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  • Al-Dury, Nooraldeen, et al. (författare)
  • Identifying the relative importance of predictors of survival in out of hospital cardiac arrest : a machine learning study
  • 2020
  • Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central. - 1757-7241 .- 1757-7241. ; 28:1, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Studies examining the factors linked to survival after out of hospital cardiac arrest (OHCA) have either aimed to describe the characteristics and outcomes of OHCA in different parts of the world, or focused on certain factors and whether they were associated with survival. Unfortunately, this approach does not measure how strong each factor is in predicting survival after OHCA. Aim: To investigate the relative importance of 16 well-recognized factors in OHCA at the time point of ambulance arrival, and before any interventions or medications were given, by using a machine learning approach that implies building models directly from the data, and arranging those factors in order of importance in predicting survival. Methods: Using a data-driven approach with a machine learning algorithm, we studied the relative importance of 16 factors assessed during the pre-hospital phase of OHCA We examined 45,000 cases of OHCA between 2008 and 2016. Results: Overall, the top five factors to predict survival in order of importance were: initial rhythm, age, early Cardiopulmonary Resuscitation (CPR, time to CPR and CPR before arrival of EMS), time from EMS dispatch until EMS arrival, and place of cardiac arrest The largest difference in importance was noted between initial rhythm and the remaining predictors. A number of factors, including time of arrest and sex were of little importance. Conclusion: Using machine learning, we confirm that the most important predictor of survival in OHCA is initial rhythm, followed by age, time to start of CPR, EMS response time and place of OHCA. Several factors traditionally viewed as important e.g. sex, were of little importance.
  • Albert, Malin, et al. (författare)
  • Cardiac arrest after pulmonary aspiration in hospitalised patients : a national observational study.
  • 2020
  • Ingår i: BMJ Open. - 2044-6055 .- 2044-6055. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To study characteristics and outcomes among patients with in-hospital cardiac arrest (IHCA) due to pulmonary aspiration.DESIGN: A retrospective observational study based on data from the Swedish Registry of Cardiopulmonary Resuscitation (SRCR).SETTING: The SRCR is a nationwide quality registry that covers 96% of all Swedish hospitals. Participating hospitals vary in size from secondary hospitals to university hospitals.PARTICIPANTS: The study included patients registered in the SRCR in the period 2008 to 2017. We compared patients with IHCA caused by pulmonary aspiration (n=127), to those with IHCA caused by respiratory failure of other causes (n=2197).PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was 30-day survival. Secondary outcome was sustained return of spontaneous circulation (ROSC) defined as ROSC at the scene and admitted alive to the intensive care unit.RESULTS: In the aspiration group 80% of IHCA occurred on general wards, as compared with 63.6% in the respiratory failure group (p<0.001). Patients in the aspiration group were less likely to be monitored at the time of the arrest (18.5% vs 38%, p<0.001) and had a significantly lower rate of sustained ROSC (36.5% vs 51.6%, p=0.001). The unadjusted 30-day survival rate compared with the respiratory failure group was 7.9% versus 18.0%, p=0.024. In a propensity score analysis (including variables; year, age, gender, location of arrest, initial heart rhythm, ECG monitoring, witnessed collapse and a previous medical history of; cancer, myocardial infarction or heart failure) the OR for 30-day survival was 0.46 (95% CI 0.19 to 0.94).CONCLUSIONS: In-hospital cardiac arrest preceded by pulmonary aspiration occurred more often on general wards among unmonitored patients. These patients had a lower 30-day survival rate compared with IHCA caused by respiratory failure of other causes.
  • Dankiewicz, J., et al. (författare)
  • Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
  • 2021
  • Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
  • Dankiewicz, J., et al. (författare)
  • Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
  • 2019
  • Ingår i: American Heart Journal. - : Mosby. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
  • Eyjolfsdottir, H., et al. (författare)
  • Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device
  • 2016
  • Ingår i: Alzheimers Research & Therapy. - 1758-9193. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. Methods: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day. Results: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable. Conclusions: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.
  • Fredman, David, et al. (författare)
  • Use of a geographic information system to identify differences in automated external defibrillator installation in urban areas with similar incidence of public out-of-hospital cardiac arrest : A retrospective registry-based study
  • 2017
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055 .- 2044-6055. ; 7:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Early defibrillation in out-of-hospital cardiac arrest (OHCA) is of importance to improve survival. In many countries the number of automated external defibrillators (AEDs) is increasing, but the use is low. Guidelines suggest that AEDs should be installed in densely populated areas and in locations with many visitors. Attempts have been made to identify optimal AED locations based on the incidence of OHCA using geographical information systems (GIS), but often on small datasets and the studies are seldom reproduced. The aim of this paper is to investigate if the distribution of public AEDs follows the incident locations of public OHCAs in urban areas of Stockholm County, Sweden. Method OHCA data were obtained from the Swedish Register for Cardiopulmonary Resuscitation and AED data were obtained from the Swedish AED Register. Urban areas in Stockholm County were objectively classified according to the pan-European digital mapping tool, Urban Atlas (UA). Furthermore, we reclassified and divided the UA land cover data into three classes (residential, non-residential and other areas). GIS software was used to spatially join and relate public AED and OHCA data and perform computations on relations and distance. Results Between 1 January 2012 and 31 December 2014 a total of 804 OHCAs occurred in public locations in Stockholm County and by December 2013 there were 1828 AEDs available. The incidence of public OHCAs was similar in residential (47.3%) and non-residential areas (43.4%). Fewer AEDs were present in residential areas than in non-residential areas (29.4% vs 68.8%). In residential areas the median distance between OHCAs and AEDs was significantly greater than in non-residential areas (288 m vs 188 m, p<0.001). Conclusion The majority of public OHCAs occurred in areas classified in UA as 'residential areas' with limited AED accessibility. These areas need to be targeted for AED installation and international guidelines need to take geographical location into account when suggesting locations for AED installation.
  • Jonsson, M., et al. (författare)
  • Survival after out-of-hospital cardiac arrest is associated with area-level socioeconomic status
  • 2019
  • Ingår i: Heart. - 1355-6037 .- 1468-201X. ; 105:8, s. 632-638
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Out-of-hospital cardiac arrest (OHCA) is a major cause of death in the Western world. In this study we aimed to investigate the relationship between area-level socioeconomic status (SES) and 30-day survival after OHCA. We hypothesised that high SES at an area level is associated with an improved chance of 30-day survival. Methods Patients with OHCA in Stockholm County between 1 January 2006 and 31 December 2015 were analysed retrospectively. To quantify area-level SES, we linked the patient's home address to 250 x 250/1000 x 1000 meter grids with aggregated information about income and education. We constructed multivariable logistic regression models in which area-level SES measures were adjusted for age, sex, emergency medical services response time, witnessed status, initial rhythm, aetiology, location and year of cardiac arrest. Results We included 7431 OHCAs. There was significantly greater 30-day survival (p=0.003) in areas with a high proportion of university-educated people. No statistically significant association was seen between median disposable income and 30-day survival. The adjusted OR for 30-day survival among patients in the highest educational quintile was 1.70 (95% CI 1.15 to 2.51) compared with patients in the lowest educational quintile. We found no significant interaction for sex. Positive trend with increasing area-level education was seen in both men and women but the trend was only statistically significant among men (p=0.012) Conclusions Survival to 30 days after OHCA is positively associated with the average educational level of the residential area. Area-level income does not independently predict 30-day survival after OHCA.
  • Karami, Azadeh, et al. (författare)
  • Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 11:11, s. 1316-1328
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase. Method: Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed. Results: Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-beta, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. Discussion: A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.
  • Libungan, Berglind, et al. (författare)
  • Out-of-hospital cardiac arrest in the elderly : A large-scale population-based study.
  • 2015
  • Ingår i: Resuscitation. - 0300-9572 .- 1873-1570. ; 94
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There is little information on elderly people who suffer from out-of-hospital cardiac arrest (OHCA).AIM: To determine 30-day mortality and neurological outcome in elderly patients with OHCA.METHODS: OHCA patients ≥ 70 years of age who were registered in the Swedish Cardiopulmonary Resuscitation Register between 1990 and 2013 were included and divided into three age categories (70-79, 80-89, and ≥ 90 years). Multiple logistic regression analyses were performed to identify independent predictors of 30-day survival.RESULTS: Altogether, 36,605 cases were included in the study. Thirty-day survival was 6.7% in patients aged 70-79 years, 4.4% in patients aged 80-89 years, and 2.4% in those over 90 years. For patients with witnessed OHCA of cardiac aetiology found in a shockable rhythm, survival was higher: 20%, 15%, and 11%, respectively. In 30-day survivors, the distribution according to the cerebral performance categories (CPC) score at discharge from hospital was similar in the three age groups. In multivariate analysis, in patients over 70 years of age, the following factors were associated with increased chance of 30-day survival: younger age, OHCA outside the home, witnessed OHCA, CPR before arrival of EMS, shockable first-recorded rhythm, and short emergency response time.CONCLUSIONS: Advanced age is an independent predictor of mortality in OHCA patients over 70 years of age. However, even in patients above 90 years of age, defined subsets with a survival rate of more than 10% exist. In survivors, the neurological outcome remains similar regardless of age.
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