28 results on '"Hyttel-Sorensen S"'
Search Results
2. Central data monitoring in the multicentre randomised SafeBoosC-III trial:a pragmatic approach
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Olsen, M. H., Hansen, M. L., Safi, S., Jakobsen, J. C., Greisen, G., Gluud, C., Pellicer, A., Bargiel, A., Hopper, A., Truttmann, A., Klamer, A., Heuchan, A. M., Memisoglu, A., Krolak-Olejnik, B., Rzepecka, B., Loureiro, B., Lecart, C., Hagmann, C., Ergenekon, E., Hatzidaki, E., Mastretta, E., Dempsey, E., Papathoma, E., Lou, F., Dimitriou, G., Pichler, G., Vento, G., Hahn, G. H., Naulaers, G., Cheng, G., Fuchs, H., Ozkan, H., De Las Cuevas, I., Sadowska-Krawczenko, I., Tkaczyk, J., Sirc, J., Zhang, J., Mintzer, J., De Buyst, J., Mccall, K., Bober, K., Sarafidis, K., Bender, L., Lopez, L. S., Chalak, L., Yang, L., Cornette, L., Arruza, L., Baserga, M., Stocker, M., Agosti, M., Cetinkaya, M., Alsina, M., Fumagalli, M., Suarez, O. L., Otero, O., Baud, O., Zafra, P., Agergaard, P., Maton, P., Viellevoye, R., del Rio Florentino, R., Lauterbach, R., Borregas, S. P., Nesargi, S., Rite, S., Rao, S., Zeng, S., Pisoni, S., Hyttel-Sorensen, S., Fredly, S., Oguz, S., Karen, T., Szczapa, T., Gao, X., Xu, X., Yin, Z., University of Zurich, and Olsen, Markus Harboe
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Medicine (General) ,medicine.medical_specialty ,Monitoring ,Computer science ,Epidemiology ,Missing data ,610 Medicine & health ,Health Informatics ,Health informatics ,03 medical and health sciences ,R5-920 ,0302 clinical medicine ,Documentation ,Clinical trials ,medicine ,Humans ,Medical physics ,030212 general & internal medicine ,Physiologic ,Premature ,2718 Health Informatics ,Monitoring, Physiologic ,Protocol (science) ,Central monitoring ,business.industry ,Research ,Data quality ,Infant, Newborn ,Infant ,Newborn ,10027 Clinic for Neonatology ,Clinical trial ,Data deviations ,Mahalanobis distance ,Infant, Premature ,Identification (information) ,10036 Medical Clinic ,030220 oncology & carcinogenesis ,Good clinical practice ,business ,2713 Epidemiology - Abstract
Background Data monitoring of clinical trials is a tool aimed at reducing the risks of random errors (e.g. clerical errors) and systematic errors, which include misinterpretation, misunderstandings, and fabrication. Traditional ‘good clinical practice data monitoring’ with on-site monitors increases trial costs and is time consuming for the local investigators. This paper aims to outline our approach of time-effective central data monitoring for the SafeBoosC-III multicentre randomised clinical trial and present the results from the first three central data monitoring meetings. Methods The present approach to central data monitoring was implemented for the SafeBoosC-III trial, a large, pragmatic, multicentre, randomised clinical trial evaluating the benefits and harms of treatment based on cerebral oxygenation monitoring in preterm infants during the first days of life versus monitoring and treatment as usual. We aimed to optimise completeness and quality and to minimise deviations, thereby limiting random and systematic errors. We designed an automated report which was blinded to group allocation, to ease the work of data monitoring. The central data monitoring group first reviewed the data using summary plots only, and thereafter included the results of the multivariate Mahalanobis distance of each centre from the common mean. The decisions of the group were manually added to the reports for dissemination, information, correcting errors, preventing furture errors and documentation. Results The first three central monitoring meetings identified 156 entries of interest, decided upon contacting the local investigators for 146 of these, which resulted in correction of 53 entries. Multiple systematic errors and protocol violations were identified, one of these included 103/818 randomised participants. Accordingly, the electronic participant record form (ePRF) was improved to reduce ambiguity. Discussion We present a methodology for central data monitoring to optimise quality control and quality development. The initial results included identification of random errors in data entries leading to correction of the ePRF, systematic protocol violations, and potential protocol adherence issues. Central data monitoring may optimise concurrent data completeness and may help timely detection of data deviations due to misunderstandings or fabricated data.
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- 2021
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3. The SafeBoosC phase II clinical trial: an analysis of the interventions related with the oximeter readings
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Riera J, Hyttel-Sorensen S, Mc, Bravo, Cabañas F, López-Ortego P, Sanchez L, Ybarra M, Eugene Michael Dempsey, Greisen G, Austin T, Claris O, Fumagalli M, Gluud C, Lemmers P, Pichler G, Am, Plomgaard, van Bel F, Wolf M, and Pellicer A
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Intensive Care, Monitoring, Neonatology - Abstract
Background The SafeBoosC phase II randomised clinical trial recently demonstrated the benefits of a combination of cerebral regional tissue oxygen saturation (rStO(2)) by near-infrared spectroscopy (NIRS) and a treatment guideline to reduce the oxygen imbalance in extremely preterm infants. Aims To analyse rStO(2)-alarm-related clinical decisions and their heterogeneity in the NIRS experimental group (NIRS monitoring visible) and their impact on rStO(2) and SpO(2). Methods Continuous data from NIRS devices and the alarms (area under the curve of the rStO(2) out of range had accumulated 0.2% h during 10 min), clinical data at discrete time points and interventions prompted by the alarms were recorded. Results Sixty-seven infants had data that fulfilled the requirements for this analysis. 1107 alarm episodes were analysed. The alarm triggered a treatment guideline intervention in 25% of the cases; the type of intervention chosen varied among clinical sites. More than 55% of alarms were not followed by an intervention ('No action'); additionally, in 5% of alarms the rStO(2) value apparently was considered non-reliable and the sensor was repositioned. The percentage of unresolved alarms at 30 min after 'No action' almost doubled the treatment guideline intervention (p
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- 2016
4. Comparison of near-infrared oximeters in a liquid optical phantom with varying intralipid and blood content
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Elwell, Clare E, Elwell, C E ( Clare E ), Kleiser, S, Hyttel-Sorensen, S, Greisen, G, Wolf, M, Elwell, Clare E, Elwell, C E ( Clare E ), Kleiser, S, Hyttel-Sorensen, S, Greisen, G, and Wolf, M
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The interpretation of cerebral tissue oxygen saturation values (StO2) in clinical settings is currently complicated by the use of different near-infrared spectrophotometry (NIRS) devices producing different StO2 values for the same oxygenation due to differences in the algorithms and technical aspects. The aim was to investigate the effect of changes in scattering and absorption on the StO2 of different NIRS devices in a liquid optical phantom. We compared three continuous-wave (CW) with a frequency domain (FD) NIRS device. Responsiveness to oxygenation changes was only slightly altered by different intralipid (IL) concentrations. However, alterations in haematocrit (htc) showed a strong effect: increased htc led to a 20-35% increased response of all CW devices compared to the FD device, probably due to differences in algorithms regarding the water concentration.
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- 2016
5. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial
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Hyttel-Sorensen, S., primary, Pellicer, A., additional, Alderliesten, T., additional, Austin, T., additional, van Bel, F., additional, Benders, M., additional, Claris, O., additional, Dempsey, E., additional, Franz, A. R., additional, Fumagalli, M., additional, Gluud, C., additional, Grevstad, B., additional, Hagmann, C., additional, Lemmers, P., additional, van Oeveren, W., additional, Pichler, G., additional, Plomgaard, A. M., additional, Riera, J., additional, Sanchez, L., additional, Winkel, P., additional, Wolf, M., additional, and Greisen, G., additional
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- 2015
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6. O-221 Safeboosc – A Phase Ii Randomised Clinical Trial On Cerebral Near-infrared Spectroscopy Oximetry In Extremely Preterm Infants: Abstract O-221 Table 1
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Hyttel-Sorensen, S, primary, Pellicer, A, additional, Alderliesten, T, additional, Austin, T, additional, van Bel, F, additional, Benders, M, additional, Claris, O, additional, Dempsey, E, additional, Franz, AR, additional, Fumagalli, M, additional, Gluud, C, additional, Grevstad, B, additional, Hagmann, C, additional, Lemmers, P, additional, van Oeveren, W, additional, Pichler, G, additional, Plomgaard, AM, additional, Riera, J, additional, Sanchez, L, additional, Winkel, P, additional, Wolf, M, additional, and Greisen, G, additional
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- 2014
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7. 1142 Safeguarding the Brains of Our Smallest Children: Safeboosc - the Pilot Study
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Hyttel-Sorensen, S., primary, Austin, T., additional, Benders, M., additional, Claris, O., additional, Dempsey, G., additional, Fumagalli, M., additional, Gluud, C., additional, Hagmann, C., additional, Hellstrom-Westas, L., additional, Lemmers, P., additional, Naulaers, G., additional, Pellicer, A., additional, Pichler, G., additional, Stoy, L. S., additional, Bel, F. v., additional, Oeveren, W. v., additional, Wolf, M., additional, and Greisen, G., additional
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- 2012
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8. 975 Peripheral Tissue Nirs Oximetry: Reproducibility and Dynamic Range of Invos 5100C, Nonin Equanox, and Fore-Sight
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Hyttel-Sorensen, S., primary, Hessel, T. W., additional, and Greisen, G., additional
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- 2012
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9. The SafeBoosC phase II randomised clinical trial: a treatment guideline for targeted near-infrared-derived cerebral tissue oxygenation versus standard treatment in extremely preterm infants
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Pellicer A, Gorm Greisen, Benders M, Claris O, Dempsey E, Fumagalli M, Gluud C, Hagmann C, Hellström-Westas L, Hyttel-Sorensen S, Lemmers P, Naulaers G, Pichler G, Roll C, van Bel F, van Oeveren W, Skoog M, Wolf M, and Austin T
10. Early cerebral hypoxia in extremely preterm infants and neurodevelopmental impairment at 2 year of age: A post hoc analysis of the SafeBoosC II trial.
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Plomgaard AM, Schwarz CE, Claris O, Dempsey EM, Fumagalli M, Hyttel-Sorensen S, Lemmers P, Pellicer A, Pichler G, and Greisen G
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- Child, Preschool, Female, Humans, Hypoxia, Brain etiology, Hypoxia, Brain prevention & control, Hypoxia, Brain therapy, Infant, Infant, Newborn, Male, Spectroscopy, Near-Infrared methods, Treatment Outcome, Hypoxia, Brain complications, Infant, Extremely Premature growth & development, Neurodevelopmental Disorders etiology
- Abstract
Background: The SafeBoosC II, randomised clinical trial, showed that the burden of cerebral hypoxia was reduced with the combination of near infrared spectroscopy and a treatment guideline in extremely preterm infants during the first 72 hours after birth. We have previously reported that a high burden of cerebral hypoxia was associated with cerebral haemorrhage and EEG suppression towards the end of the 72-hour intervention period, regardless of allocation. In this study we describe the associations between the burden of cerebral hypoxia and the 2-year outcome., Methods: Cerebral oxygenation was continuously monitored from 3 to 72 hours after birth in 166 extremely preterm infants. At 2 years of age 114 of 133 surviving children participated in the follow-up program: medical examination, Bayley II or III test and the parental Ages and Stages Questionnaire. The infants were classified according to the burden of hypoxia: within the first three quartiles (n = 86, low burden) or within in the 4th quartile (n = 28, high burden). All analyses were conducted post hoc., Results: There were no statistically significant differences between the quantitative assessments of neurodevelopment in the groups of infants with the low burden of cerebral hypoxia versus the group of infants with the high burden of cerebral hypoxia. The infants in the high hypoxia burden group had a higher-though again not statistically significant-rate of cerebral palsy (OR 2.14 (0.33-13.78)) and severe developmental impairment (OR 4.74 (0.74-30.49)., Conclusions: The burden of cerebral hypoxia was not significantly associated with impaired 2-year neurodevelopmental outcome in this post-hoc analysis of a feasibility trial., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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11. Correction: Comparison of INVOS 5100C and Nonin SenSmart X-100 oximeter performance in preterm infants with spontaneous apnea.
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Andresen B, Greisen G, and Hyttel-Sorensen S
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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12. Comparison of INVOS 5100C and Nonin SenSmart X-100 oximeter performance in preterm infants with spontaneous apnea.
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Andresen B, Greisen G, and Hyttel-Sorensen S
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- Adult, Female, Humans, Infant, Newborn, Infant, Premature, Male, Spectroscopy, Near-Infrared, Apnea physiopathology, Monitoring, Physiologic instrumentation, Oximetry instrumentation
- Abstract
Background: Tissue oximeters are not interchangeable. Two instruments with sensors dedicated to preterm infants-INVOS 5100C and Nonin SenSmart X-100-have not yet been compared., Methods: By measuring cerebral oxygenation in ten preterm infants with spontaneous apneic episodes defined by pulse oximeter readings (SpO
2 ) below 80%, as well as tissue oxygenation during vascular occlusion on the forearm of ten adults, simultaneously we compared performance in the hypoxic range., Results: We found the mean conversion equations to be StO2,SenSmart X-100 = 0.34 × StO2,INVOS 5100C + 44.8% during apnea in infants and StO2,SenSmart X-100 = 0.59 × StO2,INVOS 5100C + 34.4% during vascular occlusion. The individual regressions displayed large and statistically significant variations in both infants and adults. In three infants the INVOS sensor showed very little reaction to decreases in SpO2 ., Conclusions: These findings confirm that different NIRS devices give very different estimates when the oxygenation is low. The large variation when compared to SpO2 suggest that the sensor placement is very important in preterm infants.- Published
- 2020
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13. Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants.
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Hansen ML, Pellicer A, Gluud C, Dempsey E, Mintzer J, Hyttel-Sorensen S, Heuchan AM, Hagmann C, Dimitriou G, Pichler G, Naulaers G, Cheng G, Vilan A, Tkaczyk J, Kreutzer KB, Fumagalli M, Claris O, Fredly S, Szczapa T, Lange T, Jakobsen JC, and Greisen G
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- Brain metabolism, Brain pathology, Clinical Trials, Phase III as Topic, Humans, Hypoxia, Brain diagnosis, Hypoxia, Brain epidemiology, Infant, Newborn, Intensive Care Units, Neonatal, Monitoring, Physiologic instrumentation, Multicenter Studies as Topic, Pragmatic Clinical Trials as Topic, Randomized Controlled Trials as Topic, Spectroscopy, Near-Infrared instrumentation, Spectroscopy, Near-Infrared methods, Brain diagnostic imaging, Emergency Treatment methods, Hypoxia, Brain therapy, Infant, Extremely Premature, Monitoring, Physiologic methods, Oxygen metabolism
- Abstract
Background: Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses., Methods/design: The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis., Discussion: In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis., Trial Registration: ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.
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- 2019
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14. No neurodevelopmental benefit of cerebral oximetry in the first randomised trial (SafeBoosC II) in preterm infants during the first days of life.
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Plomgaard AM, Alderliesten T, van Bel F, Benders M, Claris O, Cordeiro M, Dempsey E, Fumagalli M, Gluud C, Hyttel-Sorensen S, Lemmers P, Pellicer A, Pichler G, and Greisen G
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- Child, Preschool, Female, Humans, Hypoxia, Brain therapy, Infant, Extremely Premature, Infant, Newborn, Male, Oximetry methods, Spectroscopy, Near-Infrared, Hypoxia, Brain diagnosis, Neurodevelopmental Disorders prevention & control
- Abstract
Aim: Cerebral hypoxia has been associated with neurodevelopmental impairment. We studied whether reducing cerebral hypoxia in extremely preterm infants during the first 72 hours of life affected neurological outcomes at two years of corrected age., Methods: In 2012-2013, the phase II randomised Safeguarding the Brains of our smallest Children trial compared visible cerebral near-infrared spectroscopy (NIRS) monitoring in an intervention group and blinded NIRS monitoring in a control group. Cerebral hypoxia was significantly reduced in the intervention group. We followed up 115 survivors from eight European centres at two years of corrected age, by conducting a medical examination and assessing their neurodevelopment with the Bayley Scales of Infant and Toddler Development, Second or Third Edition, and the parental Ages and Stages Questionnaire (ASQ)., Results: There were no differences between the intervention (n = 65) and control (n = 50) groups with regard to the mean mental developmental index (89.6 ± 19.5 versus 88.4 ± 14.7, p = 0.77), ASQ score (215 ± 58 versus 213 ± 58, p = 0.88) and the number of children with moderate-to-severe neurodevelopmental impairment (10 versus six, p = 0.58)., Conclusion: Cerebral NIRS monitoring was not associated with long-term benefits or harm with regard to neurodevelopmental outcome at two years of corrected age., (©2018 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)
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- 2019
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15. In vivo validation of cerebral near-infrared spectroscopy: a review.
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la Cour A, Greisen G, and Hyttel-Sorensen S
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We summarize the available in vivo validation of cerebral near-infrared spectroscopy (NIRS) oximetry to inform future in vivo validation strategies. In particular, to establish a way forward in the assessment of NIRS instrumentation for future randomized trials, a systematic literature search is performed. The records are screened and abstracts are assessed to select studies fulfilling our inclusion criteria. Twenty-two pediatric and 28 adult studies are analyzed after exclusion of three articles in each group. All studies compare regional cerebral tissue oxygenation measured by cerebral NIRS to invasive measurement of central or jugular venous oxygen saturation. In studies without Bland-Altman plots, we extracted data from scatter plots enabling estimation of mean difference (MD), standard deviation (SD), and limits of agreement (LOA). To assess the agreement between rStO 2 (regional cerebral tissue oxygenation) estimated by NIRS and by blood samples, weighted averages of the MDs and SDs from each study are calculated. We found a fair agreement between the overall mean of cerebral tissue oxygenation and the mean of a reference value measured by co-oximetry whatever NIRS instrument or site of blood sampling used. Cerebral oxygenation overestimates the reference at low values, some instruments apparently more than others. Thus, a high degree of scatter and a lack of a good reference method complicate in vivo validation of NIRS. It is difficult to draw any firm conclusions despite the large number of studies, and the result of this review leaves us questioning if more of such validation studies of cerebral NIRS oximetry are really needed. Furthermore, the combination of lack of validation and poor repeatability is an important issue when designing a randomized clinical trial of implementing cerebral NIRS oximetry into clinical care.
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- 2018
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16. Cerebral near-infrared spectroscopy monitoring for prevention of brain injury in very preterm infants.
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Hyttel-Sorensen S, Greisen G, Als-Nielsen B, and Gluud C
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- Humans, Infant, Newborn, Randomized Controlled Trials as Topic, Brain metabolism, Brain Injuries prevention & control, Infant, Extremely Premature, Oxygen Consumption, Spectroscopy, Near-Infrared
- Abstract
Background: Cerebral injury and long-term neurodevelopmental impairment is common in extremely preterm infants. Cerebral near-infrared spectroscopy (NIRS) enables continuous estimation of cerebral oxygenation. This diagnostic method coupled with appropriate interventions if NIRS is out of normal range (that is cerebral oxygenation within the 55% to 85% range) may offer benefits without causing more harms. Therefore, NIRS coupled with appropriate responses to abnormal findings on NIRS needs assessment in a systematic review of randomised clinical trials and quasi-randomised studies., Objectives: To evaluate the benefits and harms of interventions that attempt to alter cerebral oxygenation guided by cerebral NIRS monitoring in order to prevent cerebral injury, improve neurological outcome, and increase survival in preterm infants born more than 8 weeks preterm., Search Methods: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 8), MEDLINE via PubMed (1966 to 10 September 2016), Embase (1980 to 10 September 2016), and CINAHL (1982 to 10 September 2016). We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised clinical trials and quasi-randomised studies., Selection Criteria: Randomised clinical trials and quasi-randomised clinical studies comparing continuous cerebral NIRS monitoring for at least 24 hours versus blinded NIRS or versus no NIRS monitoring., Data Collection and Analysis: Two review authors independently selected, assessed the quality of, and extracted data from the included trials and studies. If necessary, we contacted authors for further information. We conducted assessments of risks of bias; risks of design errors; and controlled the risks of random errors with Trial Sequential Analysis. We assessed the quality of the evidence with GRADE., Main Results: One randomised clinical trial met inclusion criteria, including infants born more than 12 weeks preterm. The trial employed adequate methodologies and was assessed at low risk of bias. One hundred and sixty-six infants were randomised to start continuous cerebral NIRS monitoring less than 3 hours after birth until 72 hours after birth plus appropriate interventions if NIRS was out of normal range according to a guideline versus conventional monitoring with blinded NIRS. There was no effect of NIRS plus guideline of mortality until term-equivalent age (RR 0.50, 95% CI 0.29 to 1.00; one trial; 166 participants). There were no effects of NIRS plus guideline on intraventricular haemorrhages: all grades (RR 0.93, 95% CI 0.65 to 1.34; one trial; 166 participants); grade III/IV (RR 0.57, 95% CI 0.25 to 1.31; one trial; 166 participants); and cystic periventricular leukomalacia (which did not occur in either group). Likewise, there was no effect of NIRS plus guideline on the occurrence of a patent ductus arteriosus (RR 1.96, 95% CI 0.94 to 4.08; one trial; 166 participants); chronic lung disease (RR 1.27, 95% CI 0.94 to 1.50; one trial; 166 participants); necrotising enterocolitis (RR 0.83, 95% CI 0.33 to 1.94; one trial; 166 participants); and retinopathy of prematurity (RR 1.64, 95% CI 0.75 to 3.00; one trial; 166 participants). There were no serious adverse events in any of the intervention groups. NIRS plus guideline caused more skin marks from the NIRS sensor in the control group than in the experimental group (unadjusted RR 0.31, 95% CI 0.10 to 0.92; one trial; 166 participants). There are no data regarding neurodevelopmental outcome, renal impairment or air leaks.The quality of evidence for all comparisons discussed above was assessed as very low apart from all-cause mortality and adverse events: these were assessed as low and moderate, respectively. The validity of all comparisons is hampered by a small sample of randomised infants, risk of bias due to lack of blinding, and indirectness of outcomes., Authors' Conclusions: The only eligible randomised clinical trial did not demonstrate any consistent effects of NIRS plus a guideline on the assessed clinical outcomes. The trial was, however, only powered to detect difference in cerebral oxygenation, not morbidities or mortality. Our systematic review did not reach sufficient power to prove or disprove effects on clinical outcomes. Further randomised clinical trials with low risks of bias and low risks of random errors are needed.
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- 2017
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17. Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial.
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Plomgaard AM, Alderliesten T, Austin T, van Bel F, Benders M, Claris O, Dempsey E, Fumagalli M, Gluud C, Hagmann C, Hyttel-Sorensen S, Lemmers P, van Oeveren W, Pellicer A, Petersen TH, Pichler G, Winkel P, and Greisen G
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- Electroencephalography methods, Female, Gestational Age, Humans, Infant, Extremely Premature metabolism, Infant, Newborn, Male, Monitoring, Physiologic methods, Oximetry methods, Oxygen metabolism, Spectroscopy, Near-Infrared methods, Biomarkers metabolism, Brain Injuries diagnosis, Brain Injuries metabolism, Hyperoxia diagnosis, Hyperoxia metabolism, Hypoxia, Brain diagnosis, Hypoxia, Brain metabolism
- Abstract
Background: The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the intervention and the control group. The primary outcome was the reduction in the burden of cerebral hypo- and hyperoxia between the two groups. In this study we describe the associations between the burden of cerebral hypo- and hyperoxia, regardless of allocation to intervention or control group, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial., Methods: Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1,4,7,14, and 35 and at term. Electroencephalogram (EEG) was recorded at 64h. Blood-samples taken at 6 and 64 hours were analysed for the brain injury biomarkers; S100beta, brain-fatty-acid-binding-protein, and neuroketal. All analyses were conducted post hoc., Results: Significantly more infants with a cerebral burden of hypoxia within the 4th quartile versus infants within quartile 1-3 were diagnosed with severe intracranial haemorrhage (11/39 versus 11/117, p = 0.003), had low burst rate on EEG (12/28 versus 21/103, p = 0.015), or died (14/41 versus 18/123, p = 0.006), whereas none of these events were significantly associated with cerebral hyperoxia. The blood biomarkers were not significantly associated with the burden of cerebral hypo- or hyperoxia., Conclusions: The explorative analysis showed that early burden of cerebral hypoxia, but not hyperoxia was significantly associated with low brain electrical activity and severe intracranial haemorrhage while none of the three blood biomarkers were associated with the burden of either cerebral hypo- or hyperoxia.
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- 2017
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18. The SafeBoosC II randomized trial: treatment guided by near-infrared spectroscopy reduces cerebral hypoxia without changing early biomarkers of brain injury.
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Plomgaard AM, van Oeveren W, Petersen TH, Alderliesten T, Austin T, van Bel F, Benders M, Claris O, Dempsey E, Franz A, Fumagalli M, Gluud C, Hagmann C, Hyttel-Sorensen S, Lemmers P, Pellicer A, Pichler G, Winkel P, and Greisen G
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- Electroencephalography, Humans, Hypoxia, Brain metabolism, Hypoxia, Brain physiopathology, Infant, Newborn, Biomarkers metabolism, Brain Injuries metabolism, Hypoxia, Brain prevention & control, Spectroscopy, Near-Infrared methods
- Abstract
Background: The SafeBoosC phase II multicentre randomized clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by near-infrared spectroscopy (NIRS) combined with an evidence-based treatment guideline vs. no NIRS data and treatment as usual in the control group during the first 72 h of life. The trial demonstrated a significant reduction in the burden of cerebral hypoxia in the experimental group. We now report the blindly assessed and analyzed treatment effects on electroencephalographic (EEG) outcomes (burst rate and spectral edge frequency 95% (SEF95)) and blood biomarkers of brain injury (S100β, brain fatty acid-binding protein, and neuroketal)., Methods: One hundred and sixty-six extremely preterm infants were randomized to either experimental or control group. EEG was recorded at 64 h of age and blood samples were collected at 6 and 64 h of age., Results: One hundred and thirty-three EEGs were evaluated. The two groups did not differ regarding burst rates (experimental 7.2 vs. control 7.7 burst/min) or SEF95 (experimental 18.1 vs. control 18.0 Hz). The two groups did not differ regarding blood S100β, brain fatty acid-binding protein, and neuroketal concentrations at 6 and 64 h (n = 123 participants)., Conclusion: Treatment guided by NIRS reduced the cerebral burden of hypoxia without affecting EEG or the selected blood biomarkers.
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- 2016
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19. Brain injury in the international multicenter randomized SafeBoosC phase II feasibility trial: cranial ultrasound and magnetic resonance imaging assessments.
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Plomgaard AM, Hagmann C, Alderliesten T, Austin T, van Bel F, Claris O, Dempsey E, Franz A, Fumagalli M, Gluud C, Greisen G, Hyttel-Sorensen S, Lemmers P, Pellicer A, Pichler G, and Benders M
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- Birth Weight, Brain Injuries pathology, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage pathology, Cerebrovascular Circulation, Feasibility Studies, Gestational Age, Hemorrhage physiopathology, Humans, Hypoxia physiopathology, Infant, Newborn, Infant, Premature, Diseases pathology, International Cooperation, Observer Variation, Oxygen chemistry, Perfusion, Skull diagnostic imaging, Skull pathology, Brain Injuries diagnostic imaging, Infant, Premature, Diseases diagnostic imaging, Magnetic Resonance Imaging, Ultrasonography
- Abstract
Background: Abnormal cerebral perfusion during the first days of life in preterm infants is associated with higher grades of intraventricular hemorrhages and lower developmental score. In SafeBoosC II, we obtained a significant reduction of cerebral hypoxia by monitoring cerebral oxygenation in combination with a treatment guideline. Here, we describe (i) difference in brain injury between groups, (ii) feasibility of serial cranial ultrasound (cUS) and magnetic resonance imaging (MRI), (iii) local and central cUS assessment., Methods: Hundred and sixty-six extremely preterm infants were included. cUS was scheduled for day 1, 4, 7, 14, and 35 and at term-equivalent age (TEA). cUS was assessed locally (unblinded) and centrally (blinded). MRI at TEA was assessed centrally (blinded). Brain injury classification: no, mild/moderate, or severe., Results: Severe brain injury did not differ significantly between groups: cUS (experimental 10/80, control 18/77, P = 0.32) and MRI (5/46 vs. 3/38, P = 0.72). Kappa values for local and central readers were moderate-to-good for severe and poor-to-moderate for mild/moderate injuries. At TEA, cUS and MRI were assessed in 72 and 64%, respectively., Conclusion: There was no difference in severe brain injury between groups. Acquiring cUS and MRI according the standard operating procedures must be improved for future trials. Whether monitoring cerebral oxygenation during the first 72 h of life prevents brain injury should be evaluated in larger multicenter trials.
- Published
- 2016
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20. A comparison between two NIRS oximeters (INVOS, OxyPrem) using measurement on the arm of adults and head of infants after caesarean section.
- Author
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Hyttel-Sorensen S, Hessel TW, la Cour A, and Greisen G
- Abstract
Previously the NIRS oximeter OxyPrem was calibrated by comparison to the INVOS in a blood-lipid phantom. The aim of the present study was to test this calibration clinically. During vasculur occlusions in 10 adults and after birth in 25 term infants the relationship was OxyPrem = 1.24 x INVOS - 23.6% and OxyPrem = 1.15 x INVOS - 16.2% on the adult arm and infant head, respectively. The precsion during steady state was 4.0% (CI 3.4% to 4.6%) and 3.4% (CI 2.9% to 3.9%) on the arm, and 6.7% (CI 5.9% to 7.6%) and 4.7% (CI 3.5% to 5.9%) on the infant head for OxyPrem and INVOS, respectively. We conclude that the calibration on the blood-lipid phantom was unsuccessful in achieving agreement in clinical measurements.
- Published
- 2014
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21. Sidestream dark field images of the microcirculation: intra-observer reliability and correlation between two semi-quantitative methods for determining flow.
- Author
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Petersen SM, Greisen G, Hyttel-Sorensen S, and Hahn GH
- Subjects
- Animals, Observer Variation, Reproducibility of Results, Software, Swine, Blood Flow Velocity, Microcirculation, Microscopy, Video methods
- Abstract
Background: Since analysis of Sidestream Dark Field images still requires subjective interpretation, we wanted to determine intra-observer repeatability and to estimate the correlation between different evaluation methods., Methods: Fifty-four Sidestream Dark Field videos were analyzed twice by the same blinded observer using validated software. Vessels were detected, generating the parameter Total Vessel Density (TVD), and flow was determined by (i) classifying each vessel separately, generating the parameters Perfused Vessel Density (PVD) and Proportion of Perfused Vessels (PPV), and by (ii) the "Boerma" method, generating a Microvascular Flow Index (MFI) by quadrants., Results: Intraclass Correlation Coefficients (ICCs) were above 0.9 for TVD and above 0.8 for PDV and PPV. MFIby quadrants had the lowest reliability (ICC = 0.52 for capillaries and ICC = 0.59 for all vessels), significantly lower than for PVD (ICC = 0.89, p < 0.001 for capillaries and ICC = 0.90, p < 0.001 for all vessels) and PPV (ICC = 0.82, p = 0.003 for capillaries and ICC = 0.83, p = 0.01 for all vessels). Correlation coefficient (r) between PPV and MFIby quadrants corrected for measurement error was 0.39 (0.10 - 0.64) for capillaries and 1.01 (0.85 - 1.16) for all vessels., Conclusions: Intra-observer reliability for full evaluation of Sidestream Dark Field images was good for vessel detection and for flow classification but significantly poorer for the faster "Boerma" method. Furthermore, the Boerma method is likely to estimate different aspects of capillary flow than do the standard methods.
- Published
- 2014
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22. Cerebral oxygenation after birth - a comparison of INVOS(®) and FORE-SIGHT™ near-infrared spectroscopy oximeters.
- Author
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Hessel TW, Hyttel-Sorensen S, and Greisen G
- Subjects
- Cesarean Section, Elective Surgical Procedures, Female, Humans, Infant, Newborn, Oximetry methods, Pregnancy, Prospective Studies, Reproducibility of Results, Brain blood supply, Oximetry instrumentation, Spectroscopy, Near-Infrared instrumentation
- Abstract
Aim: To compare absolute values of regional cerebral tissue oxygenation (cStO2 ) during haemodynamic transition after birth and repeatability during steady state for two commercial near-infrared spectroscopy (NIRS) devices., Methods: In a prospective observational study, the INVOS 5100C and FORE-SIGHT were compared on 12 term newborns delivered by elective caesarean section. During the 10 min following umbilical cord clamping, cStO2 was measured simultaneously with the neonatal sensors from each device. Repeated measurements were taken the following day., Results: Three and 8 min after clamping, the mean cStO2 value increased from 53.4% (CI 36.8-69.9%) to 86.0% (CI 80.2-91.7%) for INVOS and from 61.6% (CI 55.4-67.8%) to 82.2% (CI 77.7-86.7%) for FORE-SIGHT. The Bland-Altman plot revealed decreasing difference (INVOS minus FORE-SIGHT) (D) in absolute values (A) with increasing cStO2 (D = 0.5A - 38.19 p = <0.001). The mean steady-state value on day two was 78.4% (CI 74.6-82.2%) and 86.2% (CI 85.0-87.4%) for INVOS and FORE-SIGHT, respectively. The within-subject standard deviation during steady-state repeated measurements was 4.8% ± 0.86 for INVOS and 2.8% ± 0.5 for FORE-SIGHT., Conclusion: The INVOS and FORE-SIGHT cStO2 estimates showed oxygenation-level-dependent difference during birth transition. The better repeatability of FORE-SIGHT could be due to the lower response to change in saturation., (© 2014 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)
- Published
- 2014
- Full Text
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23. Peripheral tissue oximetry: comparing three commercial near-infrared spectroscopy oximeters on the forearm.
- Author
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Hyttel-Sorensen S, Hessel TW, and Greisen G
- Subjects
- Adult, Equipment Design, Equipment Failure Analysis, Forearm blood supply, Forearm physiology, Humans, Reproducibility of Results, Sensitivity and Specificity, Young Adult, Hemoglobins metabolism, Muscle, Skeletal physiology, Oximetry instrumentation, Oxygen Consumption physiology, Regional Blood Flow physiology, Spectroscopy, Near-Infrared instrumentation
- Abstract
Estimation of regional tissue oxygenation (rStO2) by near infrared spectroscopy enables non-invasive end-organ oxygen balance monitoring and could be a valuable tool in intensive care. However, the diverse absolute values and dynamics of different devices, and overall poor repeatability of measurements are a problem. The aim of the present study is to test the hypothesis that INVOS 5100C, FORE-SIGHT and NONIN EQUANOX 7600 have similar properties concerning absolute values, repeatability, and sensitivity to changes in rStO2. To test repeatability the sensors were repositioned 20 times during hemodynamic steady state on the adult forearm. Afterwards six vascular occlusions by inflation of an upper arm cuff were done to achieve low oxygenation in the forearm. Absolute values were compared by repeated-measures ANOVA, repeatability was estimated by the within-subject standard deviation, Sw, and response to changing oxygenation by the down slope of rStO2 during vascular occlusion in the respective arm. 10 healthy adults, 21-29 years old, with double skinfolds on the forearm less than 10 mm participated. The median rStO2 was 70.7% (interquartile range (IQR) 7.7%), 68.4% (IQR 8.4%), and 64.6% (IQR 4.8) with INVOS, NONIN, and FORE-SIGHT, respectively, the median rate of decline was 13.2%/min (IQR 9.6), 22.8 %/min (IQR 18.0), and 10.8%/min (IQR 6.0), and the same-site repeatability was 2.9% (95% CI 2.4-3.3), 4.6% (CI 3.9-5.3), and 2.0% (CI 1.7-2.3). INVOS gave significantly higher steady state values than FORE-SIGHT, and NONIN had the steepest decline in rStO2, but the poorest repeatability. Two measures of signal-to-noise were similar among devices. This suggests that good repeatability comes at the expense of low sensitivity to changes in oxygenation. Values of rStO2 on the forearm from INVOS, NONIN and FORE-SIGTH cannot be used interchangeably.
- Published
- 2014
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24. Calibration of a prototype NIRS oximeter against two commercial devices on a blood-lipid phantom.
- Author
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Hyttel-Sorensen S, Kleiser S, Wolf M, and Greisen G
- Abstract
In a blood-lipid liquid phantom the prototype near-infrared spectroscopy oximeter OxyPrem was calibrated against the INVOS® 5100c adult sensor in respect to values of regional tissue oxygen haemoglobin saturation (rStO2) for possible inclusion in the randomised clinical trial - SafeBoosC. In addition different commercial NIRS oximeters were compared on changing haemoglobin oxygen saturation and compared against co-oximetry. The best calibration was achieved with a simple offset and a linear scaling of the OxyPrem rStO2 values. The INVOS adult and pediatric sensor gave systematically different values, while the difference between the NIRO® 300 and the two INVOS sensors were magnitude dependent. The co-oximetry proved unreliable on such low haemoglobin and high Intralipid levels.
- Published
- 2013
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25. Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets.
- Author
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Hahn GH, Hyttel-Sorensen S, Petersen SM, Pryds O, and Greisen G
- Subjects
- Animals, Animals, Newborn, Blood Pressure drug effects, Cell Hypoxia, Cerebral Cortex drug effects, Cerebral Cortex metabolism, Muscle Contraction drug effects, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular physiology, Oxygen Consumption drug effects, Regional Blood Flow drug effects, Sus scrofa, Cerebral Cortex blood supply, Dopamine pharmacology, Epinephrine pharmacology, Norepinephrine pharmacology, Vasoconstrictor Agents pharmacology
- Abstract
Background: Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline) by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenation., Methods: Twenty-four piglets had long and short infusions of the three vasopressor-inotropes titrated to raise mean arterial blood pressure (MAP) 10 mmHg in random order. Nonpharmacological increases in MAP were induced by inflation of a balloon in the descending aorta. We measured cerebral oxygenation (near-infrared spectroscopy), perfusion (laser-Doppler), oxygen consumption (co-oximetry of arterial and superior sagittal sinus blood), and microvascular heterogeneity (side stream dark field video microscopy)., Results: Vasopressor-inotropes increased cerebral oxygenation significantly less (p≤0.01) compared to non-pharmacological MAP increases, whereas perfusion was similar. Furthermore, cerebral total hemoglobin concentration increased significantly less during vasopressor-inotrope infusions (p = 0.001). These physiologic responses were identical between the three vasopressor-inotropes (p>0.05). Furthermore, they induced a mild, although insignificant increase in cerebral metabolism and microvascular heterogeneity (p>0.05). Removal of the scalp tissue did not influence the mismatch (p>0.05)., Conclusion: We demonstrated a moderate vasopressor-inotrope induced mismatch between cerebral perfusion and oxygenation. Scalp removal did not affect this mismatch, why vasopressor-inotropes appear to have direct cerebral actions. The statistically nonsignificant increases in cerebral metabolism and/or microvascular heterogeneity may explain the mismatch. Alternatively, it may simply reflect a vasopressor-inotrope-induced decrease in the arterial-to-venous volume ratio as detected by near-infrared spectroscopy.
- Published
- 2013
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26. A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial.
- Author
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Hyttel-Sorensen S, Austin T, van Bel F, Benders M, Claris O, Dempsey E, Fumagalli M, Greisen G, Grevstad B, Hagmann C, Hellström-Westas L, Lemmers P, Lindschou J, Naulaers G, van Oeveren W, Pellicer A, Pichler G, Roll C, Skoog M, Winkel P, Wolf M, and Gluud C
- Subjects
- Biomarkers blood, Brain growth & development, Brain metabolism, Child Development, Clinical Protocols, Electroencephalography, Europe, Gestational Age, Guideline Adherence, Humans, Hyperoxia etiology, Hyperoxia prevention & control, Hypoxia etiology, Hypoxia prevention & control, Infant Mortality, Infant, Newborn, Intensive Care Units, Neonatal, Intensive Care, Neonatal standards, Magnetic Resonance Imaging, Monitoring, Physiologic standards, Oxygen blood, Practice Guidelines as Topic, Time Factors, Treatment Outcome, Brain blood supply, Cerebrovascular Circulation, Infant, Extremely Premature blood, Intensive Care, Neonatal methods, Monitoring, Physiologic methods, Oximetry standards, Oxygen Inhalation Therapy adverse effects, Oxygen Inhalation Therapy standards, Research Design, Spectroscopy, Near-Infrared standards
- Abstract
Background: Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2., Methods/design: SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the 'burden of hypoxia and hyperoxia' expressed in '%hours'. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events., Discussion: Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia., Trial Registration: ClinicalTrial.gov, NCT01590316.
- Published
- 2013
- Full Text
- View/download PDF
27. The SafeBoosC phase II randomised clinical trial: a treatment guideline for targeted near-infrared-derived cerebral tissue oxygenation versus standard treatment in extremely preterm infants.
- Author
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Pellicer A, Greisen G, Benders M, Claris O, Dempsey E, Fumagalli M, Gluud C, Hagmann C, Hellström-Westas L, Hyttel-Sorensen S, Lemmers P, Naulaers G, Pichler G, Roll C, van Bel F, van Oeveren W, Skoog M, Wolf M, and Austin T
- Subjects
- Algorithms, Clinical Trials, Phase II as Topic methods, Clinical Trials, Phase II as Topic standards, Humans, Infant, Newborn, Oxygen administration & dosage, Practice Guidelines as Topic, Randomized Controlled Trials as Topic methods, Randomized Controlled Trials as Topic standards, Brain physiology, Infant, Extremely Premature physiology, Oximetry methods, Oxygen physiology, Spectroscopy, Near-Infrared standards
- Abstract
Unlabelled: Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rStO2) reflects venous oxygen saturation. If cerebral metabolism is stable, rStO2 can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the burden of hypo- and hyperoxia can be reduced by the combined use of close monitoring of the cerebral rStO2 and a treatment guideline to correct deviations in rStO2 outside a predefined target range., Aims: To describe the rationale for and content of this treatment guideline., Methods: Review of the literature and assessment of the quality of evidence and the grade of recommendation for each of the interventions., Results and Conclusions: A clinical intervention algorithm based on the main determinants of cerebral perfusion-oxygenation changes during the first hours after birth was generated. The treatment guideline is presented to assist neonatologists in making decisions in relation to cerebral oximetry readings in preterm infants within the SafeBoosC phase II randomised clinical trial. The evidence grades were relatively low and the guideline cannot be recommended outside a research setting., (© 2013 S. Karger AG, Basel.)
- Published
- 2013
- Full Text
- View/download PDF
28. Tissue oximetry: a comparison of mean values of regional tissue saturation, reproducibility and dynamic range of four NIRS-instruments on the human forearm.
- Author
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Hyttel-Sorensen S, Sorensen LC, Riera J, and Greisen G
- Abstract
We compared absolute values of regional tissue hemoglobin saturation (StO(2)), reproducibility, and dynamic range of four different instruments on the forearm of adults. The sensors were repositioned 10 times on each subject. Dynamic range was estimated by exercise with subsequent arterial occlusion. Mean StO(2) was 70.1% ± 6.7 with INVOS 5100, 69.4% ± 5.0 with NIRO 200 NX, 63.4% ± 4.5 with NIRO 300, and 60.8% ± 3.6 with OxyPrem. The corresponding reproducibility S(w) was 5.4% (CI 4.4-6.9), 4.4% (CI 3.5-5.2), 4.1% (CI 3.3-4.9), and 2.7% (CI 2.2-3.2), respectively. The dynamic ranges ΔStO(2) were 45.0%, 46.8%, 44.8%, and 27.8%, respectively. In conclusion, the three commercial NIRS instruments showed different absolute values, whereas reproducibility and dynamic range were quite similar.
- Published
- 2011
- Full Text
- View/download PDF
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