| 1. |
- Butler, C. C., et al.
(författare)
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Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial
- 2020
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 395:10217, s. 42-52
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Tidskriftsartikel (refereegranskat)abstract
- Background Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. Methods We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. Findings Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1.29, 95% Bayesian credible interval [BCrI] 1.20-1.39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1.13 to 1.72. The estimated absolute mean benefit from oseltamivir was 1.02 days (95% [BCrI] 0.74-1.31) overall, and in the prespecified subgroups, ranged from 0.70 (95% BCrI 0.30-1.20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3.20 (95% BCrI 1.00-5.50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. Interpretation Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 2. |
- Li, X., et al.
(författare)
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Cost-effectiveness of adding oseltamivir to primary care for influenza-like-illness: economic evaluation alongside the randomised controlled ALIC(4)E trial in 15 European countries
- 2023
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Ingår i: European Journal of Health Economics. - : Springer Science and Business Media LLC. - 1618-7598 .- 1618-7601. ; 24:6, s. 909-922
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Tidskriftsartikel (refereegranskat)abstract
- Background Oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries. Methods Direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers' and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed. Results The healthcare payers' expected ICERs of oseltamivir were euro22,459 per QALY gained in adults/adolescents and euro13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is euro8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged euro1-euro35 per patient). Conclusion Adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers' perspective (if willingness-to-pay per QALY gained > euro22,459) and cost-saving in adults/adolescents from a societal perspective.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Ouchi, D., et al.
(författare)
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Clinical prediction of laboratory-confirmed influenza in adults with influenza-like illness in primary care. A randomized controlled trial secondary analysis in 15 European countries
- 2022
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Ingår i: Family Practice. - : Oxford University Press (OUP). - 0263-2136 .- 1460-2229. ; 39:3, s. 398-405
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Tidskriftsartikel (refereegranskat)abstract
- Lay Summary Influenza is usually diagnosed clinically. However, the accuracy of a diagnosis of influenza based on clinical features is limited because symptoms overlap considerably with those caused by other microorganisms. This study examined whether identification of the severity rather than the presence of key signs and symptoms could aid in the diagnosis of influenza, thereby helping clinicians to determine when antiviral agent use is appropriate. The authors used the database of a previous randomized clinical trial on the effectiveness of an antiviral carried out in primary care centers in 15 countries in Europe during three epidemic periods from 2015/2016 to 2017/2018. Participants with influenza symptoms were included and they were asked about the presence and severity of different symptoms during the baseline visit with their doctors and a nasopharyngeal swab was taken for microbiological analysis. Overall, only 51% of the patients aged 18 or older had a confirmed influenza infection. Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza. However, the results of our study recommend considering how intense the different symptoms are, since key symptoms rated as moderate or severe are slightly better for predicting flu rather than the presence or absence of these symptoms. Background Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. Objective We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. Methods Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. Results A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 +/- 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). Conclusion Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.
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| 8. |
- Verheij, T. J., et al.
(författare)
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Clinical presentation, microbiological aetiology and disease course in patients with flu-like illness: A post hoc analysis of randomised controlled trial data
- 2022
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Ingår i: British Journal of General Practice. - 0960-1643. ; 72:716
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Tidskriftsartikel (refereegranskat)abstract
- Background There is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections. Aim To investigate whether clinical presentation and illness course differ between RTIs where a viral pathogen was detected and those where a potential bacterial pathogen was found. Design and setting Post hoc analysis of data from a pragmatic randomised trial on the effects of oseltamivir in patients with flu-like illness in primary care (n = 3266) in 15 European countries. Method Patient characteristics and their signs and symptoms of disease were registered at baseline. Nasopharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for polymerase chain reaction analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relationship between aetiology, clinical presentation at baseline, and course of disease including complications. Results Except for a less prominent congested nose (odds ratio [OR] 0.55, 95% confidence interval [CI] = 0.35 to 0.86) and acute cough (OR 0.42, 95% CI = 0.27 to 0.65) in patients with flu-like illness in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology compared with those with a viral aetiology. Also, course of disease and complications were not related to aetiology. Conclusion Given current available microbiological tests and antimicrobial treatments, and outside pandemics such as COVID-19, microbiological testing in primary care patients with flu-like illness seems to have limited value. A wait-andsee policy in most of these patients with flu-like illness seems the best option. © 2022 Royal College of General Practitioners. All rights reserved.
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| 9. |
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| 10. |
- Bongard, E., et al.
(författare)
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Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC(4) E): the ALIC(4) E protocol
- 2018
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. Methods and analysis Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5days. We aim to recruit at least 2500 participants 1year presenting with influenza-like illness (ILI), with symptom duration 72hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12-64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (48hours/>48-72hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. Ethics and dissemination Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations.
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| 11. |
- Buena-Atienza, E, et al.
(författare)
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De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28253-
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Tidskriftsartikel (refereegranskat)abstract
- X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. ‘LIAVA’, ‘LVAVA’) with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the ‘LIAVA’ haplotype derived from an ancestral less deleterious ‘LIAVS’ haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.
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| 12. |
- Hartman, E. A. R., et al.
(författare)
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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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Ingår i: Age and ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 51:6
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Tidskriftsartikel (refereegranskat)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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| 13. |
- Hartman, E. A. R., et al.
(författare)
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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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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 11:10
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Tidskriftsartikel (refereegranskat)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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| 14. |
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| 15. |
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| 16. |
- Alberts, R, et al.
(författare)
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Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:8, s. 1517-1524
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes.ResultsWe identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10–9). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells.ConclusionWe present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.
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| 17. |
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| 18. |
- Bezemer, Geert, et al.
(författare)
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Long-term effects of treatment and response in patients with chronic hepatitis C on quality of life
- 2012
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Ingår i: BMC Gastroenterology. - 1471-230X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Hepatitis C decreases health related quality of life (HRQL) which is further diminished by antiviral therapy. HRQL improves after successful treatment. This trial explores the course of and factors associated with HRQL in patients given individualized or standard treatment based on early treatment response (Ditto-study). Methods The Short Form (SF)-36 Health Survey was administered at baseline (n = 192) and 24 weeks after the end of therapy (n = 128). Results At baseline HRQL was influenced by age, participating center, severity of liver disease and income. Exploring the course of HRQL (scores at follow up minus baseline), only the dimension general health increased. In this dimension patients with a relapse or sustained response differed from non-responders. Men and women differed in the dimension bodily pain. Treatment schedule did not influence the course of HRQL. Conclusions Main determinants of HRQL were severity of liver disease, age, gender, participating center and response to treatment. Our results do not exclude a more profound negative impact of individualized treatment compared to standard, possibly caused by higher doses and extended treatment duration in the individualized group. Antiviral therapy might have a more intense and more prolonged negative impact on females.
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| 19. |
- Davidov, Eugene, et al.
(författare)
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Methods for the differential integrative omic analysis of plasma from a transgenic disease animal model
- 2004
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Ingår i: Omics. - : Mary Ann Liebert. - 1536-2310 .- 1557-8100. ; 8:4, s. 267-288
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Tidskriftsartikel (refereegranskat)abstract
- Multitiered quantitative analysis of biological systems is rapidly becoming the desired approach to study hierarchical functional interactions between proteins and metabolites. We describe here a novel systematic approach to analyze organisms with complex metabolic regulatory networks. By using precise analytical methods to measure biochemical constituents and their relative abundance in whole plasma of transgenic ApoE*3-Leiden mice and an isogenic wild-type control group, simultaneous snapshots of metabolic and protein states were obtained. Novel data processing and multivariate analysis tools such as Impurity Resolution Software (IMPRESS) and Windows-based linear fit program (WINLIN) were used to compare protein and metabolic profiles in parallel. Canonical correlations of the resulting data show quantitative relationships between heterogeneous components in the TG animals. These results, obtained solely from whole plasma analysis allowed us, in a rapid manner, to corroborate previous findings as well as find new events pertaining to dominant and peripheral events in lipoprotein metabolism of a genetically modified mammalian organism in relation to ApoE3, a key mediator of lipoprotein metabolism.
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| 20. |
- Dittrich, Christian, et al.
(författare)
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ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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| 21. |
- Gunnarsson, Ronny K, 1955, et al.
(författare)
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Best management of patients with an acute sore throat - a critical analysis of current evidence and a consensus of experts from different countries and traditions
- 2023
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 55:6, s. 384-395
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThere is a very large body of publications discussing the management of patients with an acute sore throat. Advocates for a restrictive antibiotic policy and advocates for a more liberal use of antibiotics emphasise different and valid arguments and to date have not been able to unite in a consensus. Contradicting guidelines based on the same body of knowledge is not logical, may cause confusion and cause unwanted variation in clinical management.MethodsIn multiple video meetings and email correspondence from March to November 2022 and finally in a workshop at the annual meeting for the North American Primary Care Group in November 2022, experts from different countries representing different traditions agreed on how the current evidence should be interpreted.ResultsThis critical analysis identifies that the problem can be resolved by introducing a new triage scheme considering both the acute risk for suppurative complications and sepsis as well as the long-term risk of developing rheumatic fever.ConclusionsThe new triage scheme may solve the long-standing problem of advocating for a restrictive use of antibiotics while also satisfying concerns that critically ill patients might be missed with severe consequences. We acknowledge that the perspective of this problem is vastly different between high- and low-income countries. Furthermore, we discuss the new trend which allows nurses and pharmacists to independently manage these patients and the increased need for safety netting required for such management.
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| 22. |
- Harbin, N. J., et al.
(författare)
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Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis
- 2021
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 39:4, s. 527-532
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Tidskriftsartikel (refereegranskat)abstract
- Objective Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of >= 30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. Design Secondary analysis of randomized controlled trial data. Setting Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016-2018. Subjects A total of 277 ILI patients aged one year or older and symptom duration of <= 72 h. Main outcome measures Capillary blood CRP concentration at baseline, and ILI recovery time defined as having 'returned to usual daily activity' with residual symptoms minimally interfering. Results At baseline, 20% (55/277) had CRP concentrations >= 30mg/L (range 0-210). CRP concentration >= 30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50-1.3; p = 0.33). Interaction analysis of CRP concentration >= 30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37-1.3; p = 0.23). Conclusion There was no association between CRP concentration of >= 30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.
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| 23. |
- Hartman, Esther A R, et al.
(författare)
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Effect of a multifaceted antibiotic stewardship intervention to improve antibiotic prescribing for suspected urinary tract infections in frail older adults (ImpresU): pragmatic cluster randomised controlled trial in four European countries.
- 2023
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 0959-535X .- 1756-1833. ; 380
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate whether antibiotic prescribing for suspected urinary tract infections in frail older adults can be reduced through a multifaceted antibiotic stewardship intervention.Pragmatic, parallel, cluster randomised controlled trial, with a five month baseline period and a seven month follow-up period.38 clusters consisting of one or more general practices (n=43) and older adult care organisations (n=43) in Poland, the Netherlands, Norway, and Sweden, from September 2019 to June 2021.1041 frail older adults aged 70 or older (Poland 325, the Netherlands 233, Norway 276, Sweden 207), contributing 411 person years to the follow-up period.Healthcare professionals received a multifaceted antibiotic stewardship intervention consisting of a decision tool for appropriate antibiotic use, supported by a toolbox with educational materials. A participatory-action-research approach was used for implementation, with sessions for education, evaluation, and local tailoring of the intervention. The control group provided care as usual.The primary outcome was the number of antibiotic prescriptions for suspected urinary tract infections per person year. Secondary outcomes included the incidence of complications, all cause hospital referrals, all cause hospital admissions, all cause mortality within 21 days after suspected urinary tract infections, and all cause mortality.The numbers of antibiotic prescriptions for suspected urinary tract infections in the follow-up period were 54 prescriptions in 202 person years (0.27 per person year) in the intervention group and 121 prescriptions in 209 person years (0.58 per person year) in the usual care group. Participants in the intervention group had a lower rate of receiving an antibiotic prescription for a suspected urinary tract infection compared with participants in the usual care group, with a rate ratio of 0.42 (95% confidence interval 0.26 to 0.68). No differences between intervention and control group were observed in the incidence of complications (<0.01 v 0.05 per person year), hospital referrals (<0.01 v 0.05), admissions to hospital (0.01 v 0.05), and mortality (0 v 0.01) within 21 days after suspected urinary tract infections, nor in all cause mortality (0.26 v 0.26).Implementation of a multifaceted antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infections in frail older adults.ClinicalTrials.gov NCT03970356.
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| 24. |
- Jonsson, Pär, et al.
(författare)
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A strategy for modelling dynamic responses in metabolic samples characterized by GC/MS
- 2006
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Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 2:3, s. 135-143
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Tidskriftsartikel (refereegranskat)abstract
- A multivariate strategy for studying the metabolic response over time in urinary GC/MS data is presented and exemplified by a study of drug-induced liver toxicity in the rat. The strategy includes the generation of representative data through hierarchical multivariate curve resolution (H-MCR), highlighting the importance of obtaining resolved metabolite profiles for quantification and identification of exogenous (drug related) and endogenous compounds (potential biomarkers) and for allowing reliable comparisons of multiple samples through multivariate projections. Batch modelling was used to monitor and characterize the normal (control) metabolic variation over time as well as to map the dynamic response of the drug treated animals in relation to the control. In this way treatment related metabolic responses over time could be detected and classified as being drug related or being potential biomarkers. In summary the proposed strategy uses the relatively high sensitivity and reproducibility of GC/MS in combination with efficient multivariate curve resolution and data analysis to discover individual markers of drug metabolism and drug toxicity. The presented results imply that the strategy can be of great value in drug toxicity studies for classifying metabolic markers in relation to their dynamic responses as well as for biomarker identification.
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| 25. |
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| 26. |
- Kirwan, Gemma M, et al.
(författare)
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Building Multivariate Systems Biology Models
- 2012
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Ingår i: Analytical Chemistry. - Washington : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 84:16, s. 7064-7071
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Tidskriftsartikel (refereegranskat)abstract
- Systems biology methods using large-scale "omics" data sets face unique challenges: integrating and analyzing near limitless data space, while recognizing and removing systematic variation or noise. Herein we propose a complementary multivariate analysis workflow to both integrate "omics" data from disparate sources and analyze the results for specific and unique sample correlations. This workflow combines principal component analysis (PCA), orthogonal projections to latent structures discriminate analysis (OPLS-DA), orthogonal 2 projections to latent structures (O2PLS), and shared and unique structures (SUS) plots. The workflow is demonstrated using data from a study in which ApoE3Leiden mice were fed an atherogenic diet consisting of increasing cholesterol levels followed by therapeutic intervention (fenofibrate, rosuvastatin, and LXR activator T-0901317). The levels of structural lipids (lipidomics) and free fatty acids in liver were quantified via liquid chromatography-mass spectrometry (LC-MS). The complementary workflow identified diglycerides as key hepatic metabolites affected by dietary cholesterol and drug intervention. Modeling of the three therapeutics for mice fed a high-cholesterol diet further highlighted diglycerides as metabolites of interest in atherogenesis, suggesting a role in eliciting chronic liver inflammation. In particular, O2PLS-based SUS2 plots showed that treatment with T-0901317 or rosuvastatin returned the diglyceride profile in high-cholesterol-fed mice to that of control animals.
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| 27. |
- Lindh, Christina, et al.
(författare)
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Quantitative analysis of the tradigraphic trabecular pattern as a predictor for BMD-values : the OSTEODENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: To determine the diagnostic validity of computer aided analysis of the radiographic trabecular pattern as a predictor of BMD-values of peri- and post-menopausal women to support the diagnosis of osteoporosis. Methods: Panoramic and intra-oral radiographs were obtained from volunteer female subjects in the 45 to 70 year age band, recruited from four European centres. These volunteers also underwent dual x-ray energy absorptiometry (DXA) of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis. A computer aided analysis of the radiographic trabecular pattern was performed on the radiographs in relevant regions of interest, and used to predict the BMD values of hip and spine by multiple regression techniques. Results: Data of 525 subjects (mean age 54.6 y; sd = 6.0 y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. The most suitable ROIs for the panoramic images were in the mandibular premolar region and in the ramus. For the intra-oral radiographs (upper- and lower jaw) an area in between the first and second premolar was chosen. Including age as a parameter improved the results. Az values are given below: ROI BMD-hip BMD-spine panoramic radiograph 0.65 0.71 panoramic radiograph + age 0.77 0.79 intra-oral radiograph 0.71 0.73 intra-oral radiograph + age 0.79 0.82 panoramic + intraoral radiographs 0.72 0.75 panoramic + intraoral radiographs + age 0.80 0.84 Conclusions: Quantitative analysis of the radiographic trabecular pattern together with the age of the patient is a promising parameter for the prediction of BMD values as an indicator of osteoporosis. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 30. |
- Stoop, Thomas F., et al.
(författare)
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Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy
- 2024
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection.Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
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| 32. |
- Van Olden, C. C., et al.
(författare)
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A systems biology approach to understand gut microbiota and host metabolism in morbid obesity: design of the BARIA Longitudinal Cohort Study
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 289:3, s. 340-354
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples. Methods The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years. Results Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra-individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference. Conclusion The BARIA study can add more understanding in how gut-microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity-associated disease epidemic.
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| 33. |
- van Schalkwijk, D. B., et al.
(författare)
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Dietary Medium Chain Fatty Acid Supplementation Leads to Reduced VLDL Lipolysis and Uptake Rates in Comparison to Linoleic Acid Supplementation
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51 +/- 7 years; BMI 28.5 +/- 0.8 kg/m(2)), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a washout period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates.
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