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| 2. |
- Ringlander, Johan, et al.
(author)
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Enrichment Reveals Extensive Integration of Hepatitis B Virus DNA in Hepatitis Delta Virus-Infected Patients
- 2024
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In: JOURNAL OF INFECTIOUS DISEASES. - 0022-1899 .- 1537-6613.
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Journal article (peer-reviewed)abstract
- Background. Hepatitis B virus (HBV) DNA may become integrated into the human genome of infected human hepatocytes. Expression of integrations can produce the surface antigen (HBsAg) that is required for synthesis of hepatitis D virus (HDV) particles and the abundant subviral particles in the blood of HBV- and HDV-infected subjects. Knowledge about the extent and variation of HBV integrations and impact on chronic HDV is still limited. Methods. We investigated 50 pieces of liver explant tissue from 5 patients with hepatitis D-induced cirrhosis, using a deep-sequencing strategy targeting HBV RNA. Results. We found that integrations were abundant and highly expressed, with large variation in the number of integration-derived (HBV/human chimeric) reads, both between and within patients. The median number of unique integrations for each patient correlated with serum levels of HBsAg. However, most of the HBV reads represented a few predominant integrations. Conclusions. The results suggest that HBV DNA integrates in a large proportion of hepatocytes, and that the HBsAg output from these integrations vary >100-fold depending on clone size and expression rate. A small proportion of the integrations seems to determine the serum levels of HBsAg and HDV RNA in HBV/HDV coinfected patients with liver cirrhosis.
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| 3. |
- Berg, Hans E., et al.
(author)
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Threshold-automated CT measurements of muscle size and radiological attenuation in multiple lower-extremity muscles of older individuals
- 2020
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In: Clinical Physiology and Functional Imaging. - : WILEY. - 1475-0961 .- 1475-097X. ; 40:3, s. 165-172
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Journal article (peer-reviewed)abstract
- Muscle atrophy and fat infiltration, two indicators of deconditioning and weakness in elderly frail patients, are typically assessed by means of manual image analysis from computed tomography (CT) scans. As this time-consuming image analysis limits its wider use in clinical studies, the use of tissue thresholds to semi-automatically assess muscle composition has been suggested. Here, we aimed to investigate the relationship between manual and semi-automated analysis of both cross-sectional area (CSA) and radiological attenuation (RA), in multiple muscles of the lower extremities in aged (77 +/- 6 years) sedentary individuals (n = 40). The participants underwent CT scans of their lower limbs, including hip, thigh and calf muscles. The subsequent analysis of CSA and RA was conducted using both manual segmentation and semi-automatic thresholds (-30 to +150 Hounsfield units). Automated measurements were generally strongly correlated with manually encircled CSA in all muscle groups (R = 0.79-0.99, p < .05) and shortened the analysis time by 70% (p < .05). In m. iliopsoas, however, the CSA became overestimated (15%, p < .05) with thresholded measurements, while the assessment of both CSA and RA was underestimated in muscles with high-fat content (i.e., the gluteal muscles) and in individuals with high-fat infiltration. In conclusion, using the semi-automated technique with conventional thresholds is a time-saving method that delivers accurate gross size of the muscle groups, particularly in the thigh. However, caution should be exercised when using semi-automated techniques for assessing CSA and fat infiltration in muscles with high-fat content.
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| 4. |
- Gudmundsson, T., et al.
(author)
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Importance of hospital and clinical factors in predicting of 30-day mortality in Takotsubo syndrome : data from the Swedish Coronary Angiography and Angioplasty Registry
- 2023
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:Suppl. 2
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Journal article (other academic/artistic)abstract
- Background: Takotsubo syndrome (TS) is an acute heart failure condition that presents with symptoms similar to acute myocardial infarction. TS is often triggered by emotional or physical stress and is an important cause of morbidity and mortality but predictors of mortality in TS patients are not well understood. There is a need to identify high-risk patients and tailor treatment accordingly.Purpose: The purpose of this study was to assess the importance of various clinical factors in predicting 30-day mortality in TS patients using a machine-learning algorithm capable of identifying complex relationships between variables.Methods: We analyzed data from the nationwide Swedish Coronary Angiography and Angioplasty Registry for all TS patients between 2015-2022. Gradient boosting was used to assess the relative importance of variables in predicting 30-day mortality in TS patients.Results: Of the 3,180 hospitalized TS patients, 76% were women. The average age was 68.3 ± 11.2 years. The crude all-cause mortality rate was 2.57% at 30 days. The most important variable in predicting 30-day mortality was the hospital where the patient was treated, with a relative importance of 35.5%. This was followed by the clinical presentation for angiography (21.1%), creatinine level (11.9%), Killip class (8.9%), and age at angioplasty (6.5%). Other less important factors included weight, height, and certain medical conditions such as hyperlipidemia, smoking status, and hypertension. Gender and previous stroke history had a low impact on 30-day mortality in TS patients.Conclusions: The treating hospital was the most important factor in predicting 30-day mortality in TS. Since the level of evidence for recommended treatments of TS is low, our findings highlight the importance of conducting randomized studies in this patient group to improve care.
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| 5. |
- Hartman, E. A. R., et al.
(author)
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Decisions on antibiotic prescribing for suspected urinary tract infections in frail older adults: a qualitative study in four European countries
- 2022
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In: Age and ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 51:6
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Journal article (peer-reviewed)abstract
- Background a suspected urinary tract infection (UTI) is the most common reason to prescribe antibiotics in a frail older patient. Frequently, antibiotics are prescribed unnecessarily. To increase appropriate antibiotic use for UTIs through antibiotic stewardship interventions, we need to thoroughly understand the factors that contribute to these prescribing decisions. Objectives (1) to obtain insight into factors contributing to antibiotic prescribing for suspected UTIs in frail older adults. (2) To develop an overarching model integrating these factors to guide the development of antibiotic stewardship interventions for UTIs in frail older adults. Methods we conducted an exploratory qualitative study with 61 semi-structured interviews in older adult care settings in Poland, the Netherlands, Norway and Sweden. We interviewed physicians, nursing staff, patients and informal caregivers. Results participants described a chain of decisions by patients, caregivers and/or nursing staff preceding the ultimate decision to prescribe antibiotics by the physician. We identified five themes of influence: (1) the clinical situation and its complexity within the frail older patient, (2) diagnostic factors, such as asymptomatic bacteriuria, (3) knowledge (gaps) and attitude, (4) communication: interprofessional, and with patients and relatives and (5) context and organisation of care, including factors such as availability of antibiotics (over the counter), antibiotic stewardship efforts and factors concerning out-of-hours care. Conclusions decision-making on suspected UTIs in frail older adults is a complex, multifactorial process. Due to the diverse international setting and stakeholder variety, we were able to provide a comprehensive overview of factors to guide the development of antibiotic stewardship interventions.
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| 6. |
- Hartman, E. A. R., et al.
(author)
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Multifaceted antibiotic stewardship intervention using a participatory-action-research approach to improve antibiotic prescribing for urinary tract infections in frail elderly (ImpresU): study protocol for a European qualitative study followed by a pragmatic cluster randomised controlled trial
- 2021
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In: Bmj Open. - : BMJ. - 2044-6055. ; 11:10
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Journal article (peer-reviewed)abstract
- Introduction Almost 60% of antibiotics in frail elderly are prescribed for alleged urinary tract infections (UTIs). A substantial part of this comprises prescriptions in case of non-specific symptoms or asymptomatic bacteriuria, for which the latest guidelines promote restrictiveness with antibiotics. We aim to reduce inappropriate antibiotic use for UTIs through an antibiotic stewardship intervention (ASI) that encourages to prescribe according to these guidelines. To develop an effective ASI, we first need a better understanding of the complex decision-making process concerning suspected UTIs in frail elderly. Moreover, the implementation approach requires tailoring to the heterogeneous elderly care setting. Methods and analysis First, we conduct a qualitative study to explore factors contributing to antibiotic prescribing for UTIs in frail elderly, using semi-structured interviews with general practitioners, nursing staff, patients and informal caregivers. Next, we perform a pragmatic cluster randomised controlled trial in elderly care organisations. A multifaceted ASI is implemented in the intervention group; the control group receives care as usual. The ASI is centred around a decision tool that promotes restrictive antibiotic use, supported by a toolbox with educational materials. For the implementation, we use a modified participatory-action-research approach, guided by the results of the qualitative study. The primary outcome is the number of antibiotic prescriptions for suspected UTIs. We aim to recruit 34 clusters with in total 680 frail elderly residents >= 70 years. Data collection takes place during a 5-month baseline period and a 7-month follow-up period. Finally, we perform a process evaluation. The study has been delayed for 6 months due to COVID-19 and is expected to end in July 2021. Ethics and dissemination Ethical approvals and/or waivers were obtained from the ethical committees in Poland, the Netherlands, Norway and Sweden. The results will be disseminated through publication in peer-reviewed journals and conference presentations.
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| 7. |
- Hober, Sophia, Professor, 1965-, et al.
(author)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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In: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Journal article (peer-reviewed)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 8. |
- Hoste, M. E., et al.
(author)
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The experiences of patients ill with COVID-19-like symptoms and the role of testing for SARS-CoV-2 in supporting them: A qualitative study in eight European countries during the first wave of the pandemic
- 2023
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In: European Journal of General Practice. - 1381-4788. ; 29:2
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Journal article (peer-reviewed)abstract
- BackgroundAccess to testing during the first wave of the COVID-19 pandemic was limited, impacting patients with COVID-19-like symptoms. Current qualitative studies have been limited to one country or were conducted outside Europe.ObjectivesTo explore - in eight European countries - the experiences of patients consulting in primary care with COVID-19-like symptoms during the first wave of the pandemic.MethodsSixty-six semi-structured interviews, informed by a topic guide, were conducted by telephone or in person between April and July 2020. Patients with COVID-19-like symptoms were purposively recruited in primary care sites in eight countries and sampled based on age, gender, and symptom presentation. Deductive and inductive thematic analysis techniques were used to develop a framework representing data across settings. Data adequacy was attained by collecting rich data.ResultsSeven themes were identified, which described the experiences of patients consulting. Two themes are reported in this manuscript describing the role of COVID-19 testing in this experience. Patients described significant distress due to their symptoms, especially those at higher risk of complications from COVID-19, and those with severe symptoms. Patients wanted access to testing to identify the cause of their illness and minimise the burden of managing uncertainty. Some patients testing positive for COVID-19 assumed they would be immune from future infection.ConclusionPatients experiencing novel and severe symptoms, particularly those with comorbidities, experienced a significant emotional and psychological burden due to concerns about COVID-19. Testing provided reassurance over health status and helped patients identify which guidance to follow. Testing positive for SARS-CoV-2 led to some patients thinking they were immune from future infection, thus influencing subsequent behaviour.
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| 9. |
- Hällås, E., et al.
(author)
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“That’s probably how you would want care to be” - experiences of sick leave teams at a health center, a mixed method study
- 2023
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In: BMC Primary Care. - 2731-4553. ; 24:1
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Journal article (peer-reviewed)abstract
- Background: The health center where this study was performed the management wanted to test whether a sick leave team provided the physicians with better conditions for the task of assessing sick leave. The goals were to ensure the quality of the assessment of patients with sick leave needs and to improve the work environment. The aim of this study was to take part in the staff's experiences of having access to and working in sick leave teams and how the working method affected the number of sick leave patients and sick leave pattern. Methods: A mixture of qualitative and quantitative methods. Two focus groups were conducted with a total of 11 participants. The head of the health center formed the focus groups, which consisted of 6 doctors, 3 district nurses, 1 rehab coordinator and 1 psychologist. Aggregated sick leave data for full-time and part-time sick leave of more than 90, 180 and 360days, respectively, were obtained and compiled at project start and end, and from the corresponding period 18months before project start. Results: The introduction of sick leave teams with physicians and rehabilitation coordinator for patients who turn to the health center for mental illness and / or musculoskeletal problems emerged three main categories from the analysis of the focus group discussions: working environment, clear roles and in-depth competence. The total number of people who were on sick leave more than 365days decreased by 27% between start and the end of the project, and the proportion of women increased by 11%. Conclusions: The study shows that the complex task of sick leave can be perceived as positive by physicians with the support of teamwork. The working method is similar to that applied in occupational health care, where the physician is not alone with this task. This can also be a way to make primary care a more attractive workplace.
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| 10. |
- Nekouei, E., et al.
(author)
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A Model Randomization Approach to Statistical Parameter Privacy
- 2022
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In: IEEE Transactions on Automatic Control. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9286 .- 1558-2523. ; , s. 1-1
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Journal article (peer-reviewed)abstract
- In this article, we study a privacy filter design problem for a sequence of sensor measurements whose joint probability density function (p.d.f.) depends on a private parameter. To ensure parameter privacy, we propose a filter design framework which consists of two components: a randomizer and a nonlinear transformation. The randomizer takes the private parameter as input and randomly generates a pseudo parameter. The nonlinear mapping transforms the measurements such that the joint p.d.f. of the filter's output depends on the pseudo parameter rather than the private parameter. It also ensures that the joint p.d.f. of the filter's output belongs to the same family of distributions as that of the measurements. The design of the randomizer is formulated as an optimization problem subject to a privacy constraint, in terms of mutual information, and it is shown that the optimal randomizer is the solution of a convex optimization problem. Using information-theoretic inequalities, we show that the performance of any estimator of the private parameter, based on the output of the privacy filter, is limited by the privacy constraint. The structure of the nonlinear transformation is studied in the special cases of independent and identically distributed, Markovian, and Gauss-Markov measurements. Our results show that the privacy filter in the Gauss-Markov case can be implemented as two one-step ahead Kalman predictors and a set of minimum mean square error predictors. A numerical example on occupancy privacy in a building automation system illustrates the approach.
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