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- Adeloye, Davies, et al.
(författare)
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Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade
- 2021
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Ingår i: Journal of Global Health. - : International Global Health Society. - 2047-2986 .- 2047-2978. ; 11, s. 15003-15003
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Tidskriftsartikel (refereegranskat)abstract
- Background: The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD. Methods: We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities. Results: 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity. Conclusions: The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.
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- Antti, Henrik, et al.
(författare)
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Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria. Methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) were used and for infecting mice, while natural MSSA infection was studied in humans. Samples of bacterial growth media, the blood of infected mice and of humans were analyzed with combined Gas Chromatography/Mass Spectrometry. Multivariate data analysis was used to reveal the metabolic profiles of infection and the responses to different antibiotic treatments. experiments resulted in the detection of 256 putative metabolites and mice infection experiments resulted in the detection of 474 putative metabolites. Importantly, ineffective and effective antibiotic treatments were differentiated already two hours after treatment start in both experimental systems. That is, the ineffective treatment of MRSA using cloxacillin and untreated controls produced one metabolic profile while all effective treatment combinations using cloxacillin or vancomycin for MSSA or MRSA produced another profile. For further evaluation of the concept, blood samples of humans admitted to intensive care with severe sepsis were analyzed. One hundred thirty-three putative metabolites differentiated severe MSSA sepsis (n = 6) from severe sepsis (n = 10) and identified treatment responses over time. Combined analysis of human, , and mice samples identified 25 metabolites indicative of effective treatment of sepsis. Taken together, this study provides a proof of concept of the utility of analyzing metabolite patterns in blood for early differentiation between ineffective and effective antibiotic treatment in acute infections.
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- Buhl, Roland, et al.
(författare)
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Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4).
- 2015
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 45:4, s. 969-979
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Tidskriftsartikel (refereegranskat)abstract
- Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials. Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment. Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies. Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg. Incidence of adverse events was comparable between the FDCs and the mono-components. These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.
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- Jungebluth, Philipp, et al.
(författare)
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Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite : a proof-of-concept study
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9808, s. 1997-2004
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Tidskriftsartikel (refereegranskat)abstract
- Background Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. Methods A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 mu g/kg) and epoetin beta (40 000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. Findings We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after trans plantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Post-operatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. Interpretation Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome.
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- Watz, Henrik, et al.
(författare)
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Letter to the editor : Indacaterol/glycopyrronium/mometasone furoate compared with salmeterol/fluticasone propionate in patients with asthma: A randomized controlled cross-over study
- 2020
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Indacaterol (IND; 150 μg), glycopyrronium (GLY; 50 μg) and mometasone furoate (MF; 160 μg [high-dose ICS] and 80 μg [medium-dose ICS]) have been formulated as a once-daily (o.d.) fixed-dose combination treatment delivered via the Breezhaler® device for the treatment of patients with asthma. In this randomized (n = 116), double-blind, double-dummy, active comparator-controlled, three-period cross-over study we evaluated the benefit of o.d. IND/GLY/MF versus twice daily (b.i.d.) salmeterol/fluticasone propionate combination (SFC; 50/500 μg; high-dose ICS) treatment (NCT03063086). Overall, 107 patients completed the study. The study met its primary objective by demonstrating superiority of o.d. IND/GLY/MF at medium and high-dose ICS over b.i.d. SFC (high-dose ICS) in peak FEV1 after 21 days of treatment (+ 172 mL with high-dose and + 159 mL with medium-dose IND/GLY/MF versus SFC, p < 0.0001 for each comparison). We also observed that a higher percentage of patients did not need rescue medicine with IND/GLY/MF (high-dose ICS, 58%; medium-dose ICS, 52%) compared with SFC (45%) during the last week of each treatment period. Study treatments were well-tolerated with no relevant differences in tolerability between both IND/GLY/MF doses and SFC. In conclusion, both doses of IND/GLY/MF provided superior lung function benefits compared with twice-daily, standard-of-care SFC at the highest approved dose.
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- Watz, Matilda, et al.
(författare)
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Using group model building to support strategic sustainable development
- 2020
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Ingår i: 38th International Conference of the System Dynamics Society 2020. - : System Dynamics Society. - 9781713820215
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Konferensbidrag (refereegranskat)abstract
- This paper discusses how group model building can be used to support strategic sustainable development. Four cases in which causal loop diagrams and, or, system dynamics have been used are described. In addition, some recent and adjacent research studies are discussed to expand the ideas for future applications. The paper suggests how different means of visualization, that is, qualitative or quantitative modelling can support different levels of strategic sustainability thinking and planning.
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