Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial.

BACKGROUND: Relationships between plasma morphine concentrations and neonatal responses to endotracheal tube (ETT) suctioning are unknown in preterm neonates. METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly assigned to placebo (n=449) or morphine (n=449). After an i.v. loading dose (100 microg kg(-1)), morphine infusions [23-26 weeks postmenstrual age (PMA) 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); and 30-32 weeks 30 microg kg(-1) h(-1)] were established for a maximum of 14 days. Open-label morphine (20-100 microg kg(-1)) was given for pain or agitation. Morphine assay and neonatal response to ETT suctioning was measured at 20-28 and 70-76 h after starting the drug infusion and at 10-14 h after discontinuation of the study drug. The concentration-effect response was investigated using non-linear mixed effects models. RESULTS: A total of 5119 data points (1598 measured morphine concentrations and 3521 effect measures) were available from 875 neonates for analysis. Clearance was 50% that of the mature value at 54.2 weeks PMA (CLmat(50)) and increased from 2.05 litre h(-1) 70 kg(-1) at 24 weeks PMA to 6.04 litre h(-1) 70 kg(-1) at 32 weeks PMA. The volume of distribution in preterm neonates was 190 litre 70 kg(-1) (CV 51%) and did not change with age. There was no relationship between morphine concentrations (range 0-440 microg litre(-1)) and heart rate changes associated with ETT suctioning or with the Premature Infant Pain Profile. CONCLUSIONS: A sigmoid curve describing maturation of morphine clearance is moved to the right in preterm neonates and volume of distribution is increased compared with term neonates. Morphine does not alter the neonatal response to ETT suctioning.

Pharmacological therapy for analgesia and sedation in the newborn.

Rapid advances have been made in the use of pharmacological analgesia and sedation for newborns requiring neonatal intensive care. Practical considerations for the use of systemic analgesics (opioids, non-steroidal anti-inflammatory agents, other drugs), local and topical anaesthetics, and sedative or anaesthetic agents (benzodiazepines, barbiturates, other drugs) are summarised using an evidence-based medicine approach, while avoiding mention of the underlying basic physiology or pharmacology. These developments have inspired more humane approaches to neonatal intensive care. Despite these advances, little is known about the clinical effectiveness, immediate toxicity, effects on special patient populations, or long-term effects after neonatal exposure to analgesics or sedatives. The desired or adverse effects of drug combinations, interactions with non-pharmacological interventions or use for specific conditions also remain unknown. Despite the huge gaps in our knowledge, preliminary evidence for the use of neonatal analgesia and sedation is available, but must be combined with a clear definition of clinical goals, continuous physiological monitoring, evaluation of side effects or tolerance, and consideration of long-term clinical outcomes.

Infective endocarditis following human-to-human enterococcal transmission: a complication of intravenous narcotic abuse.

Two heroin addicts, husband and wife, who shared injection paraphernalia extensively, developed enterococcal endocarditis within six weeks of one another. The etiologic organisms were of the same subspecies and had identical antibiotic susceptibilities and biochemical profiles. The clinical, epidemiologic, and bacteriologic data strongly suggest human-to-human transmission of the pathogen.

Telemedicine: Pediatric Applications.

Telemedicine is a technological tool that is improving the health of children around the world. This report chronicles the use of telemedicine by pediatricians and pediatric medical and surgical specialists to deliver inpatient and outpatient care, educate physicians and patients, and conduct medical research. It also describes the importance of telemedicine in responding to emergencies and disasters and providing access to pediatric care to remote and underserved populations. Barriers to telemedicine expansion are explained, such as legal issues, inadequate payment for services, technology costs and sustainability, and the lack of technology infrastructure on a national scale. Although certain challenges have constrained more widespread implementation, telemedicine's current use bears testimony to its effectiveness and potential. Telemedicine's widespread adoption will be influenced by the implementation of key provisions of the Patient Protection and Affordable Care Act, technological advances, and growing patient demand for virtual visits.

ADHD and developmental speech/language disorders in late preterm, early term and term infants.

OBJECTIVE: We sought to compare the long-term neurodevelopmental outcomes of late preterm, early term and term infants while controlling for a wide range of maternal complications and comorbidities. STUDY DESIGN: Data for the study was obtained from the South Carolina Medicaid claims and vital records databases from 1 January 2000 to 31 December 2003. We included infants weighing between 1500 and 4500 g, born between 34 0/7 and 41 6/7 weeks, and with no congenital anomalies. Outcome measures were based on the presence of ICD-9-CM codes for attention deficit hyperactivity disorders and developmental speech or language disorders. RESULT: A total of 3270 late preterm (LPIs), 11,527 early term (ETIs) and 24,005 term infants met the eligibility criteria. Rates for all outcome variables were statistically significant and elevated for LPI, but adjusted hazard ratios (AHRs) were only significant for the risk of developmental speech and/or language delay (LPI: AHR 1.36 95% confidence interval (CI) 1.23 to 1.50; ETI: AHR 1.27 95% CI 1.17 to 1.37). CONCLUSION: Late preterm and early term deliveries have adverse long-term neurodevelopmental outcomes, and these outcomes should be considered when determining the timing of delivery.

Efficient spiral search in bounded spaces.

This correspondence defines approaches for the efficient generation of a spiral-like search pattern within bounded rectangularly tessellated regions. The defined spiral-like search pattern grows outward from a given source in a two-dimensional space, thus tending to minimize search time in many sequential tracking tasks. Efficient spiral generation is achieved by minimizing the number of operations required for interaction with boundaries. Algorithms are developed for both rectangular search regions and for arbitrary convex search regions.

Production and persistence of antibodies in chickens to sheep erythrocytes. 2. Resistance to infectious diseases.

A line of chickens selected for ability to product high antibody titers to sheep red blood cells exhibited stronger antibody to Newcastle disease, was more resistant to Mycoplasma gallisepticum, Eimeria necatrix, a splenomeglia virus, and feather mites and less resistant to Escherichia coli and Staphylococcus aureus infection than a line selected for a lack of ability to produce antibody titers. A line of chickens selected for a nonpersistance of antibody titers to sheep red blood cells was relatively more susceptible to all infectious agents tested than a line selected for a persistence of atibody titers.

Effects of daily kangaroo care on cardiorespiratory parameters in preterm infants.

BACKGROUND/AIMS: Kangaroo care (KC) has possible benefits for promoting physiological stability and positive developmental outcomes in preterm infants. The purpose of this study was to compare bradycardia and oxygen desaturation events in preterm infants in standard incubator care versus KC. METHODS: Thirty-eight infants 27 to 30 weeks gestational age were randomly assigned to 2 hours of KC daily between days of life 5 to 10 or to standard incubator care. Infants were monitored for bradycardia (heart rate <80) or oxygen desaturation (<80%). Analysis of hourly events was based on three sets of data: standard care group 24 hours daily, KC group during incubator time 22 hours daily, and KC group during holding time 2 hours daily. RESULTS: The KC group had fewer bradycardia events per hour while being held compared to time spent in an incubator (p = 0.048). The KC group also had significantly fewer oxygen desaturation events while being held than while in the incubator (p = 0.017) and significantly fewer desaturation events than infants in standard care (p = 0.02). CONCLUSION: KC reduces bradycardia and oxygen desaturation events in preterm infants, providing physiological stability and possible benefits for neurodevelopmental outcomes.

Telemedicine collaboration improves perinatal regionalization and lowers statewide infant mortality.

OBJECTIVE: We assessed a telemedicine (TM) network's effects on decreasing deliveries of very low birth weight (VLBW, <1500 g) neonates in hospitals without Neonatal Intensive Care Units (NICUs) and statewide infant mortality. STUDY DESIGN: This prospective study used obstetrical and neonatal interventions through TM consults, education and census rounds with 9 hospitals from 1 July 2009 to 31 March 2010. Using a generalized linear model, Medicaid data compared VLBW birth sites, mortality and morbidity before and after TM use. Arkansas Health Department data and χ(2) analysis were used to compare infant mortality. RESULT: Deliveries of VLBW neonates in targeted hospitals decreased from 13.1 to 7.0% (P=0.0099); deliveries of VLBW neonates in remaining hospitals were unchanged. Mortality decreased in targeted hospitals (13.0% before TM and 6.7% after TM). Statewide infant mortality decreased from 8.5 to 7.0 per 1000 deliveries (P=0.043). CONCLUSION: TM decreased deliveries of VLBW neonates in hospitals without NICUs and was associated with decreased statewide infant mortality.

Quantifying risks of preterm birth in the Arkansas Medicaid population, 2001-2005.

OBJECTIVE: The objective of this study was to examine risks of preterm births, quantify the explanatory power achieved by adding medical and obstetric risk factors to the models and to examine temporal changes in preterm birth due to changes in Medicaid eligibility and the establishment of a maternal-fetal medicine referral system. STUDY DESIGN: The study used data from the 2001 to 2005-linked Arkansas (AR) Medicaid claims and birth certificates of preterm and term singleton deliveries (N=89 459). Logistic regression modeled the association among gestational age, demographic characteristics and risk factors, pooled and separately by year. RESULT: Physiological risk factors were additive with demographic factors and explained more of the preterm birth ≤32 weeks than later preterm birth. Changing eligibility requirements for Medicaid recipients and increasing the financial threshold from 133 to 200% of federal poverty level had an impact on temporal changes. The proportion of births ≤32 weeks declined to 33%, from 3.0 to 2.0. However, later preterm births declined and then increased in the last year. CONCLUSION: Physiological conditions are strongly associated with early preterm birth. Maternal behaviors and other stressors are predictive of later preterm birth. Unmeasured effects of poverty continue to have a role in preterm birth. Further examination of the referral system is needed.

Aspirin and Reye's syndrome--do parents know?

Amid growing concern over the association between aspirin and Reye's syndrome, the Aspirin Foundation has recently mounted a publicity campaign advising against the use of aspirin in children. Of 50 parents questioned at a children's ward of a district general hospital, 46 (92%) had heard of the publicity, 38 via the television. The number of parents who would give aspirin to their child had dropped significantly from 45 before the campaign to five after it (P<0.001); only one parent chose to ignore the advice. The media, particularly television, is again shown to be a potent means of publicity. Despite the very high response to the advice about aspirin none of the parents mentioned Reye's syndrome as the reason.

Image processing algorithms for eye movement monitoring.

Image processing algorithms useful for the optical monitoring of eye movements have been developed and evaluated. Specifically, algorithms have been developed which track the positions of moving convex targets. Three search strategies are considered which make varying use of a priori knowledge of target position and require varying levels of random access to the image space. Results indicate that straightforward algorithms implemented with relatively slow microcomputers can yield sample rates well in excess of standard TV field rates.

Pattern processing and slow-wave activity in visual cortex of cat.

Animal models play a significant role in research on human disorders. In vision research, the recording of single-neuron activity from animals has been of great value to our understanding of pattern processing mechanisms. In humans, investigations of visual function have typically utilized slow-wave activity. We have studied in cats the relationship between pattern processing and the slow-wave evoked response recorded from cortical areas 17, 18, 19 and 4 in the awake cat. We have found that within a restricted latency range the response in 17, 18 and 19 reflects the processing of the patterness of a visual stimulus. A comparison of response components occurring prior to 50 msec poststimulus showed few significant differences (P less than 0.05) between peak amplitudes evoked by a diffuse and a checkerboard pattern stimulus. A much higher proportion of response components occurring after 50 msec but prior to 300 msec poststimulus were significantly different (P less than 0.05). The response recorded from area 4 (motor cortex) did not show significant differences as a function of the diffuse and patterned stimuli. Our findings show that the slow wave recorded from cat visual cortex can reflect the pattern processing mechanisms of visual cortex. Since slow waves are used in the study of visual functions in humans, the slow wave may have an important role to play in animal models of visual disorders in humans.

The effect of artificial cryptorchidism on serum oestrogen and testosterone levels in the adult male rat.

Oestrone, oestradiol and testosterone levels were measured by radioimmunoassay in male rats 0.5, 1, 4, 8 and 16 days after rats were either made artifically cryptorchid or sham-operated. Oestradiol levels were not significantly different between cryptorchid and control rats 12 h or 1 day after surgery, but levels in cryptorchid animals fell to 35% of controls on day 4 (P less than 0.05), 31% on day 8, and 29% on day 16 (P less than 0.01). Conversely, oestrone and the total of the two oestrogens was higher in cryptorchid rats at one-half day (P less than 0.05), but did not differ at any other time. Testosterone levels were generally lower in cryptorchid rats than in controls. The minor contribution of oestradiol to total oestrogen levels and the lack of change of total oestrogens in cryptorchid rats led to the conclusion that oestrogens are probably not the tubular regulator of FSH in the male.

Pattern processing and slow waves in visual cortex of visually deprived cats.

The slow-wave response recorded from electrodes within the visual cortex of the awake cat has been shown to reflect the pattern processing activities of the visual cortex. In a cat deprived of pattern vision by monocular lid closure, the response evoked from the non-deprived eye by patterned and diffuse stimuli show differences similar to those found in a normal cat. However, when these same stimuli are presented to the deprived eye, the differences are not present. These slow-wave data confirm previous data from single unit recordings in showing that pattern processing is altered by deprivation.