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1.
J Cardiovasc Dev Dis ; 10(11)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37998499

RESUMO

INTRODUCTION: Although transfemoral aortic valve replacement (TAVR) is a safe treatment for elderly patients with severe aortic valve stenosis, postoperative microembolism has been described. In this secondary endpoint analysis of the POST-TAVR trial, we aimed to investigate whether changes in neuron-specific enolase (NSE)-a biomarker of neuronal damage-are associated with changes in memory function or postoperative delirium (POD). MATERIALS AND METHODS: This was a prospective single-center study enrolling patients undergoing elective TAVR. Serum NSE was measured before and 24 h after TAVR. POD was diagnosed using CAM-ICU testing. Memory function was assessed before TAVR and before hospital discharge using the "Consortium to Establish a Registry for Alzheimer's Disease" (CERAD) word list and the digit span task (DST) implemented in "∆elta-App". RESULTS: Subjects' median age was 82 years (25th to 75th percentile: 77.5-85.0), 42.6% of subjects were women. CERAD scores significantly increased from pre- to post-TAVR, with p < 0.001. POD occurred in 4.4% (6/135) of subjects at median 2 days after TAVR. After TAVR, NSE increased from a median of 1.85 ng/mL (1.30-2.53) to 2.37 ng/mL (1.69-3.07), p < 0.001. The median increase in NSE was 40.4% (13.1-138.0) in patients with POD versus 17.3% (3.3-43.4) in those without POD (p = 0.17). CONCLUSIONS: Memory function improved after TAVR, likely due to learning effects, with no association to change in NSE. Patients with POD appear to have significantly higher postoperative levels of NSE compared to patients without POD after TAVR. This finding suggests that neuronal damage, as indicated by NSE elevation, may not significantly impair assessed memory function after TAVR.

2.
Biomark Med ; 17(10): 475-485, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37675894

RESUMO

Background: This study aimed to determine whether novel and conventional cardiorenal biomarkers in patients before transcatheter aortic valve implantation may be associated with cardiorenal syndrome (CRS) type 1. Methods: Serum NT-proBNP and urine biomarkers (hepcidin-25, NGAL, IL-6) were measured before and 24 h after transcatheter aortic valve implantation. Results: 16/95 patients had CRS type 1. Those patients had longer length of stay in hospital (12.5 [9.0-16.0] vs 9.0 [8-12] days; p = 0.025) and were more frequently readmitted to hospital within 6 months after discharge (46.7 vs 15.6%; odds ratio: 4.7; 95% CI: 1.5-15.5; p = 0.007). The NT-proBNP/urine hepcidin-25 ratio (odds ratio: 2.89; 95% CI: 1.30-6.41; p = 0.009) was an independent modifier of CRS type 1. Conclusion: The NT-proBNP/urine hepcidin-25 ratio appears to be a modifier of risk of CRS type 1.


Assuntos
Estenose da Valva Aórtica , Síndrome Cardiorrenal , Humanos , Hepcidinas , Peptídeo Natriurético Encefálico , Estenose da Valva Aórtica/complicações
3.
Acta Paediatr ; 112(7): 1443-1452, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37073106

RESUMO

AIM: To investigate the relation between autonomic regulation, measured using heart rate variability (HRV), body weight and degree of prematurity in infants. Further to assess utility to include body weight in a machine learning-based sepsis prediction algorithm. METHODS: Longitudinal cohort study including 378 infants hospitalised in two neonatal intensive care units. Continuous vital sign data collection was performed prospectively from the time of NICU admission to discharge. Clinically relevant events were annotated retrospectively. HRV described using sample entropy of inter-beat intervals and assessed for its correlation with body weight measurements and age. Weight values were then added to a machine learning-based algorithm for neonatal sepsis detection. RESULTS: Sample entropy showed a positive correlation with increasing body weight and postconceptual age. Very low birth weight infants exhibited significantly lower HRV compared to infants with a birth weight >1500 g. This persisted when reaching similar weight and at the same postconceptual age. Adding body weight measures improved the algorithm's ability to predict sepsis in the overall population. CONCLUSION: We revealed a positive correlation of HRV with increasing body weight and maturation in infants. Restricted HRV, proven helpful in detecting acute events such as neonatal sepsis, might reflect prolonged impaired development of autonomic control.


Assuntos
Sepse Neonatal , Sepse , Recém-Nascido , Lactente , Humanos , Estudos Longitudinais , Estudos Retrospectivos , Peso ao Nascer , Unidades de Terapia Intensiva Neonatal , Frequência Cardíaca/fisiologia , Sepse/diagnóstico
4.
Acta Paediatr ; 112(4): 686-696, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36607251

RESUMO

AIM: Sepsis is a leading cause of morbidity and mortality in neonates. Early diagnosis is key but difficult due to non-specific signs. We investigate the predictive value of machine learning-assisted analysis of non-invasive, high frequency monitoring data and demographic factors to detect neonatal sepsis. METHODS: Single centre study, including a representative cohort of 325 infants (2866 hospitalisation days). Personalised event timelines including interventions and clinical findings were generated. Time-domain features from heart rate, respiratory rate and oxygen saturation values were calculated and demographic factors included. Sepsis prediction was performed using Naïve Bayes algorithm in a maximum a posteriori framework up to 24 h before clinical sepsis suspicion. RESULTS: Twenty sepsis cases were identified. Combining multiple vital signs improved algorithm performance compared to heart rate characteristics alone. This enabled a prediction of sepsis with an area under the receiver operating characteristics curve of 0.82, up to 24 h before clinical sepsis suspicion. Moreover, 10 h prior to clinical suspicion, the risk of sepsis increased 150-fold. CONCLUSION: The present algorithm using non-invasive patient data provides useful predictive value for neonatal sepsis detection. Machine learning-assisted algorithms are promising novel methods that could help individualise patient care and reduce morbidity and mortality.


Assuntos
Sepse Neonatal , Sepse , Recém-Nascido , Humanos , Teorema de Bayes , Aprendizado de Máquina , Sinais Vitais
5.
Front Pediatr ; 10: 921444, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928685

RESUMO

Background: Survival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants. Methods: Twenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured. Results: The CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18-24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development. Conclusion: Our data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.

6.
Psychophysiology ; 59(11): e14092, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35569101

RESUMO

Response conflict evoked by a distractor stimulus object in interference tasks is associated with longer reaction times and a pronounced ERP component referred to as the fronto-central N2. Increasing the proportion congruency (PC, i.e., the proportion of trials in which target and distractor are associated with the same response) is assumed to enhance distractor-evoked conflict via defocusing of attention. Findings concerning the effect of the PC on the N2 in Eriksen flanker task experiments have been inconsistent, however, lending little support to the notion that the N2 reflects a conflict monitoring process. Here, we analyze the N2 in a temporal flanker task, in which the distractor stimuli, presented in advance of the target, elicit pronounced activation of the associated responses (as inferred from the lateralized readiness potential) when the PC is high. Consistent with result pattern obtained in other tasks involving successive presentation of the distractor and the target, conflict trials in a high-PC condition evoked a particularly large N2. These findings accord with the assumption that the N2 reflects either conflict monitoring or conflict-induced regulatory measures (i.e., reactive control). In light of the discrepancy of results obtained under conditions of simultaneous and successive distractor-target presentation, we speculate that the N2 is pronounced in situations that offer strong hints for classifying dominating response activation as incorrect, possibly reflecting particular control to counter this activation. Additional properties of the temporal flanker task, related to ERP investigations, are discussed.


Assuntos
Atenção , Conflito Psicológico , Atenção/fisiologia , Eletroencefalografia , Fenômenos Eletrofisiológicos , Potenciais Evocados/fisiologia , Humanos , Tempo de Reação/fisiologia
7.
Pediatr Res ; 91(3): 572-580, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34601494

RESUMO

BACKGROUND: Apnea of prematurity cannot be reliably measured with current monitoring techniques. Instead, indirect parameters such as oxygen desaturation or bradycardia are captured. We propose a Kalman filter-based detection of respiration activity and hence apnea using multichannel esophageal signals in neonatal intensive care unit patients. METHODS: We performed a single-center observational study with moderately preterm infants. Commercially available nasogastric feeding tubes containing multiple electrodes were used to capture signals with customized software. Multichannel esophageal raw signals were manually annotated, processed using extended Kalman filter, and compared with standard monitoring data including chest impedance to measure respiration activity. RESULTS: Out of a total of 405.4 h captured signals in 13 infants, 100 episodes of drop in oxygen saturation or heart rate were examined. Median (interquartile range) difference in respiratory rate was 0.04 (-2.45 to 1.48)/min between esophageal measurements annotated manually and with Kalman filter and -3.51 (-7.05 to -1.33)/min when compared to standard monitoring, suggesting an underestimation of respiratory rate when using the latter. CONCLUSIONS: Kalman filter-based estimation of respiratory activity using multichannel esophageal signals is safe and feasible and results in respiratory rate closer to visual annotation than that derived from chest impedance of standard monitoring.


Assuntos
Apneia , Doenças do Prematuro , Apneia/diagnóstico , Frequência Cardíaca/fisiologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Doenças do Prematuro/diagnóstico , Monitorização Fisiológica/métodos , Taxa Respiratória
8.
Pediatr Res ; 91(3): 481, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34893695
9.
Acta Paediatr ; 110(12): 3201-3226, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34432903

RESUMO

AIM: To systematically summarise the current evidence of employing clinical decision support algorithms (CDSAs) using non-invasive parameters for sepsis prediction in neonates. METHODS: A comprehensive search in PubMed, CENTRAL and EMBASE was conducted. Screening, data extraction and risk of bias were performed by two authors. The certainty of the evidence was assessed using GRADE. PROSPERO ID: CRD42020205143. RESULTS: After abstract and full-text screening, 36 studies comprising 18,096 infants were included. Most CDSAs evaluated heart rate (HR)-based parameters. Two publications derived from one randomised-controlled trial assessing HR characteristics reported significant reduction in 30-day septicaemia-related mortality. Thirty-four non-randomised studies found promising yet inconclusive results. CONCLUSION: Heart rate-based parameters are reliable components of CDSAs for sepsis prediction, particularly in combination with additional vital signs and demographics. However, inconclusive evidence and limited standardisation restricts clinical implementation of CDSAs outside of a controlled research environment. Further experimentation and comparison of parameter combinations and testing of new CDSAs are warranted.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Sepse Neonatal , Sepse , Algoritmos , Viés , Humanos , Lactente , Recém-Nascido , Sepse Neonatal/diagnóstico , Sepse/diagnóstico
10.
J Pharmacokinet Pharmacodyn ; 48(3): 401-410, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33523331

RESUMO

The objectives are to characterize oscillations of physiological functions such as heart rate and body temperature, as well as the sleep cycle from behavioral states in generally stable preterm neonates during the first 5 days of life. Heart rate, body temperature as well as behavioral states were collected during a daily 3-h observation interval in 65 preterm neonates within the first 5 days of life. Participants were born before 32 weeks of gestational age or had a birth weight below 1500 g; neonates with asphyxia, proven sepsis or malformation were excluded. In total 263 observation intervals were available. Heart rate and body temperature were analyzed with mathematical models in the context of non-linear mixed effects modeling, and the sleep cycles were characterized with signal processing methods. The average period length of an oscillation in this preterm neonate population was 159 min for heart rate, 290 min for body temperature, and the average sleep cycle duration was 19 min. Oscillation of physiological functions as well as sleep cycles can be characterized in very preterm neonates within the first few days of life. The observed parameters heart rate, body temperature and sleep are running in a seemingly uncorrelated pace at that stage of development. Knowledge about such oscillations may help to guide nursing and medical care in these neonates as they do not yet follow a circadian rhythm.


Assuntos
Ritmo Circadiano/fisiologia , Recém-Nascido Prematuro/fisiologia , Temperatura Corporal/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos , Sono/fisiologia
11.
IEEE Trans Biomed Eng ; 68(6): 1903-1912, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33044926

RESUMO

OBJECTIVE: Autonomic dysregulation in preterm infants requires continuous monitoring of vital signs such as heart rate over days to months. Unfortunately, common surface electrodes are prone to electrocardiography (ECG) signal artifacts and cause serious skin irritations during long-term use. In contrast, esophageal ECG is known to be very sensitive due to the proximity of electrodes and heart and insensitive to external influences. This study addresses if multichannel esophageal ECG qualifies for heart rate monitoring in preterm infants. METHODS: We recorded esophageal leads with a multi-electrode gastric feeding tube in a clinical study with 13 neonates and compared the heartbeat detection performance with standard surface leads. A computationally simple and versatile ECG wave detection algorithm was used. RESULTS: Multichannel esophageal ECG manifested heartbeat sensitivity and positive predictive value greater than 98.5% and significant less false negative (FN) ECG waves as compared to surface ECG due to site-typical electrode motion artifacts. False positive bradycardia as indicated with more than 13 consecutive FN ECG waves was equally expectable in esophageal and surface channels. No adverse events were reported for the multi-electrode gastric feeding tube. CONCLUSION: Heart rate monitoring of preterm infants with multiple esophageal electrodes is considered as feasible and reliable. Less signal artifacts will improve the detection of bradycardia, which is crucial for immediate interventions, and reduce alarm fatigue. SIGNIFICANCE: Due to the possibility to integrate the multichannel ECG into a gastric feeding tube and meanwhile omit harmful skin electrodes, the presented system has great potential to facilitate future intensive care of preterm infants.


Assuntos
Eletrocardiografia , Recém-Nascido Prematuro , Artefatos , Eletrodos , Frequência Cardíaca , Humanos , Lactente , Recém-Nascido , Monitorização Fisiológica
12.
Pharmacol Res Perspect ; 8(3): e00596, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32412185

RESUMO

Caffeine is widely used in preterm neonates suffering from apnea of prematurity (AOP), and it has become one of the most frequently prescribed medications in neonatal intensive care units. Goal of this study is to investigate how caffeine citrate treatment affects sleep-wake behavior in preterm neonates. The observational study consists of 64 preterm neonates during their first 5 days of life with gestational age (GA) <32 weeks or very low birthweight of < 1500 g. A total of 52 patients treated with caffeine citrate and 12 patients without caffeine citrate were included. Sleep-wake behavior was scored in three stages: active sleep, quiet sleep, and wakefulness. Individual caffeine concentration of every neonate was simulated with a pharmacokinetic model. In neonates with GA ≥ 28 weeks, wakefulness increased and active sleep decreased with increasing caffeine concentrations, whereas quiet sleep remained unchanged. In neonates with GA < 28 weeks, no clear caffeine effects on sleep-wake behavior could be demonstrated. Caffeine increases fraction of wakefulness, alertness, and most probably also arousability at cost of active but not quiet sleep in preterm neonates. As such, caffeine should therefore not affect time for physical and cerebral regeneration during sleep in preterm neonates.


Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Citratos/farmacologia , Sono/efeitos dos fármacos , Vigília/efeitos dos fármacos , Cafeína/administração & dosagem , Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/farmacocinética , Citratos/administração & dosagem , Citratos/farmacocinética , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Modelos Biológicos
13.
Pediatr Res ; 86(3): 348-354, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31086292

RESUMO

BACKGROUND: Cardiorespiratory stability of preterm infants is a prerequisite for discharge from the neonatal intensive care unit (NICU) but very difficult to predict. We aimed to assess whether characterizing heart rate fluctuation (HRF) within the first days of life has prognostic utility. METHODS: We conducted a prospective cohort study in 90 preterm infants using a previously validated surface diaphragmatic electromyography (sEMG) method to derive interbeat intervals. We characterized HRF by time series parameters including sample entropy (SampEn) and scaling exponent alpha (ScalExp) obtained from daily 3-h measurements. Data were analyzed by multivariable, multilevel linear regression. RESULTS: We obtained acceptable raw data from 309/330 sEMG measurements in 76/90 infants born at a mean (range) of 30.2 (24.7-34.0) weeks gestation. We found a significant negative association of SampEn with duration of respiratory support (R2 = 0.53, p < 0.001) and corrected age at discontinuation of caffeine therapy (R2 = 0.35, p < 0.001) after adjusting for sex, gestational age, birth weight z-score, and sepsis. CONCLUSIONS: Baseline SampEn calculated over the first 5 days of life carries prognostic utility for an estimation of subsequent respiratory support and pre-discharge cardiorespiratory stability in preterm infants, both important for planning of treatment and utilization of health care resources.


Assuntos
Eletromiografia , Frequência Cardíaca , Terapia Intensiva Neonatal/métodos , Peso ao Nascer , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Modelos Lineares , Masculino , Análise Multivariada , Alta do Paciente , Prognóstico , Estudos Prospectivos , Processamento de Sinais Assistido por Computador , Suíça , Resultado do Tratamento
14.
Psychol Res ; 83(2): 297-307, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30712104

RESUMO

Electrophysiological recording in a temporal flanker task (i.e., distractors preceding the targets) has demonstrated that distractor processing is adjusted to the overall utility of the distractors. Under high utility, that is, distractors are predictive of the target/response, distractors immediately activate the corresponding response (as indicated by the lateralized readiness potential, LRP). This activation has been shown to be markedly postponed when the target predictably occurs delayed. To investigate the occurrence and time course of distractor-related response activation under conditions of unpredictable target onset, we randomly varied the stimulus-onset asynchrony (SOA) between distractors and targets and recorded the distractor-evoked LRP. When the distractor utility was high, an LRP occurred shortly after distractor presentation. In case of a long SOA the time course of this LRP was characterized by a drop back to baseline and a subsequent re-activation that reached a substantial level before target onset. These results suggest that distractor processing is characterized by sophisticated adjustments to experienced utility and temporal constraints of the task as well as by further control processes that regulate premature response activation.


Assuntos
Potenciais Evocados/fisiologia , Processos Mentais/fisiologia , Incerteza , Adulto , Sinais (Psicologia) , Feminino , Humanos , Masculino , Estimulação Luminosa , Tempo de Reação/fisiologia , Adulto Jovem
15.
ERJ Open Res ; 4(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29497618

RESUMO

Nitrogen multiple-breath washout (N2MBW) is increasingly used in patients with cystic fibrosis. The current European Respiratory Society/American Thoracic Society consensus statement for MBW recommends the rejection of measurements with leaks. However, it is unclear whether this is necessary for all types of leaks. Here, our aim was to 1) model and 2) apply air leaks, and 3) to assess their influence on the primary MBW outcomes of lung clearance index and functional residual capacity. We investigated the influence of air leaks at various locations (pre-, intra- and post-capillary), sizes, durations and stages of the washout. Modelled leaks were applied to existing N2MBW data from 10 children by modifying breath tables. In addition, leaks were applied to the equipment during N2MBW measurements performed by one healthy adolescent. All modelled and applied leaks resulted in statistically significant but heterogeneous effects on lung clearance index and functional residual capacity. In all types of continuous inspiratory leaks exceeding a certain size, the end of the washout was not reached. For practical application, we illustrated six different "red flags", i.e. signs that enable easy identification of leaks during measurements. Air leaks during measurement significantly influence N2MBW outcomes. The influence of leaks on MBW outcomes is dependent on the location, relation to breath cycle, duration, stage of washout and size of the leak. We identified a range of signs to help distinguish leaks from physiological noise.

16.
Cochrane Database Syst Rev ; 3: CD011893, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29499081

RESUMO

BACKGROUND: Retinopathy of prematurity (ROP) is a vision-threatening disease of preterm neonates. The use of beta-adrenergic blocking agents (beta-blockers), which modulate the vasoproliferative retinal process, may reduce the progression of ROP or even reverse established ROP. OBJECTIVES: To determine the effect of beta-blockers on short-term structural outcomes, long-term functional outcomes, and the need for additional treatment, when used either as prophylaxis in preterm infants without ROP, stage 1 ROP (zone I), or stage 2 ROP (zone II) without plus disease or as treatment in preterm infants with at least prethreshold ROP. SEARCH METHODS: We searched the Cochrane Neonatal Review Group Specialized Register; CENTRAL (in the Cochrane Library Issue 7, 2017); Embase (January 1974 to 7 August 2017); PubMed (January 1966 to 7 August 2017); and CINAHL (January 1982 to 7 August 2017). We checked references and cross-references and handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings. SELECTION CRITERIA: We considered for inclusion randomised or quasi-randomised clinical trials that used beta-blockers for prevention or treatment of ROP in preterm neonates of less than 37 weeks' gestational age. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane and the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: We included three randomised trials (N = 366) in this review. Two of these studies were at high risk of bias. All studies reported on prevention of ROP and compared oral propranolol with placebo or no treatment. We found no trials assessing beta-blockers in infants with established stage 2 or higher ROP with plus disease.In one trial, study medication was started after one week of life, i.e. prior to the first ROP screening. The other two trials included preterm infants if they had stage 2 or lower ROP without plus disease. Based on the GRADE assessment, we considered evidence to be of low quality for the following outcomes: rescue treatment with anti-VEGF or laser therapy; and arterial hypotension or bradycardia requiring inotropic support. Evidence was of moderate quality for the following outcomes: progression to stage 2 with plus disease; progression to stage 3 ROP; and progression to stage 4 or 5 ROP.Meta-analysis of three trials (N = 366) suggested beneficial effects of oral beta-blockers on the risk of requiring anti-VEGF agents (typical risk ratio (RR) 0.32, 95% confidence interval (CI) 0.12 to 0.86; I² = 0%; typical risk difference (RD) -0.06, 95% CI -0.10 to -0.01; I² = 75%; number needed to treat for an additional beneficial outcome (NNTB) 18, 95% CI 14 to 84) and laser therapy (typical RR 0.54, 95% CI 0.32 to 0.89; typical RD -0.09, 95% CI -0.16 to -0.02; I² = 31%; NNTB 12, 95% CI 8 to 47). Meta-analysis of two trials (N = 161) demonstrated a beneficial effect of oral beta-blockers on progression to stage 3 ROP (typical RR 0.60, 95% CI 0.37 to 0.96; I² = 0%; typical RD -0.15, 95% CI -0.28 to -0.02; I² = 73%; NNTB 7, 95% CI 5 to 67). There was no significant effect of oral beta-blockers on progression to stage 2 ROP with plus disease or to stage 4 or 5 ROP. Although meta-analysis did not indicate a significant effect of beta-blockers on arterial hypotension or bradycardia, propranolol dosage in one study was reduced by 50% in infants of less than 26 weeks' gestational age due to severe hypotension, bradycardia, and apnoea in several participants. Analyses did not indicate significant effects of beta-blockers on complications of prematurity or mortality. None of the trials reported on long-term visual impairment. AUTHORS' CONCLUSIONS: Limited evidence of low-to-moderate quality suggests that prophylactic administration of oral beta-blockers might reduce progression towards stage 3 ROP and decrease the need for anti-VEGF agents or laser therapy. The clinical relevance of those findings is unclear as no data on long-term visual impairment were reported. Adverse events attributed to oral propranolol at a dose of 2 mg/kg/d raise concerns regarding systemic administration of this drug for prevention of ROP at the given dose. There is insufficient evidence to determine the efficacy and safety of beta-blockers for prevention of ROP due to high risk of bias in two included trials and the lack of long-term functional outcomes. We would encourage researchers to conduct large, well-designed trials to confirm or refute the role of beta-blockers for prevention and treatment of ROP in preterm infants. Trials should report on long-term visual impairment. Researchers should consider dose-finding studies of systemic beta-blockers and topical administration of beta-blockers, in order to optimise drug delivery and minimise adverse events.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Propranolol/uso terapêutico , Retinopatia da Prematuridade/prevenção & controle , Crioterapia , Progressão da Doença , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Fotocoagulação a Laser/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de Salvação/métodos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
17.
J Pediatr ; 191: 50-56.e1, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29173321

RESUMO

OBJECTIVE: To identify dosing strategies that will assure stable caffeine concentrations in preterm neonates despite changing caffeine clearance during the first 8 weeks of life. METHODS: A 3-step simulation approach was used to compute caffeine doses that would achieve stable caffeine concentrations in the first 8 weeks after birth: (1) a mathematical weight change model was developed based on published weight distribution data; (2) a pharmacokinetic model was developed based on published models that accounts for individual body weight, postnatal, and gestational age on caffeine clearance and volume of distribution; and (3) caffeine concentrations were simulated for different dosing regimens. RESULTS: A standard dosing regimen of caffeine citrate (using a 20 mg/kg loading dose and 5 mg/kg/day maintenance dose) is associated with a maximal trough caffeine concentration of 15 mg/L after 1 week of treatment. However, trough concentrations subsequently exhibit a clinically relevant decrease because of increasing clearance. Model-based simulations indicate that an adjusted maintenance dose of 6 mg/kg/day in the second week, 7 mg/kg/day in the third to fourth week and 8 mg/kg/day in the fifth to eighth week assures stable caffeine concentrations with a target trough concentration of 15 mg/L. CONCLUSIONS: To assure stable caffeine concentrations during the first 8 weeks of life, the caffeine citrate maintenance dose needs to be increased by 1 mg/kg every 1-2 weeks. These simple adjustments are expected to maintain exposure to stable caffeine concentrations throughout this important developmental period and might enhance both the short- and long-term beneficial effects of caffeine treatment.


Assuntos
Apneia/tratamento farmacológico , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Citratos/administração & dosagem , Doenças do Prematuro/tratamento farmacológico , Peso ao Nascer , Cafeína/farmacocinética , Cafeína/uso terapêutico , Estimulantes do Sistema Nervoso Central/farmacocinética , Estimulantes do Sistema Nervoso Central/uso terapêutico , Citratos/farmacocinética , Citratos/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Aumento de Peso
18.
Physiol Meas ; 39(1): 015004, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29120348

RESUMO

OBJECTIVE: Characterizing heart rate variability (HRV) in neonates has gained increased attention and is helpful in quantifying maturation and risk of sepsis in preterm infants. Raw data used to derive HRV in a clinical setting commonly contain noise from motion artifacts. Thoracic surface electromyography (sEMG) potentially allows for pre-emptive removal of motion artifacts and subsequent detection of interbeat interval (IBI) of heart rate to calculate HRV. We tested the feasibility of sEMG in preterm infants to exclude noisy raw data and to derive IBI for HRV analysis. We hypothesized that a stepwise quality control algorithm can identify motion artifacts which influence IBI values, their distribution in the time domain, and outcomes of nonlinear time series analysis. APPROACH: This is a prospective observational study in preterm infants <6 days of age. We used 100 sEMG measurements from 24 infants to develop a semi-automatic quality control algorithm including synchronized video recording, threshold-based sEMG envelope curve, optimized QRS-complex detection, and final targeted visual inspection of raw data. MAIN RESULTS: Analysis of HRV from sEMG data in preterm infants is feasible. A stepwise algorithm to exclude motion artifacts and improve QRS detection significantly influenced data quality (34% of raw data excluded), distribution of IBI values in the time domain, and nonlinear time series analysis. The majority of unsuitable data (94%) were excluded by automated steps of the algorithm. SIGNIFICANCE: Thoracic sEMG is a promising method to assess motion artifacts and calculate HRV in preterm neonates.


Assuntos
Eletromiografia/métodos , Frequência Cardíaca , Recém-Nascido Prematuro/fisiologia , Algoritmos , Artefatos , Eletrodos , Eletromiografia/instrumentação , Feminino , Humanos , Recém-Nascido , Masculino , Movimento , Dinâmica não Linear , Fatores de Tempo
19.
Front Psychol ; 8: 755, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28539907

RESUMO

Switching between tasks is assumed to be accompanied by inhibiting currently irrelevant, but competing tasks. A dominant task that strongly interferes with performing a weaker task may receive especially strong inhibition. We tested this prediction by letting participants switch among three tasks that differ in dominance: a location discrimination task with strong stimulus-response bindings (responding with left-hand and right-hand button presses to stimuli presented left or right to the fixation cross) was combined with a color/pattern and a shape discrimination task, for which stimulus-response mappings were arbitrary (e.g., left-hand button press mapped to a red stimulus). Across three experiments, the dominance of the location task was documented by faster and more accurate responses than in the other tasks. This even held for incompatible stimulus-response mappings (i.e., right-hand response to a left-presented stimulus and vice versa), indicating that set-level compatibility (i.e., "dimension overlap") was sufficient for making this location task dominant. As a behavioral marker for backward inhibition, we utilized n-2 repetition costs that are defined by higher reaction times for a switch back to a just abandoned and thus just inhibited task (ABA sequence) than for a switch to a less recently inhibited task (CBA, n-2 non-repetition). Reliable n-2 task repetition costs were obtained for all three tasks. Importantly, these costs were largest for the location task, suggesting that inhibition indeed was stronger for the dominant task. This finding adds to other evidence that the amount of inhibition is adjusted in a context-sensitive way.

20.
PLoS One ; 12(4): e0176670, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28448569

RESUMO

BACKGROUND: Poor control of body temperature is associated with mortality and major morbidity in preterm infants. We aimed to quantify its dynamics and complexity to evaluate whether indices from fluctuation analyses of temperature time series obtained within the first five days of life are associated with gestational age (GA) and body size at birth, and presence and severity of typical comorbidities of preterm birth. METHODS: We recorded 3h-time series of body temperature using a skin electrode in incubator-nursed preterm infants. We calculated mean and coefficient of variation of body temperature, scaling exponent alpha (Talpha) derived from detrended fluctuation analysis, and sample entropy (TSampEn) of temperature fluctuations. Data were analysed by multilevel multivariable linear regression. RESULTS: Data of satisfactory technical quality were obtained from 285/357 measurements (80%) in 73/90 infants (81%) with a mean (range) GA of 30.1 (24.0-34.0) weeks. We found a positive association of Talpha with increasing levels of respiratory support after adjusting for GA and birth weight z-score (p<0.001; R2 = 0.38). CONCLUSION: Dynamics and complexity of body temperature in incubator-nursed preterm infants show considerable associations with GA and respiratory morbidity. Talpha may be a useful marker of autonomic maturity and severity of disease in preterm infants.


Assuntos
Regulação da Temperatura Corporal , Temperatura Corporal , Recém-Nascido Prematuro/fisiologia , Tamanho Corporal , Comorbidade , Feminino , Idade Gestacional , Humanos , Incubadoras para Lactentes , Recém-Nascido , Modelos Lineares , Masculino , Análise de Regressão
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