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Sökning: WFRF:(Wijk H)

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1.
  • 2017
  • swepub:Mat__t
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  • Bousquet, Jean, et al. (författare)
  • Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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  • Bousquet, J, et al. (författare)
  • Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
  • 2020
  • Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
  • 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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  • Menditto, Enrica, et al. (författare)
  • Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
  • 2019
  • Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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  • Ageron, M., et al. (författare)
  • ANTARES : The first undersea neutrino telescope
  • 2011
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 656:1, s. 11-38
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given. (C) 2011 Elsevier B.V. All rights reserved.
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8.
  • Aguilar, J. A., et al. (författare)
  • First results of the instrumentation line for the deep-sea ANTARES neutrino telescope
  • 2006
  • Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 26:4-5, s. 314-324
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2005, the ANTARES Collaboration deployed and operated at a depth of 2500 m a so-called Mini Instrumentation Line equipped with Optical Modules (MILOM) at the ANTARES site. The various data acquired during the continuous operation from April to December 2005 of the MILOM confirm the satisfactory performance of the Optical Modules, their front-end electronics and readout system. as well as the calibration devices of the detector. The in situ measurement of the Optical Module time response yields a resolution better than 0.5 ns. The performance of the acoustic positioning system, which enables the spatial reconstruction of the ANTARES detector with a precision of about 10 cm, is verified. These results demonstrate that with the full ANTARES neutrino telescope the design angular resolution of better than 0.3 degrees can be realistically achieved.
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  • Aguilar, J. A., et al. (författare)
  • The data acquisition system for the ANTARES neutrino telescope
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 570:1, s. 107-116
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES neutrino telescope is being constructed in the Mediterranean Sea. It consists of a large three-dimensional array of photo-multiplier tubes. The data acquisition system of the detector takes care of the digitisation of the photo-multiplier tube signals, data transport, data filtering, and data storage. The detector is operated using a control program interfaced with all elements. The design and the implementation of the data acquisition system are described. (c) 2006 Elsevier B.V. All rights reserved.
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10.
  • Ageron, M., et al. (författare)
  • Studies of a full-scale mechanical prototype line for the ANTARES neutrino telescope and tests of a prototype instrument for deep-sea acoustic measurements
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 581:3, s. 695-708
  • Tidskriftsartikel (refereegranskat)abstract
    • full-scale mechanical prototype line was deployed to a depth of 2500 m to test the leak tightness of the electronics containers and the pressure-resistant properties of an electromechanical cable under evaluation for use in the ANTARES deep-sea neutrino telescope. During a month-long immersion study, line parameter data were taken using miniature autonomous data loggers and shore-based optical time domain reflectometry. Details of the mechanical prototype line, the electromechanical cable and data acquisition are presented. Data taken during the immersion study revealed deficiencies in the pressure resistance of the electromechanical cable terminations at the entry points to the electronics containers. The improvements to the termination, which have been integrated into subsequent detection lines, are discussed. The line also allowed deep-sea acoustic measurements with a prototype hydrophone system. The technical setup of this system is described, and the first results of the data analysis are presented. (c) 2007 Elsevier B.V. All rights reserved.
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11.
  • Ageron, M., et al. (författare)
  • The ANTARES optical beacon system
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 578:3, s. 498-509
  • Tidskriftsartikel (refereegranskat)abstract
    • ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three-dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular, when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented. (C) 2007 Elsevier B.V. All rights reserved.
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  • Bousquet, Jean, et al. (författare)
  • Development and implementation of guidelines in allergic rhinitis – an ARIA-GA2LEN paper.
  • 2010
  • Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 65:10, s. 1212-21
  • Tidskriftsartikel (refereegranskat)abstract
    • The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients’ values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.
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  • Zuberbier, T., et al. (författare)
  • 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
  • Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:6, s. 1736-1750
  • 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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  • Herrmann, Job J., et al. (författare)
  • Fluid REStriction in Heart Failure vs Liberal Fluid UPtake : Rationale and Design of the Randomized FRESH-UP Study
  • 2022
  • Ingår i: Journal of Cardiac Failure. - : Churchill Livingstone. - 1071-9164 .- 1532-8414. ; 28:10, s. 1522-1530
  • 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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  • Van Wijk, Rob C., 1991-, et al. (författare)
  • Anti‐tuberculosis effect of isoniazid scales accurately from zebrafish to humans
  • 2020
  • Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 177:24, s. 5518-5533
  • 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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  • Van Wijk, Rob C., 1991-, et al. (författare)
  • Quantification of Natural Growth of Two Strains of Mycobacterium Marinum for Translational Antituberculosis Drug Development
  • 2020
  • Ingår i: Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 13:6, s. 1060-1064
  • 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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21.
  • Van Wijk, Rob C, 1991-, et al. (författare)
  • Seasonal influence on respiratory tract infection severity including COVID-19 quantified through Markov Chain modeling
  • 2023
  • Ingår i: CPT. - : John Wiley & Sons. - 2163-8306. ; 12:9, s. 1250-1261
  • 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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  • Bousquet, J, et al. (författare)
  • Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
  • 2012
  • Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
  • Tidskriftsartikel (refereegranskat)abstract
    • Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
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26.
  • De Jager, Veronique, et al. (författare)
  • Early Bactericidal Activity of Meropenem plus Clavulanate (with or without Rifampin) for Tuberculosis : The COMRADE Randomized, Phase 2A Clinical Trial
  • 2022
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 205:10, s. 1228-1235
  • 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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27.
  • Mockeliunas, Laurynas, et al. (författare)
  • Risk Factors for COVID-19 and Respiratory Tract Infections during the Coronavirus Pandemic
  • 2024
  • Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 12:3
  • 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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28.
  • Mockeliunas, Laurynas, et al. (författare)
  • Standards for model-based early bactericidal activity analysis and sample size determination in tuberculosis drug development
  • 2023
  • Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 14
  • 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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29.
  • Mooij, Wolf M., et al. (författare)
  • Modeling water quality in the Anthropocene : directions for the next-generation aquatic ecosystem models
  • 2019
  • Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 36, s. 85-95
  • Forskningsöversikt (refereegranskat)abstract
    • Everything changes and nothing stands still (Heraclitus). Here we review three major improvements to freshwater aquatic ecosystem models - and ecological models in general - as water quality scenario analysis tools towards a sustainable future. To tackle the rapid and deeply connected dynamics characteristic of the Anthropocene, we argue for the inclusion of eco-evolutionary, novel ecosystem and social-ecological dynamics. These dynamics arise from adaptive responses in organisms and ecosystems to global environmental change and act at different integration levels and different time scales. We provide reasons and means to incorporate each improvement into aquatic ecosystem models. Throughout this study we refer to Lake Victoria as a microcosm of the evolving novel social-ecological systems of the Anthropocene. The Lake Victoria case clearly shows how interlinked eco-evolutionary, novel ecosystem and social-ecological dynamics are, and demonstrates the need for transdisciplinary research approaches towards global sustainability.
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30.
  • Upton, Caryn M., et al. (författare)
  • 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
  • Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 48
  • 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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31.
  • Van Wijk, Rob C, 1991-, et al. (författare)
  • Reproducibility in pharmacometrics applied in a phase III trial of BCG-vaccination for COVID-19
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13
  • 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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32.
  • Alexiou, Eirini, et al. (författare)
  • 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
  • Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12
  • 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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33.
  • Alexiou, Eirini, et al. (författare)
  • 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
  • Ingår i: BMJ open. - 2044-6055. ; 14:2
  • 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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34.
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35.
  • Björk, Lisa, 1981, et al. (författare)
  • Under pressure - The working situation of Swedish healthcare managers during the first wave of COVID-19
  • 2023
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 13
  • 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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36.
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37.
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38.
  • Edberg, Anna-Karin, 1961-, et al. (författare)
  • Specialistsjuksköterskan inom vård av äldre gör skillnad
  • 2013
  • Ingår i: Ä : en tidning för Riksföreningen sjuksköterskan inom äldrevård : geriatriker, dietister inom geriatrik samt alla professioner runt den äldre patienten. - 2001-1164. ; :4, s. 33-36
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
39.
  • Edberg, Anna-Karin, et al. (författare)
  • Specialistsjuksköterskan inom vård av äldre gör skillnad
  • 2013
  • Ingår i: Ä : en tidning för Riksföreningen sjuksköterskan inom äldrevård : geriatriker, dietister inom geriatrik samt alla professioner runt den äldre patienten. - 2001-1164. ; :4, s. 33-36
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
40.
  •  
41.
  • Faraj, Alan, et al. (författare)
  • Model-informed pediatric dose selection of marzeptacog alfa (activated) : An exposure matching strategy
  • 2023
  • Ingår i: CPT. - : John Wiley & Sons. - 2163-8306. ; 12:7, s. 977-987
  • 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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42.
  • Gillberg, Nanna, et al. (författare)
  • Resilience Capability and Capacity in Unexpected Crises: Experiences and Lessons Learned in a Healthcare Organisation during the COVID-19 Pandemic
  • 2023
  • Ingår i: Journal of Nursing Management. - 0966-0429 .- 1365-2834.
  • 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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43.
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44.
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45.
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46.
  • Johansson, Karl H., et al. (författare)
  • Teaching multivariable control using the Quadruple-Tank Process
  • 1999
  • Ingår i: Proceedings of the 38th IEEE Conference on Decision and Control, 1999. - : IEEE. ; , s. 807-812
  • Konferensbidrag (refereegranskat)abstract
    • A multivariable laboratory process is presented together with its use in a graduate control course. The process is called the quadruple-tank process and demonstrates a multivariable level control problem. The multivariable zero dynamics of the system can be made both minimum phase and nonminimum phase by simply changing a valve. This makes the quadruple-tank process suitable for illustrating many concepts in linear and nonlinear multivariable control. In the paper some of these are described together with the basic setup of the process. Two computer exercises and one laboratory exercise have been developed as part of a course in multivariable and nonlinear control. These are detailed and some experience from the course is presented.
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47.
  • Johansson, Linda, et al. (författare)
  • Improving nutritional status among persons with dementia by performing individualized interventions
  • 2016
  • Ingår i: The Gerontologist. - : Oxford University Press (OUP). - 1758-5341.
  • Konferensbidrag (refereegranskat)abstract
    • Poor nutritional status is common among persons with dementia and negatively associated with subjective health, mobility and mortality. When malnutrition occurs it is challenging to improve the nutritional status. The aim of the study was to investigate if a structured preventive care process could increase body weight, among persons with dementia at risk of malnutrition or malnourished. The structured preventive care process includes four steps which have been registered in a national quality register: 1) Risk assessment by Mini nutritional assessment-Short Form. 2) Team-based analysis of underlying causes (19 evidence-based risk factors) performed by staff including professionals like nurses, nurse assistants, occupational therapists and physiotherapists. 3)  Planning and performing interventions based on the need and problems of the individual (28 evidence-based actions) and 4) evaluation of performed interventions (body weight). A prepost design was used with body weight measured during baseline (0) and follow-up (7–106 days later). In total 526 persons with dementia at risk of malnutrition 176 The Gerontological Society of America Copyedited by: OUP at :: on January 10, 2017 http://gerontologist.oxfordjournals.org/ Downloaded from or malnourished, 65 years and older and with a care contact, were included. Results: 109 persons was registered in all four steps i.e. a team-based analysis of underlying causes have been performed. An improvement in the nutritional status was observed in these individuals (baseline Md 60.0 kg; follow-up Md 62.0  kg; p-value 0.013). No improvement was detected among those missing an analysis of underlying causes. Accordingly, by planning care in a structured way and give individualized interventions based on underlying causes can help improve nutritional status among persons with dementia at risk of malnutrition or malnourished.
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48.
  • Johansson, Nina, et al. (författare)
  • 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
  • Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 22:1
  • 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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49.
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50.
  • Jonsdottir, Ingibjörg H, 1966, et al. (författare)
  • 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
  • Ingår i: Journal of Public Health Research. - : SAGE Publications. - 2279-9028 .- 2279-9036. ; 10:4
  • 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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