| 1. |
- Djekic, Demir, 1989-, et al.
(författare)
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Effects of a Vegetarian Diet on Cardiometabolic Risk Factors, Gut Microbiota, and Plasma Metabolome in Subjects With Ischemic Heart Disease: A Randomized, Crossover Study
- 2020
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Ingår i: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 9:18, s. e016518-e016518
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Tidskriftsartikel (refereegranskat)abstract
- Background A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease. Methods and Results A randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4-week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4-week washout period. The primary outcome was difference in oxidized low-density lipoprotein cholesterol (LDL-C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short-chain and branched-chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL-C (-2.73 U/L), total cholesterol (-5.03 mg/dL), LDL-C (-3.87 mg/dL), and body weight (-0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, including l-carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL-C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae. Conclusions The VD in conjunction with optimal medical therapy reduced levels of oxidized LDL-C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL-C observed with the VD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02942628.
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| 2. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 3. |
- Darehed, David, 1986-
(författare)
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The impact of organizational and temporal factors on acute stroke care in Sweden
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Acute stroke carries a high risk of morbidity and death, but early treatment can improve outcomes. Intravenous stroke thrombolysis (IVT) is one such treatment, it is however time-sensitive and show better outcomes the sooner it is given. Most studies on time to IVT so far have looked at fixed time-intervals, and studies of short delays in clinical practice are relatively scarce. Another well-established treatment is managing acute stroke patients in stroke units (SU). Admission rates to a SU as first destination of hospital care have improved over time in Sweden. In the past decade however, the rates have leveled out at around 75-80% without further improvement. A hypothesis is that in-hospital overcrowding contributes. Previous studies have shown that outcomes after stroke differ between hospital types, and also vary depending on time of admission, with higher mortality seen for off-hours, weekend and winter admissions. The reasons behind temporal variations are not fully understood, but it has been proposed that environmental, patient-related and organizational factors contribute. The overall aim of this thesis was to study the effect of organizational factors on quality of care and outcomes after stroke, primarily focusing on the role of in-hospital overcrowding, in-hospital time to IVT and time of admission, while also studying differences between hospitals.Methods: All papers in this thesis were based on data from the Swedish stroke register (Riksstroke), a national quality register that holds data on patient related factors, acute care and outcomes. Paper I included 13,955 patient admissions from 14 hospitals in Region Norrbotten and Region Skåne from 2011-2014, enriched with data on in-hospital bed occupancy. Papers II-IV included all 72 Swedish hospitals caring for patients with acute stroke. Paper II included data from 2011-2015 (N=113,862), paper III from 2011-2016 (N=132,744) and paper IV from 2010-2017 (N=14,132). Analyses included descriptive statistics, unadjusted analyses and multivariable adjusted analyses.Results: We found that each percent increase in in-hospital bed occupancy above 85% decreased admission rates to a SU as first destination of hospital care by 1.5% (odds ratio (OR) 0.985, 95% confidence interval (CI) 0.978-0.992), with significant differences between hospitals. Admission rates were also lower off-hours, compared to on-hours (OR 0.73, 95% CI 0.70-0.75). Over time, admission rates to a SU as first destination of hospital care decreased in university hospitals, while they increased in specialized non-university hospitals and community hospitals. Each minute delay in door-to-needle time (DNT) decreased the odds of 90-day survival by 0.6% (OR 0.994, 95% CI 0.992-0.996), increased the odds of ICH within 36 hours by 0.3% (OR 1.003, 95% CI 1.000-1.006), and led to significantly higher odds of a worsening in functional outcomes at 3 months by 0.3-0.4%. DNT within 30 minutes was most likely daytime, and varied between hospital types. 90-day survival was lowest for patients admitted in January (81.5%), and highest for those admitted in May (84.1%) (OR 1.28, 95% CI 1.17-1.40).Conclusion: We found that in-hospital overcrowding decrease admission rates to a SU as first destination of hospital care, and that even short delays in DNT decreases survival, increases ICH complications and leads to a worsening in functional outcomes in routine clinical practice. We also found that quality of care varied depending on time of admission and between hospitals, indicating unequal care. Organizational differences should be accessible through quality improvement efforts aiming to implement robust local guidelines for in-hospital stroke treatment.
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| 4. |
- Henein, Michael Y., et al.
(författare)
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Diastolic function assessment by echocardiography : A practical manual for clinical use and future applications
- 2020
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Ingår i: Echocardiography. - : John Wiley & Sons. - 0742-2822 .- 1540-8175. ; 37:11, s. 1908-1918
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Forskningsöversikt (refereegranskat)abstract
- Diastole is an important component of the cardiac cycle, during which time optimum filling of the ventricle determines physiological stroke volume ejected in the succeeding systole. Many factors contribute to optimum ventricular filling including venous return, left atrial filling from the pulmonary circulation, and emptying into the left ventricle. Left ventricular filling is also impacted by the cavity emptying function and also its synchronous function which may suppress early diastolic filling in severe cases of dyssynchrony. Sub-optimum LA emptying increases cavity pressure, causes enlarged left atrium, unstable myocardial function, and hence atrial arrhythmia, even atrial fibrillation. Patients with clear signs of raised left atrial pressure are usually symptomatic with exertional breathlessness. Doppler echocardiography is an ideal noninvasive investigation for diagnosing raised left atrial pressure as well as following treatment for heart failure. Spectral Doppler based increased E/A, shortened E-wave deceleration time, increased E/e', and prolonged atrial flow reversal in the pulmonary veins are all signs of raised left atrial pressure. Left atrial reduced myocardial strain is another correlate of raised cavity pressure (>15 mm Hg). In patients with inconclusive signs of raised left atrial pressure at rest, exercise/stress echocardiography or simply passive leg lifting should identify those with stiff left ventricular which suffers raised filling pressures with increased venous return.
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| 5. |
- Hylander, Johan, 1986-, et al.
(författare)
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Senior ambulance officers in Swedish emergency medical services : a qualitative study of perceptions and experiences of a new management role in challenging incidents
- 2020
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Increased demands are placed on emergency services and their role and ability to act in incidents in challenging environments, for example, road tunnels. Collaboration between officers from emergency services (fire brigade, police and ambulance services) is important for an effective rescue effort. In Gothenburg, Sweden, a position as a senior ambulance officer (SAO) within the emergency medical services (EMS) has been introduced to support the regular force during major incidents. The aim of this paper was to explore the perceptions and experiences of the SAO's new management role in challenging incidents, such as those occurring in road tunnels.DESIGN: A qualitative interview study.SETTING: The study was carried out from February to June 2019 in Gothenburg, Sweden, which is a municipality with several road tunnels and a population of approximately 580 000 people. SAOs collaborate with the corresponding function within the police and fire brigade, both having senior officers at major incident sites.PARTICIPANTS: Twelve SAOs.METHODS: The study used semistructured interviews. The collected data were analysed using qualitative content analysis.RESULTS: According to SAOs' experience, prehospital medical management included not only leadership, but also planning, training and indepth knowledge of, for example, tunnel environments. Furthermore, SAOs adopted an encouraging and teaching role for their colleagues. SAOs' responsibilities also included proactive planning together with the fire brigade and police, which was regarded as enhancing interorganisational collaboration. An overall theme emerged which the SAOs described as 'A new holistic approach to EMS leadership and management'.CONCLUSIONS: The participants considered that the new SAO role not only seems to improve the prehospital medical management, but also makes the EMS command structure during challenging incidents symmetrical with the fire brigade and police command structure. The implementation of national guidelines is desirable and is requested by the SAOs.
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| 6. |
- Johanson, Suzanne, et al.
(författare)
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Implementation of a novel return-to-work approach for persons with affective disorders in a traditional vocational rehabilitation context: a case study
- 2020
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Ingår i: International Journal of Mental Health Systems. - : Springer Science and Business Media LLC. - 1752-4458. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The person-centred Individual Enabling and Support (IES) model is a novel return-to-work (RTW) intervention for people with affective disorders that was developed from evidence-based supported employment for persons with severe mental illness. Typically, supported employment is integrated into mental healthcare and provides a network around the service user and close collaboration with employment and insurance services and employers. Introducing integrated models into a highly sectored welfare system that includes traditional mental healthcare and vocational rehabilitation is challenging. Greater knowledge is needed to understand how facilitating or hindering factors influence this introduction. The aim of this study was to investigate essential components in implementation of the IES model. Methods A case-study was conducted and included four mental healthcare services. Data collection was comprised of semi-structured interviews with 19 key informants, documentation from meetings, and reflection notes. Analyses were performed according to directed content analysis, using the components of the Consolidated Framework of Implementation Research (CFIR) as a guiding tool. Fidelity assessments were performed at 6 and 12 months. Results Anticipating RTW support for the target group, and building collaborative relationships and a network with employment specialists that engaged staff in every organization were components that resulted in the greatest facilitation if IES implementation. Barriers consisted of difficulty in integrating employment specialists into the mental healthcare teams, insufficient engagement of first line managers, reorganization and differing perceptions of the IES model fit into a traditional vocational context. Delivery of the IES model had good fidelity. Conclusions The IES model can be implemented with good fidelity, several model advantages, and context adaptation. Team integration difficulties and negative perceptions of model fit in a traditional vocational rehabilitation context can be overcome to a certain degree, but this is insufficient for sustainable implementation on a larger scale. Policy and guidelines need to promote integrative and person-centred RTW approaches rather than a segregated stepwise approach. Further implementation studies in the traditional vocational rehabilitation context are needed.
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| 7. |
- Tabatabaei, Pedram, 1978-
(författare)
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Stereotactic microdialysis for metabolic assessment and experimental treatment of malignant glioma
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glioblastoma multiforme, the most common primary brain tumor, has a dire prognosis despite multimodal treatments that include surgery and radio-chemotherapy. To improve the outcome of this destructive disease, we need to improve our understanding of its tumor biology. Furthermore, the development of new treatment strategies will improve with a better understanding of the interplay between malignant cells and their direct surrounding microenvironment.This thesis aims to increase the understanding of the processes within high-grade glioma and its microenvironment during normal conditions as well as during the distress associated with treatment. Specifically, we have investigated the metabolic response to radiotherapy (study I and II), the immunologic response to radiotherapy (study II), and the metabolic response pattern to loco-regional treatment with cisplatin (study III and IV). Using microdialysis, we collected samples from the extracellular space in both normal brain and tumor tissue during radiotherapy (study I and II) and loco-regional cisplatin treatment (study III and IV). Theses samples were analyzed for glucose metabolites, glycerol, and glutamate (study I, II, and III) and for cytokines (study II). In addition, we analyzed the global metabolism with mass spectrometry to identify and assess the response pattern of malignant glioma cells to loco-regional cisplatin treatment (study IV).In study I and II, we found that malignant glioma cells used glucose at a higher rate than normal cells and preferred glycolysis for glucose metabolism. The given radiation dose (2 Gray (Gy) daily for five days) did not significantly affect glucose metabolism, glycerol levels, or glutamate levels in tumor tissue or the microenvironment. However, in study II, we observed an induced inflammatory effect due to the given radiation dose as several of the cytokines investigated showed significantly increased levels during radiotherapy. In study IV, we observed a complex and strong metabolic response to the loco-regional cisplatin therapy. At baseline, we found a metabolic pattern corresponding well with highly proliferating tumor tissue–i.e., high levels of amino acids, their metabolites, and other metabolic end products and low levels of sugar derivatives, antioxidants, and nucleotides. During the loco-regional therapy, we observed a clearly localized cytotoxic effect within the tumor and a metabolic response pattern corresponding with cisplatin’s complex mechanism of action, affecting several metabolic pathways within the malignant cell. Glutamate and glycerol also increased in tumor tissue following loco-regional treatment, a finding that further supported the observation of local toxicity.In study III, we investigated microdialysis as a method to assess the microenvironment in high-grade glioma and as a method for drug delivery (retrograde microdialysis). All studies demonstrated the usefulness of microdialysis as a tool for in vivo real-time assessment of molecular events in malignant glioma tissue. Although the method is invasive, no complications related to the surgical procedure or assessment were noted. In study III, we also demonstrated that retrograde microdialysis is a feasible method for locally delivering clinically significant doses of drugs such as cisplatin to tumor tissue in the brain. However, in addition to having a cytotoxic effect on tumor cells, cisplatin may induce clinically significant edema.
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