Immunogenicity and safety of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine as a pre-school booster in UK children.

This open, randomised controlled trial studied the immunogenicity and reactogenicity of two combined low-dose diphtheria, tetanus and acellular pertussis vaccines (Td5aP-IPV, REPEVAX, Aventis Pasteur MSD; and Td5aP, COVAXIS, Aventis Pasteur MSD + OPV, GlaxoSmithKline) in comparison with a standard dose diphtheria pre-school booster vaccine (DT2aP-IPV, TETRAVAC, Aventis Pasteur MSD) in a population of 3.5-5-year-old children administered concomitantly with measles, mumps and rubella vaccine (M-M-R II, Aventis Pasteur MSD). A linked sub-study aimed to evaluate the immunogenicity and reactogenicity of Td5aP-IPV in a population of younger children, aged 3-3.5 years. This study demonstrated non-inferiority of seroprotection rates for diphtheria and tetanus for the study vaccines and comparable immunogenicity for pertussis and polio components of the vaccines. Reactogenicity was similar for all three vaccines. The study vaccines containing low-dose diphtheria antigen (Td5aP-IPV and Td5aP + OPV) are immunogenic and have acceptable reactogenicity for use as a pre-school booster vaccine administered concomitantly with MMR.

Implementation of the Ottawa Ankle Rules by nurses working in an accident and emergency department.

OBJECTIVE: To assess whether accident and emergency (A&E) nurses using the Ottawa Ankle Rules could detect all ankle fractures. DESIGN: Prospective observational study. SETTING: A&E department of a university teaching hospital. SUBJECTS: All patients who presented with ankle injuries who were initially assessed by a nurse taught the Ottawa Ankle Rules. OUTCOME MEASURES: (1) The numbers of patients referred by the nurse for ankle radiography; (2) of these, the number with ankle fractures; (3) of those not sent for radiography initially by the nurse, the number who subsequently had x rays (ordered by the doctor) and had a fracture; (4) of those having no x rays, the number who reattended later. RESULTS: 324 patients were eligible; 238 had x rays at the request of the nurse (73%); 48 of these (20%) were diagnosed as having a fracture. Of those 86 patients not sent for radiography by the nurse, 19 subsequently had x ray examinations at the request of a doctor and no fracture was detected. Of the 67 not sent for radiography, none returned within the subsequent eight weeks. CONCLUSIONS: Nurses can apply the Ottawa Ankle Rules safely without missing acute fractures; that is, of those who were not sent for radiography by nurses, none subsequently reattended the A&E department or the trauma service of the Bristol Royal Infirmary during the following two months.

Sustained change in parents receiving preventive interventions for families with depression.

OBJECTIVE: The purpose of this study was to compare the sustained effects of two cognitive, psychoeducational preventive interventions for families in which a parent had an affective disorder. METHOD: Thirty-seven families, in which there was a child between the ages of 8 and 15 years (mean = 11.5 years) and at least one parent who had experienced a recent episode of affective disorder according to the Research Diagnostic Criteria, were studied 1.5 years after enrollment in the study. The families were randomly assigned to one of two interventions, clinician-facilitated or lecture. The two interventions were similar in content but differed in the degree of involvement of the children and the linking of information to the families' life experiences. Nineteen families participated in the clinician-facilitated intervention, which consisted of six to 10 sessions. Eighteen families were assigned to the lecture condition, which consisted of two lectures attended only by parents. Family members were interviewed both before and after the interventions with diagnostic interviews and semistructured measures designed to assess response to the interventions. RESULTS: Sustained effects of the interventions were reported 1.5 years after enrollment. The clinician-facilitated intervention was associated with more positive self-reported and assessor-rated changes than the lecture intervention. CONCLUSIONS: These short-term preventive interventions, particularly the clinician-facilitated one, have long-term benefits for families with parental affective disorder.

Examination of children's responses to two preventive intervention strategies over time.

OBJECTIVE: To examine long-term effects of two forms of preventive intervention designed to increase families' understanding of parental affective disorder and to prevent depression in children. METHOD: Thirty-six families who had a nondepressed child between ages 8 and 15 years and a parent who had experienced affective disorder were enrolled and randomly assigned to either a clinician-facilitated intervention or a lecture discussion group. Each parent and child were assessed prior to randomization, after intervention, and approximately 1 1/2 years after enrollment. Assessments included standard diagnostic interviews, measures of child and family functioning, and interviews about experience of parental affective disorder and intervention effects. RESULTS: Children in the clinician-facilitated group reported greater understanding of parental affective disorder, as rated by self-report, rater-generated scales, and parent report, and had better adaptive functioning after intervention. Parents in the clinician-facilitated intervention group reported significantly more change. CONCLUSION: Findings from both interventions support the value of a future-oriented resiliency-based approach. The greater effects of the clinician-facilitated intervention support the need for linking cognitive information to families' life experience and involving children directly in order to achieve long-term effects.

Examination of preventive interventions for families with depression: evidence of change.

Thirty-seven families who had a child between the ages of 8 and 15 (mean age = 12.0 years) and had at least one parent, who had experienced a recent episode of affective disorder were assigned randomly to one of two psychoeducational interventions. The interventions (clinician-facilitated or lecture-group discussion) were designed to prevent childhood depression and related problems through decreasing the impact of related risk factors and encouraging resiliency-promoting behaviors and attitudes. They were similar in content but differed in the level of the children's involvement and the degree to which the families' individual life experiences were linked to the educational material. Assessments included standard diagnostic and social functioning instruments and interviews designed specifically for this project to assess behavior and attitude change. Each parent and child was individually assessed by separate assessors who were blind to information about the other family members. Parent participants in both groups reported being satisfied with the intervention. Clinician group participants reported a significantly larger number of overall changes, as well as higher levels of change regarding communications about the illness with their children and increased understanding by the children of their illness. Significantly more children in the clinician group also reported they gained a better understanding of parental affective illness as a result of their participation in the project.

Response of families to two preventive intervention strategies: long-term differences in behavior and attitude change.

OBJECTIVE: To explore the long-term impact of two forms of preventive intervention designed to diminish risk to children in families in which one or both parents suffered from affective disorder. METHOD: Fifty-four parents in 18 families were initially assessed and randomly assigned to one of two interventions--a clinician-facilitated, manual-based, psychoeducational preventive intervention or a standardized lecture-group discussion in which similar educational information was presented. Assessments included standard diagnostic interviews, child behavior scales, and semistructured interviews with parents about the effects of the intervention. Follow-up assessments were conducted three times over the 3-year follow-up interval. RESULTS: No harmful effects were reported for either intervention, and ratings of degree of upset about reported concerns declined across time for both conditions. Families receiving the clinician-facilitated intervention reported more behavior and attitude changes than did lecture-group families when assessed after intervention. The difference between the two groups was sustained at further follow-up assessments. CONCLUSION: Although both preventive interventions produced changes in behaviors and attitudes, parents in the clinician-facilitated intervention reported more benefit. These data support the hypothesis that linking cognitive information to the family's life experience produces long-term changes.

Comparison of preventive interventions for families with parental affective disorder.

Twenty families participated in a random assignment trial of two cognitive psychoeducational preventive interventions for families with parental affective disorder. Twelve families were assigned to a clinician-based intervention and eight to a lecture-based intervention, with assessment prior to intervention and an average of 18 weeks following intervention. Both groups were satisfied and believed they received help from the intervention. The clinician-based group was significantly more satisfied overall, and reported significantly more changes in both behaviors and attitudes about their illness from pre- to postintervention. Both groups showed significant decrease in degree of upset over issues of concern from pre- to postintervention. The clinician-based group reported receiving significantly more help with their primary concern. The implications of these findings are discussed.

Biological measures and cellular immunological function in depressed psychiatric inpatients.

Thirty depressed psychiatric inpatients, including 18 with a diagnosis of major depression, and 25 hospital staff controls were compared with respect to cellular immune function--that is, mitogen responsiveness to concanavalin A (con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM); natural killer cell (NK) activity; and T cell subsets, including helper/inducer T cells (CD4) and suppressor/cytotoxic cells (CD8). Only physically healthy subjects, who had not used psychoactive medications (except for low dose benzodiazepines) or other medications known to affect the immune system for at least 14 days, were included. Paired comparisons of the immune measures of patients with a DSM-III diagnosis of major depression (n = 18) with their controls demonstrated a statistically significant reduction of the patients' con A response. In addition, the patients with major depression had significantly lower con A and PHA responses than the combined patients with other forms of depression (atypical, dysthymic, or atypical bipolar). There was no indication that severity of depression, dexamethasone suppression test status, benzodiazepine use, or age accounted for the differences in immune function. A possibly important, unexpected finding was that antihistamine use was associated with lower immune function.

The long-term effects of early kwashiorkor compared with marasmus. IV. Performance on the national high school entrance examination.

This is one of a series of studies on the long-term effects of early childhood malnutrition in Barbadian school children. This is the first report of the relationship between early malnutrition and later performance on a national examination administered to all 11-y-old children in Barbados to assign high school seats. We compared scores achieved on the 11-plus examination by 103 boys and girls with histories of marasmus or kwashiorkor with those obtained by 63 healthy comparison children and also with scores obtained by the total island population of children during the same years. We report that children with histories of either type of malnutrition confined to infancy had significantly lower scores on the national high school examination than healthy comparison children. Reduced 11-plus scores were closely associated with teacher reports of attention deficits in the classroom documented when the children were as young as 5 to 8 y of age and also with IQ and academic performance. Early malnutrition had independent effects on performance on the 11-plus examination even when home environmental conditions were controlled for. These findings have important implications for future opportunities available to children with histories of infantile malnutrition.

The long-term effects of early kwashiorkor compared with marasmus. IV. Performance on the national high school entrance examination

This one of a series of studies on the long-term effects of early childhood malnutrition in Barbadian school children. This is the first report of the relationship between early malnutrition and later performance on a national examination administered to all 11-y-old children in Barbados to assign high school seats. We compared scores achieved on 11-plus examination by 103 boys and girls with histories of marasmus or kwashiorkor with those obtained by 63 healthy comparison children and also with scores obtained by the total island population of children during the same years. We report that children with histories of either type of malnutrition confined to infancy had significantly lower scores on the national high school examination than health comparison children. Reduced 11-plus scores were closely associated with teacher reports of attention deficits in the classroom documented when the children were as young as 5 to 8 y of age and also with IQ and academic performance. Early malnutrition had independent effects on performance on the 11-plus examination even when home environmental conditions were controlled for. These findings have important implications for future opportunities available to children with histories of infantile malnutrition. (AU)

Effect of anaesthetic agents on bile flow and biliary excretion of 131I-cholylglycyltyrosine in the rat.

We have compared in the rat the effects of i.v. anaesthetic agents on bile flow rate and on the biliary excretion of a novel bile acid, 131I-cholylglycyltyrosine (131I-cholylgly.tyr.). Etomidate 1-mg bolus and 2-mg h-1 infusion, Althesin 3-mg bolus and 14.5-mg h-1 infusion and propofol 3.3-mg bolus and 3.3-mg h-1 were given via a tail vein cannula and pentobarbitone 50 mg kg-1 was given by the intraperitoneal route, to groups of six rats. Each animal received only one anaesthetic agent. One hour after cannulation of the common bile duct, 131I-cholylgly.tyr. 5 microCi was injected into the jugular vein and bile was collected every 1 min for 10 min. The mean (SD) percentage cumulative biliary excretion of 131I-cholylgly.tyr. at the end of 10 min was: propofol group 74.1 (5.2)%; Althesin group 82.3 (2.2)%; etomidate group 69.4 (17.6)%; pentobarbitone group 76.4 (3.2)%. Propofol and Althesin were relatively more choleretic, causing bile flow rates twice that produced by pentobarbitone. Only Althesin caused a significant increase in biliary excretion of 131I-cholylgly.tyr. relative to that in rats that received pentobarbitone. Bile flow rates for the respective anaesthetic techniques (microliter min-1/100 g body weight) (mean (SD)) were: propofol group 14.1 (1.8); Althesin group 12.5 (1.7); etomidate 8.5 (1.4); pentobarbitone group 7.3 (1.0). There was a marked metabolic acidosis in all rats except in the propofol group, in which normal acid-base status and oxygenation were observed.

Anxiety, depression, and menstrual symptoms among freshman medical students.

Based on data from a larger longitudinal study of medical students and physicians, this study establishes the incidence of some menstrual symptoms in a nonclinical population of 82 healthy, female, first-year medical students and investigates the correlation of self-reported anxiety and depression scores with these symptoms. Findings show that nearly half reported the frequent occurrence of at least one menstrual symptom that appeared to cause discomfort but did not interfere with performance. The data suggest an association between anxiety and depression scores and certain self-reported menstrual symptoms in this population. The study suggests the need for further investigation of the nature of the relationship between dysphoric moods and menstrual symptoms in healthy women.

The influence of early malnutrition on subsequent behavioral development. VII. The effects on maternal depressive symptoms.

A self-rating scale was used to assess the presence or absence of depressive symptoms among mothers of 129 Barbadian school children, ages 5 to 11 years, who had experienced marasmus in the first year of life. They were matched with the same number of mothers of comparison children who had no documented histories of malnutrition. Depressive symptoms, especially feelings of hopelessness, occurred more often among the mothers of previously malnourished children than among mothers of comparison children. Depressive symptoms were also more common in association with disadvantaged socioeconomic and home conditions. Maternal depressive symptoms were significantly correlated with the behavioral and cognitive functioning of the child during the school years. When both nutritional history and environmental conditions were controlled, maternal hopelessness had significant effects on school attendance and grades in reading, but there was no association with IQ. This led us to hypothesize that maternal depressive feelings may be an independent factor contributing to long-term behavioral and cognitive deficits in children with histories of early malnutrition.

Long-term effects of early kwashiorkor compared with marasmus. II. Intellectual performance.

Intellectual performance including IQ (Wechsler Intelligence Scale for Children-Revised) and conservation was measured at ages 11-18 years in a follow-up study of Barbadian girls and boys who had histories of kwashiorkor (n = 53) or marasmus (n = 55) in their first year of life. They were compared with healthy neighborhood children matched by sex and age who had normal patterns of growth in early childhood (n = 58). On both IQ and conservation tests, children with previous kwashiorkor or marasmus had similar scores, which were significantly lower than scores of healthy comparison children. These findings were examined in relationship to current environmental conditions, which were similar in children with histories of kwashiorkor or marasmus and somewhat less advantaged than those of the comparison children. The effect of early malnutrition and related conditions at the time of episode still emerged as significant even when the current environmental factors were controlled for.

Long-term effects of early kwashiorkor compared with marasmus. I. Physical growth and sexual maturation.

Physical growth and sexual maturation were measured in a follow-up study of Barbadian girls and boys aged 11-18 years with histories of kwashiorkor (n = 54) or marasmus (n = 56) in their first year of life. They were compared with healthy neighborhood children matched by sex and age who had normal patterns of growth in early childhood (n = 59). Girls with histories of marasmus had significant delays in the onset of menarche compared with healthy comparison girls. However, their rate of growth during the previous 2 years was accelerated, and the differences in size were smaller than at the earlier testing, confirming catch-up. This pattern was not evident for girls with histories of kwashiorkor, who did not differ from the healthy comparison girls on either onset of menarche, Tanner ratings of sexual maturation, or measures of physical growth. In contrast, boys with histories of kwashiorkor or marasmus did not differ from healthy comparison boys in physical growth or Tanner ratings at these ages.

Long-term effects of early kwashiorkor compared with marasmus. III. Fine motor skills.

Children with histories of marasmus (n = 53) or kwashiorkor (n = 50) in the first year of life and healthy comparison children (n = 50) were tested for fine motor skills by the Purdue pegboard test at ages 11-18 years. The performance of children with histories of marasmus was impaired on two of the four test measures. However, the performance of children with a history of kwashiorkor was impaired on three measures. The presence of soft neurologic signs measured 6 years earlier in the same children was significantly correlated with current pegboard performance, implying that early malnutrition has effects on nervous system function that are evident at least through 18 years of age.

Coping resources and health responses among men and women medical students.

The structures and pressures of medical education raise particular concerns about how coping resources vary among students as they enter training. Most past studies have focussed on male students. Our data considers the coping and health-related responses of men and women students during the initial phase of their socialization into medicine. Subjects were 179 men and 80 women in entering classes of two medical schools who completed a variety of self-report measures. A multivariate analysis of these data revealed profile differences between men and women on measures of coping and health-related responses. Univariate tests demonstrated sex differences in mastery, number of health symptoms and reliance on alcohol. Men and women, however, showed similarly high esteem and use of social networks. The variation observed between men and women medical students as they begin their training suggests different potential sources of vulnerability. The importance of these findings is to provide a context of initial coping repertoires of men and women medical students for future evaluation of the effects of socialization.