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Sökning: WFRF:(Svensson Johan) > Karolinska Institutet

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1.
  • Bergström, Göran, et al. (författare)
  • Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis : The Swedish CardioPulmonary BioImage Study
  • 2024
  • Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 13:14
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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2.
  • Herlitz, Johan, et al. (författare)
  • Characteristics of cardiac arrest and resuscitation by age group : an analysis from the Swedish Cardiac Arrest Registry
  • 2007
  • Ingår i: American Journal of Emergency Medicine. - : W. B. Saunders Co.. - 0735-6757 .- 1532-8171. ; 25:9, s. 1025-1031
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The objective of this study was to describe patients who experienced an out-of-hospital cardiac arrest (OHCA) by age group.METHODS: All patients who suffered from an OHCA between 1990 and 2005 and are included in the Swedish Cardiac Arrest Registry (n = 40,503) were classified into the following age groups: neonates, younger than 1 year; young children, between 1 and 4 years; older children, between 5 and 12 years; adolescents, between 13 and 17 years; young adults, between 18 and 35 years; adults not retired, between 36 and 64 years; adults retired, between 65 and 79 years; and older adults, 80 years or older.RESULTS: Ventricular fibrillation was lowest in young children (3%) and highest in adults (35%). Survival to 1 month was lowest in neonates (2.6%) and highest in older children (7.8%). Children (<18 years), young adults (18-35 years), and adults (>35 years) survived to 1 month 24.5%, 21.2%, and 13.6% of cases, respectively (P = .0003 for trend) when found in a shockable rhythm. The corresponding figures for nonshockable rhythms were 3.8%, 3.2%, and 1.6%, respectively (P < .0001 for trend).CONCLUSIONS: There is a large variability in characteristics and outcome among patients in various age groups who experienced an OHCA. Among the large age groups, there was a successive decline in survival with increasing age in shockable and nonshockable rhythms.
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3.
  • Liwing, Johan, et al. (författare)
  • Improved survival in myeloma patients : starting to close in on the gap between elderly patients and a matched normal population
  • 2014
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 164:5, s. 684-693
  • Tidskriftsartikel (refereegranskat)abstract
    • The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population (n = 9 340 682). Median overall survival for non-high-dose treated patients was 2.8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4.9 years) compared to conventional treatment (2.3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6.9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.
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5.
  • Sundström, Johan, Professor, 1971-, et al. (författare)
  • Are there lost opportunities in chronic kidney disease? A region-wide cohort study
  • 2024
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:4
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Identify the windows of opportunity for the diagnosis of chronic kidney disease (CKD) and the prevention of its adverse outcomes and quantify the potential population gains of such prevention.DESIGN AND SETTING: Observational, population-wide study of residents in the Stockholm and Skåne regions of Sweden between 1 January 2015 and 31 December 2020.PARTICIPANTS: All patients who did not yet have a diagnosis of CKD in healthcare but had CKD according to laboratory measurements of CKD biomarkers available in electronic health records.OUTCOME MEASURES: We assessed the proportions of the patient population that received a subsequent diagnosis of CKD in healthcare, that used guideline-directed pharmacological therapy (statins, renin-angiotensin aldosterone system inhibitors (RAASi) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2i)) and that experienced adverse outcomes (all-cause mortality, cardiovascular mortality or major adverse cardiovascular events (MACE)). The potential to prevent adverse outcomes in CKD was assessed using simulations of guideline-directed pharmacological therapy in untreated subsets of the study population.RESULTS: We identified 99 382 patients with undiagnosed CKD during the study period. Only 33% of those received a subsequent diagnosis of CKD in healthcare after 5 years. The proportion that used statins or RAASi was of similar size to the proportion that didn't, regardless of how advanced their CKD was. The use of SGLT2i was negligible. In simulations of optimal treatment, 22% of the 21 870 deaths, 27% of the 14 310 cardiovascular deaths and 39% of the 22 224 MACE could have been avoided if every patient who did not use an indicated medication for their laboratory-confirmed CKD was treated with guideline-directed pharmacological therapy for CKD.CONCLUSIONS: While we noted underdiagnosis and undertreatment of CKD in this large contemporary population, we also identified a substantial realisable potential to improve CKD outcomes and reduce its burden by treating patients early with guideline-directed pharmacological therapy.
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6.
  • Sundström, Johan, et al. (författare)
  • Heart failure outcomes by left ventricular ejection fraction in a contemporary region-wide patient cohort
  • 2024
  • Ingår i: ESC Heart Failure. - 2055-5822. ; 11:3, s. 1377-1388
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: This study aimed to characterize a contemporary population with subtypes of incident or prevalent heart failure (HF) based on reduced (HFrEF), mildly reduced, or preserved (HFpEF) left ventricular ejection fraction (LVEF) and to assess how outcomes, healthcare, treatments, and healthcare costs vary between each subtype of incident HF.METHODS AND RESULTS: Using Swedish data from the CardioRenal and Metabolic disease Heart Failure (CaReMe HF) study, updated to cover a more recent time period, this population-based study characterized patients from Stockholm County, Sweden, with incident HF (patients with a first HF diagnosis between 1 January 2015 and 31 December 2019) or prevalent HF (patients with a first HF diagnosis before 1 January 2020). Patients with incident HF had LVEF measured by echocardiography within ±90 days of their first HF diagnosis, and patients with prevalent HF within 5 years prior to the index date. The 13 375 patients with prevalent HF (39.2% women, mean age 73.9 years) had multiple comorbidities (cardiovascular diseases, chronic kidney disease, diabetes, and cancer). These were already highly prevalent at the time of the first HF diagnosis in the 8042 patients with incident HF (40.5% women, mean age 72.3 years). Patients with incident HFpEF received less specialist HF care at outpatient secondary care facilities following their first HF diagnosis than those with incident HFrEF. Patients with HFrEF had higher risks of complications and exerted a higher burden, in terms of care for and costs of HF, on the healthcare system.CONCLUSIONS: This study of contemporary patients with incident HF demonstrates that those with HFpEF and HFrEF differ considerably in terms of clinical presentation, prognosis, and care, highlighting a potential to improve HF outcomes.
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7.
  • Borgegård, Tomas, et al. (författare)
  • Alzheimer's Disease : Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy
  • 2012
  • Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
  • Tidskriftsartikel (refereegranskat)abstract
    • γ-Secretase inhibition represents a major therapeutic strategy for lowering amyloid β (Aβ) peptide production in Alzheimer's disease (AD). Progress toward clinical use of γ-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The γ-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between Aβ production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of γ-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain Aβ levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious γ-secretase targeting strategy for AD.
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8.
  • Claesson, Andreas, et al. (författare)
  • Characteristics and outcome among patients suffering out-of-hospital cardiac arrest due to drowning.
  • 2008
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 76:3, s. 381-7
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To describe the characteristics and outcome among patients with out-of-hospital cardiac arrest (OHCA) caused by drowning as compared with OHCA caused by a cardiac etiology (outside home). PATIENTS AND METHODS: All the patients included in the Swedish OHCA Registry between 1990 and 2005 which were not crew witnessed, in whom cardio-pulmonary resuscitation (CPR) was attempted, were evaluated for inclusion. Those caused by drowning were compared with those with a cardiac etiology (outside home). RESULTS: Patients with OHCA due to drowning (n=255) differed from patients with OHCA with a cardiac etiology (n=7494) as they were younger, less frequently suffered a witnessed OHCA, more frequently received bystander CPR and less frequently were found in a shockable rhythm. Patients with OHCA due to drowning had a prolonged ambulance response time as compared with patients with OHCA with a cardiac etiology. Patients with OHCA due to drowning had a survival rate to 1 month of 11.5% as compared with 8.8% among patients with OHCA due to a cardiac etiology (NS). Among patients with OHCA due to drowning, only one independent predictor of survival was defined, i.e. time from calling for an ambulance until the arrival of the rescue team, with a much higher survival among patients with a shorter ambulance response time. CONCLUSION: Among patients with OHCA 0.9% were caused by drowning. They had a similar survival rate to 1 month as compared with OHCA outside home with a cardiac etiology. The factor associated with survival was the ambulance response time; a higher survival with a shorter response time.
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9.
  • Claesson, Andreas, et al. (författare)
  • Defibrillation before EMS arrival in western Sweden
  • 2017
  • Ingår i: American Journal of Emergency Medicine. - : Elsevier. - 0735-6757 .- 1532-8171. ; 35:8, s. 1043-1048
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Bystanders play a vital role in public access defibrillation (PAD) in out-of-hospital cardiac arrest (OHCA). Dual dispatch of first responders (FR) alongside emergency medical services (EMS) can reduce time to first defibrillation. The aim of this study was to describe the use of automated external defibrillators (AEDs) in OHCAs before EMS arrival.METHODS: All OHCA cases with a shockable rhythm in which an AED was used prior to the arrival of EMS between 2008 and 2015 in western Sweden were eligible for inclusion. Data from the Swedish Register for Cardiopulmonary Resuscitation (SRCR) were used for analysis, on-site bystander and FR defibrillation were compared with EMS defibrillation in the final analysis.RESULTS: Of the reported 6675 cases, 24% suffered ventricular fibrillation (VF), 162 patients (15%) of all VF cases were defibrillated before EMS arrival, 46% with a public AED on site. The proportion of cases defibrillated before EMS arrival increased from 5% in 2008 to 20% in 2015 (p<0.001). During this period, 30-day survival increased in patients with VF from 22% to 28% (p=0.04) and was highest when an AED was used on site (68%), with a median delay of 6.5min from collapse to defibrillation. Adjusted odds ratio for on-site defibrillation versus dispatched defibrillation for 30-day survival was 2.45 (95% CI: 1.02-5.95).CONCLUSIONS: The use of AEDs before the arrival of EMS increased over time. This was associated with an increased 30-day survival among patients with VF. Thirty-day survival was highest when an AED was used on site before EMS arrival.
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10.
  • Emami Khoonsari, Payam, et al. (författare)
  • The human CSF pain proteome
  • 2019
  • Ingår i: Journal of Proteomics. - : ELSEVIER SCIENCE BV. - 1874-3919 .- 1876-7737. ; 190, s. 67-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic pain represents one of the major medical challenges in the 21st century, affecting > 1.5 billion of the world population. Overlapping and heterogenous symptoms of various chronic pain conditions complicate their diagnosis, emphasizing the need for more specific biomarkers to improve the diagnosis and understand the disease mechanisms. We have here investigated proteins found in human CSF with respect to known "pain" genes and in a cohort of patients with dysfunctional pain (fibromyalgia, FM), inflammatory pain (rheumatoid arthritis patients, RA) and non-pain controls utilized semi-quantitative proteomics using mass spectrometry (MS) to explore quantitative differences between these cohorts of patients. We found that "pain proteins" detected in CSF using MS are typically related to synaptic transmission, inflammatory responses, neuropeptide signaling- and hormonal activity. In addition, we found ten proteins potentially associated with chronic pain in FM and RA: neural cell adhesion molecule L1, complement C4-A, lysozyme C, receptor-type tyrosine-protein phosphatase zeta, apolipoprotein D, alpha-1-antichymotrypsin, granulins, calcium/calmodulin-dependent protein kinase type II subunit alpha, mast/stem cell growth factor receptor Kit, prolow-density lipoprotein receptor-related protein 1. These proteins might be of importance for understanding the mechanisms of dysfunctional/inflammatory chronic pain and also for use as potential biomarkers. Significance: Chronic pain is a common disease and it poses a large burden on worldwide health. Fibromyalgia (FM) is a heterogeneous disease of unknown etiology characterized by chronic widespread pain (CWP). The diagnosis and treatment of FM is based on the analysis of clinical assessments and no measurable biomarkers are available. Cerebrospinal fluid (CSF) has been historically considered as a rich source of biomarkers for diseases of nervous system including chronic pain. Here, we explore CSF proteome of FM patients utilizing mass spectrometry based quantitative proteomics method combined with multivariate data analysis in order to monitor the dynamics of the CSF proteome. Our findings in this exploratory study support notable presence of pain related proteins in CSF yet with specific domains including inflammatory responses, neuropeptide signaling- and hormonal activity. We have investigated molecular functions of significantly altered proteins and demonstrate presence of 176 known pain related proteins in CSF. In addition, we found ten proteins potentially associated with pain in FM and RA: neural cell adhesion molecule L1, complement C4-A, lysozyme C, receptor-type tyrosine-protein phosphatase zeta, apolipoprotein D, alpha-1-antichymotrypsin, granulins, calcium/calmodulindependent protein kinase type II subunit alpha, mast/stem cell growth factor receptor Kit, prolow-density lipoprotein receptor-related protein 1. These proteins are novel in the context of FM but are known to be involved in pain mechanisms including inflammatory response and signal transduction. These results should be of clear significance and interest for researchers and clinicians working in the field of pain utilizing human CSF and MS based proteomics.
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