| 1. |
- Andersen, Maria Goul, et al.
(author)
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Population Pharmacokinetics of Piperacillin in Sepsis Patients : Should Alternative Dosing Strategies Be Considered?
- 2018
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In: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 62:5
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Journal article (peer-reviewed)abstract
- Sufficient antibiotic dosing in septic patients is essential for reducing mortality. Piperacillin-tazobactam is often used for empirical treatment, but due to the pharmacokinetic (PK) variability seen in septic patients, optimal dosing may be a challenge. We determined the PK profile for piperacillin given at 4 g every 8 h in 22 septic patients admitted to a medical ward. Piperacillin concentrations were compared to the clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter), and the following PK/pharmacodynamic (PD) targets were evaluated: the percentage of the dosing interval that the free drug concentration is maintained above the MIC (fTMIC) of 50% and 100%. A two-compartment population PK model described the data well, with clearance being divided into renal and nonrenal components. The renal component was proportional to the estimated creatinine clearance (eCLCR) and constituted 74% of the total clearance in a typical individual (eCLCR, 83.9 ml/min). Patients with a high eCLCR (>130 ml/min) were at risk of subtherapeutic concentrations for the current regimen, with a 90% probability of target attainment being reached at MICs of 2.0 (50% fTMIC) and 0.125 mg/liter (100% fTMIC). Simulations of alternative dosing regimens and modes of administration showed that dose increment and prolonged infusion increased the chance of achieving predefined PK/PD targets. Alternative dosing strategies may therefore be needed to optimize piperacillin exposure in septic patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02569086.)
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| 2. |
- Gunnulfsen, Ann Elisabeth, et al.
(author)
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Introduction
- 2023
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In: Education and Democracy in the Nordic Countries. - Cham : Springer. - 9783031331947 - 9783031331954 ; , s. 1-9
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Book chapter (peer-reviewed)
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| 3. |
- Gunnulfsen, Ann Elisabeth, et al.
(author)
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Making Sense of Nordic School Leadership – Four Perspectives on Similarities and Variations
- 2023
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In: Education and Democracy in the Nordic Countries. - Cham : Springer. - 9783031331947 - 9783031331954 ; , s. 173-182
-
Book chapter (peer-reviewed)abstract
- This book can be regarded as a follow up to the series of Springer-editions about the Nordic perspectives on studies in educational leadership. Lejf Moos is a prominent forerunner with the first “Nordic” edition of Transnational Influences on Values and Practices in Nordic Educational Leadership: Is there a Nordic Model? published 10 years ago. In his edition, Moos (2013) stated that the Nordic countries are similar in many respects. The similarities are expressed through their differences from the UK and USA, where democratic thinking is built upon so-called liberal democracy, which values the idea that the purpose of society is to advantage the individual in her/his development (Louis, 2003). In contrast, Nordic social democracies focus on the welfare state perspective of social rights and equality (Andersen et al. 2007), a unified society where democracy and social welfare systems build on the necessity of a strong state that is willing and able to redistribute some of the wealth. This is combined with ideas of free speech and participation where citizens in a society are expected to participate in conversations on matters of mutual interest as a mean to strengthen all individual’s rights and well-being. This current book aimed to examine perspectives of contemporary school leadership practices and thinking based on the premise that schools play a vital role in forming societies. Moreover, the purpose of this book is to address and discuss principal prerequisites and work within democratic welfare states in Nordic countries.
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| 4. |
- Gunnulfsen, Ann Elisabeth, et al.
(author)
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Preface
- 2023
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In: Education and Democracy in the Nordic Countries. - Cham : Springer. - 9783031331947 - 9783031331954 ; , s. xv-xvi
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Book chapter (other academic/artistic)
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| 5. |
- Gunst, Jesper D., et al.
(author)
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Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
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In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
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Journal article (peer-reviewed)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
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| 6. |
- Klastrup, Vibeke, et al.
(author)
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Population Pharmacokinetics of Piperacillin following Continuous Infusion in Critically Ill Patients and Impact of Renal Function on Target Attainment
- 2020
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In: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 64:7
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Journal article (peer-reviewed)abstract
- Pharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations (n = 196) were assessed in 78 critically ill patients following continuous infusion of piperacillin-tazobactam (ratio 8:1). The initial dose of 8, 12, or 16 g (piperacillin component) was determined by individual creatinine clearance (CRCL). Piperacillin concentrations were compared to the EUCAST clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter), and the following PK/PD targets were evaluated: 100% free time (fT) > 1× MIC and 100% fT > 4× MIC. A population pharmacokinetic model was developed using NONMEM 7.4.3 consisting of a one-compartment disposition model with linear elimination separated into nonrenal and renal (linearly increasing with patient CRCL) clearances. Target attainment was predicted and visualized for all individuals based on the utilized CRCL dosing algorithm. The target of 100% fT > 1× MIC was achieved for all patients based on the administered dose, but few patients achieved the target of 100% fT > 4× MIC. Probability of target attainment for a simulated cohort of patients showed that increasing the daily dose by 4-g increments (piperacillin component) did not result in substantially improved target attainment for the 100% fT > 4× MIC target. To conclude, in patients with high CRCL combined with high-MIC bacterial infections, even a continuous infusion (CI) regimen with a daily dose of 24 g may be insufficient to achieve therapeutic concentrations.
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| 7. |
- Moseholm, Ellen, et al.
(author)
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Perception and Emotional Experiences of Infant Feeding Among Women Living With HIV in a High-Income Setting: A Longitudinal Mixed Methods Study
- 2024
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In: Journal of acquired immune deficiency syndromes (1999). - 1944-7884. ; 95:1, s. 52-64
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Journal article (peer-reviewed)abstract
- BACKGROUND: The recommendation of breastfeeding avoidance for women living with HIV in high-income settings may be influenced by cultural beliefs and come at an emotional cost. This multicenter, longitudinal, convergent mixed methods study aimed to compare differences in attitudes, concerns, and experiences surrounding breastfeeding in women living with HIV of Nordic and non-Nordic origin. SETTING: High-income setting. METHODS: Pregnant women living with HIV in the Nordic countries Denmark, Finland, and Sweden were recruited in 2019-2020. Quantitative data on attitudes surrounding infant feeding were assessed using the Positive Attitudes Concerning Infant Feeding questionnaire completed in the third trimester (T1), and 3 (T2) and 6 (T3) months postpartum. Women who completed the survey were also invited to participate in semistructured interviews at T1 and T3. The findings from the quantitative survey and qualitative interviews were brought together through merging to assess for concordance, complementarity, expansion, or discordance between the data sets and to draw metainferences. RESULTS: In total, 44 women completed the survey, of whom 31 also participated in qualitative interviews. The merged analyses identified three overarching domains representing commonalities across the quantitative and qualitative data: emotional impact, justifying not breastfeeding, and coping strategies. Not being able to breastfeed was emotionally challenging. Cultural expectations influenced the women's experiences and the strategies they used to justify their infant feeding choice. CONCLUSIONS: For women living with HIV in Nordic countries not breastfeeding was a complex, multilayered process substantially influenced by social and cultural expectations.
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