Temperament and behavior of preterm infants: a six-year follow-up

To test the commonly held premise that prematurity is a risk factor for problems of behavior and social interaction, as well as cognitive and physical development, temperament and behavior of children born preterm and full-term control subjects were compared at five separate time periods from infancy through early school age. All the preterm infants (n = 126) of a representative group of infants enrolled in a longitudinal study (n = 2443) were surveyed at 4 to 8 months corrected age. Subsamples of the group were studied further in successive years as young toddlers (n = 65), older toddlers (n = 60), preschoolers (n = 84), and at early school age (n = 81). At each period there were no differences between those studied and those not studied on socioeconomic status, gestational age, sex, or birth order. Parental ratings of temperament and behavior were used at appropriate ages: the Revised Infant Temperament Questionnaire, the Toddler Temperament Scale, the Childhood Temperament Questionnaire, Behaviour Checklist, Preschool Behaviour Questionnaire, and Rutter's Childhood Behaviour Questionnaire (CBQ), as well as mother's overall rating of temperament. In infancy there were no significant differences on temperament dimensions, clinical temperament categories, or parental ratings of individual or composite behaviors between the preterm and full-term groups. For toddlers, temperament scores were similar for the two groups but preterm subjects were significantly more likely (P less than .01) to have an easy temperament and less likely to have a difficult temperament. There were no differences on any of the other temperament or behavior ratings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temperament in Australian toddlers

A revised validated version of the Toddler Temperament Scale (TTS) was used to develop normative data for temperament in Australian toddlers. Results confirm the accepted practice of dividing the group into younger and older toddlers, with normative data reported for those younger and older than 24 months. The TTS can be used above the normal cut-off age of 36 months. Care must be taken with interpretation of temperament scores, especially when comparing children of different backgrounds.     

Dose ranging pharmacokinetic trial of high-dose alicaforsen (intercellular adhesion molecule-1 antisense oligodeoxynucleotide) (ISIS 2302) in active Crohn's disease

BACKGROUND AND AIMS: To evaluate the safety, pharmacokinetics and clinical efficacy of the intercellular adhesion molecule-1 antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) at 250-350 mg in Crohn's disease. METHODS: : Patients (> 50 kg) with active Crohn's disease (Crohn's disease activity index > or = 220) were assigned by gender, randomly, to two alicaforsen treatment groups: 300 or 350 mg, infused intravenously three times a week for 4 weeks. All patients weighing 36-50 kg received 250 mg of alicaforsen. Background aminosalicylates, antibiotics, immunosuppressives and corticosteroids were permitted, but tumour necrosis factor-alphainhibitors were prohibited. The primary end-point was clinical remission (Crohn's disease activity index < or = 150). RESULTS: Twenty-two patients were enrolled with a mean baseline Crohn's disease activity index of 304. Steroids were used by 27%, 5-aminosalicylic acid by 68% and immunosuppressives by 27%; 23% had previously received infliximab. Five subjects withdrew after one to three infusions for infusion-related symptoms. Nine patients (41%) experienced clinical remission. Fifty-three per cent of the evaluable subjects receiving more than three infusions experienced remission (18% at week 8; 29% at week 12). The overall response, using a minimum decrease of 70 in the Crohn's disease activity index, was 41-47% for the evaluable group, at weeks 8 and 12. The median duration of remission was 14 weeks. Plasma pharmacokinetic results showed overlapping levels (Cmax, AUC) for the three doses. The infusion-related reaction profile consisted of fever, chills, headache, nausea, emesis or arthralgias, typically occurring 2-4 h after completion of the first infusion. Reactions were less frequent in patients receiving background corticosteroids. The 2-4-h transient post-infusion partial thromboplastin time prolongation values, a class effect of phosphorothioate oligonucleotides, were 18, 21 and 23 s for 250, 300 and 350 mg, respectively. CONCLUSIONS: Alicaforsen (ISIS 2302), at fixed doses of 300 and 350 mg, achieved the desired drug exposure and may be an effective therapy for Crohn's disease. Infusion-related reactions were observed less frequently in patients on corticosteroids, and with decreasing frequency with continued treatment.     

Using Monte Carlo Simulation to Determine Combination Vaccine Price Distributions for Childhood Diseases

The Recommended Childhood Immunization Schedule provides guidelines that allow pediatricians to administer childhood vaccines in an efficient and effective manner. Research by vaccine manufacturers has resulted in the development of new vaccines that protect against a growing number of diseases. This has created a dilemma for how to insert such new vaccines into an already crowded immunization schedule, and prompted vaccine manufacturers to develop vaccine products that combine several individual vaccines into a single injection. Such combination vaccines permit new vaccines to be inserted into the immunization schedule without requiring children to be exposed to an unacceptable number of injections during a single clinic visit. Given this advantage, combination vaccines merit an economic premium. The purpose of this paper is to describe how Monte Carlo simulation can be used to assess and quantify this premium by studying four combination vaccines that may become available for distribution within the United States. Each combination vaccine is added to twelve licensed vaccine products for six childhood diseases (diphtheria, tetanus, pertussis, haemophilus influenzae type B, hepatitis B, and polio). Monte Carlo simulation with an integer programming model is used to determine the (maximal) inclusion price distribution of four combination vaccines, by randomizing the cost of an injection. The results of this study suggest that combination vaccines warrant price premiums based on the cost assigned to administering an injection, and that further developments and innovations in this area by vaccine manufacturers may provide significant economic and societal benefits.     

Drug dependence: neuropharmacology and management

This overview has attempted to highlight the brain regions associated with reward, and the pathways and neurotransmitters responsible for communication between these regions. Work conducted in this field has shown that stimulants and opioids, despite interactions with different receptor types and different neurotransmitter reuptake transporters, appear to share a common action on brain reward pathways. Their effects on these pathways (the distinct brain regions making up the mesocorticolimbic dopaminergic system) are predominantly mediated through changes in dopamine neurotransmission, and compounds aimed at selectively modulating these effects may form the basis of drugs to treat addiction. Other transmitters such as GABA, acetylcholine and serotonin inevitably have a role to play in reward, although at present the exact nature of their effects remains unclear. Diverging from manipulating the CNS directly as a management strategy for dependence, it might be possible to exploit the immune system to prevent administered psychostimulants penetrating the brain, but antibody saturation and specificity are problematic.     

Structured group therapy for posttraumatic stress disorder in incarcerated male juveniles

This is the first study to evaluate the efficacy of a structured group therapy for posttraumatic stress disorder (PTSD) in incarcerated male juveniles. Ten groups of juveniles (n = 45) completed a 12-session intervention with pre- and postassessments composed of the Post Traumatic Stress Disorder Reaction Index (C. Frederick, 1985) and supplementary measures of anxiety, anger, and depression. Overall, group participants experienced significant reductions in self-reported PTSD symptoms. Supplemental analyses suggest that this treatment was most beneficial for youth with trauma related to gang and community violence.     

Preliminary trial of a noninvasive brain acoustic monitor in trauma patients with severe closed head injury

BACKGROUND: There is no simple way to assess the injured patient after a loss of consciousness. Computed tomographic scanning is required to rule out anatomic injuries, and invasive intracranial pressure monitoring is needed for the patient with severe traumatic brain injury (TBI). We hypothesized that a noninvasive acoustic monitoring system could provide useful clinical data on the severity and progression of TBI. METHODS: Twenty-eight consecutive patients with severe TBI and an indication for invasive intracranial pressure monitoring were studied using the Brain Acoustic Monitor (BAM). Monitoring occurred for 1- to 3-hour time periods on the day of enrollment and each day until the patient's condition stabilized. BAM signals were categorized on the basis of amplitude and positive-to-negative deflection ratio, and then compared with the patient's clinical outcome. RESULTS: BAM signal correlated very strongly with clinical outcome: in 27 of 29 sessions with a normal signal, patients were discharged at a Glasgow Coma Scale score > 13, whereas in 36 of 42 sessions with an abnormal signal, the patient either died or left the hospital with a Glasgow Coma Scale score < 9 (p < 0.00001). The correlation between clinical outcome and initial BAM reading was even stronger: 10 of 10 patients with a normal signal did well, as compared with 3 of 18 patients with an abnormal signal. CONCLUSION: Noninvasive monitoring of the injured brain can discriminate those patients who will have a poor clinical outcome from those who will do well. Further trials of the BAM are indicated.