| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Burdett, S., et al.
(författare)
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Adjuvant chemotherapy for resected early-stage non-small cell lung cancer
- 2015
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Ingår i: Cochrane Database of Systematic Reviews. - 1469-493X. ; :3
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Forskningsöversikt (refereegranskat)abstract
- Background To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC), we performed two systematic reviews andmeta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010. Objectives To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival: A. Surgery versus surgery plus adjuvant chemotherapy B. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy in patients with histologically diagnosed early stage NSCLC. (2) To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival. Search methods We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, hand-searching relevant meeting proceedings and by discussion with trialists and organisations. Selection criteria We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment. Data collection and analysis We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status. Main results We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p< 0.0001), with an absolute increase in survival of 4% at five years. We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years. For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup. We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low. Authors' conclusions Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- Best, Myron G., et al.
(författare)
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Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
- 2017
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 32:2, s. 238-252
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Tidskriftsartikel (refereegranskat)abstract
- Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.
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| 6. |
- Maurer, H, et al.
(författare)
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When is a bystander not a bystander any more? A European Survey.
- 2018
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There is international variation in the rates of bystander cardiopulmonary resuscitation (CPR). 'Bystander CPR' is defined in the Utstein definitions, however, differences in interpretation may contribute to the variation reported. The aim of this cross-sectional survey was to understand how the term 'bystander CPR' is interpreted in Emergency Medical Service (EMS) across Europe, and to contribute to a better definition of 'bystander' for future reference.METHODS: During analysis of the EuReCa ONE study, uncertainty about the definition of a 'bystander' emerged. Sixty scenarios were developed, addressing the interpretation of 'bystander CPR'. An electronic version of the survey was sent to 27 EuReCa National Coordinators, who distributed it to EMS representatives in their countries. Results were descriptively analysed.RESULTS: 362 questionnaires were received from 23 countries. In scenarios where a layperson arrived on scene by chance and provided CPR, up to 95% of the participants agreed that 'bystander CPR' had been performed. In scenarios that included community response systems, firefighters and/or police personnel, the percentage of agreement that 'bystander CPR' had been performed ranged widely from 16% to 91%. Even in scenarios that explicitly matched examples provided in the Utstein template there was disagreement on the definition.CONCLUSION: In this survey, the interpretation of 'bystander CPR' varied, particularly when community response systems including laypersons, firefighters, and/or police personnel were involved. It is suggested that the definition of 'bystander CPR' should be revised to reflect changes in treatment of OHCA, and that CPR before arrival of EMS is more accurately described.
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| 7. |
- Rosell, A., et al.
(författare)
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Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease
- 2005
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Ingår i: Arch Intern Med. - 0003-9926. ; 165:8, s. 891-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The culture of bronchial secretions from the lower airway has been reported to be positive for potentially pathogenic microorganisms (PPMs) in patients with stable chronic obstructive pulmonary disease (COPD), but the determinants and effects of this bacterial load in the airway are not established. METHODS: To determine the bronchial microbial pattern in COPD and its relationship with exacerbation, we pooled analysis of crude data from studies that used protected specimen brush sampling, with age, sex, smoking, lung function, and microbiologic features of the lower airway as independent variables and exacerbation as the outcome, using logistic regression modeling. RESULTS: Of 337 study participants, 70 were healthy, 181 had stable COPD, and 86 had exacerbated COPD. Differences in the microbial characteristics in the participating laboratories were not statistically significant. A cutoff point of 10(2) colony-forming units (CFU) per milliliter or greater for the identification of abnormal positive culture results for PPMs was defined using the 95th percentile in the pooled analysis of healthy individuals. Bronchial colonization of 10(2) CFU/mL or greater by PPMs was found in 53 patients with stable COPD (29%) and in 46 patients with exacerbated COPD (54%) (P<.001, chi(2) test), with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Higher microbial loads were associated with exacerbation and showed a statistically significant dose-response relationship after adjustment for covariates (odds ratio, 3.62; 95% confidence interval, 1.47-8.90), but P aeruginosa persisted as a statistically significant risk factor after adjustment for microbial load (odds ratio, 11.12; 95% confidence interval, 1.17-105.82). CONCLUSIONS: One quarter of the patients with COPD are colonized by PPMs during their stable periods. Exacerbation is associated with the overgrowth of PPMs and with the appearance of P aeruginosa in the lower airway, which is associated with exacerbation symptoms independent of load.
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| 8. |
- Gräsner, Jan-Thorsten, et al.
(författare)
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EuReCa ONE-27 Nations, ONE Europe, ONE Registry : A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe.
- 2016
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 105, s. 188-195
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.METHODS: This was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.RESULTS: Data on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.CONCLUSION: The results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe. EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events.
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| 9. |
- Rosell, Magdalena, et al.
(författare)
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Generation Pep Study: A population‐based survey on diet and physical activity in 12,000 Swedish children and adolescents
- 2021
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 110:9, s. 2597-2606
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Tidskriftsartikel (refereegranskat)abstract
- Aim This study presents dietary intake and physical activity in a large nationally representative sample of children and adolescents in Sweden. It also reports the study protocol for the Generation Pep Study that will be used for yearly repeated measurements. Methods A random sample of children and adolescents aged 4–17 years living in Sweden was invited to fill in a Web‐based questionnaire on dietary intake and physical activity. For participants aged <12 years, the parents were asked to fill in the questionnaire together with their child. Information on socio‐economic background was collected from the parents. Results A total number of 12,441 children and adolescents participated in the study (participation rate 43%). The results indicate that 13‐ to 17‐year‐olds have notably less healthy dietary intake and lower physical activity compared with younger age groups. In general, the dietary intake was most healthy among 4‐ to 6‐year‐olds. A socio‐economic gradient was seen for many of the studied variables. Conclusion Participants of a high socio‐economic status and younger age generally had healthier dietary intake and higher physical activity. The study provides novel national data as it includes a wide age of children and adolescents (4–17 years).
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