| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Carbajal, Ricardo, et al.
(författare)
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Pain Assessment In Ventilated And Non-ventilated Neonates In Nicus Across Europe : European Pain Audit In Neonates (europain Survey)
- 2014
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Ingår i: Archives of Disease in Childhood. - London, United Kingdom : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 99, s. A68-A68
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neonates undergo many painful procedures during their NICU stay. These may include tracheal intubation/ventilation, skin-breaking procedures, drainage/suctioning of body orifices or cavities. Inherent subjectivity and difficulties of neonatal pain assessment contribute to a wide variety of assessment tools and clinical practices. To date, these practices have been not studied at a large scale.Objective: To determine current clinical practices for neonatal pain assessment in NICUs across Europe.Methods: An epidemiological observational study on bedside pain assessment practices collected data for all neonates in participating NICUs until infants left the unit (discharge, death, transfer to another hospital) or for 28 days. Data collection occurred via an online database for 1 month at each NICU. All neonates up to a gestational age of 44 weeks were included.Results: From October 2012 to June 2013, 243 NICUs from 18 European countries collected pain assessment data in 6680 neonates. Of these, 2142 received tracheal ventilation (TV), 1496 non-invasive ventilation (NIV) and 3042 only spontaneous ventilation (SV). The median (IQR) gestational age of TV, NIV and SV neonates were 32.1 (28.1–37.4), 33.6 (31.0–36.6) and 37.9 (35.0–39.9), respectively (p < 0.001). Overall, 58.5% of TV neonates, 45.0% of NIV neonates and 30.4% of SV neonates received bedside pain assessments (p < 0.001). Fig. shows pain assessments by country.Conclusions: Over half (58.5%) of TV neonates and less than half (45.0%) of NIV neonates had pain assessments performed in European NICUs. Wide variations in the rates of pain assessment exist among countries and an important improvement seems necessary.
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| 3. |
- Carbajal, Ricardo, et al.
(författare)
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Sedation And Analgesia For Neonates In Nicus Across Europe : The Europain Survey
- 2014
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Ingår i: Archives of Disease in Childhood. - London, United Kingdom : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 99, s. A64-A64
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pain and stress induced by mechanical ventilation, invasive procedures, or painful diseases supports the use of sedation/analgesia (S/A) in newborns admitted to Neonatal Intensive Care Units (NICUs). To date, these practices have not been studied at a large scale.Objective: To determine current clinical practices regarding the use of S/A drugs in NICUs across Europe.Methods: This epidemiological observational study on bedside clinical practices regarding S/A collected data for all neonates in participating NICUs until the infant left the unit (discharge, death, transfer) or for up to 28 days. Data collection occurred via an online database for 1 month at each NICU. All neonates up to 44 weeks gestation were included.Results: From October 2012 to June 2013, 243 NICUs from 18 European countries collected data on 6680 eligible neonates. Of these, 2142 received tracheal ventilation (TV), 1496 non-invasive ventilation (NIV) and 3042 only spontaneous ventilation (SV). The median (IQR) gestational age of TV, NIV and SV neonates were 32.1 (28.1–37.4), 33.6 (31.0–36.6) and 37.9 (35.0–39.9), respectively (p < 0.001). Overall, more TV neonates [81.5% (n = 1746)] received S/A drugs than NIV neonates [17.8% (n = 266)] and SV neonates [9.3% (n = 282)]; p < 0.001. Fig. shows the rate of S/A use by country; table shows S/A drugs used.Conclusions: Most ventilated but few non-ventilated neonates (NIV and SV) receive S/A therapy in European NICUs. Wide variations in S/A use, drugs used, and mode of administration (continuous, bolus, or both) exist among countries.
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| 4. |
- De Groot, Natasja M.S., et al.
(författare)
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Critical appraisal of technologies to assess electrical activity during atrial fibrillation : a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology
- 2022
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129. ; 24:2, s. 313-330
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Forskningsöversikt (refereegranskat)abstract
- We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.
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| 5. |
- Anand, Kanwlajeet J. S., et al.
(författare)
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Assessment of continuous pain in newborns admitted to NICUs in 18 European countries
- 2017
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 106:8, s. 1248-1259
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown.Methods: A prospective cohort study in 243 Neonatal Intensive Care Units (NICUs) from 18 European countries recorded frequency of pain assessments, use of mechanical ventilation, sedation, analgesia, or neuromuscular blockade for each neonate upto 28 days after NICU admission.Results: Only 2113/6648 (31·8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46·0%), noninvasive ventilation (NiV, 35·0%), and no ventilation (NoV, 20·1%) groups (p<0·001). Daily assessments for continuous pain occurred in only 10·4% of all neonates (TrV: 14·0%, NiV: 10·7%, NoV: 7·6%; p<0·001). More frequent assessments of continuous pain occurred in NICUs with pain guidelines, nursing champions, and surgical admissions prompted (all p<0·01), and for newborns <32 weeks gestational age, those requiring ventilation, or opioids, sedatives-hypnotics, general anesthetics (O-SH-GA) (all p<0·001), or surgery (p=0·028). Use of O-SH-GA drugs increased the odds for pain assessment in the TrV (OR:1·60, p<0·001) and NiV groups (OR:1·40, p<0·001).Conclusion: Assessments of continuous pain occurred in less than one-third of NICU admissions, and daily in only 10% of neonates. NICU clinical practices should consider including routine assessments of continuous pain in newborns.
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| 6. |
- Anand, K J S, et al.
(författare)
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Effects of morphine analgesia in ventilated preterm neonates : primary outcomes from the NEOPAIN randomised trial
- 2004
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 363:9422, s. 1673-82
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates.METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1)) were continued as long as clinically justified (maximum 14 days). Open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Analyses were by intention to treat.FINDINGS: Baseline variables were similar in the randomised groups. The placebo and morphine groups had similar rates of the composite outcome (105/408 [26%] vs 115/419 [27%]), neonatal death (47/449 [11%] vs 58/449 [13%]), severe IVH (46/429 [11%] vs 55/411 [13%]), and PVL (34/367 [9%] vs 27/367 [7%]). For neonates who were not given open-label morphine, rates of the composite outcome (53/225 [24%] vs 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs 6/189 [3%], p=0.0209) were higher in the morphine group than the placebo group. Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine (78/228 [34%] vs 27/179 [15%], p<0.0001). Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH (36/190 [19%] vs 19/219 [9%], p=0.0024).INTERPRETATION: Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.
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| 7. |
- Carbajal, Ricardo, et al.
(författare)
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Pain Assessment in Ventilated and Non-Ventilated Neonates in NICUS across Europe : Results from the EUROPAIN Study
- 2016
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Konferensbidrag (refereegranskat)abstract
- Aim of Investigation: Pain from invasive or noninvasive procedures, mechanical ventilation, or painful medical and surgical conditions is commonplace in neonatal intensive care units (NICUs). While prevention and treatment of neonatal pain seem essential, an adequate analgesic approach cannot be implemented without relevant and timely pain assessments. Data on neonatal pain assessment practices are scarce, with undefined best practices or clinical benefits. We aimed to describe pain assessment practices in 243 NICUs from 18 European countries and to examine the NICU and patient characteristics influencing pain assessments at the bedside.Methods: Demographic data, modes of respiration, use of sedation, analgesia, or neuromuscular blockers, frequency and types of pain assessments were recorded for all newborns during the first 28 days of NICU admission. Multivariable models tested the associations between the performance of pain assessments and center and neonatal factors.Results: Among 6648 neonates enrolled, highest level of ventilation during the study period classified patients into tracheal ventilation (TV, n=2138 [32%]), non-invasive ventilation (NIV, n=1493 [23%]), and spontaneous ventilation groups (SV, n=3017 [45%]). Pain assessments were performed in 1250 (58%), 672 (45%), and 916 (30%) of these groups respectively (p<0.001). Using data from 78,742 patient-days, we found that 2,838 (43%) neonates received 4.3 (5.2) pain assessments per neonate and per day (median (IQR): 2.4 (1-5)), whereas 3810 (57%) neonates did not receive any pain assessments. Pain assessments occurred on every day of the NICU stay in 461/2138 (22%) TV patients, 236/1493 (16%) NIV patients, and 393/3016 (13%) SV patients (p<0.001).Many different pain assessment methods were used; the EDIN scale was used most frequently (42.3% among those who had at least one pain assessment). We analysed 33,625 patient-days in the TV group to test for associations between pain assessment and the use of opioids, sedatives-hypnotics, or general anaesthetics (O-SH-GA). The rates of pain assessments on patient-days with and without O-SH-GA use were, respectively, 57% vs. 43% while receiving mechanical ventilation, and 60% vs. 34% while not receiving mechanical ventilation (both p<0.001). Multivariable analyses showed that NICU-based guidelines, nursing leadership, and increased surgical admissions promoted the use of routine pain assessments (p<0.001). More pain assessments were performed in newborns below 32-weeks gestational age, those with decreased severity of illness, those already intubated at admission, those requiring mechanical or non-invasive ventilation, or surgery, or use of O-SH-GA.Conclusion: Even though pain is considered the 5th vital sign, only 43% of NICU neonates received bedside pain assessments. Clinical practice variability and low rates of pain assessments in NICUS may reflect weaknesses in the current paradigm used for neonatal pain assessments, their subjectivity, lack of inter-rater reliability, and other long-standing concerns. Results suggest that training to improve the rate of pain assessment in NICUs will enhance pain management in NICUs.Trial Registration: ClinicalTrials.gov #NCT01694745
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| 8. |
- Carbajal, Ricardo, et al.
(författare)
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Sedation and analgesia for neonates in NICUs across the United Kingdom : The Europain survey.
- 2014
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Ingår i: Archives of Disease in Childhood. - London, United Kingdom : BMJ Group. - 1359-2998 .- 1468-2052. ; 99 (Suppl 1), s. A62-A62
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pain and stress induced by mechanical ventilation, invasive procedures, or painful diseases supports the use of sedation/analgesia (S/A) in newborns admitted to Neonatal Units (NNUs). To date, these practices have not been studied on a large scale.Objective: To determine current clinical practices regarding the use of S/A drugs in NNUs across the United Kingdom (UK).Design/Methods: A European epidemiological observational study on clinical practices regarding bedside use of S/A collected data for all neonates in participating NNUs until the infant left the unit (discharge, death, transfer) or for up to 28 days. Data collection occurred via an online database for 1 month at each NNU. Neonates up to 44 weeks gestation were included.Results: From February 2013 to May 2013, 66 UK NNUs collected data on 2691 eligible neonates. Of these, 713 received tracheal ventilation and 1978 had spontaneous breathing or non-invasive ventilation. The median (IQR) gestational age of ventilated neonates [32.1 (27.9-38.6)] was lower than for non-ventilated neonates [37.0 (34.1-39.7), p < 0.001]. Overall, more ventilated neonates [83.0% (n = 592)] received S/A drugs than non-ventilated neonates [7.4% (n = 147); p < 0.001]. The table shows S/A drugs used in ventilated neonates. fetalneonatal;99/Suppl_1/A62-b/T1T1T1 Abstract PC.77 Table Ventilated and S/A, n = 592 Non-ventilated, and S/A n = 147 Fentanyl 105 (17.7%) 4 (2;7%) Midazolam 55 (9.3%) 3 (2.0%) Paracetamol 17 (2.9%) 92 (62.6%) Morphine 592 (91.6%) 44 (29.9%) Sufentanil 2 (0.3%) 0 Neuroblocker 352 (59.4%) 0 CONCLUSIONS: Most ventilated but few non-ventilated neonates receive S/A therapy in UK NNUs. Wide variations in rates of S/A use and drugs used exist among centres.
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