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T N Raju

Publications and source records attributed to T N Raju.

At least 19 recordsLinked to original sources
PubMed1992

How much 'better' is good enough? The magnitude of treatment effect in clinical trials.

OBJECTIVES: Among the various factors required to calculate sample size for clinical trials, the magnitude of treatment effect anticipated is an important component. The objective of this report is to present some of the complexities involved in selection of treatment effect size in clinical trials. As a framework for discussion, an analysis of published reports related to surfactant therapy was carried out. DESIGN: Twenty-one consecutive exogenous surfactant trials for neonatal respiratory distress syndrome were analyzed. The "Methods" sections were reviewed for evaluating various components of sample size calculation, including the anticipated treatment effect size. RESULTS: Sixteen (76%) of the 21 reports provided a description of sample size calculations, and 12 of these gave some reasons for the choice of the anticipated treatment effect size. Expressed as percent change, the median treatment effect from intervention anticipated by the investigators was 50% (range, 15% to 90%), with a positively skewed distribution. The actual median percent reduction in adverse events from treatment (as compared with baseline) was 36% (range, 75% reduction to 5% excess). When the treatment effect was expressed as difference in adverse event rate, in the 14 (of 16) trials that could be analyzed, the median observed reduction in adverse events (death, bronchopulmonary dysplasia, or occurrence of respiratory distress syndrome) was 14.5% (range, 52% reduction to 2% excess). All trials except one concluded, however, that the intervention was effective, mostly based on additional subgroup calculations. CONCLUSIONS: Researchers often select sample sizes capable of detecting only large treatment effects, thus risking type II error, although sometimes a much smaller effect could be clinically important. While pragmatic considerations must be considered during the design of randomized clinical trials, researchers ought to present a rationale for anticipating a given magnitude of treatment effect in their sample size calculations. It may be possible to consider innovative trial designs that help determine the most appropriate treatment choice with the least possible sample size.

Confidence Intervals↗
PubMed1992

Some animal models for the study of perinatal asphyxia.

Much of our current understanding concerning the pathophysiology of perinatal brain disorders has evolved from animal studies over the past three decades. Fetal and neonatal nonhuman primate, pregnant sheep, lamb, puppy, piglet and immature rodents, all have been important animal models for perinatal brain research. Although no model can be considered 'perfect' in reflecting the variety and complexity of human brain pathology, the investigator must assess the merits and limitations of each model within the framework of the research questions being asked. A variety of experimental designs have been used over the years and variations of particular interest are the animal age, the method of producing brain insult and the procedures used for evaluating outcomes. Most models relating to the study of intracranial hemorrhage, cerebral blood flow and cerebral energy metabolism have generally been acute preparations. Some important long-term survival models have also been developed in recent years for the study of hypoxic-ischemic encephalopathy. The latter include the nonhuman primate, piglet, sheep and immature rat models. In this article, I have reviewed some important animal models used in perinatal brain research with emphasis on those relating to perinatal asphyxia and intracranial hemorrhage.

Animals↗
PubMed1992

Cranial Doppler applications in neonatal critical care.

Although Doppler methods have been validated, it must be stressed that, at their best, Doppler results reflect qualitative circulatory changes, and suggest the direction of change. Because the large conduit arteries may also be controlling changes in flow volume, a direct extrapolation of the numeric findings from Doppler studies may lead to incorrect conclusions. Doppler methods have not made their way into routine neonatal critical care until now, but several studies have concluded that Doppler-derived information can be used as adjunct to clinical management in cases with shock, asphyxia, brain death, vascular malformations, and increased intracranial pressure. As with any physiologic variable, serial measurements may be of greater value than a single measurement. The Doppler techniques already are powerful investigative tools, but with continued improvements in technology, they hold promise of becoming important adjuncts in the monitoring of cerebral hemodynamics in perinatal-neonatal critical care units.

Blood Flow Velocity↗
PubMed1991

Cerebral Doppler studies in the fetus and newborn infant.

The goal of developing reliable commercial Doppler systems for measuring vessel diameter and velocity changes during the cardiac cycle appears to be near. Reaching this goal would enable us to obtain volume-flow information continuously. In animal experiments, continuous measurements of Doppler velocity, pressure, and flow add important insights into hemodynamic measurements. Incorporating Doppler methods in microcirculatory research could also provide a link between the microcirculatory and the macrocirculatory hemodynamic research. Although Doppler methods have been validated, Doppler findings in clinical research (using commercial systems) must be considered at best to reflect qualitative circulatory alterations indicating directions of change. Because of inherent technologic limitations and considerable intersubject and intrasubject variability, direct extrapolation of the numeric findings from one study to the other can lead to misleading conclusions. The Doppler results are also influenced by measurement conditions and equipment settings. However, Doppler-derived information can be used as an adjunct to clinical management in many of the diseases discussed above. As with any physiologic variable, serial measurements probably are of greater value than single measurements. With continued improvement in technology, Doppler methods hold promise of becoming an important adjunct in cerebral hemodynamic monitoring in perinatal-neonatal intensive care units.

Brain Diseases↗
PubMed1991

Improving handwashing habits in the newborn nurseries.

In five separate sessions over a 13-month period, the authors monitored the handwashing habits of doctors, nurses, and other healthcare professionals in the nursery. Compliance rates regarding three specific items related to handwashing prophylaxis were noted by a group of observers without the knowledge of the subjects involved. Good handwashing prophylaxis was carried out by the doctors only 37.5% prior to handling infants, and 29.2% after contact with inanimate objects, whereas for these items the nurses complied 53.9% and 29.2%, respectively. Wrist ornaments were removed prior to handwashing in 72.7% and 75.3% of contacts. The data for other healthcare professionals were generally similar. The information from this study was used for educational purposes, which seemed to have had an impact on handwashing habits. The compliance rates during the later part of the study for the first two items combined improved from 28.4% to 62.6% (p less than 0.001). The authors conclude that in the newborn units, the compliance with handwashing is generally poor. They believe that with continued monitoring and educational efforts, it may be possible to improve habits regarding handwashing prophylaxis.

Cross Infection↗
PubMed1991

Cerebellar dimensions in assessment of gestational age in neonates.

To determine whether cerebellar dimensions measured with cranial ultrasonography help assess gestational age in neonates, the authors measured the area, circumference, and vertical length of the vermis and the area, circumference, and maximum transverse width of the cerebellar body in 80 healthy neonates. These dimensions were correlated with the clinically assessed gestational age. All three measurements of the vermis and cerebellar body strongly correlated with gestational age. The area and circumference of the vermis were superior to the maximum transverse cerebellar width in prediction of gestational age. Multiple regression models made with a single vermis measurement along with either the cerebellar area or its circumference further improved gestational age prediction (r = .88; P less than .0001). The cerebellar dimensions also correlated strongly with clinically assessed gestational age in 13 neonates between 500 and 750 g birth weight, 18 neonates small for gestational age, and 12 neonates in whom clinical and obstetric assessments of gestational age were discrepant by more than 2 weeks.

Anthropometry↗
PubMed1991

The effect of hematocrit alterations on cerebral vascular CO2 reactivity in newborn baboons.

To evaluate whether baseline hematocrit affects cerebral vascular reactivity to CO2, we studied the cerebral blood flow velocity in the internal carotid artery of newborn baboons, using a pulsed Doppler technique with direct imaging. Velocity responses to varying arterial CO2 tension (PaCO2) levels were first tested under baseline hematocrit (mean +/- SD, 35.9 +/- 4.7%), after hemodilution (hematocrit 20.3 +/- 2.7%), and after hemoconcentration (hematocrit 52.7 +/- 5.2%). The data were analyzed using multiple regression models, in which blood flow velocity values were the dependent variables, and PaCO2, hematocrit, and their interaction terms (product) were the independent variables. Models for the maximum systolic velocity, time-averaged mean velocity, and the end-diastolic velocity revealed a highly significant PaCO2 effect; with each mm Hg PaCO2 increase, the velocities increased between 2.9 and 3.6% (21.8-27% per 1 kPa). PaCO2 and hematocrit interaction terms were also highly significant and inversely related to velocity (negative slopes) in the maximum systolic velocity and time-averaged mean velocity models, suggesting that when the hematocrit is high, the PaCO2-induced increase in flow velocity would be attenuated, and when the hematocrit is low, such a response would be accentuated. The hematocrit effect on PaCO2 reactivity was maximal on maximum systolic velocity and least on end-diastolic velocity. Systolic velocity acceleration slope was significantly reduced when the hematocrit was high, and increased when the hematocrit was low. Based on these findings, we conclude that hematocrit is an important variable affecting the rate of kinetic energy change in the large vessels, thereby influencing cerebral vascular PaCO2 reactivity as assessed in Doppler studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Serious error.

Explore the source record for details and available documents.

Animals↗
PubMed1990

Effect of exogenous surfactant on the development of bronchopulmonary dysplasia in a baboon hyaline membrane disease model.

To test the effect of exogenous surfactant on the evolution of histopathologic changes of bronchopulmonary dysplasia (BPD), we conducted a study in a premature baboon hyaline membrane disease model. One hundred mg/kg bovine surfactant sonicated in saline or 3 ml/kg saline placebo was instilled via the trachea at about 10 min of age. The clinical status and physiologic changes were monitored for 9 days, and pulmonary histopathology was evaluated after death. Compared to the control, the surfactant-treated animals showed a significant improvement in arterial/alveolar oxygen ratio and pulmonary compliance, facilitating rapid weaning from assisted ventilation. Lung histology revealed that pulmonary parenchyma expanded 70% to 95% without features of early BPD. Dysplastic maturation, air trapping, or cellular atypia was not seen. In contrast, lung histology in the control group revealed alveolar expansion less than or equal to 50%, basal cell hyperplasia in the bronchial and bronchiolar epithelium, dysplastic maturation with cellular atypia, extensive epithelial erosion, and type II cell hyperplasia, all features of early BPD. The results of this study suggest that in the premature baboon model, exogenous surfactant therapy improves pulmonary functional abnormalities and lessens the histologic features of BPD, perhaps because of rapid weaning and reduced barotrauma.

Animals↗
PubMed1990

Chest radiographic course after exogenous surfactant therapy in baboons with respiratory distress syndrome.

Exogenous surfactant materials have been used under a variety of treatment protocols in cases of neonatal respiratory distress syndrome (RDS). To evaluate the differences in radiologic changes that follow either an early or late therapy with exogenous bovine surfactant, we reviewed 189 serially obtained chest radiographs from 48 premature baboons with RDS studied under different treatment regimen. Twenty-six animals were controls (100 chest films), and 22 received 100 mg/kg bovine surfactant instilled via the trachea in three study protocols (89 chest films). Surfactant was given within 10 min of birth in one group and at 2 h of age in the other. In 25/26 controls, radiologic evidence of severe RDS was seen by 2 h of age; these changes persisted in 15 animals at 24 h. By contrast, a rapid clearing of radiologic features of RDS was seen following surfactant instillation in all 22 (100%) animals within 4 h, but one (4.5%) of these 22 deteriorated at 9 h of age. Pulmonary interstitial emphysema (PIE) was seen in 9/26 (34.6%) and pneumothorax in 5/26 (19.2%) control animals, while 1/22 (4.5%) surfactant-treated animals developed PIE, and none had pneumothorax. The presence of a shunt via the patent ductus arteriosus did not affect radiographic findings in 20 animals studied by contrast injection. Therapy for patent ductus arteriosus (PDA) also had no substantial influence on the radiographic findings, or with regard to the pulmonary course. Radiographic clearing of RDS occurred approximately 18 to 20 h prior to the improvement in pulmonary compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Medication errors in neonatal and paediatric intensive-care units.

In a 4-year prospective quality assurance study, 315 iatrogenic medication errors were reported among the 2147 neonatal and paediatric intensive-care admissions, an error rate of 1 per 6.8 admissions (14.7%). The frequency of iatrogenic injury of any sort due to a medication error was 66/2147 (3.1%)--1 injury for each 33 intensive-care admissions. 33 (10.5%) errors were potentially serious, 32 (10.2%) caused mild patient injuries, and 1 patient had acute aminophylline poisoning after receiving five intravenous doses of the drug at a dosage ten times higher than prescribed, owing to a calculation error during dilution. A longitudinal monitoring system helps to identify iatrogenic complications due to medication errors and may help in implementing preventive measures.

Child↗
PubMed1989

A multicenter randomized, placebo-controlled trial of surfactant therapy for respiratory distress syndrome.

We carried out a multicenter randomized, placebo-controlled trial to evaluate the efficacy and safety of surfactant in the treatment of respiratory distress syndrome. The study population was made up of newborn infants weighing 750 to 1750 g who were receiving assisted ventilation with 40 percent or more oxygen. The eligible infants received a single dose of either surfactant (100 mg of phospholipid per kilogram of body weight [4 ml per kilogram]) or an air placebo (4 ml per kilogram), administered into the trachea within eight hours of birth by an investigator not involved in the clinical care of the infant. When compared with the infants who received the placebo (n = 81), the infants who were treated with surfactant (n = 78) had a 0.12 greater average increase in the ratio of arterial to alveolar oxygen tension (P less than 0.0001), a 0.20 greater average decrease in the fractional inspiratory oxygen concentration (P less than 0.0001), and a 0.26-kPa greater average decrease in the mean airway pressure (P less than 0.0001) during the 72 hours after treatment. Pneumothorax was less frequent among the infants treated with surfactant than in the control group (13 percent vs. 37 percent; P = 0.0005). There were no statistically significant differences between the groups in the proportion of infants in each of five ordered clinical-status categories on day 7 (P = 0.08) or day 28 (P = 0.75) after treatment. There were also no significant differences between the groups in the frequency of bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, or periventricular-intraventricular hemorrhage. In each group, 17 percent of the infants died by day 28. We conclude that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 72 hours after treatment and decreases the frequency of pneumothorax, but that it does not significantly improve clinical status later in the neonatal period and does not reduce neonatal mortality. Further study of different surfactant regimens and patient-selection criteria will be required to determine whether this initial improvement can be translated into reductions in mortality or serious morbidity.

Bronchopulmonary Dysplasia↗
PubMed1989

Treatment of patent ductus arteriosus after exogenous surfactant in baboons with hyaline membrane disease.

The effect of early treatment of patent ductus arteriosus (PDA) on the acute course of hyaline membrane disease was tested in a primate model, after intratracheal administration of 100 mg/kg exogenous bovine surfactant phospholipids at mean ages between 2.3-2.4 h. Twenty-two premature baboons were divided into four groups: seven animals were controls (group A); five were treated with surfactant but PDA was not intervened (group B); in five surfactant treatment was followed by three doses of 0.2 mg/kg intravenous indomethacin beginning at a mean age of 5.5 h (group C); and in five surfactant treatment was followed by a surgical ligation of PDA between 5-5.5 h of age. After surfactant instillation in groups B, C, and D, a prompt and sustained improvement was noted in a/APO2, mean airway pressure, ventilator efficiency index and pulmonary compliance. However, no consistent differences were found in the respiratory variables within the surfactant treated groups during the 72-h experiment: the respiratory course in the animals treated for PDA (groups C and D) was generally similar to the animals in which PDA was not treated (group B). In animals treated with surfactant and indomethacin (group C) the mean aortic blood pressure was maintained more optimally as compared to the other three groups. These findings suggest that although a significant early ductal shunting does occur after exogenous surfactant therapy in this animal model, the expected pulmonary deterioration does not occur, and an early abrupt interruption of PDA does not seem to provide additional advantage to the immediate course of hyaline membrane disease.

Animals↗
PubMed1989

Cerebral artery flow velocity acceleration and deceleration characteristics in newborn infants.

To evaluate maturational differences in the cerebral artery blood flow velocity characteristics, we measured the middle cerebral (MCA) and basilar artery blood flow velocity and time intervals using a real-time imaging pulsed Doppler system in 39 preterm and 25 term infants. Preterm MCA and basilar artery mean Doppler spectral area under the curve were approximately 22 and 25% lower than the corresponding term values, with a significant increase during gestation as revealed by regression models. Paradoxically, the mean MCA systolic acceleration and deceleration slopes were approximately 28 and 18% higher in preterm than in term infants: acceleration 701.2 +/- 160 cm/s2 versus 546.4 +/- 156.5/s2 (p less than 0.005), and deceleration 222.2 +/- 71.6 cm/s2 versus 188.2 +/- 52.2 cm/s2 (p less than 0.05), respectively. Similarly, acceleration and deceleration pressure half times for MCA were about 15 and 18% shorter in the preterm (p less than 0.01 and less than 0.005). Multiple regression models controlling for velocity and frequency terms revealed an inverse relationship between gestational age and MCA acceleration (p less than 0.005), and a positive relationship between gestational age and MCA acceleration pressure half times (p less than 0.02). In preterm infants the MCA specific index of pulsatility was about 32% higher (p less than 0.05) than in the term, which was also inversely related to gestational age in a regression model controlling for velocity terms (p less than 0.02). However, the basilar artery acceleration and deceleration slopes were not significantly different between term and preterm groups, nor showed a significant gestational age effect in the multiple regression models.(ABSTRACT TRUNCATED AT 250 WORDS)

Basilar Artery↗
PubMed1989

Circle of Willis blood velocity and flow direction after common carotid artery ligation for neonatal extracorporeal membrane oxygenation.

The velocity and direction of blood flow in the circle of Willis arteries were measured in three infants who underwent right common carotid artery ligation for extracorporeal membrane oxygenation treatment. Within 15 minutes of common carotid artery ligation, blood flow was detected in one infant's right middle cerebral artery; however, the velocity was reduced to 50% of the preextracorporeal membrane oxygenation level. The velocity remained 50% to 70% lower than normal during the 88 hours of extracorporeal membrane oxygenation therapy. In the other two infants, the velocity changes were less severe. By 2 to 10 weeks after weaning from extracorporeal membrane oxygenation, the velocities in the left cerebral arteries were increased to 116% to 217% of the corresponding right cerebral vessels. Following common carotid artery ligation, a retrograde direction of flow was noted in the first (A1) segment of the right anterior cerebral artery and in the right posterior communicating artery, whereas the direction of flow was normal in the corresponding vessels on the left. After common carotid artery ligation, the vertebrobasilar and the contralateral internal carotid systems appear to be the main sources of reperfusion of the right cerebral hemisphere via the circle of Willis. Furthermore, because of the known variants of the circle anatomy, a noninvasive pulsed Doppler method could be used to evaluate the flow patterns in the circle of Willis arteries, both before and after common carotid artery ligation for extracorporeal membrane oxygenation.

Arteriovenous Shunt, Surgical↗