| 1. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 2. |
- Castelo-Branco, Anna, et al.
(författare)
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Infections in patients with multiple sclerosis : A national cohort study in Sweden
- 2020
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple sclerosis (MS) patients have an increased risk of infections, but few population-based studies have reported infections occurring in MS in the years immediately after diagnosis.OBJECTIVE: To explore incident infections in MS, stratified by age and sex.METHODS: In a Swedish population-based cohort study 6602 incident MS patients (aged ≥18 years), matched at diagnosis with 61,828 matched MS-free individuals were identified between 1st January 2008 and 31st December 2016, using national registers. Incidence rates (IR) and incidence rate ratios (IRR) with 95% CI were calculated for each outcome.RESULTS: The IRRs were 2.54 (95% CI 2.28-2.83) for first serious infection and 1.61 (1.52-1.71) for first non-serious infection. Compared with MS-free individuals, MS patients had higher IRs for skin, respiratory/throat infections, pneumonia/influenza, bacterial, viral, and fungal infections, with the highest IRR observed for urinary tract/kidney infections (2.44; 2.24-2.66). The cumulative incidence for most of these infections was higher among MS patients than MS-free individuals, both 0 to <5 and 5 to <9 years after index date.CONCLUSION: The burden of infections around the time of MS diagnosis and subsequent infection risk, underscore the need for careful considerations regarding the risk-benefit across different disease-modifying therapies.
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| 3. |
- Castelo-Branco, Anna, et al.
(författare)
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Non-infectious comorbidity in patients with multiple sclerosis : A national cohort study in Sweden
- 2020
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Ingår i: Multiple Sclerosis Journal, Experimental, Translational and Clinical. - California, USA : Sage Publications. - 2055-2173. ; , s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comorbidity is of significant concern in multiple sclerosis (MS). Few population-based studies have reported conditions occurring in MS after diagnosis, especially in contemporary cohorts.Objective: To explore incident comorbidity, mortality and hospitalizations in MS, stratified by age and sex.Methods: In a Swedish population-based cohort study 6602 incident MS patients (aged ≥18 years) and 61,828 matched MS-free individuals were identified between 1 January 2008 and 31 December 2016, using national registers. Incidence rates (IRs) and incidence rate ratios (IRRs) with 95% CI were calculated for each outcome.Results: IRs of cardiovascular disease (CVD) were higher among MS patients than MS-free individuals, (major adverse CVD: IRR 1.42; 95% CI 1.12-1.82; hemorrhagic/ischemic stroke: 1.46; 1.05-2.02; transient ischemic attack: 1.65; 1.09-2.50; heart failure: 1.55; 1.15-2.10); venous thromboembolism: 1.42; 1.14-1.77). MS patients also had higher risks of several non-CVDs such as autoimmune conditions (IRR 3.83; 3.01-4.87), bowel dysfunction (2.16; 1.86-2.50), depression (2.38; 2.11-2.68), and fractures (1.32; 1.19-1.47), as well as being hospitalized and to suffer from CVD-related deaths ((1.91; 1.00-3.65), particularly in females (3.57; 1.58-8.06)).Conclusion: MS-patients experience a notable comorbidity burden which emphasizes the need for integrated disease management in order to improve patient care and long-term outcomes of MS.
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| 4. |
- Lindmark, Krister, et al.
(författare)
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Epidemiology of heart failure and trends in diagnostic work-up : a retrospective, population-based cohort study in Sweden
- 2019
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Ingår i: Clinical Epidemiology. - : Dove medical press. - 1179-1349. ; 11, s. 231-244
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to examine the trends in heart failure (HF) epidemiology and diagnostic work-up in Sweden.Methods: Adults with incident HF (>= 2 ICD-10 diagnostic codes) were identified from linked national health registers (cohort 1, 2005-2013) and electronic medical records (cohort 2, 2010-2015; primary/secondary care patients from Uppsala and Vasterbotten). Trends in annual HF incidence rate and prevalence, risk of all-cause and cardiovascular disease (CVD)-related 1-year mortality and use of diagnostic tests 6 months before and after first HF diagnosis (cohort 2) were assessed.Results: Baseline demographic and clinical characteristics were similar for cohort 1 (N=174,537) and 2 (N=8,702), with mean ages of 77.4 and 76.6 years, respectively; almost 30% of patients were aged >= 85 years. From 2010 to 2014, age-adjusted annual incidence rate of HF/1,000 inhabitants decreased (from 3.20 to 2.91, cohort 1; from 4.34 to 3.33, cohort 2), while age-adjusted prevalence increased (from 1.61% to 1.72% and from 2.15% to 2.18%, respectively). Age-adjusted 1-year all-cause and CVD-related mortality was higher in men than in women among patients in cohort 1 (all-cause mortality hazard ratio [HR] men vs women 1.07 [95% CI 1.06-1.09] and CVD-related mortality subdistribution HR for men vs women 1.04 [95% CI 1.02-1.07], respectively). While 83.5% of patients underwent N-terminal pro-B-type natriuretic peptide testing, only 36.4% of patients had an echocardiogram at the time of diagnosis, although this increased overtime. In the national prevalent HF population (patients with a diagnosis in 1997-2004 who survived into the analysis period; N=273,999), death from ischemic heart disease and myocardial infarction declined between 2005 and 2013, while death from HF and atrial fibrillation/flutter increased (P<0.0001 for trends over time).Conclusion: The annual incidence rate of HF declined over time, while prevalence of HF has increased, suggesting that patients with HF were surviving longer over time. Our study confirms that previously reported epidemiological trends persist and remain to ensure proper diagnostic evaluation and management of patients with HF.
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| 5. |
- Lindmark, Krister, et al.
(författare)
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Recurrent heart failure hospitalizations increase the risk of cardiovascular and all-cause mortality in patients with heart failure in Sweden: a real-world study
- 2021
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 8:3, s. 2144-2153
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Heart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality. We examined the impact of recurrent HF hospitalizations (HFHs) on cardiovascular (CV) mortality among patients with HF in Sweden.Methods and results: Adults with incident HF were identified from linked national health registers and electronic medical records from 01 January 2005 to 31 December 2013 for Uppsala and until 31 December 2014 for Västerbotten. CV mortality and all-cause mortality were evaluated. A time-dependent Cox regression model was used to estimate relative CV mortality rates for recurrent HFHs. Assessment was also done for ejection fraction-based HF phenotypes and for comorbid atrial fibrillation, diabetes, or chronic renal impairment. Overall, 3878 patients with HF having an index hospitalization were included, providing 9691.9 patient-years of follow-up. Patients were relatively old (median age: 80 years) and were more frequently male (55.5%). Compared with patients without recurrent HFHs, the adjusted hazard ratio (HR [95% confidence interval; CI]) for CV mortality and all-cause mortality were statistically significant for patients with one, two, three, and four or more recurrent HFHs. The risk of CV mortality and all-cause mortality increased approximately six-fold in patients with four or more recurrent HFHs vs. those without any HFHs (HR [95% CI]: 6.26 [5.24–7.48] and 5.59 [4.70–6.64], respectively). Similar patterns were observed across the HF phenotypes and patients with comorbidities.Conclusions: There is a strong association between recurrent HFHs and CV and all-cause mortality, with the risk increasing progressively with each recurrent HFH.
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| 6. |
- Pisani, Luigi, et al.
(författare)
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Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome : a pooled analysis of four observational studies
- 2022
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Ingår i: The Lancet Global Health. - 2214-109X. ; 10:2, s. 227-235
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Tidskriftsartikel (refereegranskat)abstract
- Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference –1·69 [–9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5–8] vs 6 [5–8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52–23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75–0·86]; p<0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding.
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| 7. |
- Stenqvist Castelo-Branco, Anna
(författare)
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Neurotrophic factors in peripheral nervous system development : function and specificity
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neurotrophic factors control a range of activities in developing neurons, including survival, proliferation, migration and neuronal differentiation. Two classes of neurotrophic factors that are strongly linked to neuronal development of the peripheral nervous system are the neurotrophins and GDNF family ligands. Like other trophic factors they act by triggering signalling through receptor tyrosine kinases. This thesis addresses novel functions for the receptor of GDNF family ligands in peripheral nervous system development and how specificity is achieved at different levels of the trophic factor signalling pathway. In paper I, NT3, which has been considered to be a promiscuous neurotrophin, is demonstrated to only signal through the TrkC receptor, despite the presence of TrkB. In genetically modified mice, NT3/TrkC, but not NT3/TrkB, could promote survival in the majority of cochleovestibular neurons. Furthermore, NT3/TrkC could not substitute for BDNF/TrkB in final target innervation of the vestibular system of the inner ear. In paper II and III, Ret, the receptor for GDNF family ligands, is shown to require the binding of the adaptor protein Frs2 to its phosphorylated tyrosine 1062 for migration. In addition, phosphorylated tyrosine 981 was also necessary for a full migratory response, showing cooperation between these tyrosines. Moreover, the subcellular localization of Ret was dependent on which adaptor that binds to tyrosine 1062, highlighting a new function for adaptor proteins. In paper IV we have ablated Ret in a subpopulation of nociceptive neurons in vivo. We show that Ret was important for the proper expression of ion channels and G protein-coupled receptors. The loss of Ret also led to behavioural changes when mechanical and hot stimuli were applied to the genetically modified mice. This demonstrates the necessity of Ret for normal development of mechano- and thermosensation. In conclusion this thesis contributes to the elucidation of how specificity in neurotrophic factor signalling is achieved and the definition of new roles for neurotrophic factors in development.
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| 8. |
- Zeisel, Amit, et al.
(författare)
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Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6226, s. 1138-1142
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Tidskriftsartikel (refereegranskat)abstract
- The mammalian cerebral cortex supports cognitive functions such as sensorimotor integration, memory, and social behaviors. Normal brain function relies on a diverse set of differentiated cell types, including neurons, glia, and vasculature. Here, we have used large-scale single-cell RNA sequencing (RNA-seq) to classify cells in the mouse somatosensory cortex and hippocampal CA1 region. We found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex. We identified numerous marker genes, which allowed alignment with known cell types, morphology, and location. We found a layer I interneuron expressing Pax6 and a distinct postmitotic oligodendrocyte subclass marked by Itpr2. Across the diversity of cortical cell types, transcription factors formed a complex, layered regulatory code, suggesting a mechanism for the maintenance of adult cell type identity.
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