumulative fluid balance, and age. In the secondary outcome analysis, the adjusted odds ratio for dialysis or sustained renal dysfunction was 1.06 (95% CI 1.01-1.11) per litre cumulative fluid balance. On separate sensitivity analyses, lower urine output and early acute kidney injury, respectively, were independently associated with MAKE30, whereas higher fluid input was not. Conclusions In ICU patients with sepsis, a higher cumulative fluid balance after 2 days in ICU was associated with subsequent development of major adverse kidney events within 30 days, including death, renal replacement requirement, or persistent renal dysfunction.
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15.
  • Munch, Marie W., et al. (författare)
  • Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
  • 2021
  • Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
  • Tidskriftsartikel (refereegranskat)abstract
    • Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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16.
  • Munch, Marie Warrer, et al. (författare)
  • Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial : Protocol and statistical analysis plan
  • 2021
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:6, s. 834-845
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. Methods The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. Discussion The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.
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17.
  • Roberts, Daniel N., et al. (författare)
  • Perioperative water and electrolyte balance and water homeostasis regulation in children with acute surgery
  • 2023
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 94:4, s. 1373-1379
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hospital-acquired hyponatremia remains a feared event in patients receiving hypotonic fluid therapy. Our objectives were to assess post-operative plasma-sodium concentration and to provide a physiological explanation for plasma-sodium levels over time in children with acute appendicitis. Methods: Thirteen normonatremic (plasma-sodium ≥135 mmol/L) children (8 males), median age 12.3 (IQR 11.5–13.5) years participated in this prospective observational study (ACTRN12621000587808). Urine was collected and analyzed. Blood tests, including renin, aldosterone, arginine-vasopressin, and circulating nitric oxide substrates were determined on admission, at induction of anesthesia, and at the end of surgery. Results: On admission, participants were assumed to be mildly dehydrated and were prescribed 50 mL/kg of Ringer’s acetate intravenously followed by half-isotonic saline as maintenance fluid therapy. Blood tests, urinary indices, plasma levels of aldosterone, arginine-vasopressin, and net water-electrolyte balance indicated that participants were dehydrated on admission. Although nearly 50% of participants still had arginine-vasopressin levels that would have been expected to produce maximum antidiuresis at the end of surgery, electrolyte-free water clearance indicated that almost all participants were able to excrete net free water. No participant became hyponatremic. Conclusions: The use of moderately hypotonic fluid therapy after correction of extracellular fluid deficit is not necessarily associated with post-operative hyponatremia. Impact: Our observations show that in acutely ill normonatremic children not only the composition but also the amount of volume infused influence on the risk of hyponatremia.Our observations also suggest that perioperative administration of hypotonic fluid therapy is followed by a tendency towards hyponatremia if extracellular fluid depletion is left untreated.After correcting extracellular deficit almost all patients were able to excrete net free water. This occurred despite nearly 50% of the cohort having high circulating plasma levels of arginine-vasopressin at the end of surgery, suggesting a phenomenon of renal escape from arginine-vasopressin-induced antidiuresis.
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18.
  • Scheeren, Thomas W. L., et al. (författare)
  • Current use of inotropes in circulatory shock
  • 2021
  • Ingår i: Annals of Intensive Care. - : Springer. - 2110-5820. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundTreatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock.MethodsFrom November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions.ResultsA total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement).ConclusionInotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.
  •  
19.
  • Weurlander, Maria, 1969-, et al. (författare)
  • Engineering students’ experiences of interactive teaching in calculus
  • 2017
  • Ingår i: Higher Education Research and Development. - : Taylor & Francis. - 0729-4360 .- 1469-8366. ; 36:4, s. 852-865
  • Tidskriftsartikel (refereegranskat)abstract
    • This study reports on an educational development initiative where peer instruction was used instead of traditional lectures in a calculus course for first-year engineering students. The aim of the study was to explore students’ experiences of this method. Data were collected by means of an open-ended questionnaire on two occasions: early and late in the course. The data were analyzed with an inductive content analysis. The findings comprise three qualitatively different ways to experience the interactive teaching method in calculus: (1) enthusiasm, (2) nuanced skepticism and (3) aversion. The categories differed regarding emotional reactions to the teaching, experiences of learning, conceptions of teaching and learning, and experiences of meaningfulness. Many students expressed enthusiasm for learning with peer instruction and noted that the method gave both teachers and students feedback on what students have difficulties with. These students perceived that they were responsible for their own learning. Other students experienced that peer instruction had some advantages and disadvantages, and preferred a mix between traditional lectures and peer instruction sessions. They seemed to believe that teachers and students share responsibility for learning. Some students expressed an aversion for peer instruction and the method seemed to challenge their beliefs of how teaching and learning is best conducted. Our study illustrates that educational development initiatives, even though based on research on student learning, do not benefit all students. One of the major obstacles seems to be that students’ underlying beliefs regarding teaching and learning may be counterproductive to the ideas behind the educational initiative. We suggest that beliefs regarding teaching and learning need to be addressed when introducing new teaching and learning methods.
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