| 1. |
- Kristan, M., et al.
(författare)
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The Eighth Visual Object Tracking VOT2020 Challenge Results
- 2020
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Ingår i: Computer Vision. - Cham : Springer International Publishing. - 9783030682378 ; , s. 547-601
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2020 is the eighth annual tracker benchmarking activity organized by the VOT initiative. Results of 58 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The VOT2020 challenge was composed of five sub-challenges focusing on different tracking domains: (i) VOT-ST2020 challenge focused on short-term tracking in RGB, (ii) VOT-RT2020 challenge focused on “real-time” short-term tracking in RGB, (iii) VOT-LT2020 focused on long-term tracking namely coping with target disappearance and reappearance, (iv) VOT-RGBT2020 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2020 challenge focused on long-term tracking in RGB and depth imagery. Only the VOT-ST2020 datasets were refreshed. A significant novelty is introduction of a new VOT short-term tracking evaluation methodology, and introduction of segmentation ground truth in the VOT-ST2020 challenge – bounding boxes will no longer be used in the VOT-ST challenges. A new VOT Python toolkit that implements all these novelites was introduced. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website (http://votchallenge.net ).
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| 2. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 3. |
- Alffenaar, J. W. C., et al.
(författare)
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Clinical standards for the dosing and management of TB drugs
- 2022
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - Paris, France : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 26:6, s. 483-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice' for dosing and management of TB drugs.Methods: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.Results: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.Conclusion: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
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| 4. |
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| 5. |
- Agrawal, K., et al.
(författare)
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Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 150:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with asthma often suffer from frequent respiratory viral infections and reduced virus clearance. Lung resident memory T cells provide rapid protection against viral reinfections. Objective: Because the development of resident memory T cells relies on the lung microenvironment, we investigated the impact of allergen sensitization on the development of virus-specific lung resident memory T cells and viral clearance. Methods: Mice were sensitized with house dust mite extract followed by priming with X47 and a subsequent secondary influenza infection. Antiviral memory T-cell response and protection to viral infection was assessed before and after secondary influenza infection, respectively. Gene set variation analysis was performed on data sets from the U-BIOPRED asthma cohort using an IFN-γ–induced epithelial cell signature and a tissue resident memory T-cell signature. Results: Viral loads were higher in lungs of sensitized compared with nonsensitized mice after secondary infection, indicating reduced virus clearance. X47 priming induced fewer antiviral lung resident memory CD8 T cells and resulted in lower pulmonary IFN-γ levels in the lungs of sensitized as compared with nonsensitized mice. Using data from the U-BIOPRED cohort, we found that patients with enrichment of epithelial IFN-γ–induced genes in nasal brushings and bronchial biopsies were also enriched in resident memory T-cell–associated genes, had more epithelial CD8 T cells, and reported significantly fewer exacerbations. Conclusions: The allergen-sensitized lung microenvironment interferes with the formation of antiviral resident memory CD8 T cells in lungs and virus clearance. Defective antiviral memory response might contribute to increased susceptibility of patients with asthma to viral exacerbations.
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| 6. |
- Pollinger, F., et al.
(författare)
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Metrology for long distance surveying : A joint attempt to improve traceability of long distance measurements
- 2016
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Ingår i: IAG 150 Years. - Cham : Springer International Publishing. - 9783319246031 ; , s. 651-656
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Konferensbidrag (refereegranskat)abstract
- Based on the current state of technology, distance measurements over a few hundred metres in air with relative uncertainties significantly better than 10_6 are still an almost impossible challenge. In the European Joint Research Project (JRP) “Metrology for long distance surveying” measurement uncertainties in GNSS-based and optical distance metrology are going to be thoroughly investigated, novel technologies and primary standards developed and guidelines to improve surveying practice in the field worked out. A better understanding and a decrease of measurement uncertainty is also targeted for the critical local tie measurement at geodetic fundamental stations.
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| 7. |
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| 8. |
- Abate, E., et al.
(författare)
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Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial
- 2015
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Ingår i: International Journal of Parasitology. - : Elsevier. - 0020-7519 .- 1879-0135. ; 45:2-3, s. 133-140
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Tidskriftsartikel (refereegranskat)abstract
- Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400 mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (Delta TB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-gamma, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (Delta TB score: 5.6 +/- 2.9 for albendazole versus 5.9 +/- 2.5 for placebo, P = 0.59). The albendazole-treated group showed a decline in eosinophil cells (P = 0.001) and IL-10 (P = 0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2 +/- 8.5 kg versus 8.2 +/- 8.7 kg, P = 0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation. (C) 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
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| 9. |
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| 10. |
- Lange, C., et al.
(författare)
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Management of patients with multidrug-resistant tuberculosis
- 2019
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D). - 1027-3719 .- 1815-7920. ; 23:6, s. 645-662
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.
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| 11. |
- Lange, C., et al.
(författare)
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Perspectives for personalized therapy for patients with multidrug-resistant tuberculosis
- 2018
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Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 284:2, s. 163-188
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Forskningsöversikt (refereegranskat)abstract
- According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR-TB. The management of MDR-TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug-resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor-made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR-TB. The challenge now is to bring these adances to those patients that need them most.
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| 12. |
- Petäjä, Tuukka, et al.
(författare)
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Overview : Integrative and Comprehensive Understanding on Polar Environments (iCUPE) - concept and initial results
- 2020
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:14, s. 8551-8592
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Tidskriftsartikel (refereegranskat)abstract
- The role of polar regions is increasing in terms of megatrends such as globalization, new transport routes, demography, and the use of natural resources with consequent effects on regional and transported pollutant concentrations. We set up the ERA-PLANET Strand 4 project iCUPE - integrative and Comprehensive Understanding on Polar Environments to provide novel insights and observational data on global grand challenges with an Arctic focus. We utilize an integrated approach combining in situ observations, satellite remote sensing Earth observations (EOs), and multi-scale modeling to synthesize data from comprehensive long-term measurements, intensive campaigns, and satellites to deliver data products, metrics, and indicators to stakeholders concerning the environmental status, availability, and extraction of natural resources in the polar areas. The iCUPE work consists of thematic state-of-the-art research and the provision of novel data in atmospheric pollution, local sources and transboundary transport, the characterization of arctic surfaces and their changes, an assessment of the concentrations and impacts of heavy metals and persistent organic pollutants and their cycling, the quantification of emissions from natural resource extraction, and the validation and optimization of satellite Earth observation (EO) data streams. In this paper we introduce the iCUPE project and summarize initial results arising out of the integration of comprehensive in situ observations, satellite remote sensing, and multi-scale modeling in the Arctic context.
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| 13. |
- Akuffo, H, et al.
(författare)
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Worms and Humans: A Happy Divorce?
- 2015
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Ingår i: Forum on immunopathological diseases and therapeutics. - 2151-8017. ; 6:1-2, s. 27-32
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Bendz, Hans, et al.
(författare)
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Lithium nephropathy in Sweden
- 2008
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Ingår i: European Psychiatry. - : Cambridge University Press (CUP). - 1778-3585 .- 0924-9338. ; 23:Suppl. 2, s. 288-288
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Konferensbidrag (refereegranskat)
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| 15. |
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| 16. |
- Deshpande, Devyani, et al.
(författare)
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D-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal
- 2018
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Ingår i: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 67, s. S308-S316
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Tidskriftsartikel (refereegranskat)abstract
- Background. D-cycloserine is used to treat multidrug-resistant tuberculosis. Its efficacy, contribution in combination therapy, and best clinical dose are unclear, also data on the D-cycloserine minimum inhibitory concentration (MIC) distributions is scant. Methods. We performed a systematic search to identify pharmacokinetic and pharmacodynamic studies performed with D-cycloserine. We then performed a combined exposure-effect and dose fractionation study of D-cycloserine in the hollow fiber system model of tuberculosis (HFS-TB). In parallel, we identified D-cycloserine MICs in 415 clinical Mycobacterium tuberculosis (Mtb) isolates from patients. We utilized these results, including intracavitary concentrations, to identify the clinical dose that would be able to achieve or exceed target exposures in 10 000 patients using Monte Carlo experiments (MCEs). Results. There were no published D-cycloserine pharmacokinetics/pharmacodynamics studies identified. Therefore, we performed new HFS-TB experiments. Cyloserine killed 6.3 log(10) colony-forming units (CFU)/mL extracellular bacilli over 28 days. Efficacy was driven by the percentage of time concentration persisted above MIC (% T-MIC), with 1.0 log(10) CFU/mL kill achieved by % T-MIC = 30% (target exposure). The tentative epidemiological cutoff value with the Sensititre MYCOTB assay was 64 mg/L. In MCEs, 750 mg twice daily achieved target exposure in lung cavities of 92% of patients whereas 500 mg twice daily achieved target exposure in 85% of patients with meningitis. The proposed MCE-derived clinical susceptibility breakpoint at the proposed doses was 64 mg/L. Conclusions. Cycloserine is cidal against Mtb. The susceptibility breakpoint is 64 mg/L. However, the doses likely to achieve the cidality in patients are high, and could be neurotoxic.
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| 17. |
- Dulski, J., et al.
(författare)
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Clinical variability of neuroacanthocytosis syndromes : A series of six patients with long follow-up
- 2016
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Ingår i: Clinical Neurology and Neurosurgery. - : Elsevier BV. - 0303-8467. ; 147, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Objective To provide clinical clues to differential diagnosis in patients with chorea and other movement disorders with blood acanthocytes. Methods We present a long-term video accompanied follow-up of six Caucasian patients with neuroacanthocytosis from several centers, three diagnosed with chorea-acanthocytosis (ChAc): 34-y.o.(no.1), 36-y.o.(no.2), 43-y.o.(no.3), two diagnosed with McLeod Syndrome (MLS): 52-y.o.(no.4), 61-y.o.(no.5) and one 63-y.o.(no.6), a brother of no.5, with clinical suspicion of MLS. Additionally we report pathological findings of the mother of two brothers with MLS reported in our series with acanthocytes on peripheral blood smear Results The patients had an unremarkable family history and were asymptomatic until adulthood. Patients no. 1,2,4,5,6 developed generalized chorea and patient no. 3 had predominant bradykinesia. Patients no. 1,2,3 had phonic and motor tics, additionally patients no. 1 and 2 exhibited peculiar oromandibular dystonia with tongue thrusting. In patients no. 2 and 3 dystonic supination of feet was observed, patient no. 3 subsequently developed bilateral foot drop. Patients no. 2 and 4 had signs of muscle atrophy. Tendon reflexes were decreased or absent and electroneurography demonstrated sensorimotor neuropathy in patients no. 1,2,3,4,5, except no. 6. Generalized seizures were seen in patients no. 2,3,5,6 and myoclonic jerks in patient no. 1. Cognitive deterioration was reported in patients no. 1,2,3,5,6. Serum creatine kinase levels were elevated in all six patients. Conclusion We highlight the variability of clinical presentation of neuroacanthocytosis syndromes and the long time from the onset to diagnosis with the need to screen the blood smears in uncertain cases, however, as in one of our cases acanthocytes may even be not found. Based on our observations and data from the literature we propose several red flags that should raise the suspicion of an NA syndrome in a patient with a movement disorder: severe orofacial dyskinesia with tongue and lip-biting (typical of ChAc), feeding dystonia, psychiatric and cognitive disturbances, seizures, peripheral neuropathy, elevation of creatine kinase, elevation of transaminases, hepatosplenomegaly, cardiomyopathy and arrhythmias, and an X-linked pattern of inheritance (McLeod Syndrome, MLS).
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| 18. |
- Dulski, J., et al.
(författare)
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Neuroacanthocytosis - Clinical variability (a report on six cases)
- 2014
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 29:Suppl 1, s. 194-194
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Konferensbidrag (refereegranskat)abstract
- Objective: To provide clinical clues to differential diagnosis in patients with chorea and other movement disorders with blood acanthocytes. Background: Neuroacanthocytosis (NA) is an umbrella term for neurological conditions associated with acanthocytosis. Core NA syndromes, with basal ganglia involvement and in which acanthocytosis is a frequent finding, include autosomal recessive choreaacanthocytosis (Ch-Ac) and X-linked McLeod syndrome (MLS). Due to the very low prevalence, scarcity of data and high clinical variability they may be underdiagnosed. Methods: Six male patients (pts), three diagnosed with Ch-Ac: 33-y.o.(no.1), 35-y.o.(no.2), 42-y.o.(no.3), two diagnosed with MLS: 52-y.o.(no.4), 60-y.o.(no.5) and one 62-y.o.(no.6), a brother of no.5, with clinical suspicion of MLS. The patients had an unremarkable family history and were asymptomatic until adulthood. Pts no.1,2,4,5,6 developed generalized chorea and patient no.3 had predominant bradykinesia. Pts no.1,2,3 had phonic and motor tics, additionally pts no.1 and 2 exhibited peculiar oromandibular dystonia with tongue thrusting. In pts no.2 and 3 dystonic supination of feet was observed, patient no.3 subsequently developed bilateral foot drop. Pts no. 2 and 4 had signs of muscle atrophy. Tendon reflexes were decreased or absent and electroneurography demonstrated sensorimotor neuropathy in patients no. 1,2,3,4,5, except no. 6. Generalized seizures were seen in patients no.2,3,5,6 and myoclonic jerks in patient no 1. Cognitive deterioration was reported in patients no.1,2,3,5,6. Serum creatine kinase levels were elevated in all six patients. Results: Peripheral blood smears revealed acanthocytosis in patients no.1,2,3,5,6, except no. 4. In patients no. 1 and 3 reduced expression of chorein was detected on Western blot. In patient no. 2 genetic testing showed mutations in VPS13A gene and in no.4 and 5 genetic analysis confirmed mutations in XK gene (MLS). The time from the onset of symptoms till establishing the diagnosis in patients no. 1,2,3,4,5 was 11,5,7,6,32 years respectively. Patient no.4 suddenly developed multiple organ failure and died of cardiac arrhythmia at the age of 52. Conclusions: We highlight the variability of clinical presentation of NA syndromes and the long time from the onset to diagnosis with the need to screen the blood smears in uncertain cases, however, as in one of our cases acanthocytes may even be not found.
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| 19. |
- Elias, D., et al.
(författare)
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Schistosoma mansoni infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis
- 2005
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 23:11, s. 1326-1334
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that the ability of BCG vaccination to protect against Mycobacterium tuberculosis is less in hosts exposed to chronic helminthes infection compared to unexposed individuals. To test this hypothesis we evaluated the efficacy of BCG vaccination in protecting against M. tuberculosis challenge in Schistosoma mansoni pre-infected mice by analyzing their ability to limit the replication of TB bacilli in the lung and liver and the histology of lung sections. The results show that BCG vaccinated mice with prior S. mansoni infection show significantly higher number of colony forming units of TB bacilli as well as significant reduction in air exchange area in the lung compared to controls. In addition, spleen cells from S. mansoni infected mice were found to produce significantly less IFN-? and nitric oxide when stimulated in vitro with PPD and several fold higher soluble egg antigen (SEA) and Concanavalin A induced IL-4 and IL-5 secretion. Taken together, our data show that S. mansoni infection reduces the protective efficacy of BCG vaccination against M. tuberculosis possibly by attenuation of protective immune responses to mycobacterial antigens and/or by polarizing the general immune responses to the Th2 profile. © 2004 Published by Elsevier Ltd.
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| 20. |
- Forsman, Lina Davies, et al.
(författare)
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Plasma concentrations of second-line antituberculosis drugs in relation to minimum inhibitory concentrations in multidrug-resistant tuberculosis patients in China : a study protocol of a prospective observational cohort study
- 2018
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Individualised treatment through therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes but is not routinely implemented. Prospective clinical studies of drug exposure and minimum inhibitory concentrations (MICs) in multidrug-resistant TB (MDR-TB) are scarce. This translational study aims to characterise the area under the concentration-time curve of individual MDR-TB drugs, divided by the MIC for Mycobacterium tuberculosis isolates, to explore associations with markers of treatment progress and to develop useful strategies for clinical implementation of TDM in MDR-TB.Methods and analysis: Adult patients with pulmonary MDR-TB treated in Xiamen, China, are included. Plasma samples for measure of drug exposure are obtained at 0, 1, 2, 4, 6, 8 and 10 hours after drug intake at week 2 and at 0, 4 and 6 hours during weeks 4 and 8. Sputum samples for evaluating time to culture positivity and MIC determination are collected at days 0, 2 and 7 and at weeks 2, 4, 8 and 12 after treatment initiation. Disease severity are assessed with a clinical scoring tool (TBscore II) and quality of life evaluated using EQ-5D-5L. Drug concentrations of pyrazinamide, ethambutol, levofloxacin, moxifloxacin, cycloserine, prothionamide and para-aminosalicylate are measured by liquid chromatography tandem-mass spectrometry and the levels of amikacin measured by immunoassay. Dried blood spot on filter paper, to facilitate blood sampling for analysis of drug concentrations, is also evaluated. The MICs of the drugs listed above are determined using custom-made broth microdilution plates and MYCOTB plates with Middlebrook 7H9 media. MIC determination of pyrazinamide is performed in BACTEC MGIT 960.Ethics and dissemination: This study has been approved by the ethical review boards of Karolinska Institutet, Sweden and Fudan University, China. Informed written consent is given by participants. The study results will be submitted to a peer-reviewed journal. Trial registration number NCT02816931; Pre-results.
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| 21. |
- Friberg, Anders, et al.
(författare)
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Cross-cultural aspects of perceptual features in K-pop : A pilot study comparing Chinese and Swedish listeners
- 2017
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Ingår i: 2017 ICMC/EMW - 43rd International Computer Music Conference and the 6th International Electronic Music Week. - : Shanghai Conservatory of Music. - 9780984527465 ; , s. 291-296
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Konferensbidrag (refereegranskat)abstract
- In previous studies it has been shown that perceptual features can be used as an intermediate representation in music processing to model higher-level semantic descriptions. In this pilot study, we focused on the cross-cultural aspect of such perceptual features, by asking both Chinese and Swedish listeners to rate a set of K-Pop samples using a web-based questionnaire. The music samples were selected from a larger set, previously rated in terms of different emotion labels. The selection procedure of the subset was carefully designed to maximize both the variation of emotion and genre. The listeners rated eight perceptual features: dissonance, speed, rhythmic complexity, rhythmic clarity, articulation, harmonic complexity, modality, and pitch. The results indicated a small but significant difference in the two groups, regarding the average speed and rhythmic complexity. In particular the perceived speed of hip hop was different for the two groups. We discuss the overall consistency of the ratings using this methodology in relation to the interface, selection and number of subjects.
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| 22. |
- Golic, Mihaela, et al.
(författare)
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The low risk for early renal damage during lithium treatment has not changed over time
- 2022
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Modern lithium management guidelines were introduced to improve the renal prognosis of lithium patients. Aims: To examine whether prospects for severe renal impairment (defined as chronic kidney disease at least stage 4 (CKD4)), in long-term lithium patients, have changed over time after the introduction of lithium monitoring guidelines. Methods: The time to and hazard for CKD4 were compared between three patient cohorts who started long-term lithium in three consecutive decades: 1980s, 1990s and 2000s. The follow-up time was 10 years after completion of 1-year treatment. The data were collected from Sahlgrenska University Hospital’s laboratory database. Results: In all, 2169 patients were included: 623 in Cohort 1 (started lithium during 1980s), 874 in Cohort 2 (1990s) and 672 in Cohort 3 (2000s). Compliance with lithium monitoring guidelines improved, and mean serum lithium decreased, through the cohorts. In all, 22 patients developed CKD4 during follow-up. The time to CKD4 was the same in all three cohorts (overall: 10.96 years, 95% confidence interval: 10.94–11 years). Age and serum creatinine concentration at start were significant risk factors, while sex had no prognostic value. After adjusting for the significant covariates, there was no statistically significant difference in the hazard for CKD4 between the three cohorts. Conclusion: The risk for severe renal damage during the first decade of long-term lithium is low, but has not changed over time. Our data suggest that improved compliance with lithium guidelines is not reflected in less risk for severe renal damage. © The Author(s) 2022.
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| 23. |
- Juréen, P., et al.
(författare)
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Wild-type MIC distributions for aminoglycoside and cyclic polypeptide antibiotics used for treatment of Mycobacterium tuberculosis infections
- 2010
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Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 48:5, s. 1853-1858
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Tidskriftsartikel (refereegranskat)abstract
- The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type strains is an important but rarely used tool for indicating susceptibility breakpoints against Mycobacterium tuberculosis. In this study, we established wild-type MIC distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin, and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed +/-1 MIC dilution step, and validation of MIC values in Bactec 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin, which currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin- and kanamycin-resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10 mg/liter) but were non-wild type according to the ECOFF (4 mg/liter), suggesting that the critical concentration may be too high. All amikacin- and kanamycin-resistant isolates were clearly below the ECOFF for viomycin, and two of them were below the ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacin-resistant strains. Pharmacodynamic indices (peak serum concentration [Cmax]/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild-type MIC distributions for improving the quality of drug susceptibility testing against Mycobacterium tuberculosis.
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| 24. |
- Kuehlewein, Laura, et al.
(författare)
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Clinical phenotype and course of PDE6A-associated retinitis pigmentosa disease, characterized in preparation for a gene supplementation trial
- 2020
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Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 138:12, s. 1241-1250
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Treatment trials require sound knowledge on the natural course of disease. OBJECTIVE To assess clinical features, genetic findings, and genotype-phenotype correlations in patients with retinitis pigmentosa (RP) associated with biallelic sequence variations in the PDE6A gene in preparation for a gene supplementation trial. DESIGN, SETTING, AND PARTICIPANTS This prospective, longitudinal, observational cohort study was conducted from January 2001 to December 2019 in a single center (Centre for Ophthalmology of the University of Tübingen, Germany) with patients recruited multinationally from 12 collaborating European tertiary referral centers. Patients with retinitis pigmentosa, sequence variants in PDE6A, and the ability to provide informed consent were included. EXPOSURES Comprehensive ophthalmological examinations; validation of compound heterozygosity and biallelism by familial segregation analysis, allelic cloning, or assessment of next-generation sequencing-read data, where possible. MAIN OUTCOMES AND MEASURES Genetic findings and clinical features describing the entire cohort and comparing patients harboring the 2 most common disease-causing variants in a homozygous state (c.304C>A;p.(R102S) and c.998 + 1G>A;p.?). RESULTS Fifty-seven patients (32 female patients [56%]; mean [SD], 40 [14] years) from 44 families were included. All patients completed the study. Thirty patients were homozygous for disease-causing alleles. Twenty-seven patients were heterozygous for 2 different PDE6A variants each. The most frequently observed alleles were c.304C>A;p.(R102S), c.998 + 1G>A;p.?, and c.2053G>A;p.(V685M). The mean (SD) best-corrected visual acuity was 0.43 (0.48) logMAR (Snellen equivalent, 20/50). The median visual field area with object III4e was 660 square degrees (5th and 95th percentiles, 76 and 11 019 square degrees; 25th and 75th percentiles, 255 and 3923 square degrees). Dark-adapted and light-adapted full-field electroretinography showed no responses in 88 of 108 eyes (81.5%). Sixty-nine of 108 eyes (62.9%) showed additional findings on optical coherence tomography imaging (eg, cystoid macular edema or macular atrophy). The variant c.998 + 1G>A;p.? led to a more severe phenotype when compared with the variant c.304C>A;p.(R102S). CONCLUSIONS AND RELEVANCE Seventeen of the PDE6A variants found in these patients appeared to be novel. Regarding the clinical findings, disease was highly symmetrical between the right and left eyes and visual impairment was mild or moderate in 90% of patients, providing a window of opportunity for gene therapy.
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| 25. |
- Nakatani, Yoshio, et al.
(författare)
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Role of Alanine Racemase Mutations in Mycobacterium tuberculosis D-Cycloserine Resistance
- 2017
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Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 61:12
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Tidskriftsartikel (refereegranskat)abstract
- A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to D-cycloserine.
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| 26. |
- Niward, Katarina, et al.
(författare)
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Distribution of plasma concentrations of first-line anti-TB drugs and individual MICs: a prospective cohort study in a low endemic setting
- 2018
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 73:10, s. 2838-2845
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Tidskriftsartikel (refereegranskat)abstract
- Background: Therapeutic drug monitoring (TDM) could improve current TB treatment, but few studies have reported pharmacokinetic data together with MICs. Objectives: To investigate plasma concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol along with MICs. Methods: Drug concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol were analysed pre-dose and 2, 4 and 6 h after drug intake at week 2 in 31 TB patients and MICs in BACTEC 960 MGIT were determined at baseline. The highest plasma concentrations at 2, 4 and 6 h post-dose (C-high) were determined, as well as estimates of C-high/MIC and area under the concentration-time curve (AUC(0-6))/MIC including the corresponding ratios based on calculated free-drug concentrations. This trial was registered at www.clinicaltrials.gov (NCT02042261). Results: After 2 weeks of treatment, the median C-high values for rifampicin, isoniazid, pyrazinamide and ethambutol were 10.0, 5.3, 41.1 and 3.3 mg/L respectively. Lower than recommended drug concentrations were detected in 42% of the patients for rifampicin (amp;lt;8 mg/L), 19% for isoniazid (amp;lt;3 mg/L), 27% for pyrazinamide (amp;lt;35 mg/L) and 16% for ethambutol (amp;lt;2 mg/L). The median Chigh/MIC values for rifampicin, isoniazid, pyrazinamide and ethambutol were 164, 128, 1.3 and 2.5, respectively, whereas the AUC(0-6)/MIC was 636 (range 156-2759) for rifampicin and 351 (range 72-895) for isoniazid. Conclusions: We report low levels of first-line TB drugs in 16%-42% of patients, in particular for rifampicin. There was a wide distribution of the ratios between drug exposures and MICs. The future use of MIC determinations in TDM is dependent on the development of a reference method and clinically validated pharmacokinetic/pharmacodynamic targets.
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| 27. |
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| 28. |
- Rahman, S M Atiqur, 1986-
(författare)
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People living with dementia using eldercare in Sweden
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dementia is a major public health concern. Due to the progressive nature of the disease, people living with dementia (PlwD) may experience challenges at different stages of dementia deriving from functional, cognitive, and communicative disabilities and as a consequence experience restriction in performing everyday tasks. As a result, PlwD have an increasing demand for eldercare (including homecare and residential care), especially during the last years of life. This thesis aims at contributing to the understanding of the utilization of eldercare among older adults with and without dementia aged 65+ in Sweden. Although previous studies on eldercare use largely focused on older adults in general, less attention has been paid to PlwD. Little is also known about the group of PlwD who do not have any eldercare at all and the relationship between the likelihood of having or not having eldercare, the number of years with a dementia diagnosis, and the influence of social demographic factors. In order to be able to offer an integrated life in society for PlwD it is important to understand the structure of care provisions. The objective of this thesis is to investigate (1) what type of eldercare services people with and without dementia aged 65+ use during the last years of life; (2) who the people diagnosed with dementia are that do not use any eldercare at all; and (3) which socio-demographic factors influence the use of eldercare among PlwD. Using multiple health registers, the thesis captured cross-sectional as well as longitudinal data in order to examine the utilization of eldercare among people with and without dementia. The main findings showed that (1) the use of residential care was more common among PlwD compared with those without dementia diagnosis during the last years of life; (2) PlwD with no eldercare were comprised of people in their early stage of dementia, living with partners/married/cohabiting, were more likely men as well as foreign-born; and (3) cohabitation status of PlwD was one of the crucial factors for utilizing eldercare during the last years of life. The thesis identified that a considerable proportion of older adults aged 65+ do not use dementia care even if they have a dementia diagnosis—something that is especially true for people with an older age, women, and living alone. The main argument drawn from this thesis is that not only the diagnosis of dementia but the years living with the diagnosis was the primary predictor for eldercare utilization among older adults aged 65+ years in Sweden. More explorative research is needed about the care needs of PlwD and policy makers must be aware of the need for individualized homecare services for PlwD in order to provide possibilities for a good life quality for PlwD.
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| 29. |
- Ribeiro, Antônio H., et al.
(författare)
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Automatic diagnosis of the 12-lead ECG using a deep neural network
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. Deep Neural Networks (DNNs) are models composed of stacked transformations that learn tasks by examples. This technology has recently achieved striking success in a variety of task and there are great expectations on how it might improve clinical practice. Here we present a DNN model trained in a dataset with more than 2 million labeled exams analyzed by the Telehealth Network of Minas Gerais and collected under the scope of the CODE (Clinical Outcomes in Digital Electrocardiology) study. The DNN outperform cardiology resident medical doctors in recognizing 6 types of abnormalities in 12-lead ECG recordings, with F1 scores above 80% and specificity over 99%. These results indicate ECG analysis based on DNNs, previously studied in a single-lead setup, generalizes well to 12-lead exams, taking the technology closer to the standard clinical practice. The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. In that context, the authors present a Deep Neural Network (DNN) that recognizes different abnormalities in ECG recordings which matches or outperform cardiology and emergency resident medical doctors.
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| 30. |
- Ringborg, A., et al.
(författare)
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Prevalence and incidence of Type 2 diabetes and its complications 1996-2003 : estimates from a Swedish population-based study
- 2008
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 25:10, s. 1178-1186
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Tidskriftsartikel (refereegranskat)abstract
- AIMS To determine the prevalence and incidence of Type 2 diabetes and its complications in Uppsala county, Sweden between 1996 and 2003. METHODS Retrospective population-based study of patients with Type 2 diabetes identified in computerized medical records at 26 county primary care centres. Prevalence and incidence of Type 2 diabetes were estimated in the population aged 30-39, 40-49, 50-59, 60-69, 70-79 and > or = 80 years. Mortality, prevalence and incidence of complications in patients with Type 2 diabetes were determined through linkage to national inpatient, uraemia and cause-of-death registers. RESULTS Crude prevalence of Type 2 diabetes increased from 2.2 to 3.5% between 1996 and 2003. In the population aged > or = 30 years, the age- and sex-adjusted period increase was 53%[odds ratio (OR) 1.53, 95% confidence interval (CI) 1.47-1.58]. Crude population incidence was approximately stable after 1997 (3.7 cases/1000 residents in 1997 compared with 3.8/1000 in 2003). Age- and sex-adjusted mortality rates in Type 2 diabetic patients decreased by 4% per year (OR 0.96, 95% CI 0.94-0.97). Prevalence rates of cardiovascular disease in Type 2 diabetic patients were essentially stable, affecting 13.8% of females and 18.0% of males in 2003. No trend was detected for prevalence of renal failure or incidence of acute myocardial infarction, stroke and amputation. CONCLUSIONS Prevalence of Type 2 diabetes increased in Uppsala county between 1996 and 2003 as a consequence of approximately stable incidence since 1997 and declining mortality. Rates of diabetes-related complications, notably cardiovascular disease, continued to impose a substantial burden.
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| 31. |
- Rudolf, F., et al.
(författare)
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A structured 2-week follow-up visit in the cascade of care for TB increases case detection
- 2024
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D). - 1027-3719 .- 1815-7920. ; 28:3, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Delayed detection in TB due to structural and diagnostic shortcomings is pivotal for disease transmission, morbidity and mortality. We investigated whether an inclusive screening, followed by a structured clinical follow-up (FU) could improve case -finding. METHODS: Patients were recruited from health centres in Bissau, Guinea-Bissau, and Gondar, Ethiopia. A routine FU was done at Week 2. If persisting symptoms were found, patients were investigated using chest X-ray (CXR) and Xpert (R) MTB/RIF, followed by a medical consultation. The main outcome were additional TB patients diagnosed by applying the FU strategy. RESULTS: Of 3,571 adults, 3,285 (95%) were examined at Week 2 FU, where 2,491 (72%) were asymptomatic. Screening patients presenting with cough > 2 weeks alone contributed to the diagnosis of 93 patients (45% of all patients diagnosed here), whereas a TBscore > 3 increased this by 18 (9%); adding a Week 2 FU yielded an additional 94 (46%) patients. Among the 794 (24%) with persisting symptoms, 25 were diagnosed using Xpert and 69 at clinical FU, which constituted 46% (94/205) of the total TB patients diagnosed. CONCLUSION: A Week 2 FU visit, which can be nested into routine healthcare, increased the diagnosis of TB patients by two -fold and avoids diagnostic gaps in the cascade -of -care.
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| 32. |
- Schulman, H., et al.
(författare)
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Sedimentation rate and suPAR in relation to disease activity and mortality in patients with tuberculosis
- 2019
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D). - 1027-3719 .- 1815-7920. ; 23:11, s. 1155-1161
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE : To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in pulmonary tuberculosis (PTB). DESIGN: This was a retrospective analysis of patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification according to the clinical TBscore and treatment outcome were all recorded. RESULTS : In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR (adjusted OR [aOR] 8.24, Pamp;lt; 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore amp;gt;6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P = 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality. CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers needs to be verified in prospective studies.
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| 33. |
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| 34. |
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| 35. |
- Schön, S, et al.
(författare)
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Renal replacement therapy in Sweden.
- 2004
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Ingår i: Scand J Urol Nephrol. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 38:4, s. 332-9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 36. |
- Schön, Thomas, et al.
(författare)
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Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis - A randomised trial
- 2011
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Ingår i: Tuberculosis. - : Elsevier. - 1472-9792 .- 1873-281X. ; 91:5, s. 370-377
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Tidskriftsartikel (refereegranskat)abstract
- In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from Gondar, Ethiopia (n = 180) were randomized to a food supplementation rich in arginine (peanuts, equivalent to 1 g of arginine/day) or with a low arginine content (wheat crackers, locally called daboqolo) during four weeks. The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion, weight gain, sedimentation rate, reduction of cough and chest X-ray improvement as well as levels of NO in urine (uNO) or exhaled air (eNO) at two months. There was no effect of the intervention on the primary outcome (OR 1.44, 95% CI: 0.69-3.0, p = 0.39) or secondary outcomes. In the subgroup analysis according to HIV status, peanut supplemented HIV+/TB patients showed increased cure rate (83.8% (31/37) vs 53.1% (17/32), p andlt; 0.01). A low baseline eNO (andlt; 10 ppb) in HIV+/TB patients was associated with a decreased cure rate. We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect. In the subgroup of HIV positive TB patients, it significantly increased the cure rate and as an additional finding in this subgroup, low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies.
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| 37. |
- Schön, Thomas, 1973-, et al.
(författare)
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Local production of nitric oxide in patients with tuberculosis
- 2004
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 8:9, s. 1134-1137
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO), produced by the inducible nitric oxide synthase (iNOS), is important in host defence against Mycobacterium tuberculosis in rodents, but the presence of high-output NO production in human tuberculosis has been controversial. We investigated iNOS and nitrotyrosine (Ntyr) expression in pleural (n = 7), pulmonary (n = 5) and lymph node biopsies (n = 5) from untreated, newly diagnosed tuberculosis patients. Many iNOS and Ntyr reactive macrophages were observed in granulomas, including Langhans giant cells, indicating high-output NO production at the primary site of disease in tuberculosis.
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| 38. |
- Schön, T., et al.
(författare)
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Wild-type distributions of seven oral second-line drugs against Mycobacterium tuberculosis
- 2011
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 15:4, s. 502-509
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine wild-type minimum inhibitory concentration (MIC) distributions for Mycobacterium tuberculosis, as the background data for defining susceptibility breakpoints are limited. METHODS: We determined wild-type MIC distributions of M. tuberculosis using a 96-stick replicator in Middlebrook 7H10 (7H10) medium for ethionamide (ETH), prothionamide, thiacetazone, cycloserine, rifabutin (RFB), clofazimine and linezolid in consecutive susceptible clinical isolates (n = 78). RESULTS: Tentative epidemiological wild-type cut-offs (ECOFF) were determined for all investigated drugs where World Health Organization recommended critical concentrations for 7H10 are lacking, except for ETH. As the ECOFF was closely related to the non-wild-type strains for ETH and thiacetazone, the use of an intermediary (1) category in drug susceptibility testing could increase reproducibility. The cross-resistance between ETH and isoniazid was 21%. Applying 0.5 mg/l as a breakpoint for RFB classified two non-wild type and rpoB mutated isolates as susceptible for RFB and resistant against rifampicin. CONCLUSIONS: We propose that wild-type MIC distributions should be used as a tool to define clinical breakpoints against second-line drugs. This is increasingly important considering the rapid emergence of drug resistance.
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| 39. |
- Svensson, Maria, et al.
(författare)
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Age at onset of childhood-onset type 1 diabetes and the development of end-stage renal disease: a nationwide population-based study.
- 2006
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Ingår i: Diabetes Care. ; 29:3, s. 538-42
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the impact of age at onset on the development of end-stage renal disease (ESRD) due to diabetic nephropathy in a nationwide population-based cohort with childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: A record linkage between two nationwide registers, the Swedish Childhood Diabetes Registry, including 12,032 cases with childhood-onset diabetes, and the Swedish Registry for Active Treatment of Uraemia was performed. Log-rank test was used to test differences between cumulative risk curves of developing ESRD due to diabetic nephropathy in three different strata of age at onset (0-4, 5-9, and 10-14 years). RESULTS: At a maximum follow-up of 27 years, 33 patients had developed ESRD due to diabetic nephropathy and all had a diabetes duration >15 years. In total, 4,414 patients had diabetes duration >15 years, and thus the risk in this cohort to develop ESRD was 33 of 4,414 (0.7%). A significant difference in risk of developing ESRD was found between the youngest (0-4 years) and the two older (5-9 and 10-14 years) age-at-onset strata (P = 0.03 and P = 0.001, respectively). A significant difference in the risk of developing ESRD was also found between children with prepubertal (0-4 and 5-9 years, n = 2,424) and pubertal (10-14 years, n = 2000) onset of diabetes (P = 0.002). No patient with onset of diabetes before 5 years of age had developed ESRD. CONCLUSIONS: With a median duration of 21 years in this population-based Swedish cohort with childhood-onset diabetes, <1% of the patients had developed ESRD due to diabetic nephropathy, and a prepubertal onset of diabetes seems to prolong the time to development of ESRD.
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| 40. |
- Svensson, Robin J., et al.
(författare)
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Individualised dosing algorithm and personalised treatment of high‐dose rifampicin for tuberculosis
- 2019
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 85:10, s. 2341-2350
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo propose new exposure targets for Bayesian dose optimisation suited for high‐dose rifampicin and to apply them using measured plasma concentrations coupled with a Bayesian forecasting algorithm allowing predictions of future doses, considering rifampicin's auto‐induction, saturable pharmacokinetics and high interoccasion variability.MethodsRifampicin exposure targets for Bayesian dose optimisation were defined based on literature data on safety and anti‐mycobacterial activity in relation to rifampicin's pharmacokinetics i.e. highest plasma concentration up to 24 hours and area under the plasma concentration–time curve up to 24 hours (AUC0–24h). Targets were suggested with and without considering minimum inhibitory concentration (MIC) information. Individual optimal doses were predicted for patients treated with rifampicin (10 mg/kg) using the targets with Bayesian forecasting together with sparse measurements of rifampicin plasma concentrations and baseline rifampicin MIC.ResultsThe suggested exposure target for Bayesian dose optimisation was a steady state AUC0–24h of 181–214 h × mg/L. The observed MICs ranged from 0.016–0.125 mg/L (mode: 0.064 mg/L). The predicted optimal dose in patients using the suggested target ranged from 1200–3000 mg (20–50 mg/kg) with a mode of 1800 mg (30 mg/kg, n = 24). The predicted optimal doses when taking MIC into account were highly dependent on the known technical variability of measured individual MIC and the dose was substantially lower compared to when using the AUC0–24h‐only target.ConclusionsA new up‐to‐date exposure target for Bayesian dose optimisation suited for high‐dose rifampicin was derived. Using measured plasma concentrations coupled with Bayesian forecasting allowed prediction of the future dose whilst accounting for the auto‐induction, saturable pharmacokinetics and high between‐occasion variability of rifampicin.
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| 41. |
- Szummer, Karolina, et al.
(författare)
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Relation between renal function, presentation, use of therapies and in-hospital complications in acute coronary syndrome : data from the SWEDEHEART register
- 2010
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 268:1, s. 40-49
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. Szummer K, Lundman P, Jacobson SH, Schön S, Lindbäck J, Stenestrand U, Wallentin L, Jernberg T, for SWEDEHEART. (Karolinska Institute, Karolinska University Hospital, Stockholm; Karolinska Institute, Danderyd Hospital, Danderyd; Ryhov County Hospital, Jönköping; University Hospital, Uppsala and University Hospital, Linköping; Sweden) Relation between renal function, presentation, use of therapies and in-hospital complications in acute coronary syndrome: data from the SWEDEHEART register. J Intern Med 2009; doi: 10.1111/j.1365-2796.2009.02204.x. Objective. To examine clinical characteristics, presenting symptoms, use of therapy and in-hospital complications in relation to renal function in patients with myocardial infarction (MI). Design. Observational study. Setting. Nationwide coronary care unit registry between 2003-2006 in Sweden. Subjects. Consecutive MI patients with available creatinine (n = 57 477). Results. Glomerular filtration rate was estimated with the Modification of Diet in Renal Disease Study formula. With declining renal function patients were older, had more co-morbidities and more often used cardio-protective medication on admission. Compared to patients with normal renal function, fewer with renal failure presented with chest pain (90% vs. 67%, P < 0.001), Killip I (89% vs. 58%, P < 0.001) and ST-elevation myocardial infarction (STEMI) (41% vs. 22%, P < 0.001). In a logistic regression model lower renal function was independently associated with a less frequent use of anticoagulant and revascularization in non-ST-elevation MI. The likelihood of receiving reperfusion therapy for STEMI was similar in patients with normal-to-moderate renal dysfunction, but decreased in severe renal dysfunction or renal failure. Reperfusion therapy shifted from primary percutaneous coronary intervention in 71% of patients with normal renal function to fibrinolysis in 58% of those with renal failure. Renal function was associated with a higher rate of complications and an exponential increase in in-hospital mortality from 2.5% to 24.2% across the renal function groups. Conclusion. Renal insufficiency influences the presentation and reduces the likelihood of receiving treatment according to current guidelines. Short-term prognosis remains poor.
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| 42. |
- Ängeby, Kristian A., et al.
(författare)
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Wild-type MIC distributions of four fluoroquinolones active against Mycobacterium tuberculosis in relation to current critical concentrations and available pharmacokinetic and pharmacodynamic data
- 2010
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 65:5, s. 946-952
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To describe wild-type distributions of the MIC of fluoroquinolones for Mycobacterium tuberculosis in relation to current critical concentrations used for drug susceptibility testing and pharmacokinetic/pharmacodynamic (PK/PD) data. METHODS: A 96-stick replicator on Middlebrook 7H10 medium was used to define the MICs of ciprofloxacin, ofloxacin, moxifloxacin and levofloxacin for 90 consecutive clinical strains and 24 drug-resistant strains. The MICs were compared with routine BACTEC 460 susceptibility results and with MIC determinations in the BACTEC MGIT 960 system in a subset of strains using ofloxacin as a class representative. PK/PD data for each drug were reviewed in relation to the wild-type MIC distribution. RESULTS: The wild-type MICs of ciprofloxacin, ofloxacin, moxifloxacin and levofloxacin were distributed from 0.125 to 1, 0.25 to 1, 0.032 to 0.5 and 0.125 to 0.5 mg/L, respectively. The MIC data correlated well with the BACTEC 960 MGIT and BACTEC 460 results. PD indices were the most favourable for levofloxacin, followed by moxifloxacin, ofloxacin and ciprofloxacin. CONCLUSIONS: We propose S (susceptible)
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