| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Hellings, P. W., et al.
(författare)
-
EUFOREA summit in Brussels 2023 : inspiring the future of allergy & respiratory care
- 2023
-
Ingår i: Frontiers in Allergy. - 2673-6101. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.
|
|
| 7. |
- Bunck, M. C., et al.
(författare)
-
One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial
- 2009
-
Ingår i: Diabetes Care. - 1935-5548. ; 32:5, s. 762-8
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Traditional blood glucose-lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients. Preclinical studies with exenatide have suggested sustained improvements in beta-cell function. We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp-derived measures of beta-cell function, glycemic control, and body weight. RESEARCH DESIGN AND METHODS: Sixty-nine metformin-treated patients with type 2 diabetes were randomly assigned to exenatide (n = 36) or insulin glargine (n = 33). beta-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0, at week 52, and after a 4-week off-drug period. Additional end points included effects on glycemic control, body weight, and safety. RESULTS: Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold (95% CI 2.09-2.90, P < 0.0001) greater after a 52-week exenatide treatment compared with insulin glargine treatment. Both exenatide and insulin glargine reduced A1C similarly: -0.8 +/- 0.1 and -0.7 +/- 0.2%, respectively (P = 0.55). Exenatide reduced body weight compared with insulin glargine (difference -4.6 kg, P < 0.0001). beta-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy. CONCLUSIONS: Exenatide significantly improves beta-cell function during 1 year of treatment compared with titrated insulin glargine. After cessation of both exenatide and insulin glargine therapy, beta-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.
|
|
| 8. |
- Bunck, M. C., et al.
(författare)
-
Exenatide treatment did not affect bone mineral density despite body weight reduction in patients with type 2 diabetes
- 2011
-
Ingår i: Diabetes, obesity & metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 13:4, s. 374-377
-
Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies suggest that incretin-based therapies may be beneficial for the bone; however, clinical data are largely lacking. We assessed whether the differential effects of these therapies on body weight differed with respect to their effect on bone mineral density (BMD) and markers of calcium homeostasis in patients with type 2 diabetes (T2D). Sixty-nine metformin-treated patients with T2D were randomized to exenatide twice daily (n = 36) or insulin glargine once daily (n = 33). Total body BMD, measured by dual-energy X-ray absorptiometry, and serum markers of calcium homeostasis were assessed before and after 44-week treatment. Exenatide or insulin glargine treatment decreased body weight by 6%. Endpoint BMD was similar in both groups after 44-week therapy (LSmean +/- s.e.m. between-group difference -0.002 +/- 0.007 g/cm(2) ; p = 0.782). Fasting serum alkaline phosphatase, calcium and phosphate remained unaffected. Forty-four-week treatment with exenatide or insulin glargine had no adverse effects on bone density in patients with T2D, despite differential effects on body weight.
|
|
| 9. |
- Kortekaas Krohn, I., et al.
(författare)
-
Emerging roles of innate lymphoid cells in inflammatory diseases : Clinical implications
- 2018
-
Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 73:4, s. 837-850
-
Forskningsöversikt (refereegranskat)abstract
- Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.
|
|
| 10. |
- Lahrouchi, Najim, et al.
(författare)
-
Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome
- 2020
-
Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 142:4, s. 324-338
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
|
|
| 11. |
- Mathioudakis, Alexander G., et al.
(författare)
-
Research Priorities in Pediatric Asthma : Results of a Global Survey of Multiple Stakeholder Groups by the Pediatric Asthma in Real Life (PeARL) Think Tank
- 2020
-
Ingår i: Journal of Allergy and Clinical Immunology: In Practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 8:6, s. 9-1960
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pediatric asthma remains a public health challenge with enormous impact worldwide. Objective: The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, which could be used to guide future research and policy activities. Methods: We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers, and the pharmaceutical industry). Differences across responder groups were compared. Results: A total of 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, clinical phenotypes, the children's age, and demographics were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma, and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions that highlight the importance of involving the whole range of stakeholders in formulation of recommendations. Conclusions: Different stakeholders agree in the majority of research and strategic (eg, prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider.
|
|
| 12. |
- Mathioudakis, AG, et al.
(författare)
-
Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank
- 2021
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:7, s. e048338-
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.Methods and analysisStandard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.Ethics and disseminationEthics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.PROSPERO registration numbersCRD42020132990, CRD42020171624.
|
|
| 13. |
- Roth-Walter, F., et al.
(författare)
-
Metabolic pathways in immune senescence and inflammaging : Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology
-
Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - 0105-4538.
-
Tidskriftsartikel (refereegranskat)abstract
- The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.
|
|
| 14. |
- Scadding, G. K., et al.
(författare)
-
Pre-asthma : a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1—allergic asthma
- 2023
-
Ingår i: Frontiers in Allergy. - 2673-6101. ; 4
-
Forskningsöversikt (refereegranskat)abstract
- Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.
|
|
| 15. |
- 't Hart, Leen M., et al.
(författare)
-
The CTRB1/2 Locus Affects Diabetes Susceptibility and Treatment via the Incretin Pathway
- 2013
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:9, s. 3275-3281
-
Tidskriftsartikel (refereegranskat)abstract
- The incretin hormone glucagon-like peptide 1 (GLP-1) promotes glucose homeostasis and enhances -cell function. GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which inhibit the physiological inactivation of endogenous GLP-1, are used for the treatment of type 2 diabetes. Using the Metabochip, we identified three novel genetic loci with large effects (30-40%) on GLP-1-stimulated insulin secretion during hyperglycemic clamps in nondiabetic Caucasian individuals (TMEM114; CHST3 and CTRB1/2; n = 232; all P 8.8 x 10(-7)). rs7202877 near CTRB1/2, a known diabetes risk locus, also associated with an absolute 0.51 +/- 0.16% (5.6 +/- 1.7 mmol/mol) lower A1C response to DPP-4 inhibitor treatment in G-allele carriers, but there was no effect on GLP-1 RA treatment in type 2 diabetic patients (n = 527). Furthermore, in pancreatic tissue, we show that rs7202877 acts as expression quantitative trait locus for CTRB1 and CTRB2, encoding chymotrypsinogen, and increases fecal chymotrypsin activity in healthy carriers. Chymotrypsin is one of the most abundant digestive enzymes in the gut where it cleaves food proteins into smaller peptide fragments. Our data identify chymotrypsin in the regulation of the incretin pathway, development of diabetes, and response to DPP-4 inhibitor treatment.
|
|
| 16. |
- Blaak, E E, et al.
(författare)
-
Impact of postprandial glycaemia on health and prevention of disease.
- 2012
-
Ingår i: Obesity Reviews. - 1467-7881. ; 13:10, s. 923-984
-
Tidskriftsartikel (refereegranskat)abstract
- Postprandial glucose, together with related hyperinsulinemia and lipidaemia, has been implicated in the development of chronic metabolic diseases like obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In this review, available evidence is discussed on postprandial glucose in relation to body weight control, the development of oxidative stress, T2DM, and CVD and in maintaining optimal exercise and cognitive performance. There is mechanistic evidence linking postprandial glycaemia or glycaemic variability to the development of these conditions or in the impairment in cognitive and exercise perfomance. Nevertheless, postprandial glycaemia is interrelated with many other (risk) factors as well as to fasting glucose. In many studies, meal-related glycaemic response is not sufficiently characterized, or the methodology with respect to the description of food or meal composition, or the duration of the measurement of postprandial glycaemia is limited. It is evident that more randomized controlled dietary intervention trials using effective low vs. high glucose response diets are necessary in order to draw more definite conclusions on the role of postprandial glycaemia in relation to health and disease. Also of importance is the evaluation of the potential role of the time course of postprandial glycaemia.
|
|
| 17. |
- Bunck, M. C., et al.
(författare)
-
Exenatide affected circulating cardiovascular risk biomarkers independently of changes in body composition
- 2010
-
Ingår i: Diabetes Care. - 0149-5992. ; 33:8, s. 1734-1737
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To study the effect of exenatide on body composition and circulating cardiovascular risk biomarkers. RESEARCH DESIGN AND METHODS Metformin-treated patients with type 2 diabetes (N = 69) were randomized to exenatide or insulin glargine and treated for 1 year. Body composition was evaluated by dual-energy X-ray absorptiometry. Additionally, body weight, waist circumference, and cardiovascular biomarkers were measured. RESULTS Treatment with exenatide for 1 year significantly reduced body weight, waist circumference, and total body and trunkal fat mass by 6, 5, 11, and 13%, respectively. In addition, exenatide increased total adiponectin by 12% and reduced high-sensitivity C-reactive protein by 61%. Insulin glargine significantly reduced endothelin-1 by 7%. These changes were statistically independent of the change in total body fat mass and body weight. CONCLUSIONS Exenatide treatment for 1 year reduced body fat mass and improved the profile of circulating biomarkers of cardiovascular risk. No significant changes were seen with insulin glargine except a trend for reduced endothelin-1 levels.
|
|
| 18. |
- Diamant, S. J.M., et al.
(författare)
-
Discovery of an extended G giant chromosphere in the 2019 eclipse of γ Per
- 2023
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 674
-
Tidskriftsartikel (refereegranskat)abstract
- The November 2019 eclipse of γ Per was a rare opportunity to seek evidence for a chromosphere of the G8 giant, hitherto suspected but not detected. Twenty-nine years after the only other observed eclipse, we aim to find chromospheric absorption in the strong Caa II H&K lines, and to determine its column densities and scale height. Using the Telescopio Internacional de Guanajuato Robótico-Espectroscópico (TIGRE) in Guanajuato (central Mexico) before, during and after the 8 days of total eclipse, we obtained good S/N spectra of the G8 giant alone and composite spectra of the partial phases, near eclipse and far from eclipse. In the near UV of the Caa II H&K and HÏμ lines, the G giant spectrum that was adequately scaled was subtracted from the composite spectra in partial phases, near and far from eclipse, to obtain the A3 companion spectra with and without traces of chromospheric absorption. In addition, we used PHOENIX full non-local thermodynamic equilibrium model atmospheres on the blue A star spectrum, iSpec spectral analysis of the red G giant spectrum, and evolution tracks to study both components of γ Per. For the first time, we present evidence for this rare type of a not very extended G giant chromosphere, reaching out about half of an A-star radius (~1.5 Gm) with a scale height of only 0.17 Gm. By its location in the Hertzsprung-Russell diagram, the γ Per G8 giant is very close to the onset of more extended chromospheres. Furthermore, we show that this giant has a rather inactive chromosphere, and a recent 5 ksec XMM pointing reveals only a very faint, low-energy corona. While the γ Per primary has a mass of ~3.6 M', and its A3 companion has one of ~2.4 M', the latter is too cool (8400 ± 300 K), which is too evolved on the main sequence to be the same age as the primary. The high eccentricity of the 5329.08 days long-period orbit may therefore be reminiscent of a rare capture event. Using the eclipse method, we resolve a pivotal case of a G giant chromosphere, which seems to represent a low-gravity analogue of the inactive Sun. A systematic change of giant chromospheric extent by Hertzsprung-Russell diagram position is confirmed. Compared to the solar chromosphere, the density scale height increases with gravity by É¡'1.5.
|
|
| 19. |
- Kersten, Elin T G, et al.
(författare)
-
Can a single dose response predict the effect of montelukast on exercise-induced bronchoconstriction?
- 2015
-
Ingår i: Pediatric Pulmonology. - : Wiley. - 8755-6863.
-
Tidskriftsartikel (refereegranskat)abstract
- Exercise-induced bronchoconstriction (EIB) can be prevented by a single dose of montelukast (MLK). The effect is variable, similar to the variable responsiveness observed after daily treatment with MLK. We hypothesized that the effect of a single MLK-dose (5 or 10 mg) on EIB could predict the clinical effectiveness of longer term once daily treatment.
|
|
| 20. |
- Muskiet, M H A, et al.
(författare)
-
Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial.
- 2019
-
Ingår i: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 153, s. 14-22
-
Tidskriftsartikel (refereegranskat)abstract
- To compare the effects of long-term treatment with the GLP-1RA exenatide twice-daily versus titrated insulin glargine (iGlar) on renal function and albuminuria in type 2 diabetes (T2DM) patients.We post-hoc evaluated renal outcome-data of 54 overweight T2DM patients (mean ±SD age 60±8years, HbA1c 7.5±0.9%, eGFR 86±16mL/min/1.73m2, median [IQR] urinary albumin-to-creatinine-ratio (UACR) 0.75 [0.44-1.29]mg/mmol) randomised to exenatide 10µg twice-daily or titrated iGlar on-top-of metformin for 52-weeks. Renal efficacy endpoints were change in creatinine clearance (CrCl) and albuminuria (urinary albumin-excretion [UAE] and UACR) based on 24-h urines, collected at baseline and Week-52. eGFR and exploratory endpoints were collected throughout the intervention-period, and after a 4-week wash-out.HbA1c-reductions were similar with exenatide (mean±SEM -0.80±0.10%) and iGlar (-0.79±0.14%; treatment-difference 0.02%; 95% CI -0.31 to 0.42%). Change from baseline to Week-52 in CrCl, UAE or UACR did not statistically differ; only iGlar reduced albuminuria (P<0.05; within-group). eGFR decreased from baseline to Week-4 with exenatide (-3.9±2.1mL/min/1.73m2; P=0.069) and iGlar (-2.7±1.2mL/min/1.73m2; P=0.034), without treatment-differences in ensuing trajectory. Exenatide versus iGlar reduced bodyweight (-5.4kg; 2.9-7.9; P<0.001), but did not affect blood pressure, lipids or plasma uric acid.Among T2DM patients without overt nephropathy, one-year treatment with exenatide twice-daily does not affect renal function-decline or onset/progression of albuminuria compared to titrated iGlar.ClinicalTrials.gov ID: NCT00097500.
|
|
| 21. |
|
|
| 22. |
- Diamant, Zuzana, et al.
(författare)
-
Inhaled allergen bronchoprovocation tests.
- 2013
-
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 132:5, s. 1045-1045
-
Tidskriftsartikel (refereegranskat)abstract
- The allergen bronchoprovocation test is a long-standing exacerbation model of allergic asthma that can induce several clinical and pathophysiologic features of asthma in sensitized subjects. Standardized allergen challenge is primarily a research tool, and when properly conducted by qualified and experienced investigators, it is safe and highly reproducible. In combination with validated airway sampling and sensitive detection techniques, allergen challenge allows the study of several features of the physiology of mainly TH2 cell-driven asthma in relation to the kinetics of the underlying airway pathology occurring during the allergen-induced late response. Furthermore, given the small within-subject variability in allergen-induced airway responses, allergen challenge offers an adequate disease model for the evaluation of new (targeted) controller therapies for asthma in a limited number of subjects. In proof-of-efficacy studies thus far, allergen challenge showed a fair positive predicted value and an excellent negative predictive value for the actual clinical efficacy of new antiasthma therapies, underscoring its important role in early drug development. In this review we provide recommendations on challenge methods, response measurements, sample size, safety, and harmonization for future applications.
|
|
| 23. |
- Eliasson, Björn, 1959, et al.
(författare)
-
Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study.
- 2012
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 55:4, s. 915-925
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Pharmacological augmentation of glucagon-like peptide 1 receptor signalling by dipeptidyl peptidase 4 (DPP-4) inhibition reduced intestinal lipoprotein secretion in experimental studies, suggesting that DPP-4 inhibitors may ameliorate dyslipidaemia and thus reduce cardiovascular risk in patients with type 2 diabetes. We assessed the effects of alogliptin (Alo) and Alo co-administered with pioglitazone (Pio) vs placebo (Pbo) on triacylglycerol (TG)-rich lipoproteins in type 2 diabetes before and following a high-fat meal. METHODS: Seventy-one patients (age 18-70years), who did not reach HbA(1c) 6.5% (48mmol/mol) with lifestyle and/or metformin, sulfonylurea or glinide therapy, participated in this 16week, double-centre (university hospitals) Pbo-controlled parallel-group study. All participants, people doing measurements or examinations, and people assessing the outcomes were blinded to group assignment. Fasting TG 1.7-5.0mmol/l was among the entry criteria. Patients received a high-fat mixed meal before and 4 and 16weeks after randomisation (allocation by central office) to Alo (n=25), Alo/Pio (n=22) or Pbo (n=24). Blood was sampled at pre-specified intervals, starting at 15min before and ending 8h after meal ingestion. RESULTS: At week 16, Alo (n=25) and Alo/Pio (n=21) vs Pbo (n=24) produced similar significant reductions in total postprandial TG response (incremental AUC [iAUC]; p<0.001), as well as in chylomicron TG (p<0.001) and VLDL1 TG iAUCs (p<0.001 and p=0.012, respectively). Postprandial chylomicron apolipoprotein B-48 iAUC showed a significant decrease after Alo treatment (p=0.028), and a non-significant trend towards a decrease with Alo/Pio (p=0.213). The incidence of adverse events was low and consistent with previous studies. CONCLUSIONS/INTERPRETATION: Treatment with Alo and Alo/Pio produced significant reductions in postprandial TG and TG-rich lipoproteins, contributing to an improved overall cardiometabolic risk profile in type 2 diabetes. The data support the concept that incretins not only modulate glucose metabolism but also influence chylomicron metabolism in intestinal cells. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00655863. FUNDING: The study was funded by Takeda Global Research & Development.
|
|
| 24. |
|
|
| 25. |
- Khatri, Sumita B., et al.
(författare)
-
Use of fractional exhaled nitric oxide to guide the treatment of asthma an official american thoracic society clinical practice guideline
- 2021
-
Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 204:10, s. 97-109
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidencebased answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence.
|
|
| 26. |
- Roth-Walter, Franziska, et al.
(författare)
-
Comparing biologicals and small molecule drug therapies for chronic respiratory diseases : An EAACI Taskforce on Immunopharmacology position paper
- 2019
-
Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 74:3, s. 432-448
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), together with their comorbidities, bear a significant burden on public health. Increased appreciation of molecular networks underlying inflammatory airway disease needs to be translated into new therapies for distinct phenotypes not controlled by current treatment regimens. On the other hand, development of new safe and effective therapies for such respiratory diseases is an arduous and expensive process. Antibody-based (biological) therapies are successful in treating certain respiratory conditions not controlled by standard therapies such as severe allergic and refractory eosinophilic severe asthma, while in other inflammatory respiratory diseases, such as COPD, biologicals are having a more limited impact. Small molecule drug (SMD)-based therapies represent an active field in pharmaceutical research and development. SMDs expand biologicals’ therapeutic targets by reaching the intracellular compartment by delivery as either an oral or topically based formulation, offering both convenience and lower costs. Aim of this review was to compare and contrast the distinct pharmacological properties and clinical applications of SMDs- and antibody-based treatment strategies, their limitations and challenges, in order to highlight how they should be integrated for their optimal utilization and to fill the critical gaps in current treatment for these chronic inflammatory respiratory diseases.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Zuiker, Rob G J A, et al.
(författare)
-
Kinetics of TH2 biomarkers in sputum of asthmatics following inhaled allergen.
- 2015
-
Ingår i: European clinical respiratory journal. - : Informa UK Limited. - 2001-8525. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- Allergen-induced late airway response offers important pharmacodynamic targets, including T helper 2 (TH2) biomarkers. However, detection of inflammatory markers has been limited in dithiothreitol-processed sputum.
|
|
| 31. |
- Assaf, Sara M., et al.
(författare)
-
Asthma and severe acute respiratory syndrome coronavirus 2019 : current evidence and knowledge gaps
- 2021
-
Ingår i: Current Opinion in Pulmonary Medicine. - 1531-6971. ; 27:1, s. 45-53
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Although respiratory viruses are common triggers of asthma exacerbation, it is unknown whether this also applies to infection with SARS-CoV-2. Indeed, patients with asthma and allergy appear underrepresented in large reports of COVID-19 cases worldwide. In this review, we evaluate existing literature on this topic and potential underlying mechanisms for any interrelationship between asthma and COVID-19. RECENT FINDINGS: Data from several preclinical and clinical reports suggest a lower susceptibility for COVID-19 in patients with underlying type 2 airway inflammation including asthma that may be related to a reduced expression of ACE2 and TMPRSS2 receptors for SARS-CoV-2. Corticosteroids further decrease expression of the ACE2 and TMPRSS2 receptors, hence may also have a protective effect against infection with SARS-CoV-2. In addition, some studies suggest that the reported improvement in asthma control and a reduction in asthma exacerbations during the COVID-19 pandemic may be related to improvement in adherence to controller therapy and reduced exposure to triggers, such as other respiratory viruses and air pollutants. Recent data point towards differential susceptibility for COVID-19 among asthma patients based on their phenotype and/or endotype. On the basis of existing evidence, continuation with controller therapies is recommended for all patients with asthma. For patients with severe uncontrolled asthma infected by SARS-CoV-2, adjustment of controllers and biologics should be based on a multidisciplinary decision. SUMMARY: Underrepresentation of SARS-CoV-2-infected patients with asthma and related allergic diseases may be based on potentially protective underlying mechanisms, such as type 2 airway inflammation, downregulation of ACE2/TMPRSS2 receptors, reduced exposures to triggers and improved adherence to controller medications. Although it is imperative that control should be maintained and asthma medications be continued in all patients, management of patients with severe uncontrolled asthma infected by SARS-CoV-2 including adjustment of controllers and biologics should be discussed on an individual basis.
|
|
| 32. |
- Bunck, Mathijs C, et al.
(författare)
-
Effects of Exenatide on Measures of {beta}-Cell Function After 3 Years in Metformin-Treated Patients With Type 2 Diabetes.
- 2011
-
Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 34:9, s. 2041-2047
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE We previously showed that exenatide (EXE) enhanced insulin secretion after 1 year of treatment, relative to insulin glargine (GLAR), with a similar glucose-lowering action. These effects were not sustained after a 4-week off-drug period. This article reports the results after additional 2 years of exposure. RESEARCH DESIGN AND METHODS Sixty-nine metformin-treated patients with type 2 diabetes were randomized to EXE or GLAR. Forty-six patients entered the 2-year extension study in which they continued their allocated therapy. Thirty-six completed (EXE: n = 16; GLAR: n = 20) the 3-year exposure period. Insulin sensitivity (M value) and β-cell function were measured by euglycemic hyperinsulinemic clamp followed by hyperglycemic clamp with arginine stimulation at pretreatment (week 52) and 4 weeks after discontinuation of study medication (week 56 and week 172). First-phase glucose stimulated C-peptide secretion was adjusted for M value and calculated as the disposition index (DI). RESULTS At 3 years, EXE and GLAR resulted in similar levels of glycemic control: 6.6 ± 0.2% and 6.9 ± 0.2%, respectively (P = 0.186). EXE compared with GLAR significantly reduced body weight (-7.9 ± 1.8 kg; P < 0.001). After the 4-week off-drug period, EXE increased the M value by 39% (P = 0.006) while GLAR had no effect (P = 0.647). Following the 4-week off-drug period, the DI, compared with pretreatment, increased with EXE, but decreased with GLAR (1.43 ± 0.78 and -0.99 ± 0.65, respectively; P = 0.028). CONCLUSIONS EXE and GLAR sustained HbA(1c) over the 3-year treatment period, while EXE reduced body weight and GLAR increased body weight. Following the 3-year treatment with EXE, the DI was sustained after a 4-week off-drug period. These findings suggest a beneficial effect on β-cell health.
|
|
| 33. |
- Bunck, Mathijs C, et al.
(författare)
-
One-year treatment with exenatide vs. insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress.
- 2010
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 212:1, s. 223-9
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of the present study was to investigate the effects of one-year treatment with exenatide or Insulin Glargine, followed by a 5-week off-drug period, on postprandial lipidaemia, glycaemia and measures of oxidative stress. METHODS: Sixty-nine metformin-treated patients with type 2 diabetes were randomised (using apermuted block randomisation scheme stratified by site and baseline HbA(1c) stratum (< or = 8.5% or >8.5%) of which 60 completed (exenatide n=30; Insulin Glargine n=30) the pre-treatment and on-drug meal test. Postprandial glucose, lipids and lipoproteins, and oxidative stress markers were studied at week -1, 51, and after a 5-week off-drug period following a breakfast and lunch mixed-meal containing 50 g fat, 75 g carbohydrates, and 35 g protein. RESULTS: 51-Week exenatide treatment resulted in a significant reduction of prandial glucose, triglycerides, apo-B48, calculated VLDL-C, FFA and MDA excursions whereas Insulin Glargine predominantly reduced fasting glucose, FFA and MDA. Changes in markers of oxidative stress were related to changes in postprandial glucose and triglyceride excursions, independent of treatment arm. All postprandial measures returned to pre-treatment values in both groups after 5-week cessation of study treatment. CONCLUSION: Exenatide showed beneficial effects on postprandial glycaemia and lipidaemia, and these effects were related to changes in the oxidative stress markers MDA and oxLDL during one year of treatment as compared to Insulin Glargine. Following cessation of both exenatide and Insulin Glargine measures returned to pre-treatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Coates, Allan L., et al.
(författare)
-
ERS technical standard on bronchial challenge testing : General considerations and performance of methacholine challenge tests
- 2017
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 49:5
-
Tidskriftsartikel (refereegranskat)abstract
- This international task force report updates general considerations for bronchial challenge testing and the performance of the methacholine challenge test. There are notable changes from prior recommendations in order to accommodate newer delivery devices. Rather than basing the test result upon a methacholine concentration (provocative concentration (PC20) causing a 20% fall in forced expiratory volume in 1 s (FEV1)), the new recommendations base the result upon the delivered dose of methacholine causing a 20% fall in FEV1 (provocative dose (PD20)). This end-point allows comparable results from different devices or protocols, thus any suitable nebuliser or dosimeter may be used, so long as the delivery characteristics are known. Inhalation may be by tidal breathing using a breath-actuated or continuous nebuliser for 1 min (or more), or by a dosimeter with a suitable breath count. Tests requiring maximal inhalations to total lung capacity are not recommended because the bronchoprotective effect of a deep breath reduces the sensitivity of the test.
|
|
| 37. |
- Conti, Diego M., et al.
(författare)
-
A EUFOREA comment on a lost comorbidity of asthma
- 2023
-
Ingår i: Allergy, Asthma and Clinical Immunology. - 1710-1484. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- “Epidemiology of comorbidities and their association with asthma control” (Tomisa, G., Horváth, A., Sánta, B. et al. Epidemiology of comorbidities and their association with asthma control. Allergy Asthma Clin Immunol 17, 95 (2021). https://doi.org/10.1186/s13223-021-00598-3) is an interesting paper reflecting data collection from more than 12,000 asthmatic patients in Hungary regarding their condition and associated comorbidities. We found it valuable that the paper provides an overview of asthma comorbidities not usually considered in similar reports. Nevertheless, we believe that chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP or CRSsNP) should have been listed due to its high incidence and prevalence, its association with asthma which is also endorsed in both GINA and EPOS, as well as in several peer-reviewed scientific papers, and to reflect the role of this comorbidity in poor control and a most severe presentation of asthma for the patient. Consequently, several targeted therapies (especially monoclonal antibodies) used for several years in severe forms of asthma are now indicated also for the effective treatment of nasal polyps.
|
|
| 38. |
|
|
| 39. |
- Diamant, H, et al.
(författare)
-
[Franz Kafka]
- 2006
-
Ingår i: Svensk medicinhistorisk tidskrift. - 1402-9871. ; 10:1, s. 145-51
-
Tidskriftsartikel (refereegranskat)
|
|
| 40. |
- Diamant, H, et al.
(författare)
-
Swedish otorhinolaryngology (ORL) 1880-1920
- 2005
-
Ingår i: The Journal of laryngology and otology. Supplement. - : Cambridge University Press (CUP). - 0144-2945 .- 0022-2151 .- 1748-5460. ; 119:30, s. 104-106
-
Tidskriftsartikel (refereegranskat)
|
|
| 41. |
- Diamant, Ulla-Britt, 1955-, et al.
(författare)
-
Electrophysiological phenotype in the LQTS mutations Y111C and R518X in the KCNQ1 gene
- 2013
-
Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 115:10, s. 1423-1432
-
Tidskriftsartikel (refereegranskat)abstract
- Long QT syndrome is the prototypical disorder of ventricular repolarization (VR), and a genotype-phenotype relation is postulated. Furthermore, although increased VR heterogeneity (dispersion) may be important in the arrhythmogenicity in long QT syndrome, this hypothesis has not been evaluated in humans and cannot be tested by conventional electrocardiography. In contrast, vectorcardiography allows assessment of VR heterogeneity and is more sensitive to VR alterations than electrocardiography. Therefore, vectorcardiography was used to compare the electrophysiological phenotypes of two mutations in the LQT1 gene with different in vitro biophysical properties, and with LQT2 mutation carriers and healthy control subjects. We included 99 LQT1 gene mutation carriers (57 Y111C, 42 R518X) and 19 LQT2 gene mutation carriers. Potassium channel function is in vitro most severely impaired in Y111C. The control group consisted of 121 healthy subjects. QRS, QT, and T-peak to T-end (Tp-e) intervals, measures of the QRS vector and T vector and their relationship, and T-loop morphology parameters were compared at rest. Apart from a longer heart rate-corrected QT interval (QT heart rate corrected according to Bazett) in Y111C mutation carriers, there were no significant differences between the two LQT1 mutations. No signs of increased VR heterogeneity were observed among the LQT1 and LQT2 mutation carriers. QT heart rate corrected according to Bazett and Tp-e were longer, and the Tp-e-to-QT ratio greater in LQT2 than in LQT1 and the control group. In conclusion, there was a marked discrepancy between in vitro potassium channel function and in vivo electrophysiological properties in these two LQT1 mutations. Together with previous observations of the relatively low risk for clinical events in Y111C mutation carriers, our results indicate need for cautiousness in predicting in vivo electrophysiological properties and the propensity for clinical events based on in vitro assessment of ion channel function alone.
|
|
| 42. |
- Diamant, Ulla-Britt, 1955-
(författare)
-
Long QT syndrome : studies of diagnostic methods
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Long QT Syndrome (LQTS) is a hereditary heart disease with risk of malignant ventricular arrhythmia and sudden cardiac death. Despite our increased knowledge about genotype and phenotype correlation we still rely on the 12-lead ECG for assessment of the QT interval and the T-wave morphology for diagnosis and risk stratification. Intra- and -inter individual variability in manually QT measurement and, e.g., difficulties in defining the end of the T-wave may impair the diagnosis of LQTS. Increased heterogeneity in ventricular repolarization (VR) may be an important factor in the arrhythmogenicity in cases of LQTS. In a LQTS founder population the same mutation is carried by numerous individuals in many families which provide a unique opportunity to study diagnostic methods, risk assessment, VR and the correlation between genotype and phenotype.Methods: Resting 12-lead ECG and vectorcardiogram (VCG) were recorded in 134 LQTS mutation carriers and 121 healthy controls, to investigate the capability and precision in measuring the QT interval. For assessment of the VR, VCG was compared in individuals with mutations in the KCNQ1 and KCNH2 gene. Genealogical and geographic studies were performed in 37 index cases and their relatives to determine if Swedish carriers of the Y111C mutation in the KCNQ1 gene constitute a founder population. To confirm kinship, haplotype analysis was performed in 26 of the 37 index cases. The age and prevalence of the Y111C mutation were calculated in families sharing a common haplotype.Results: VCG by automatic measurement of the QT interval provided the best combination of sensitivity (90%) and specificity (89%) in the diagnosis of LQTS. VCG showed no consistent pattern of increased VR heterogeneity among KCNQ1 and KCNH2 mutation carriers. Living carriers of the Y111C mutation shared a common genetic (haplotype), genealogic and geographic origin. The age of the Y111C mutation was approximately 600 years. The prevalence of living carriers of the Y111C mutation in the mid-northern Sweden was estimated to 1:1,500-3,000.Conclusion: We have shown that VCG provides a valuable contribution to the diagnosis and risk assessment of LQTS in adults and children. No consistent pattern of increased VR heterogeneity was found among the LQTS mutation carriers. The identified Swedish LQTS founder population will be a valuable source to future LQTS research and may contribute to increase our understanding of LQTS and the correlation of phenotype, genotype and modifying factors.
|
|
| 43. |
- Diamant, Ulla-Britt, et al.
(författare)
-
Two automatic QT algorithms compared with manual measurement in identification of long QT syndrome
- 2010
-
Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 0022-0736 .- 1532-8430. ; 43:1, s. 25-30
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Long QT syndrome (LQTS) is an inherited disorder that increases the risk of syncope and malignant ventricular arrhythmias, which may result in sudden death.METHODS: We compared manual measurement by 4 observers (QT(manual)) and 3 computerized measurements for QT interval accuracy in the diagnosis of LQTS: 1. QT measured from the vector magnitude calculated from the 3 averaged orthogonal leads X, Y, and Z (QTVCG) and classified using the same predefined QTc cut-points for classification of QT prolongation as in manual measurements; 2. QT measured by a 12-lead electrocardiogram (ECG) program (QTECG) and subsequently classified using the same cut-points as in (1) above; 3. The same QT value as in (2) above, automatically classified by a 12-lead ECG program with thresholds for QT prolongation adjusted for age and sex (QTinterpret). The population consisted of 94 genetically confirmed carriers of KCNQ1 (LQT1) and KCNH2 (LQT2) mutations and a combined control group of 28 genetically confirmed noncarriers and 66 unrelated healthy volunteers.RESULTS: QT(VCG) provided the best combination of sensitivity (89%) and specificity (90%) in diagnosing LQTS, with 0.948 as the area under the receiver operating characteristic curve. The evaluation of QT measurement by the 4 observers revealed a high interreader variability, and only 1 of 4 observers showed acceptable level of agreement in LQTS mutation carrier identification (kappa coefficient >0.75).CONCLUSION: Automatic QT measurement by the Mida1000/CoroNet system (Ortivus AB, Danderyd, Sweden) is an accurate, efficient, and easily applied method for initial screening for LQTS.
|
|
| 44. |
- Diamant, Ulla-Britt, et al.
(författare)
-
Vectorcardiographic recordings of the Q-T interval in a pediatric long Q-T syndrome population
- 2013
-
Ingår i: Pediatric Cardiology. - : Springer Science and Business Media LLC. - 0172-0643 .- 1432-1971. ; 34:2, s. 245-249
-
Tidskriftsartikel (refereegranskat)abstract
- Measurements of the Q-T interval are less reliable in children than in adults. Identification of superior diagnostic tools is warranted. This study aimed to investigate whether a vectorcardiogram (VCG) recorded from three orthogonal leads (X, Y, Z) according to Frank is superior to a 12-lead electrocardiogram (ECG) in providing a correct long Q-T syndrome (LQTS) diagnosis in children. This LQTS group consisted of 35 genetically confirmed carriers of mutations in the KCNQ1 (n = 29) and KCNH2 (n = 6) genes. The control group consisted of 35 age- and gender-matched healthy children. The mean age was 7 years in the LQTS group and 6.7 years in the control group (range, 0.5-16 years). The corrected Q-T interval (QT(c)) was measured manually (QT(man)) by one author (A.W.). The 12-lead ECG automatic measurements (QT(ECG)) and interpretation (QT(Interpret)) of QT(c) were performed with the Mac5000 (GE Medical System), and the VCG automatic measurements (QT(VCG)) were performed with the Mida1000, CoroNet (Ortivus AB, Sweden). By either method, a QT(c) longer than 440 ms was considered prolonged and indicative of LQTS. Of the 35 children with genetically confirmed LQTS, 30 (86 %) received a correct diagnosis using QT(VCG), 29 (82 %) using QT(man), 24 (69 %) using QT(ECG), and 17 (49 %) using QT(Interpret). Specificity was 0.80 for QT(VCG), 0.83 for QT(man), 0.77 for QT(ECG), and 0.83 for QT(Interpret). The VCG automatic measurement of QT(c) seems to be a better predictor of LQTS than automatic measurement and interpretation of 12-lead ECG.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Gauvreau, GM, et al.
(författare)
-
Allergen provocation tests in respiratory research: building on 50 years of experience
- 2022
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 60:2
-
Tidskriftsartikel (refereegranskat)abstract
- The allergen provocation test is an established model of allergic airway diseases, including asthma and allergic rhinitis, allowing the study of allergen-induced changes in respiratory physiology and inflammatory mechanisms in sensitised individuals as well as their associations. In the upper airways, allergen challenge is focused on the clinical and pathophysiological sequelae of the early allergic response, and is applied both as a diagnostic tool and in research settings. In contrast, bronchial allergen challenge has almost exclusively served as a research tool in specialised research settings with a focus on the late asthmatic response and the underlying type 2 inflammation. The allergen-induced late asthmatic response is also characterised by prolonged airway narrowing, increased nonspecific airway hyperresponsiveness and features of airway remodelling including the small airways, and hence allows the study of several key mechanisms and features of asthma. In line with these characteristics, allergen challenge has served as a valued tool to study the cross-talk of the upper and lower airways and in proof-of-mechanism studies of drug development. In recent years, several new insights into respiratory phenotypes and endotypes including the involvement of the upper and small airways, innovative biomarker sampling methods and detection techniques, refined lung function testing as well as targeted treatment options further shaped the applicability of the allergen provocation test in precision medicine. These topics, along with descriptions of subject populations and safety, in line with the updated Global Initiative for Asthma 2021 document, will be addressed in this review.
|
|
| 49. |
- Granberg Sandlund, M., et al.
(författare)
-
Quality of care in acute dizziness presentations
- 2019
-
Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 26:S1, s. 926-926
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Dizziness is a common symptom at emergency departments. Studies have shown poor quality of care in acute dizziness presentations, including the overuse of computed tomography (CT) and failure to detect benign causes. This study aims to evaluate whether a management algorithm has improved the quality of care for dizzy patients at Umeå University Hospital, Sweden.Methods: This was an interventional study using medical records to collect data for acute dizziness presentations before (period 1, 2012–2014) and after (period 2, 2016-2017) the implementation of a management algorithm (see figure). Outcomes were changes in a set of pre-defined quality markers and health economic effects.Results: Total n=2126 and n=1487 acute dizziness presentations were identified in period 1 and 2, respectively. Baseline characteristics were similar. The proportion of patients undergoing Dix-Hallpike testing increased, 20.8% vs. 37.7%, (p<0.01), as did BPPV diagnoses, 7.6% vs. 15.3%, (p<0.01). Hospitalization became less common, 61.5% vs. 47.6% (p<0.01). The proportion undergoing any neuroradiological investigation decreased, 44.8% vs. 36.3% (p<0.01) with a shift from CT to MRI, with unchanged sensitivity for diagnosing cerebrovascular causes. The average cost for the care of one dizzy patient decreased from $2561 during period 1 to $1808 during period 2.Conclusion: This study shows how the implementation of a management algorithm for dizzy patients can improve the quality of care and lower the expenses, without an increased number of missed stroke cases.
|
|
| 50. |
- Hallstrand, Teal S., et al.
(författare)
-
ERS technical standard on bronchial challenge testing : pathophysiology and methodology of indirect airway challenge testing
- 2018
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 52:5
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a "direct" airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.
|
|
