Neurodevelopmental disability is the most common complication for survivors of surgery for congenital heart disease (CHD).
We analyzed individual participant data from studies of children evaluated ...with the Bayley Scales of Infant Development, second edition, after cardiac surgery between 1996 and 2009. The primary outcome was Psychomotor Development Index (PDI), and the secondary outcome was Mental Development Index (MDI).
Among 1770 subjects from 22 institutions, assessed at age 14.5 ± 3.7 months, PDIs and MDIs (77.6 ± 18.8 and 88.2 ± 16.7, respectively) were lower than normative means (each P < .001). Later calendar year of birth was associated with an increased proportion of high-risk infants (complexity of CHD and prevalence of genetic/extracardiac anomalies). After adjustment for center and type of CHD, later year of birth was not significantly associated with better PDI or MDI. Risk factors for lower PDI were lower birth weight, white race, and presence of a genetic/extracardiac anomaly (all P ≤ .01). After adjustment for these factors, PDIs improved over time (0.39 points/year, 95% confidence interval 0.01 to 0.78; P = .045). Risk factors for lower MDI were lower birth weight, male gender, less maternal education, and presence of a genetic/extracardiac anomaly (all P < .001). After adjustment for these factors, MDIs improved over time (0.38 points/year, 95% confidence interval 0.05 to 0.71; P = .02).
Early neurodevelopmental outcomes for survivors of cardiac surgery in infancy have improved modestly over time, but only after adjustment for innate patient risk factors. As more high-risk CHD infants undergo cardiac surgery and survive, a growing population will require significant societal resources.
Tight glycemic control has not improved outcomes in studies involving critically ill adults or children after cardiac surgery. A controlled study involving hyperglycemic critically ill children who ...had not undergone cardiac surgery showed no benefit of tight glycemic control.
Tight glycemic control to a blood glucose level of 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter) was originally shown to reduce morbidity and mortality in a single-center, randomized clinical trial involving critically ill adult surgical patients,
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but subsequent trials involving adults have not shown benefit.
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Results of trials of tight glycemic control in critically ill children have been inconsistent
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; retrospective studies have consistently shown an association between hyperglycemia and poor outcomes.
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A single-center, randomized trial involving children, most of whom had undergone cardiac surgery, showed significantly lower mortality and infection rate . . .
Objectives To investigate the long-term impact of early-term birth (37-38 weeks' gestation) relative to full-term birth (≥39 weeks' gestation) on neurodevelopmental and psychiatric outcomes in ...adolescents with single-ventricle congenital heart disease (CHD). Study design This cross-sectional cohort study analyzed retrospective medical records from full term adolescents with single-ventricle CHD who underwent the Fontan procedure. Participants underwent neurodevelopmental and psychiatric evaluations, as well as structural brain magnetic resonance imaging. Early-term born adolescents were compared with full-term born adolescents using regression models with adjustments for family social status, birth weight, and genetic abnormality status. Medical and demographic risk factors were examined as well. Results Compared with the full-term group (n = 100), adolescents born early term (n = 33) scored significantly worse on daily-life executive functions, as measured by the Behavior Rating Inventory of Executive Function parent-report (mean scores: early term, 62.0 ± 10.9; full-term, 55.6 ± 12.2; P = .009) and self-report ( P = .02) composites. Adolescents born early term were more likely than those born full term to have a lifetime attention-deficit/hyperactivity disorder (ADHD) diagnosis (early term, 55%; full term, 26%; P = .001). The early-term group also displayed greater psychiatric symptom severity, as indicated by the clinician-reported Brief Psychiatric Rating Scale (mean score: early term, 16.1 ± 8.6; full-term, 12.5 ± 8.2; P = .007). Conclusion Early-term birth is associated with greater prevalence of executive dysfunction, ADHD diagnosis, and psychiatric problems in adolescents with single-ventricle CHD. Early-term birth should be included as a potential risk factor in the algorithm for closer developmental surveillance in CHD.
Objective
In the absence of controlled trials, treatment of neonatal seizures has changed minimally despite poor drug efficacy. We tested bumetanide added to phenobarbital to treat neonatal seizures ...in the first trial to include a standard‐therapy control group.
Methods
A randomized, double‐blind, dose‐escalation design was employed. Neonates with postmenstrual age 33 to 44 weeks at risk of or with seizures were eligible. Subjects with electroencephalography (EEG)‐confirmed seizures after ≥20 and <40mg/kg phenobarbital were randomized to receive additional phenobarbital with either placebo (control) or 0.1, 0.2, or 0.3mg/kg bumetanide (treatment). Continuous EEG monitoring data from ≥2 hours before to ≥48 hours after study drug administration (SDA) were analyzed for seizures.
Results
Subjects were randomized to treatment (n = 27) and control (n = 16) groups. Pharmacokinetics were highly variable among subjects and altered by hypothermia. The only statistically significant adverse event was diuresis in treated subjects (48% vs 13%, p = 0.02). One treated (4%) and 3 control subjects died (19%, p = 0.14). Among survivors, 2 of 26 treated subjects (8%) and 0 of 13 control subjects had hearing impairment, as did 1 nonrandomized subject. Total seizure burden varied widely, with much higher seizure burden in treatment versus control groups (median = 3.1 vs 1.2 min/h, p = 0.006). There was significantly greater reduction in seizure burden 0 to 4 hours and 2 to 4 hours post‐SDA (both p < 0.01) compared with 2‐hour baseline in treatment versus control groups with adjustment for seizure burden.
Interpretation
Although definitive proof of efficacy awaits an appropriately powered phase 3 trial, this randomized, controlled, multicenter trial demonstrated an additional reduction in seizure burden attributable to bumetanide over phenobarbital without increased serious adverse effects. Future trials of bumetanide and other drugs should include a control group and balance seizure severity. ANN NEUROL 2021;89:327–340
To generate a multidimensional predictive model of risk factors for iatrogenic withdrawal syndrome in critically ill children.
Secondary analysis of prospective data from the Randomized Evaluation of ...Sedation Titration for Respiratory Failure clinical trial.
PICU.
Children who received greater than or equal to 5 days of sedation during mechanical ventilation for acute respiratory failure.
The Randomized Evaluation of Sedation Titration for Respiratory Failure study tested the effect of a nurse-led, goal-directed sedation protocol on clinical outcomes. There was no additional intervention in this secondary analysis.
Data included 1,157 children from 31 PICUs. Iatrogenic withdrawal syndrome was defined as having at least two Withdrawal Assessment Tool-Version 1 scores greater than or equal to 3 after the start of opioid weaning. Logistic regression with generalized estimating equations to account for clustering by site was used to evaluate patient, process, and healthcare system risk factors for iatrogenic withdrawal syndrome. Subjects with iatrogenic withdrawal syndrome (544/1,157; 47%) were younger and more likely to have preexisting cognitive or functional impairment. They also received higher sedative doses and longer exposure periods. In multivariable analyses, significant predictors of iatrogenic withdrawal syndrome included younger age, preexisting cognitive impairment, higher preweaning mean daily opioid dose, longer duration of sedation, receipt of three or more preweaning sedative classes, higher nursing workload, and more one-to-one nurse staffing.
Iatrogenic withdrawal syndrome is common in children recovering from critical illness, and several risk factors are predictive, including patient characteristics, sedative exposure, additional sedative agents, and system-level factors. High-risk patients could be identified before weaning to better prevent iatrogenic withdrawal syndrome among at-risk patients.
This trial tested the hypothesis that tight glycemic control reduces morbidity after pediatric cardiac surgery. Results indicated that this therapy, as compared with standard care, does not ...significantly change infection rate, mortality, length of stay, or organ failure.
Congenital heart defects are the most common birth defects, with approximately 20,000 pediatric cardiothoracic surgical procedures performed each year in the United States.
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Postoperative morbidity and mortality among infants and young children remain relatively high
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; thus, identification of modifiable risk factors during postoperative critical care is important for continued improvement in outcomes. Tight glycemic control has emerged as a potential approach to reduce morbidity in adult cardiac medical
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and surgical
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populations, but it has not proved to be generalizable to all critical care patients.
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The incidence of hyperglycemia (blood glucose level >126 mg per deciliter . . .
Background Neurodevelopmental disability is common after operations for congenital heart defects. We previously showed that patient and preoperative factors, center, and calendar year of birth ...explained less than 30% of the variance for the Psychomotor Development Index (PDI) and the Mental Development Index (MDI) of the Bayley Scales of Infant Development-Second Edition. Here we investigate how much additional variance in PDI and MDI is contributed by operative variables and postoperative events. Methods We analyzed neurodevelopmental outcomes after operations with cardiopulmonary bypass at age 9 months or younger between 1996 and 2009. We used linear regression to investigate the effect of operative factors (age, weight, and cardiopulmonary bypass variables) and postoperative events on neurodevelopmental outcomes, adjusting for center, type of congenital heart defect, year of birth, and preoperative factors. Results We analyzed 1,770 children from 22 institutions with neurodevelopmental testing at age 13.3 months (range, 6 to 30 months). Among operative factors, longer total support time was associated with lower PDI and MDI ( p < 0.05). When postoperative events were added, use of either extracorporeal membrane oxygenation or ventricular assist device support, and longer postoperative length of stay were associated with lower PDI and MDI ( p < 0.05). Longer total support time was not a significant predictor in these models. After adjusting for patient, preoperative, intraoperative, and postoperative factors, measured intraoperative and postoperative factors accounted for 5% of the variances in PDI and MDI. Conclusions Operative factors may be less important than innate patient and preoperative factors and postoperative events in predicting early neurodevelopmental outcomes after cardiac operations in infants. Neurodevelopmental outcomes improved over calendar time when adjusted for patient and medical variables.
Objective To describe the relationship between altered white matter microstructure and neurodevelopment in children with dextro-transposition of the great arteries (d-TGA). Study design We report ...correlations between regional white matter microstructure as measured by fractional anisotropy (FA) and cognitive outcome in a homogeneous group of adolescents with d-TGA. Subjects with d-TGA (n = 49) and controls (n = 29) underwent diffusion tensor imaging and neurocognitive testing. In the group with d-TGA, we correlated neurocognitive scores with FA in 14 composite regions of interest in which subjects with d-TGA had lower FA than controls. Results Among the patients with d-TGA, mathematics achievement correlated with left parietal FA ( r = 0.39; P = .006), inattention/hyperactivity symptoms correlated with right precentral FA ( r = −0.39; P = .006) and left parietal FA ( r = −0.30; P = .04), executive function correlated with right precentral FA ( r = −0.30; P = .04), and visual-spatial skills correlated with right frontal FA ( r = 0.30; P = .04). We also found an unanticipated correlation between memory and right posterior limb of the internal capsule FA ( r = 0.29; P = .047). Conclusion Within the group with d-TGA, regions of reduced white matter microstructure are associated with cognitive performance in a pattern similar to that seen in healthy adolescents and adults. Diminished white matter microstructure may contribute to cognitive compromise in adolescents who underwent open-heart surgery in infancy.
Industrial support of biomedical research may bias scientific conclusions, as demonstrated by recent analyses of pharmaceutical studies. However, this issue has not been systematically examined in ...the area of nutrition research. The purpose of this study is to characterize financial sponsorship of scientific articles addressing the health effects of three commonly consumed beverages, and to determine how sponsorship affects published conclusions.
Medline searches of worldwide literature were used to identify three article types (interventional studies, observational studies, and scientific reviews) about soft drinks, juice, and milk published between 1 January, 1999 and 31 December, 2003. Financial sponsorship and article conclusions were classified by independent groups of coinvestigators. The relationship between sponsorship and conclusions was explored by exact tests and regression analyses, controlling for covariates. 206 articles were included in the study, of which 111 declared financial sponsorship. Of these, 22% had all industry funding, 47% had no industry funding, and 32% had mixed funding. Funding source was significantly related to conclusions when considering all article types (p = 0.037). For interventional studies, the proportion with unfavorable conclusions was 0% for all industry funding versus 37% for no industry funding (p = 0.009). The odds ratio of a favorable versus unfavorable conclusion was 7.61 (95% confidence interval 1.27 to 45.73), comparing articles with all industry funding to no industry funding.
Industry funding of nutrition-related scientific articles may bias conclusions in favor of sponsors' products, with potentially significant implications for public health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Few studies have described the neuropsychological outcomes and frequency of structural brain or genetic abnormalities in adolescents with single ventricle who underwent the Fontan procedure.
In a ...cross-sectional, single-center study, we enrolled 156 subjects with single ventricle, mean age 14.5±2.9 years, who had undergone the Fontan procedure. Scores in the entire cohort on a standard battery of neuropsychological tests were compared with those of normative populations or to those of a group of 111 locally recruited healthy adolescents. They also underwent brain magnetic resonance imaging and were evaluated by a clinical geneticist. Genetic abnormalities were definite in 16 subjects (10%) and possible in 49 subjects (31%). Mean Full-Scale IQ was 91.6±16.8, mean Reading Composite score was 91.9±17.2, and mean Mathematics Composite score was 92.0±22.9, each significantly lower than the population means of 100±15. Mean scores on other neuropsychological tests were similarly lower than population norms. In multivariable models, risk factors for worse neuropsychological outcomes were longer total support and circulatory arrest duration at first operation, presence of a genetic abnormality, more operations and operative complications, more catheterization complications, and seizure history. The frequency of any abnormality on magnetic resonance imaging was 11 times higher among Fontan adolescents than referents (66% versus 6%); 19 (13%) patients had evidence of a stroke, previously undiagnosed in 7 patients (40%).
The neuropsychological deficits and high frequencies of structural brain abnormalities in adolescents who underwent the Fontan procedure highlight the need for research on interventions to improve the long-term outcomes in this high-risk group.
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