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| 2. |
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| 3. |
- Bousquet, J, et al.
(författare)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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| 7. |
- Zuberbier, T., et al.
(författare)
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Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA(2)LEN position paper
- 2022
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:6, s. 1736-1750
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Tidskriftsartikel (refereegranskat)abstract
- Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.
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| 8. |
- Herrmann, Job J., et al.
(författare)
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Fluid REStriction in Heart Failure vs Liberal Fluid UPtake : Rationale and Design of the Randomized FRESH-UP Study
- 2022
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Ingår i: Journal of Cardiac Failure. - : Churchill Livingstone. - 1071-9164 .- 1532-8414. ; 28:10, s. 1522-1530
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Tidskriftsartikel (refereegranskat)abstract
- Aims: It is common practice for clinicians to advise fluid restriction in patients with heart failure (HF), but data from clinical trials are lacking. Moreover, fluid restriction is associated with thirst distress and may adversely impact quality of life (QoL). To address this gap in evidence, the Fluid REStriction in Heart failure vs liberal fluid UPtake (FRESH-UP) study was initiated. Methods: The FRESH-UP study is a randomized, controlled, open-label, multicenter trial to investigate the effects of a 3-month period of liberal fluid intake vs fluid restriction (1500 mL/day) on QoL in outpatients with chronic HF (New York Heart Association Classes II-III). The primary aim is to assess the effect on QoL after 3 months using the Overall Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ). Thirst distress, as assessed by the Thirst Distress Scale for patients with HF, KCCQ Clinical Summary Score, each of the KCCQ domains and clinically meaningful changes in these scores, the EQ-5D-5L, patient-reported fluid intake and safety (ie, death, HF hospitalizations) are secondary outcomes. The FRESH-UP study is registered at ClinicalTrials.gov (NCT04551729). Conclusion: The results of the FRESH-UP study will add substantially to the level of evidence concerning fluid management in chronic HF and may impact the QoL of these patients.
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| 9. |
- Van Wijk, Rob C., 1991-, et al.
(författare)
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Anti‐tuberculosis effect of isoniazid scales accurately from zebrafish to humans
- 2020
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 177:24, s. 5518-5533
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeThere is a strong need for innovation in anti-tuberculosis drug development. The zebrafish larva is an attractive disease model in tuberculosis research. To translate pharmacological findings to higher vertebrates, including humans, the internal exposure of drugs needs to be quantified and linked to observed response.Experimental approachIn zebrafish studies, drugs are commonly dissolved in the external water, posing a challenge to quantify internal exposure. We developed experimental methods to quantify internal exposure, including nano-scale blood sampling, and to quantify the bacterial burden, using automated fluorescence imaging analysis, with isoniazid as paradigm compound. We used pharmacokinetic-pharmacodynamic modelling to quantify the exposure-response relationship responsible for the antibiotic response. To translate isoniazid response to humans, the quantitative exposure-response relationship in zebrafish was linked to simulated concentration-time profiles in humans, and two quantitative translational factors on sensitivity to isoniazid and stage of infection were included.Key resultsBlood concentration was only 20% of the external drug concentration. The bacterial burden increased exponentially and an isoniazid dose corresponding to 15 mg·L-1internal concentration (minimum inhibitory concentration) lead to bacteriostasis of the mycobacterial infection in the zebrafish. The concentration-effect relationship was quantified, and based on that relationship and the translational factors, the isoniazid response was translated to humans, which correlated well with observed data.Conclusions and implicationsThis proof-of-concept confirms the potential of the zebrafish larvae as tuberculosis disease model in translational pharmacology, and contributes to innovative anti-tuberculosis drug development which is strongly needed.
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| 10. |
- Van Wijk, Rob C., 1991-, et al.
(författare)
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Quantification of Natural Growth of Two Strains of Mycobacterium Marinum for Translational Antituberculosis Drug Development
- 2020
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Ingår i: Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 13:6, s. 1060-1064
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Tidskriftsartikel (refereegranskat)abstract
- The zebrafish infected with Mycobacterium marinum (M. marinum) is an attractive tuberculosis disease model, showing similar pathogenesis to Mycobacterium tuberculosis (M. tuberculosis) infections in humans. To translate pharmacological findings from this disease model to higher vertebrates, a quantitative understanding of the natural growth of M. marinum in comparison to the natural growth of M. tuberculosis is essential. Here, the natural growth of two strains of M. marinum, E11 and MUSA, is studied over an extended period using an established model‐based approach, the multistate tuberculosis pharmacometric (MTP) model, for comparison to that of M. tuberculosis. Poikilotherm‐derived strain E11 and human‐derived strain MUSA were grown undisturbed up to 221 days and viability of cultures (colony forming unit (CFU)/mL) was determined by plating at different time points. Nonlinear mixed effects modeling using the MTP model quantified the bacterial growth, the transfer among fast, slow, and non‐multiplying states, and the inoculi. Both strains showed initial logistic growth, reaching a maximum after 20–25 days for E11 and MUSA, respectively, followed by a decrease to a new plateau. Natural growth of both E11 and MUSA was best described with Gompertz growth functions. For E11, the inoculum was best described in the slow‐multiplying state, for MUSA in the fast‐multiplying state. Natural growth of E11 was most similar to that of M. tuberculosis, whereas MUSA showed more aggressive growth behavior. Characterization of natural growth of M. marinum and quantitative comparison with M. tuberculosis brings the zebrafish tuberculosis disease model closer to the quantitative translational pipeline of antituberculosis drug development.
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| 11. |
- Van Wijk, Rob C, 1991-, et al.
(författare)
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Seasonal influence on respiratory tract infection severity including COVID-19 quantified through Markov Chain modeling
- 2023
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Ingår i: CPT. - : John Wiley & Sons. - 2163-8306. ; 12:9, s. 1250-1261
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory tract infections (RTIs) are a burden to global health, but their characterization is complicated by the influence of seasonality on incidence and severity. The Re-BCG-CoV-19 trial (NCT04379336) assessed BCG (re)vaccination for protection from coronavirus disease 2019 (COVID-19) and recorded 958 RTIs in 574 individuals followed over 1 year. We characterized the probability of RTI occurrence and severity using a Markov model with health scores (HSs) for four states of symptom severity. Covariate analysis on the transition probability between HSs explored the influence of demographics, medical history, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), or influenza vaccinations, which became available during the trial, SARS-CoV-2 serology, and epidemiology-informed seasonal influence of infection pressure represented as regional COVID-19 pandemic waves, as well as BCG (re)vaccination. The infection pressure reflecting the pandemic waves increased the risk of RTI symptom development, whereas the presence of SARS-CoV-2 antibodies protected against RTI symptom development and increased the probability of symptom relief. Higher probability of symptom relief was also found in participants with African ethnicity and with male biological gender. SARS-CoV-2 or influenza vaccination reduced the probability of transitioning from mild to healthy symptoms. Model diagnostics over calendar-time indicated that COVID-19 cases were under-reported during the first wave by an estimated 2.76-fold. This trial was performed during the initial phase of the COVID-19 pandemic in South Africa and the results reflect that situation. Using this unique clinical dataset of prospectively studied RTIs over the course of 1 year, our Markov Chain model was able to capture risk factors for RTI development and severity, including epidemiology-informed infection pressure.
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| 12. |
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| 13. |
- De Jager, Veronique, et al.
(författare)
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Early Bactericidal Activity of Meropenem plus Clavulanate (with or without Rifampin) for Tuberculosis : The COMRADE Randomized, Phase 2A Clinical Trial
- 2022
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 205:10, s. 1228-1235
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Carbapenems are recommended for treatment of drug-resistant tuberculosis. Optimal dosing remains uncertain.Objectives: To evaluate the 14-day bactericidal activity of meropenem, at different doses, with or without rifampin.Methods: Individuals with drug-sensitive pulmonary tuberculosis were randomized to one of four intravenous meropenem-based arms: 2 g every 8 hours (TID) (arm C), 2 g TID plus rifampin at 20 mg/kg once daily (arm D), 1 g TID (arm E), or 3 g once daily (arm F). All participants received amoxicillin/clavulanate with each meropenem dose. Serial overnight sputum samples were collected from baseline and throughout treatment. Median daily fall in colony-forming unit (CFU) counts per milliliter of sputum (solid culture) (EBA(CFU0-14)) and increase in time to positive culture (TTP) in liquid media were estimated with mixed-effects modeling. Serial blood samples were collected for pharmacokinetic analysis on Day 13.Measurements and Main Results: Sixty participants enrolled. Median EBA(CFU0-14) counts (2.5th-97.5th percentiles) were 0.22 (0.12-0.33), 0.12 (0.057-0.21), 0.059 (0.033-0.097), and 0.053 (0.035-0.081); TTP increased by 0.34 (0.21-0.75), 0.11 (0.052-037), 0.094 (0.034-0.23), and 0.12 (0.04-0.41) (log(10) h), for arms C-F, respectively. Meropenem pharmacokinetics were not affected by rifampin coadministration. Twelve participants withdrew early, many of whom cited gastrointestinal adverse events.Conclusions: Bactericidal activity was greater with the World Health Organization-recommended total daily dose of 6 g daily than with a lower dose of 3 g daily. This difference was only detectable with solid culture. Tolerability of intravenous meropenem, with amoxicillin/clavulanate, though, was poor at all doses, calling into question the utility of this drug in second-line regimens.
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| 14. |
- Mockeliunas, Laurynas, et al.
(författare)
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Risk Factors for COVID-19 and Respiratory Tract Infections during the Coronavirus Pandemic
- 2024
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Some individuals are more susceptible to developing respiratory tract infections (RTIs) or coronavirus disease (COVID-19) than others. The aim of this work was to identify risk factors for symptomatic RTIs including COVID-19 and symptomatic COVID-19 during the coronavirus pandemic by using infection incidence, participant baseline, and regional COVID-19 burden data. (2) Methods: Data from a prospective study of 1000 frontline healthcare workers randomized to Bacillus Calmette-Gu & eacute;rin vaccination or placebo, and followed for one year, was analyzed. Parametric time-to-event analysis was performed to identify the risk factors associated with (a) non-specific symptomatic respiratory tract infections including COVID-19 (RTIs+COVID-19) and (b) symptomatic RTIs confirmed as COVID-19 using a polymerase chain reaction or antigen test (COVID-19). (3) Results: Job description of doctor or nurse (median hazard ratio [HR] 1.541 and 95% confidence interval [CI] 1.299-1.822), the reported COVID-19 burden (median HR 1.361 and 95% CI 1.260-1.469 for 1.4 COVID-19 cases per 10,000 capita), or a BMI > 30 kg/m(2) (median HR 1.238 and 95% CI 1.132-1.336 for BMI of 35.4 kg/m(2)) increased the probability of RTIs+COVID-19, while positive SARS-CoV-2 serology at enrollment (median HR 0.583 and 95% CI 0.449-0.764) had the opposite effect. The reported COVID-19 burden (median HR 2.372 and 95% CI 2.116-2.662 for 1.4 COVID-19 cases per 10,000 capita) and a job description of doctor or nurse (median HR 1.679 and 95% CI 1.253-2.256) increased the probability of developing COVID-19, while smoking (median HR 0.428 and 95% CI 0.284-0.648) and positive SARS-CoV-2 serology at enrollment (median HR 0.076 and 95% CI 0.026-0.212) decreased it. (4) Conclusions: Nurses and doctors with obesity had the highest probability of developing RTIs including COVID-19. Non-smoking nurses and doctors had the highest probability of developing COVID-19 specifically. The reported COVID-19 burden increased the event probability, while positive SARS-CoV-2 IgG serology at enrollment decreased the probability of RTIs including COVID-19, and COVID-19 specifically.
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| 15. |
- Mockeliunas, Laurynas, et al.
(författare)
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Standards for model-based early bactericidal activity analysis and sample size determination in tuberculosis drug development
- 2023
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: A critical step in tuberculosis (TB) drug development is the Phase 2a early bactericidal activity (EBA) study which informs if a new drug or treatment has short-term activity in humans. The aim of this work was to present a standardized pharmacometric model-based early bactericidal activity analysis workflow and determine sample sizes needed to detect early bactericidal activity or a difference between treatment arms.Methods: Seven different steps were identified and developed for a standardized pharmacometric model-based early bactericidal activity analysis approach. Non-linear mixed effects modeling was applied and different scenarios were explored for the sample size calculations. The sample sizes needed to detect early bactericidal activity given different TTP slopes and associated variability was assessed. In addition, the sample sizes needed to detect effect differences between two treatments given the impact of different TTP slopes, variability in TTP slope and effect differences were evaluated.Results: The presented early bactericidal activity analysis approach incorporates estimate of early bactericidal activity with uncertainty through the model-based estimate of TTP slope, variability in TTP slope, impact of covariates and pharmacokinetics on drug efficacy. Further it allows for treatment comparison or dose optimization in Phase 2a. To detect early bactericidal activity with 80% power and at a 5% significance level, 13 and 8 participants/arm were required for a treatment with a TTP-EBA(0-14) as low as 11 h when accounting for variability in pharmacokinetics and when variability in TTP slope was 104% [coefficient of variation (CV)] and 22%, respectively. Higher sample sizes are required for smaller early bactericidal activity and when pharmacokinetics is not accounted for. Based on sample size determinations to detect a difference between two groups, TTP slope, variability in TTP slope and effect difference between two treatment arms needs to be considered.Conclusion: In conclusion, a robust standardized pharmacometric model-based EBA analysis approach was established in close collaboration between microbiologists, clinicians and pharmacometricians. The work illustrates the importance of accounting for covariates and drug exposure in EBA analysis in order to increase the power of detecting early bactericidal activity for a single treatment arm as well as differences in EBA between treatments arms in Phase 2a trials of TB drug development.
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| 16. |
- Upton, Caryn M., et al.
(författare)
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Safety and efficacy of BCG re-vaccination in relation to COVID-19 morbidity in healthcare workers : A double- blind, randomised, controlled, phase 3 trial
- 2022
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Background BCG vaccination prevents severe childhood tuberculosis (TB) and was introduced in South Africa in the 1950s. It is hypothesised that BCG trains the innate immune system by inducing epigenetic and functional reprogramming, thus providing non-specific protection from respiratory tract infections. We evaluated BCG for reduction of morbidity and mortality due to COVID-19 in healthcare workers in South Africa. Methods This randomised, double-blind, placebo-controlled trial recruited healthcare workers at three facilities in the Western Cape, South Africa, unless unwell, pregnant, breastfeeding, immunocompromised, hypersensitivity to BCG, or undergoing experimental COVID-19 treatment. Participants received BCG or saline intradermally (1:1) and were contacted once every 4 weeks for 1 year. COVID-19 testing was guided by symptoms. Hospitalisation, COVID-19, and respiratory tract infections were assessed with Cox proportional hazard modelling and time-to-event analyses, and event severity with post hoc Markovian analysis. This study is registered with ClinicalTrials.gov, NCT04379336. Findings Between May 4 and Oct 23, 2020, we enrolled 1000 healthcare workers with a median age of 39 years (IQR 30-49), 70.4% were female, 16.5% nurses, 14.4% medical doctors, 48.5% had latent TB, and 15.3% had evidence of prior SARS-CoV-2 exposure. Hospitalisation due to COVID-19 occurred in 15 participants (1.5%); ten (66.7%) in the BCG group and five (33.3%) in the placebo group, hazard ratio (HR) 2.0 (95% CI 0.69-5.9, p= 0.20), indicating no statistically significant protection. Similarly, BCG had no statistically significant effect on COVID-19 (p= 0.63, HR = 1.08, 95% CI 0.82-1.42). Two participants (0.2%) died from COVID-19 and two (0.2%) from other reasons, all in the placebo group. Interpretation BCG did not protect healthcare workers from SARS-CoV-2 infection or related severe COVID-19 disease and hospitalisation.
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| 17. |
- Van Wijk, Rob C, 1991-, et al.
(författare)
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Reproducibility in pharmacometrics applied in a phase III trial of BCG-vaccination for COVID-19
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Large clinical trials often generate complex and large datasets which need to be presented frequently throughout the trial for interim analysis or to inform a data safety monitory board (DSMB). In addition, reliable and traceability are required to ensure reproducibility in pharmacometric data analysis. A reproducible pharmacometric analysis workflow was developed during a large clinical trial involving 1000 participants over one year testing Bacillus Calmette-Guerin (BCG) (re)vaccination in coronavirus disease 2019 (COVID-19) morbidity and mortality in frontline health care workers. The workflow was designed to review data iteratively during the trial, compile frequent reports to the DSMB, and prepare for rapid pharmacometric analysis. Clinical trial datasets (n = 41) were transferred iteratively throughout the trial for review. An RMarkdown based pharmacometric processing script was written to automatically generate reports for evaluation by the DSMB. Reports were compiled, reviewed, and sent to the DSMB on average three days after the data cut-off, reflecting the trial progress in real-time. The script was also utilized to prepare for the trial pharmacometric analyses. The same source data was used to create analysis datasets in NONMEM format and to support model script development. The primary endpoint analysis was completed three days after data lock and unblinding, and the secondary endpoint analyses two weeks later. The constructive collaboration between clinical, data management, and pharmacometric teams enabled this efficient, timely, and reproducible pharmacometrics workflow.
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| 18. |
- Alexiou, Eirini, et al.
(författare)
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A Survey of Psychiatric Healthcare Workers' Perception of Working Environment and Possibility to Recover Before and After the First Wave of COVID-19 in Sweden
- 2021
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to investigate the impact of the first wave of the COVID-19 pandemic on perceived working environment, including the possibility to recover, among psychiatric healthcare workers (PHCWs) in comparison with pre-pandemic measures. Method: A link to an anonymous, web-based COVID-19 related survey was sent via email to all PHCWs at a university hospital in Sweden (n = 1,618) in September 2020. The response rate was 38% (566 of 1,507 eligible participants). Working environment survey responses collected in 2019 were used as pre-pandemic comparators. Statistical analyses were performed to assess overall impact over time on work demands, support, motivation, and recovery, stratified by professional role, and considering variables such as access to personal protective equipment. Results: The percentage of individuals responding negatively to statements about working environment increased significantly for most items after the first wave. Similarly, the increase of five of the investigated factors indicated a more negative perception of recovery during the pandemic. Registered nurses reported a greater negative impact of the pandemic on perceived working conditions and ability to recover than other professional groups. PHCWs working with patients with COVID-19 (35%) who reported being worried about becoming infected (12%) or infecting others (17%), or lacking adequate personal protective equipment (22%) were more negatively impacted regarding work environment-related items than those who did not. Conclusions: PHCWs' working environment and possibility for recovery were impacted by the first wave of the COVID-19 pandemic, nurses being most affected. Although psychiatric services do not directly care for patients with severe COVID-19 infection, the results from this study suggests that mental health services should also prepare for future pandemics.
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| 19. |
- Alexiou, Eirini, et al.
(författare)
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Worry perception and its association with work conditions among healthcare workers during the first wave of the COVID-19 pandemic: a web-based multimethod survey at a university hospital in Sweden.
- 2024
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Ingår i: BMJ open. - 2044-6055. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we explored healthcare workers' (HCWs) worry perception and its association with their work situation during the first wave of the COVID-19 pandemic.A web-based multimethods survey including multiple choice and open-ended questions was used.The study was conducted at a university hospital in Sweden.All HCWs who were working during the first wave of the COVID-19 pandemic in March-June 2020 were eligible. HCWs (n=6484, response rate=41%) from 69 departments fulfilled the study inclusion criteria and responded to the survey. Of them, we analysed data from the 3532 participants who replied to the open-ended questions (54% of the respondents).Worry perception and its association with work conditions among HCWs.29% (n=1822) and 35% (n=2235) of the responding HCWs experienced a daily or more than daily strong worry of being infected or infecting others with SARS-CoV-2. This finding could be further confirmed and explored with themes from the qualitative results: 'ambiguity of feeling safe and secure', 'being obliged to adapt to a new reality' and 'into the unknown'. The themes consisted of 6 main categories and 15 subcategories. The findings revealed that the two main drivers of worry perceived by HCWs were lack of personal protective equipment and fear of bringing the virus home to their families and friends.Worries of getting infected are common among HCWs during crises such as the COVID-19 pandemic. Several factors are raised that plausibly could minimise the negative effects of worry among HCWs. Thus, effective preventive work plans should be created, promoted and communicated in order to minimise the effects of such crises and support HCWs. By focusing on effective communication and preparedness, including access to relevant protective equipment and providing general support to HCWs, the work environment and patient care could be sustained during a crisis such as the COVID-19 pandemic.
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| 20. |
- Björk, Lisa, 1981, et al.
(författare)
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Under pressure - The working situation of Swedish healthcare managers during the first wave of COVID-19
- 2023
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe aim of this study is to provide insight into the psychosocial work situation of hospital managers during the first wave of the COVID-19 pandemic. MethodsMixed-effect modelling was used on survey data on job demands, job resources, job motivation, and work-life balance among over 500 managers working in 55 departments of a large Swedish university hospital in 2019 and 2020. Responses from 6011 employees were then used to stratify the analysis for COVID-19 exposure. Inductive content analysis was applied to open-ended questions on the managers' views on organisational prerequisites during the onset of the pandemic. ResultsThe proportion of managers reporting difficulties with role clarity, quantitative demands, decision-making authority, and emotional support, time for recovery at work, motivation deficits, or problems with work-life balance clearly increased during the first wave of the pandemic. The proportion of managers reporting negative responses was higher in departments with high COVID-19 exposure. The qualitative analysis shows that overall governance in terms of clear, fair, and well-communicated routines, resource allocation, and division of responsibilities constituted an important framework for managerial during the crisis. First-line managers also require a mandate to re-organize their roles and their teams to successfully adapt to the situation. Organisational and social support was also important resources. DiscussionThis is the first study investigating healthcare managers' work situation during the first wave of the COVID-19 pandemic in a Swedish context. As expected, it indicates an increasingly strained work situation during the crisis, but it also provides findings on organisational prerequisites that allow healthcare managers to cope with stressful situations. In line with previous research on organisational resilience, the study provides suggestions for how higher-level managers can act in order to provide front-line managers with the organisational prerequisites they need to adapt, learn and develop successfully during times of unpredictability, insecurity, and rapid change in order to offer the best possible support to health care workers.
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| 21. |
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| 22. |
- Faraj, Alan, et al.
(författare)
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Model-informed pediatric dose selection of marzeptacog alfa (activated) : An exposure matching strategy
- 2023
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Ingår i: CPT. - : John Wiley & Sons. - 2163-8306. ; 12:7, s. 977-987
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Tidskriftsartikel (refereegranskat)abstract
- Marzeptacog alfa (activated) (MarzAA) is an activated recombinant human rFVII variant intended for subcutaneous (s.c.) administration to treat or prevent bleeding in individuals with hemophilia A (HA) or B (HB) with inhibitors, and other rare bleeding disorders. The s.c. administration provides benefits over i.v. injections. The objective of the study was to support the first-in-pediatric dose selection for s.c. MarzAA to treat episodic bleeding episodes in children up through 11 years in a registrational phase III trial. Assuming the same exposure-response relationship as in adults, an exposure matching strategy was used with a population pharmacokinetics model. A sensitivity analysis evaluating the impact of doubling in absorption rate and age-dependent allometric exponents on dose selection was performed. Subsequently, the probability of trial success, defined as the number of successful trials for a given pediatric dose divided by the number of simulated trials (n = 1000) was studied. A successful trial was defined as outcome where four, three, or two out of 24 pediatric subjects per trial were allowed to fall outside the adult exposures after s.c. administration of 60 mu g/kg. A dose of 60 mu g/ kg in children with HA/HB was supported by the clinical trial simulations to match exposures in adults. The sensitivity analyses further supported selection of the 60 mu g/kg dose level in all age groups. Moreover, the probability of trial success evaluations given a plausible design confirmed the potential of a 60 mu g/kg dose level. Taken together, this work demonstrates the utility of model-informed drug development and could be helpful for other pediatric development programs for rare diseases.
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| 23. |
- Gillberg, Nanna, et al.
(författare)
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Resilience Capability and Capacity in Unexpected Crises: Experiences and Lessons Learned in a Healthcare Organisation during the COVID-19 Pandemic
- 2023
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Ingår i: Journal of Nursing Management. - 0966-0429 .- 1365-2834.
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Tidskriftsartikel (refereegranskat)abstract
- Aim. The current article aims to gain insight into (a) what characterises organisational resilience during an unexpected crisis such as COVID-19 and (b) how organisations respond to developments in their environments. Background. In times of societal crises, such as the COVID-19 pandemic, the resilience of the healthcare organisation is tested. Method. This research is based on a case study in a university hospital and a county hospital in Sweden using surveys with both structured and open answers. Results. The result shows ambiguity and “polarised” experiences, emphasising flexibility vs. structure, clear hierarchical information vs. spaces for peer learning through dialogue, and focus on acute care vs. determination to continue with core operations. Conclusion. The article concludes that the pandemic resulted in paradoxes, tensions, and new experiences in organisational processes and interactions. These create opportunities for learning not only during crises but also for improving nursing management in both acute and planned care. Three relations are important in building organisational resilience in crises: resilience capability, resilience capacity, and sustainable resilience practices. Implications for Nursing Management. Organisational resilience under extraordinary circumstances, such as a pandemic, as well as enhancing the previous literature on nursing management that offer a more individually oriented perspective.
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| 24. |
- Johansson, Nina, et al.
(författare)
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Ameliorating Child poverty through Connecting Economic Services with child health Services (ACCESS) : study protocol for a randomised controlled trial of the healthier wealthier families model in Sweden
- 2022
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSweden is often held up as an example of a country with low child deprivation; yet, rates of relative deprivation are rising. Every municipality in Sweden is required to provide free, timely and accessible budget and debt counselling under the Social Services Act. The services have been encouraged to perform preventative practice with families; however, this has not been realised. The Healthier Wealthier Families (HWF) model embeds universal screening for economic hardship into child health services and creates a referral pathway to economic support services. Given the universal child health system in Sweden, which is freely available and has excellent coverage of the child population, implementation of the HWF model has potential to support families to access the freely available municipal budget and debt counselling and ultimately improve rates of child deprivation in Sweden.Methods/designWe will conduct a two-arm randomised waitlist-control superiority trial to examine the effectiveness and cost-effectiveness of the HWF model in the Sweden. A longitudinal follow-up with the cohort will explore whether any effects are maintained in the longer-term.DiscussionHWF is a collaborative and sustainable model that could maximise the effectiveness of current services to address child deprivation in Sweden. The study outlined in this protocol is the first effectiveness evaluation of the HWF model in Sweden and is a crucial step before HWF can be recommended for national implementation within the child health services.
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| 25. |
- Jonsdottir, Ingibjörg H, 1966, et al.
(författare)
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A pre/post analysis of the impact of the COVID-19 pandemic on the psychosocial work environment and recovery among healthcare workers in a large university hospital in Sweden
- 2021
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Ingår i: Journal of Public Health Research. - : SAGE Publications. - 2279-9028 .- 2279-9036. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: The impact of the COVID-19 pandemic on workload, mental health, and well-being of healthcare workers, and particularly those on the front-line, has received considerable attention. Design and methods: We surveyed hospital employees about their working environment during the pandemic and identified departments which were negatively affected in comparison to the pre-pandemic situation, as well as factors contributing to this. Setting and participants We surveyed all hospital employees at Sahlgrenska University Hospital, Sweden in September 2020 and compared results across departments and to the results of a large employee survey from October 2019. Results: The overall impact of the pandemic on perceived working conditions and possibility for recovery differed among departments. During the pandemic, healthcare workers working with COVID-19 patients reported poorer working environments than other employees. Factors significantly related to perception of work environment and recovery during the pandemic included worries of being infected, departmental transfer, and having insufficient access to personal protective equipment. Men reported better working conditions than women in all, but one item and higher age was related to better perceived working environment. Conclusions: Our results indicate that the pandemic differentially affects hospital departments and underscores the multifactorial nature of this topic. Contributing factors to poor perceived working environment could be addressed at times of high workload, such as during the pandemic, including providing appropriate support to managers, ensuring possibility for recovery during working hours, and acknowledging worries about infection. Young healthcare workers and staff who are relocated due to the pandemic warrant special attention.
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| 26. |
- Kappen, Jasper, et al.
(författare)
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Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma : An EAACI position paper
- 2023
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - 0105-4538. ; 78:11, s. 2835-2850
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add-on intervention to pharmacological treatment. AIT is a treatment with disease-modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma. Methods: The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers. Results: Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP. Conclusion: This EAACI-PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials of AIT.
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| 27. |
- Kirvalidze, Mariam, et al.
(författare)
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Effectiveness of integrated person-centered interventions for older people's care : Review of Swedish experiences and experts' perspective
- 2024
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796.
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Tidskriftsartikel (refereegranskat)abstract
- Older adults have multiple medical and social care needs, requiring a shift toward an integrated person-centered model of care. Our objective was to describe and summarize Swedish experiences of integrated person-centered care by reviewing studies published between 2000 and 2023, and to identify the main challenges and scientific gaps through expert discussions. Seventy-three publications were identified by searching MEDLINE and contacting experts. Interventions were categorized using two World Health Organization frameworks: (1) Integrated Care for Older People (ICOPE), and (2) Integrated People-Centered Health Services (IPCHS). The included 73 publications were derived from 31 unique and heterogeneous interventions pertaining mainly to the micro- and meso-levels. Among publications measuring mortality, 15% were effective. Subjective health outcomes showed improvement in 24% of publications, morbidity outcomes in 42%, disability outcomes in 48%, and service utilization outcomes in 58%. Workshop discussions in Stockholm (Sweden), March 2023, were recorded, transcribed, and summarized. Experts emphasized: (1) lack of rigorous evaluation methods, (2) need for participatory designs, (3) scarcity of macro-level interventions, and (4) importance of transitioning from person- to people-centered integrated care. These challenges could explain the unexpected weak beneficial effects of the interventions on health outcomes, whereas service utilization outcomes were more positively impacted. Finally, we derived a list of recommendations, including the need to engage care organizations in interventions from their inception and to leverage researchers' scientific expertise. Although this review provides a comprehensive snapshot of interventions in the context of Sweden, the findings offer transferable perspectives on the real-world challenges encountered in this field. image
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| 28. |
- Kramer, Lilith, et al.
(författare)
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New paths for modelling freshwater nature futures
- 2023
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Ingår i: Sustainability Science. - 1862-4065 .- 1862-4057.
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Tidskriftsartikel (refereegranskat)abstract
- Freshwater ecosystems are exceptionally rich in biodiversity and provide essential benefits to people. Yet they are disproportionately threatened compared to terrestrial and marine systems and remain underrepresented in the scenarios and models used for global environmental assessments. The Nature Futures Framework (NFF) has recently been proposed to advance the contribution of scenarios and models for environmental assessments. This framework places the diverse relationships between people and nature at its core, identifying three value perspectives as points of departure: Nature for Nature, Nature for Society, and Nature as Culture. We explore how the NFF may be implemented for improved assessment of freshwater ecosystems. First, we outline how the NFF and its main value perspectives can be translated to freshwater systems and explore what desirable freshwater futures would look like from each of the above perspectives. Second, we review scenario strategies and current models to examine how freshwater modelling can be linked to the NFF in terms of its aims and outcomes. In doing so, we also identify which aspects of the NFF framework are not yet captured in current freshwater models and suggest possible ways to bridge them. Our analysis provides future directions for a more holistic freshwater model and scenario development and demonstrates how society can benefit from freshwater modelling efforts that are integrated with the value-perspectives of the NFF.
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| 29. |
- Kårelind, Fanny, et al.
(författare)
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Post-diagnostic support for persons with young-onset dementia - a retrospective analysis based on data from the Swedish dementia registry SveDem
- 2024
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Ingår i: BMC Health Services Research. - : BioMed Central (BMC). - 1472-6963. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Approximately 3.9 million persons worldwide have young-onset dementia. Symptoms related to young-onset dementia present distinct challenges related to finances, employment, and family. To provide tailored support, it is important to gain knowledge about the formal support available for persons with young-onset dementia. Therefore, this paper aims to describe formal support for persons with young-onset dementia in Sweden and the factors influencing this support.METHODS: This retrospective study used data on persons under 65 years of age (n = 284) from The Swedish Registry for Cognitive/Dementia Disorders (SveDem) between 2021 and 2022. SveDem was established to monitor the quality of dementia care in Sweden. Characteristics of participants were obtained, including age, sex, dementia diagnosis, MMSE, medications, accommodation, and care setting. Descriptive statistics and logistic regression were used to test for associations between participant characteristics and post-diagnostic support.RESULTS: Information and educational support were usually offered to the person with young-onset dementia (90.1%) and their family (78.9%). Approximately half of the sample were offered contact with a dementia nurse (49.3%), counsellor (51.4%), or needs assessor (47.9%). A minority (28.5%) were offered cognitive aids. Six regression models were conducted based on participant characteristics to predict the likelihood that persons were offered support. Support was not predicted by age, sex, children at home, accommodation, or medications. Lower MMSE scores (p < .05) and home help (p < .05) were significantly associated with offer of a needs assessor. Living together was a significant predictor (p < .01) for information and educational support offered to the family. Care setting significantly predicted (p < .01) an offer of information and educational support for the person and family members, as well as contact with a counsellor.CONCLUSION: This study indicates potential formal support shortages for persons with young-onset dementia in some areas of dementia care. Despite equal support across most characteristics, disparities based on care setting highlight the importance of specialised dementia care. Pre-diagnostic support is minimal, indicating challenges for persons with young-onset dementia to access these services before diagnosis. While our study has identified areas in need of improvement, we recommend further research to understand the changing support needs of those with young-onset dementia.
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| 30. |
- Kårelind, Fanny, et al.
(författare)
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Post-diagnostic support for persons with young-onset dementia - a retrospective analysis based on data from the Swedish dementia registry SveDem
- 2024
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Ingår i: BMC HEALTH SERVICES RESEARCH. - : BioMed Central (BMC). - 1472-6963. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Approximately 3.9 million persons worldwide have young-onset dementia. Symptoms related to young-onset dementia present distinct challenges related to finances, employment, and family. To provide tailored support, it is important to gain knowledge about the formal support available for persons with young-onset dementia. Therefore, this paper aims to describe formal support for persons with young-onset dementia in Sweden and the factors influencing this support. Methods This retrospective study used data on persons under 65 years of age (n = 284) from The Swedish Registry for Cognitive/Dementia Disorders (SveDem) between 2021 and 2022. SveDem was established to monitor the quality of dementia care in Sweden. Characteristics of participants were obtained, including age, sex, dementia diagnosis, MMSE, medications, accommodation, and care setting. Descriptive statistics and logistic regression were used to test for associations between participant characteristics and post-diagnostic support. Results Information and educational support were usually offered to the person with young-onset dementia (90.1%) and their family (78.9%). Approximately half of the sample were offered contact with a dementia nurse (49.3%), counsellor (51.4%), or needs assessor (47.9%). A minority (28.5%) were offered cognitive aids. Six regression models were conducted based on participant characteristics to predict the likelihood that persons were offered support. Support was not predicted by age, sex, children at home, accommodation, or medications. Lower MMSE scores (p < .05) and home help (p < .05) were significantly associated with offer of a needs assessor. Living together was a significant predictor (p < .01) for information and educational support offered to the family. Care setting significantly predicted (p < .01) an offer of information and educational support for the person and family members, as well as contact with a counsellor. Conclusion This study indicates potential formal support shortages for persons with young-onset dementia in some areas of dementia care. Despite equal support across most characteristics, disparities based on care setting highlight the importance of specialised dementia care. Pre-diagnostic support is minimal, indicating challenges for persons with young-onset dementia to access these services before diagnosis. While our study has identified areas in need of improvement, we recommend further research to understand the changing support needs of those with young-onset dementia.
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| 31. |
- Sanders-van Wijk, S., et al.
(författare)
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Proteomic Evaluation of the Comorbidity-Inflammation Paradigm in Heart Failure With Preserved Ejection Fraction Results From the PROMIS-HFpEF Study
- 2020
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 142:21, s. 2029-2044
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Tidskriftsartikel (refereegranskat)abstract
- Background: A systemic proinflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm. Methods: In 228 patients with HFpEF from the multicenter PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction), 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component analysis to summarize 47 proteins known a priori to be involved in inflammation. In an inductive approach, we performed unbiased weighted coexpression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without heart failure. Results: Comorbidity burden was associated with abnormal cardiac structure/function and with principal components/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e ' ratio, and tricuspid regurgitation velocity; and worse right ventricular function (tricuspid annular plane systolic excursion and right ventricular free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19%-35%), E/e ' ratio (18%-29%), tricuspid regurgitation velocity (27%-41%), and tricuspid annular plane systolic excursion (13%) (P<0.05 for all), but not right ventricular free wall strain. TNFR1 (tumor necrosis factor receptor 1), UPAR (urokinase plasminogen activator receptor), IGFBP7 (insulin-like growth factor binding protein 7), and GDF-15 (growth differentiation factor-15) were the top individual proteins that mediated the relationship between comorbidity burden and echocardiographic parameters. In the validation cohort, inflammation was upregulated in HFpEF cases versus controls, and the most prominent inflammation protein cluster identified in PROMIS-HFpEF was also present in HFpEF cases (but not controls) in the validation cohort. Conclusions: Proteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and right ventricular dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.
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| 32. |
- Ten Kate, Chantal A, et al.
(författare)
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Psychometric Performance of a Condition-Specific Quality-of-Life Instrument for Dutch Children Born with Esophageal Atresia.
- 2022
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Ingår i: Children (Basel, Switzerland). - : MDPI AG. - 2227-9067. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- A condition-specific instrument (EA-QOL©) to assess quality of life of children born with esophageal atresia (EA) was developed in Sweden and Germany. Before implementing this in the Netherlands, we evaluated its psychometric performance in Dutch children. After Swedish-Dutch translation, cognitive debriefing was conducted with a subset of EA patients and their parents. Next, feasibility, reliability, and validity were evaluated in a nationwide field test. Cognitive debriefing confirmed the predefined concepts, although some questions were not generally applicable. Feasibility was poor to moderate. In 2-to-7-year-old children, 8/17 items had >5% missing values. In 8-to-17-year-old children, this concerned 3/24 items of the proxy-report and 5/14 items of the self-report. The internal reliability was good. The retest reliability showed good correlation. The comparison reliability between self-reports and proxy-reports was strong. The construct validity was discriminative. The convergent validity was strong for the 2-to-7-year-old proxy-report, and weak to moderate for the 8-to-17-year-old proxy-report and self-report. In conclusion, the Dutch-translated EA-QOL questionnaires showed good reliability and validity. Feasibility was likely affected by items not deemed applicable to an individual child's situation. Computer adaptive testing could be a potential solution to customizing the questionnaire to the individual patient. Furthermore, cross-cultural validation studies and implementation-evaluation studies in different countries are needed.
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| 33. |
- Van Wijk, Rob C, 1991-, et al.
(författare)
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Finding the right hazard function for time-to-event modeling : A tutorial and Shiny application
- 2022
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Ingår i: CPT. - : John Wiley & Sons. - 2163-8306. ; 11:8, s. 991-1001
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Tidskriftsartikel (refereegranskat)abstract
- Parametric time-to-event analysis is an important pharmacometric method to predict the probability of an event up until a certain time as a function of covariates and/or drug exposure. Modeling is performed at the level of the hazard function describing the instantaneous rate of an event occurring at that timepoint. We give an overview of the parametric time-to-event analysis starting with graphical exploration by Kaplan-Meier plotting for the event data including censoring and nonparametric hazard estimators such as the kernel-based visual hazard comparison for the underlying hazard. The most common hazard functions including the exponential, Gompertz, Weibull, log-normal, log-logistic, and circadian functions are described in detail. A Shiny application was developed to graphically guide the modeler which of the most common hazard functions presents a similar shape compared to the data in order to guide which hazard functions to test in the parametric time-to-event analysis. For the chosen hazard function(s), the Shiny application can additionally be used to explore corresponding parameter values to inform on suitable initial estimates for parametric modeling as well as on possible covariate or treatment relationships to certain parameters. Moreover, it can be used for the dissemination of results as well as communication, training, and workshops on time-to-event analysis. By guiding the modeler on which functions and what parameter values to test and compare as well as to assist in dissemination, the Shiny application developed here greatly supports the modeler in complicated parametric time-to-event modeling.
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| 34. |
- Van Wijk, Rob C, 1991-, et al.
(författare)
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Implementing best practices on data generation and reporting of Mycobacterium tuberculosis in vitro assays within the ERA4TB consortium
- 2023
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Ingår i: iScience. - : Cell Press. - 2589-0042. ; 26:4
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Tidskriftsartikel (refereegranskat)abstract
- Tuberculosis (TB) is the historical leading cause of death by a single infectious agent. The European Regimen Accelerator for Tuberculosis (ERA4TB) is a public-private partnership of 30+ institutions with the objective to progress new anti-TB regimens into the clinic. Thus, robust and replicable results across independent laboratories are essential for reliable interpretation of treatment efficacy. A standardization workgroup unified in vitro protocols and data reporting templates. Time-kill assays provide essential input data for pharmacometric model-informed translation of single agents and regimens activity from in vitro to in vivo and the clinic. Five conditions were assessed by time-kill assays in six independent laboratories using four bacterial plating methods. Baseline bacterial burden varied between laboratories but variability was limited in net drug effect, confirming 2.5 mu L equally robust as 100 mu L plating. This exercise establishes the foundations of collaborative data generation, reporting, and integration within the overarching Antimicrobial Resistance Accelerator program.
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| 35. |
- Van Wijk, Rob C, 1991-, et al.
(författare)
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Model-informed drug discovery and development strategy for the rapid development of anti-tuberculosis drug combinations
- 2020
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Ingår i: Applied Sciences. - : MDPI AG. - 1454-5101 .- 2076-3417. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The increasing emergence of drug-resistant tuberculosis requires new effective and safe drug regimens. However, drug discovery and development are challenging, lengthy and costly.The framework of model-informed drug discovery and development (MID3) is proposed to be applied throughout the preclinical to clinical phases to provide an informative prediction of drug exposure and efficacy in humans in order to select novel anti-tuberculosis drug combinations. The MID3 includes pharmacokinetic-pharmacodynamic and quantitative systems pharmacology models, machine learning and artificial intelligence, which integrates all the available knowledge related to disease and the compounds. A translational in vitro-in vivo link throughout modeling and simulation is crucial to optimize the selection of regimens with the highest probability of receiving approval from regulatory authorities. In vitro-in vivo correlation (IVIVC) and physiologically-based pharmacokinetic modeling provide powerful tools to predict pharmacokinetic drug-drug interactions based on preclinical information. Mechanistic or semi-mechanistic pharmacokinetic-pharmacodynamic models have been successfully applied to predict the clinical exposure-response profile for anti-tuberculosis drugs using preclinical data. Potential pharmacodynamic drug-drug interactions can be predicted from in vitro data through IVIVC and pharmacokinetic-pharmacodynamic modeling accounting for translational factors. It is essential for academic and industrial drug developers to collaborate across disciplines to realize the huge potential of MID3.
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| 36. |
- Veje, Malin, et al.
(författare)
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Working conditions for healthcare workers at a Swedish university hospital infectious disease department during the COVID-19 pandemic: barriers and facilitators to maintaining employee wellbeing.
- 2023
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Ingår i: Frontiers in psychology. - 1664-1078. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Healthcare workers (HCWs) at infectious disease departments have held the frontline during the COVID-19 pandemic. This study aimed to identify barriers and facilitators to maintaining the employees' wellbeing that may be used to increase preparedness for future pandemics within ID Departments.In September 2020, a web-based survey on demographics and work environment was distributed to all HCWs at the Infectious Disease Department at Sahlgrenska University Hospital. Results were compared with a pre-COVID-19 survey from October 2019. A quantitative analysis of the overall effects of the pandemic on the working conditions of HCWs was conducted; in addition, a qualitative content analysis of open-ended responses was performed.In total, 222 and 149 HCWs completed the pre-COVID-19 and COVID-19 surveys (84 and 54% response rate), respectively. Overall, we found significant changes regarding increased workload, lack of emotional support in stressful work situations, and inability to recover after shifts. These factors correlated both with younger age and concern of becoming infected. The open-ended answers (n=103, 69%) revealed five generic categories (Workload; Organizational support; Worry and ethical stress; Capability; and Cooperation and unity) with a total of 14 identified factors representing plausible individual and organizational-level barriers or facilitators to sustained employee wellbeing.Younger HCWs as well as those expressing worries about contracting the infection were found to be particularly affected during the COVID-19 pandemic and these groups may require additional support in future outbreaks. Factors both increasing and decreasing the pandemic-induced negative health consequences for HCWs were identified; this knowledge may be utilized in the future.
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| 37. |
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| 38. |
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| 39. |
- Åkerström, Magnus, 1981, et al.
(författare)
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Working conditions for hospital-based maternity and neonatal health care workers during extraordinary situations-A pre-/post COVID-19 pandemic analysis and lessons learned
- 2022
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Ingår i: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to investigate how the changed work routines during the COVID-19 pandemic has been affecting the working environment for hospital-based maternity and neonatal health care workers, and to identify preventive measures to be used in future situations when health care organizations are under pressure. Methods: All maternity and neonatal health care workers in a Swedish university hospital were surveyed during October 2019 and September 2020. The data was analyzed by document analysis of implemented changes in working routines, a quantitative analysis of the overall effects on the working conditions, and a qualitative analysis of open-ended responses. Results: A total of 660 maternity and neonatal health care workers completed the pre-COVID-19 survey (74% response rate) and 382 the COVID-19 survey (35% response rate). Lack of personal protective equipment, worry about becoming infected, uncertainty whether implemented changes were enough, and challenges in commu-nicating updated routines had negative effects on maternity and neonatal health care workers' working condi-tions. Team spirit and feeling valued by peers had a positive effect. Conclusions: Results suggest that negative effects on maternity and neonatal health care workers' health can partly be prevented in future critical situations by creating a work climate that acknowledges the employees' worry about being infected, securing adequate pre-conditions for managers, creating a strong psychosocial safety climate and systematically improving the working conditions for the maternity and neonatal health care workers, as well as maintaining the positive perceived effects of increased team spirit and feeling valued by peers.
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