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| 5. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 6. |
- Gehlen, J., et al.
(författare)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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Ingår i: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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| 7. |
- Adam, A, et al.
(författare)
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Abstracts from Hydrocephalus 2016.
- 2017
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Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Gräsner, J. -T, et al.
(författare)
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Epidemiology of cardiac arrest in Europe : European Resuscitation Council Guidelines 2021
- 2021
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Ingår i: Notfall & Rettungsmedizin. - : Springer Medizin. - 1434-6222 .- 1436-0578. ; 24:4, s. 346-366
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Tidskriftsartikel (refereegranskat)abstract
- In this section of the European Resuscitation Council Guidelines 2021, key information on the epidemiology and outcome of in- and out-of-hospital cardiac arrest are presented. Key contributions from the European Registry of Cardiac Arrest (EuReCa) collaboration are highlighted. Recommendations are presented to enable health systems to develop registries as a platform for quality improvement and to provide support for health system planning and responses to cardiac arrest.
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| 11. |
- Gräsner, J. -T, et al.
(författare)
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European Resuscitation Council Guidelines 2021 : Epidemiology of cardiac arrest in Europe
- 2021
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Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 161, s. 61-79
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Tidskriftsartikel (refereegranskat)abstract
- In this section of the European Resuscitation Council Guidelines 2021, key information on the epidemiology and outcome of in and out of hospital cardiac arrest are presented. Key contributions from the European Registry of Cardiac Arrest (EuReCa) collaboration are highlighted. Recommendations are presented to enable health systems to develop registries as a platform for quality improvement and to inform health system planning and responses to cardiac arrest.
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| 12. |
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| 13. |
- Langstrom, B, et al.
(författare)
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PET i klinisk verksamhet.
- 1995
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Ingår i: Läkartidningen. ; 92, s. 3202-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Lilja, Gisela, et al.
(författare)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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Ingår i: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 17. |
- Pammi, Mohan, et al.
(författare)
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Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis : a systematic review and meta-analysis
- 2017
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Ingår i: Microbiome. - : BIOMED CENTRAL LTD. - 2049-2618. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Background: Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results. Methods and results: Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using cultureindependent molecular techniques and reported a and beta-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean +/- SD of 30.1 +/- 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha-or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5). Conclusions: Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC.
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| 18. |
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| 19. |
- Stenman, U H, et al.
(författare)
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Summary report of the TD-3 workshop: characterization of 83 antibodies against prostate-specific antigen
- 1999
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1423-0380 .- 1010-4283. ; 20:Suppl. 1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Twelve research groups participated in the ISOBM TD-3 Workshop in which the reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety of techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays and immunohistochemistry, the antibodies were categorized into six major groups which formed the basis for mapping onto two- and three-dimensional (2-D and 3-D) models of PSA. The overall findings of the TD-3 Workshop are summarized in this report. In agreement with all participating groups, three main antigenic domains were identified: free PSA-specific epitopes located in or close to amino acids 86-91; discontinuous epitopes specific for PSA without human kallikrein (hK2) cross-reactivity located at or close to amino acids 158-163; and continuous or linear epitopes shared between PSA and hK2 located close to amino acids 3-11. In addition, several minor and partly overlapping domains were also identified. Clearly, the characterization of antibodies from this workshop and the location of their epitopes on the 3-D model of PSA illustrate the importance of selecting appropriate antibody pairs for use in immunoassays. It is hoped that these findings and the epitope nomenclature described in this TD-3 Workshop are used as a standard for future evaluation of anti-PSA antibodies.
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| 20. |
- Udén, P, et al.
(författare)
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Preoperative localization in unilateral parathyroid surgery. A cost-benefit study on ultrasound, computed tomography and scintigraphy
- 1990
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Ingår i: Acta Chirurgica Scandinavica. - 0001-5482. ; 156:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- In 50 patients with primary hyperparathyroidism, investigation before initial neck exploration included ultrasonography, computed tomography and 99technetium-201thallium subtraction scintigraphy. The sensitivity for correct preoperative localization was 50%, 54% and 56%, respectively. There was marked inter-observer variation in assessment of ultrasonography and computed tomography, while scintigrams were evaluated by only one person. The scintigraphic sensitivity increased with size of the glands. In cases where correct preoperative localization permitted unilateral parathyroidectomy, the time for surgery and anesthesia was significantly reduced. A cost-benefit analysis, however, revealed that the financial saving from this time reduction was outweighed by the cost of the localization procedures. The authors conclude that investigations for definition of enlarged parathyroid glands are not indicated prior to unilateral parathyroidectomy.
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| 22. |
- Abrahamsson, P. ‐A, et al.
(författare)
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Immunohistochemical distribution of the three predominant secretory proteins in the parenchyma of hyperplastic and neoplastic prostate glands
- 1988
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 12:1, s. 39-46
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Tidskriftsartikel (refereegranskat)abstract
- Prostatic acid phosphatase (PAP), prostate‐specific antigen (PSA), and β‐microseminoprotein (β‐MSP) were regularly localized immunohistochemically to the epithelium of the acini and that of the ducts in the nodules of 24 cases of benign prostatic hyperplasia. The immunohistochemical distribution of these three prostatic‐secreted proteins was also examined, with monoclonal antisera against PAP and PSA and with polyclonal antisera against PAP, PSA, and β‐MSP, in a series of 40 cases of prostatic adenocarcinomas graded according to the WHO classification. Highly differentiated (grade I) carcinomas showed a high incidence of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells. As in the normal and hyperplastic prostate parenchyma, highly differentiated (grade I) carcinomas were found to contain an almost equal number of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells. When semiquantitatively assessed, the incidence of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells was found to be lower in the moderately and poorly differentiated (grades II and III) tumors than in the highly differentiated ones; they also showed greater staining variability. Tumor cells immunoreactive with a monoclonal antiserum raised against PAP in carcinomas of grades II and III were less frequent than tumor cells immunoreactive with antisera against PSA, β‐MSP, and a polyclonal antiserum against PAP. The almost identical distribution of PSA and β‐MSP in carcinomas of grades II and III suggests that PSA and β‐MSP are not less sensitive tumor markers than PAP for the monitoring of the course and the treatment of prostatic carcinomas.
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| 26. |
- Andersson, JLR, et al.
(författare)
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Regional cerebral blood flow and oxygen metabolism during migraine with and without aura
- 1997
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Ingår i: CEPHALALGIA. - : SCANDINAVIAN UNIVERSITY PRESS. - 0333-1024. ; 17:5, s. 570-579
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Eleven cases of migraine with and without aura were investigated with positron emission tomography (PET). Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO(2)) and oxygen extraction (rOER) were measured during baseline (n = 11), aura (n = 6),
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| 40. |
- Brawer, M. K., et al.
(författare)
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Prostate-specific antigen and other serum markers : Current concepts from the world health organization second international consultation on prostate cancer
- 1999
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Ingår i: Seminars in Urologic Oncology. - 1081-0943. ; 17:4, s. 206-221
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Forskningsöversikt (refereegranskat)abstract
- Serum prostate-specific antigen is credited with dramatic advances in the early detection, screening, and management of men with prostatic carcinoma. There has been more than a twofold increase in the number of men diagnosed during the last decade, and prostate cancer has emerged as the most common non-skin cancer and the second leading cause of cancer death in men. This report summarizes the history and current status of prostate-specific antigen and other serum markers, incorporating consensus opinions from the Second International Consultation on Prostate Cancer held in Paris in June 1999.
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| 41. |
- Cannerfelt, B., et al.
(författare)
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White matter lesions and brain atrophy in systemic lupus erythematosus patients : correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus
- 2018
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 27:7, s. 1140-1149
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods: Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results: The total volume of white matter lesions was significantly larger in SLE patients compared to HIs (p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion: SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.
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| 42. |
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| 43. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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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, .)
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| 44. |
- De Kanter, M., et al.
(författare)
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A prospective study of orthostatic blood pressure in diabetic patients
- 1998
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Ingår i: Clinical Autonomic Research. - 0959-9851. ; 8:4, s. 189-193
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Tidskriftsartikel (refereegranskat)abstract
- To clarify whether orthostatic blood pressure is affected by the type of diabetes, cardiac autonomic neuropathy, and the duration of diabetes, orthostatic blood pressure (passive 90°tilt) was evaluated in 102 patients with insulin dependent diabetes mellitus (IDDM), 51 patients with non-insulin dependent diabetes mellitus (NIDDM), and in 238 control subjects in a first study followed up after 8 to 17 years. The heart rate reaction during deep breathing (E/I ratio) and to tilt (acceleration and brake indices) assessed cardiac autonomic function. In the first study, the lowest systolic blood pressure (LSBP) and the lowest diastolic blood pressure (LDBP) after tilt were significantly lower in IDDM patients compared with NIDDM patients (p < 0.001 for LSBP and p < 0.05 for LDBP) and controls (p < 0.001). LDBP was, however, also significantly lower (p < 0.05) in NIDDM patients than in controls. Hence, although most severe in IDDM, LDBP was disturbed in both types of diabetes. In IDDM, a low E/I ratio was associated with disturbed orthostatic blood pressure. At follow-up examinations, orthostatic blood pressure deteriorated in NIDDM but not in IDDM patients. In conclusion, LSBP and LDBP were impaired in IDDM patients compared with NIDDM and control subjects; however, LDBP was also impaired in NIDDM patients compared with controls. When the duration of diabetes increased, orthostatic blood pressure deteriorated in NIDDM but not in IDDM patients.
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| 45. |
- Despotou, George, et al.
(författare)
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Localisation, Personalisation and Delivery of Best Practice Guidelines on an Integrated Care and Cure Cloud Architecture : The C3-Cloud Approach to Managing Multimorbidity
- 2020
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Ingår i: Digital Personalized Health and Medicine. - : IOS Press. - 9781643680835 - 9781643680828 ; , s. 623-627
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Konferensbidrag (refereegranskat)abstract
- BACKGROUND: C3-Cloud is an integrated care ICT infrastructure offering seamless patient-centered approach to managing multimorbidity, deployed in three European pilot sites. Challenge: The digital delivery of best practice guidelines unified for multimorbidity, customized to local practice, offering the capability to improve patient personalization and benefit.METHOD: C3-Cloud has adopted a co-production approach to developing unified multimorbidity guidelines, by collating and reconciling best practice guidelines for each condition. Clinical and technical teams at pilot sites and the C3-Cloud consortium worked in tandem to create the specification and technical implementation.RESULTS: C3-Cloud offers CDSS for diabetes, renal failure, depression and congenital heart failure, with over 300 rules and checks that deliver four best practice guidelines in parallel, customized for each pilot site.CONCLUSIONS: The process provided a traceable, maintainable and audited digitally delivered collated and reconciled guidelines.
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| 47. |
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| 49. |
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| 50. |
- Elmstahl, S., et al.
(författare)
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Body composition in patients with Alzheimer's disease and healthy controls
- 1992
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Ingår i: Journal of Clinical and Experimental Gerontology. - 0192-1193. ; 14:1, s. 17-31
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Tidskriftsartikel (refereegranskat)abstract
- In Alzheimer's disease (AD), decreased physical activity and nutritional problems are parts of the natural course with probable implications on body composition. Body fat and lean body mass were measured with a bioelectrical impedance method in 25 women who had AD according to the criteria of NINCDS- ADRDA and in 63 health age-matched controls. The patients with AD had 9.5 kg lower body weight (p<0.01), due to almost 4.0 kg lower body fat and 6.0 kg lower lean body mass (p<0.001). This might imply a higher risk for morbidity and mortality. Body weight and lean body mass decreased with age in AD patients but not in the healthy control women. In the control group, the unmarried women had more than 13 kg lower body weight and 9 kg lower body fat than the mean values of all other marital status groups (p<0.01). The maintenance of lean body mass in the very healthy old indicate the possibilities for physical activity.
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