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| 2. |
- Backman, Helena, et al.
(författare)
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Severe asthma : A population study perspective
- 2019
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Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 49:6, s. 819-828
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSevere asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.ObjectiveTo describe characteristics and estimate the prevalence of severe asthma in a large adult population‐based asthma cohort followed for 10‐28 years.MethodsN=1006 subjects with asthma participated in a follow‐up during 2012‐14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well‐known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.ResultsThe prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.Conclusions and clinical relevanceSevere asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4‐6%, corresponding to approximately 0.5% of the general population.
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| 3. |
- Backman, Helena, et al.
(författare)
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Severe asthma among adults : Prevalence and clinical characteristics
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.Methods: We estimated the prevalence and studied characteristics of severe asthma in a large adult population-based asthma cohort followed for 10-28 years in northern Sweden: 1006 subjects participated in a follow-up during 2012-14, when 830 (82.5%) still had current asthma (mean age 59y, 32-92y, 56% women). Severe asthma was defined according to three internationally well-known criteria: the US SARP, ATS/ERS and GINA. All subjects with severe asthma were undergoing respiratory specialist care, and were also contacted by telephone to verify adherence to treatment.Results: The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma and <10% had controlled asthma according to the ACT. Severe asthma was related to age >50 years, nasal polyposis, decreased FEV1, not fully reversible airway obstruction, sensitization to aspergillus, elevated neutrophils and partly to eosinophils, and tended to be more common in women.Conclusion: The prevalence of severe asthma in this asthma cohort was 4-6%, corresponding to approximately 0.5% of the population in northern Sweden. A substantial proportion of those with severe asthma had uncontrolled disease, and severe asthma differed significantly from other asthma in terms of both clinical and inflammatory characteristics.
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| 4. |
- Fadl, Helena, 1965-, et al.
(författare)
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Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
- 2019
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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| 5. |
- Hallgren Graneheim, Ulla, et al.
(författare)
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Hovering between Heaven and Hell : An Observational Study Focusing on the Interactions between One Woman with Schizophrenia, Dementia, and Challenging Behaviour and her Care Providers
- 2015
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Ingår i: Issues in Mental Health Nursing. - : Taylor & Francis. - 0161-2840 .- 1096-4673. ; 36:7, s. 543-550
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Tidskriftsartikel (refereegranskat)abstract
- This case study aims to illuminate the interactions between one woman (Alice) with schizophrenia, dementia, and challenging behaviour and her professional caregivers. We performed participant observations of these interactions and conducted informal interviews at the residential home where the woman lived. The transcripts were subjected to qualitative content analysis. The results showed that the interactions between Alice and her caregivers were experienced as hovering between heaven and hell. Alice struggled to bring order into her chaotic life world by splitting herself and others, and her caregivers struggled to protect Alice's and their own dignity by limiting her challenging behaviours. They also strived to understand their own and Alice's behaviour. Current practice in caring for people with challenging behaviour usually focuses on symptom reduction through medication and behavioural modification. Instead, we suggest moving toward an understanding of the experiences behind the challenging behaviours and designing person-centred care based on each patients' reality.
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| 6. |
- Jansson, Sven-Arne, et al.
(författare)
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Societal costs of severe asthma in Sweden
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Severe asthma is a disabling and costly disease, often poorly controlled despite high-dosage controller medications.Aims: We estimated societal costs from an adult severe asthma cohort, derived from a large-scale population survey in northern Sweden.Methods: Severe asthma was defined by US SARP criteria, and high-dosage inhaled corticosteroids (ICS) were defined by GINA 2014 criteria. The study sample was identified from general population cohorts examined within the OLIN (Obstructive Lung Disease in Northern Sweden) studies (n=1,006). Patient reported asthma-related direct (outpatient care, medicines, hospitalisations) and indirect (sick leave, early retirement) resource consumption were collected by quarterly pre-defined telephone interviews during one year. Unit costs from 2017 were applied.Results: In total, 32 patients with severe asthma (mean age 60.7y, 13 patients >65) were included. The mean annual total cost per patient was approximately €6,300. Two thirds of the costs (63%) was indirect costs (approximately €4,000). The main cost drivers in direct costs were hospitalisations and drugs: approximately €1,000 and €700, respectively. The main cost driver of indirect costs was productivity loss due to early retirement: €3,400. Patients who had received regular oral corticosteroid (OCS) treatment had greater costs compared with those without regular OCS treatment. In comparison with a previous Swedish study based on a sample of all asthmatics from the general population, a greater mean annual total cost per patient was observed.Conclusions: In this severe asthma population in Sweden, societal costs were substantial. The results indicate a need for improved treatment regimens for patients with severe asthma.
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| 7. |
- Loryan, Irena, 1977-, et al.
(författare)
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In-depth neuropharmacokinetic analysis of antipsychotics based on a novel approach to estimate unbound target-site concentration in CNS regions : link to spatial receptor occupancy
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:11, s. 1527-1536
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Tidskriftsartikel (refereegranskat)abstract
- The current study provides a novel in-depth assessment of the extent of antipsychotic drugs transport across the blood-brain barrier (BBB) into various brain regions, as well as across the blood-spinal cord barrier (BSCB) and the blood-cerebrospinal fluid barrier (BCSFB). This is combined with an estimation of cellular barrier transport and a systematic evaluation of nonspecific brain tissue binding. The study is based on the new Combinatory Mapping Approach (CMA), here further developed for the assessment of unbound drug neuropharmacokinetics in regions of interest (ROI), referred as CMA-ROI. We show that differences exist between regions in both BBB transport and in brain tissue binding. The most dramatic spatial differences in BBB transport were found for the P-glycoprotein substrates risperidone (5.4-fold) and paliperidone (4-fold). A higher level of transporter-mediated protection was observed in the cerebellum compared with other brain regions with a more pronounced efflux for quetiapine, risperidone and paliperidone. The highest BBB penetration was documented in the frontal cortex, striatum and hippocampus (haloperidol, olanzapine), indicating potential influx mechanisms. BSCB transport was in general characterized by more efficient efflux compared with the brain regions. Regional tissue binding was significantly different for haloperidol, clozapine, risperidone and quetiapine (maximally 1.9-fold). Spatial differences in local unbound concentrations were found to significantly influence cortical 5-HT2A receptor occupancy for risperidone and olanzapine. In conclusion, the observed regional differences in BBB penetration may potentially be important factors contributing to variations in therapeutic effect and side effect profiles among antipsychotic drugs.
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| 8. |
- Melander, Erik, et al.
(författare)
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Improved method for quantitative analysis of the cyclotide kalata B1 in plasma and brain homogenate
- 2016
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Ingår i: Biopolymers. - : Wiley. - 0006-3525 .- 1097-0282. ; 106:6, s. 910-916
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Tidskriftsartikel (refereegranskat)abstract
- This study provides a new method for quantifying the cyclotide kalata B1 in both plasma and brain homogenate. Cyclotides are ultra-stable peptides with three disulfide bonds that are interesting from a drug development perspective as they can be used as scaffolds. In this study we describe a new validated LC-MS/MS method with high sensitivity and specificity for kalata B1. The limit of quantification was 2 ng/mL in plasma and 5 ng/gmL in brain homogenate. The method was linear in the range 2-10,000 ng/mL for plasma and 5-2000 ng/g for brain. Liquid Chromatographic separation was performed on a HyPurity C18 column, 50 3 4.6 mm, 3 mm particle size. The method had inter-and intra-day precision and accuracy levels <15% and 12% respectively. Applying the method to in vivo plasma samples and brain homogenate samples from equilibrium dialysis yielded satisfying results and was able to describe the plasma pharmacokinetics and brain tissue binding of kalata B1. The described method is quick, reproducible and well suited to quantifying kalata B1 in biological matrices.
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| 9. |
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| 10. |
- Svahn, Sara L, et al.
(författare)
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Dietary polyunsaturated fatty acids increase survival and decrease bacterial load during septic S. aureus infection, and improve neutrophil function in mice
- 2015
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 83:2, s. 514-21
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Tidskriftsartikel (refereegranskat)abstract
- Severe infection, including sepsis, is an increasing clinical problem that causes prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of resistance to antibiotics is increasing and it is therefore critical to find new therapies for sepsis. Staphylococcus aureus (S. aureus) is a major cause of septic mortality. Neutrophils play an important role in the defense against bacterial infections. We have shown that a diet with high levels of dietary saturated fatty acids decreases survival in septic mice, but the mechanisms behind remain elusive. The aim of the present study was to investigate how the differences in dietary fat composition affect survival and bacterial load after experimental septic infection and neutrophil function in uninfected mice. We found that, after S. aureus infection, mice fed polyunsaturated high fat diet (HFD/P) for 8 weeks had increased survival and decreased bacterial load during sepsis compared with mice fed saturated high fat diet (HFD/S), and similar to that of mice fed low fat diet (LFD). Uninfected mice fed HFD/P had increased frequency of neutrophils in bone marrow compared with mice fed HFD/S. In addition, mice fed HFD/P had a higher frequency of neutrophils recruited to the site of inflammation in response to peritoneal injection of thioglycollate compared with HFD/S. Differences between the proportion of dietary protein and carbohydrate did not affect septic survival at all. In conclusion, polyunsaturated dietary fat increased both survival and efficiency of bacterial clearance during septic S. aureus infection. Moreover, this diet increased the frequency and chemotaxis of neutrophils, key components of the immune response to S. aureus infections.
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