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Lifetime patterns of social phobia: a retrospective study of the course of social phobia in a nonclinical population.

This study describes the natural course of social phobia as recalled by a sample of nonclinical subjects and explores, using qualitative research methods, perceived risk factors and factors that may cause changes in its course. Thirty-nine respondents with a lifetime diagnosis of social phobia were interviewed using a semistructured interview schedule based on DSM-IV criteria. Four main lifetime patterns emerged: a slight worsening of social phobic symptoms over time, no change, slight improvement and complete remission. Thirty-eight percent of the sample was in remission at the time of interview. The mean age of onset was 12.8 +/- 4.1 years. The average duration of illness was 29.0 +/- 12.7 years. Factors perceived by respondents to precipitate social phobia, using contract analysis, were family and school environment, onset of adolescence, low self-esteem, temperament and poverty. Factors perceived to improve symptoms were building self-esteem, exposure, determination, maturity and counseling. Factors perceived to worsen symptoms were avoidance, exposure to negative attention and comorbid disorders.

Adolescent↗

Gender-specific characteristics of 5-year-olds' play narratives and associations with behavior ratings.

OBJECTIVES: To examine the content and structure of children's play narratives in a large sample of 5-year-olds in order to replicate previous findings, explore the role of gender differences, and identify a pattern that can provide useful information about children's behavior. METHOD: The MacArthur Story Stem Battery and coding system was used to code content themes and coherence from play narratives of 652 twins in a nonclinical sample. To measure behavior problems, parents completed the Child Behavior Checklist when their children were aged 5 and 7 years; teachers completed the Teacher's Report Form when the children were aged 7 years. RESULTS: Girls told more coherent narratives with less aggression than boys. Aggressive themes were found to correlate with behavior problems as in previous studies. Upon further examination, this correlation held for girls but not boys. Children who told repeated aggressive/incoherent narratives had more behavior problems than those who did not show this narrative pattern. CONCLUSIONS: The Story Stem methodology is useful for gaining access into the young child's inner world. The gender of the child, content of the story, and coherence of the story all provide useful information in identifying narratives that may indicate more risk for behavior problems.

Aggression↗

Evaluating the psychosocial adjustment of 2- and 3-year-old pediatric burn survivors.

Very little information has been published about 2- and 3-year-old children who have experienced major burns. This study used a standardized instrument to measure the behavioral adjustment of these young burn survivors, and the results were compared with those of a nonclinical normative sample. Thirty-three pediatric burn survivors with 50%+/-28% total body surface area burns were evaluated 1.2+/-0.7 years postburn. Parental observations were assessed with the use of the Child Behavior Checklist for 2- and 3-Year-Olds, a 99-item standardized checklist designed to identify behavior problems. Forty of the questions are specific to 2- and 3-year-olds, and the scores of male and female children are not differentiated. The raw scores of the children with burns were statistically compared with the reported normative sample for this version of the Child Behavior Checklist. Pediatric burn survivors in this sample exhibited significantly more internalizing behaviors than the children in the normative group. Parents reported children who had been burned to be more depressed and to have more somatic complaints and sleep problems. Determining the relationship of behavior problems to posttrauma sequelae and preburn environmental factors would assist with the establishment of appropriate psychosocial interventions.

Adaptation, Psychological↗

Clinical and nonclinical correlates of adherence to prescribing guidelines for hypertension in a large managed care organization.

To examine correlates of guideline adherence in a population with access to health care and prescription drug benefits, the authors conducted a cross-sectional analysis among 5789 patients undergoing hypertension treatment with a single medication in a large New England managed care organization. Logistic regression was used to determine correlates of adherence, defined as use of diuretics or beta blocker as antihypertensive monotherapy during the 1-year study period. Women were more likely than men to receive guideline-adherent therapy (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.45-1.85). Compared with patients covered by health maintenance organization plans, Medicare coverage was positively associated with guideline adherence (OR, 1.38; 95% CI, 1.13-1.69), but fee-for-service coverage was negatively associated (OR, 0.66; 95% CI, 0.48-0.91). Patient age was not a significant correlate of adherence to guidelines (OR, 1.01; 95% CI, 0.94-1.09). Understanding these observations may lead to strategies to improve guideline adherence and reduce health care disparities.

Adrenergic alpha-Antagonists↗

Cluster B personality disorders are associated with allelic variation of monoamine oxidase A activity.

Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggression-related personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (chi2=7.77, p=0.005, df=1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi- or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper- (impulsive-aggressive) and hyporeactive (anxious-depressive) traits.

Adolescent↗

Complicating factors in safety testing of drug metabolites: kinetic differences between generated and preformed metabolites.

This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models.

Animals↗

Preclinical studies of [(99m)Tc]DTPA-mannosyl-dextran .

We report the preclinical testing of a synthetic receptor-binding macromolecule, [(99m)Tc]DTPA-mannosyl-dextran (36 kDa, 8 DTPA and 55 mannosyl units per dextran, K(D) = 0.12 nM), for sentinel node detection. Nonclinical safety studies included cardiac pharmacology safety studies, acute toxicology and pathology studies at 50 and 500 times the scaled human dose in both rats and rabbits after foot pad administration, and perivascular irritation studies in rabbits following intra-muscular administration at 100 and 1000 times the scaled human dose. Biodistribution studies in rabbits at 15 m, 1 h, and 3 h indicated that [(99m)Tc]DTPA-mannosyl-dextran cleared the hind foot pad with a biological half-life of 2.21 +/- 0.27 h. Other than mild hepatocyte hypertrophy in rabbits, no abnormalities in toxicology or pathology were found. Intravenous administration had no effect on survival, any clinical observations, electrocardiograms, or blood pressures. Intramuscular injection had no effect on survival, clinical observations, injection site observations, or injection site histopathology. The estimated absorbed radiation dose to the affected breast was 0.15 mGy/MBq and the effective dose was 1.06 x 10(-2) mSv/MBq. This preclinical study demonstrates that [(99m)Tc]DTPA-mannosyl-dextran has no toxicities and has an acceptable biodistribution and radiation dose.

Animals↗

Antibiotic choice and patient outcomes in community-acquired pneumonia.

BACKGROUND: We investigated whether any clinical or nonclinical variables were associated with physician choice of antibiotic therapy and whether outcome differences existed among patients given agents to treat infections caused by atypical gram-negative organisms. METHODS: A retrospective review of 157 immunocompetent patients admitted to a hospital between 1 February 1992 and 31 January 1993 with a diagnosis of community-acquired pneumonia was performed. Patient groups were defined by whether their initial antibiotic therapy was a broader spectrum antibiotic, such as a second- or third-generation cephalosporin, which would treat atypical gram-negative infection (n = 85), or narrower spectrum agents, such as ampicillin or erythromycin (n = 72). RESULTS: Patients who were given broader spectrum antibiotics were slightly older than those receiving narrower agents (73 versus 66 years, P = 0.06). Otherwise, no clinical factors or comorbid states were associated with antibiotic selection. When examining physician-related factors, internists were more likely to prescribe broad-spectrum agents than were family physicians. No differences existed in overall mortality, length of stay, readmission rate, or change in antibiotic. CONCLUSIONS: Although physicians appear to prescribe broader agents for pneumonia in older patients, there were no other clinical predictors of antibiotic selection. Physician-related factors, such as training and specialty, might influence prescribing habits.

Adult↗

Screening women in jails for chlamydial and gonococcal infection using urine tests: feasibility, acceptability, prevalence, and treatment rates.

BACKGROUND: Women entering jails are at high risk for sexually transmitted diseases; however, screening for chlamydial and gonococcal infection is not routinely performed in most jails. New urine tests have made it easier to screen for these infections in nonclinical settings. GOAL: The feasibility and acceptability of urine-based screening for women entering jails and the prevalence of and treatment rates for chlamydial and gonococcal infections were determined. STUDY DESIGN: Women entering jails in Chicago, Illinois; Birmingham, Alabama; and Baltimore, Maryland, who signed consent forms were tested for chlamydial and gonococcal infection by means of the urine ligase chain reaction assay. Those testing positive were treated in jail; health department staff members attempted to contact those already released. RESULTS: Most women who were approached agreed to be tested (range, 87-98%, depending on city), and most of these women provided a specimen (range, 92-100%). Among 5364 women aged 16 to 75 years who were tested, the prevalence of chlamydial and gonococcal infections was high, especially among those <25 years of age (range, 15.3-21.5% for chlamydial infection and 8.2-9.2% for gonorrhea, depending on city). The majority of women testing positive were treated in jail or outside of jail (61-85%). CONCLUSIONS: Screening women in jails for chlamydial and gonococcal infection with urine tests is feasible, is acceptable to most women, and leads to detection and treatment of many infections. Routine screening should reduce medical complications in this population and should prevent transmission in the community, given that many women are soon released.

Adolescent↗

Predictors of longitudinal change in sleep-disordered breathing in a nonclinic population.

STUDY OBJECTIVES: To quantify and identify the determinants of the 5-year change in the respiratory disturbance index (RDI). DESIGN: Longitudinal cohort study (Cleveland Family Study). Multivariate analyses were used to quantify baseline RDI and RDI change. SETTING: Community-based study. PARTICIPANTS: 486 cohort members (62% from families of probands with sleep-disordered breathing [SDB])--mean age 31.6 +/- 17.9 (SD) years, 60% female, 21% Black ethnicity--who underwent 2 assessments over 5.3 +/- 0.9 (SD) years. INTERVENTIONS: NA. MEASUREMENTS: The RDI was measured twice over approximately 5 years with in-home monitoring. Symptoms and medical histories were obtained from standardized questionnaires, and weight, height, and blood pressure were measured. RESULTS: The prevalence of SDB (defined by a RDI > or = 15), increased from 13.7% to 23.4% (P < 0.01) in men and from 8.3% to 11.4% (P = 0.13) in females. Baseline and follow-up mean RDIs were 6.0 +/- 10.0 and 8.6 +/- 14.3; both were higher in older individuals, in men, and in those with a higher body mass index. Median 5-year change in RDI varied nonlinearly with age (-0.1, 1.1, 2.3, and 0.9, for those < 18, 19-40, 41-54, and > or = 55 years, respectively) and obesity (2.8 vs -0.1, for the top versus lowest body mass index quartile). The effects of changing weight and aging varied in population subgroups. At any given age and weight, the RDI increased less in women. CONCLUSIONS: Longitudinal change in the RDI varies nonuniformly with age, sex, and weight. Older heavier men may experience the highest rate of increase in RDI over time and, thus, may benefit most from prospective monitoring.

Adult↗

Behaviors of children who are exposed and not exposed to intimate partner violence: an analysis of 330 black, white, and Hispanic children.

OBJECTIVE: To compare the behaviors of black, white, and Hispanic children who were 18 months to 18 years of age and exposed to intimate partner violence with an age- and ethnically similar sample of children who were not exposed to violence and to compare both exposed and nonexposed children to normative samples. METHODS: As part of a study on treatments for abused women in primary care public health clinics and Women, Infants and Children clinics in a large urban area, 258 abused mothers completed the Child Behavior Checklist (CBCL) on 1 of their randomly selected children between the ages of 18 months and 18 years. An ethnically similar sample of 72 nonabused mothers also completed the CBCL. The CBCL is a standardized instrument that provides a parental report of the extent of a child's behavioral problems and social competencies. The CBCL consists of a form for children 18 months to 5 years and a version for ages 6 to 18 years. The CBCL is orally administered to a parent, who rates the presence and frequency of certain behaviors on a 3-point scale (0 = not true, 1 = somewhat or sometimes true, and 2 = very true or often true). The time period is the last 6 months for the child 6 to 18 years of age and 2 months for the child 18 months to 5 years of age. Examples of behaviors for the child age 6 to 18 years include "gets in many fights," "truancy, skips school." Examples of behaviors for the child 18 months to 5 years of age include "cruel to animals," "physically attacks people," and "doesn't want to sleep alone." Both forms of the CBCL consist of 2 broadband factors of behavioral problems: internalizing and externalizing with mean scale scores for national normative samples as well as clinically referred and nonreferred samples of children. Internalizing behaviors include anxiety/depression, withdrawal, and somatic complaints. Externalizing behaviors include attention problems, aggressive behavior, and rule-breaking actions. Behavior scales yield a score of total behavioral problems. Scores are summed and then converted to normalized T scores. T scores >or=60 are within the borderline/clinical referral range-higher scores represent more deviant behavior. Multivariate analyses of variance (MANOVAs) were used to determine whether children from abused mothers differed significantly in their internalizing behaviors, externalizing behaviors, and total behavior problems from children of nonabused mothers. One sample t tests were used to compare children from abused and nonabused mothers to the matched clinically referred and nonreferred normative sample. Four pair-wise comparisons were considered: 1) children from abused women to referred norm, 2) children from abused women to nonreferred norm, 3) children from nonabused women to referred norm, and 4) children from nonabused to nonreferred norm. The internal, external, and total behavior problem T scores were dichotomized into a referral status: nonreferred = T score < 60, referred = T score >or= 60. Frequencies and percentages were used to describe the distribution of referral status among the children from the abused and nonabused women, and chi(2) tests of independence were used to determine whether the groups were significantly different. RESULTS: No significant differences in demographic characteristics between children from the abused women and nonabused women were observed. The sample consisted of a large number of Hispanic children (68.9%) and slightly more girls (53.6%), and nearly half (45.2%) had annual household incomes <10,000 dollars. Means, standard deviations, and results from the MANOVAs performed on internal, external, and total behavior problem scores between children from abused and nonabused women revealed no significant differences (F[3,139] = 1.21) for children ages 18 months through 5 years. Results from the MANOVA performed for ages 6 through 18 years revealed a significant group difference (F[3,183] = 3.13). Univariate tests revealed significant group differences for internalizing behavior (F[1,185] = 6.81), externalizing behav = 6.81), externalizing behavior (F[1,185] = 7.84), and total behavior problems (F[1,185] = 9.45). Overall, children of abused mothers had significantly higher internalizing (58.5 +/- 12.1), externalizing (55.5 +/- 12.4), and total behavior problems (57.6 +/- 12.3) scores than the internalizing (52.9 +/- 13.7), externalizing (49.7 +/- 10.6), and total behavior problems (51.0 +/- 13.0) scores exhibited for children of nonabused mothers. Most comparisons of children from the abused women to the referred and nonreferred norms are significant. The mean internal, external, and total behavior problem scores from children of abused women were significantly higher than the nonreferred norms and significantly lower than the referred norms. In contrast, all comparisons for children from nonabused women were not significantly different from the nonreferred norms. CONCLUSIONS: Children, ages 6 to 18 years, of abused mothers exhibit significantly more internalizing, externalizing, and total behavior problems than children for the same age and sex of nonabused mothers. In addition, the mean internalizing behavior score for boys 6 to 11 years of age as well as girls and boys 12 to 18 years of age of abused mothers were not significantly different from the clinical referral norms. Internalizing behaviors of anxiety, withdrawal, and depression are consistent with suicidal risk. The association of a child's exposure to intimate partner violence and subsequent attempted and/or completed suicide demands research. Our data demonstrate that children of abused mothers have significantly more behavioral problems than the nonclinically referred norm children but also, for most children, display significantly fewer problems than the clinically referred children. These children of abused mothers are clearly suspended above normal and below deviant, with children ages 6 to 18 being at the greatest risk. If abused mothers can be identified and treated, then perhaps behavior problems of their children can be arrested and behavioral scores improved. The American Academy of Pediatrics Committee on Child Abuse and Neglect recommends routine screening of all women for abuse at the time of the well-child visit and implementation of a protocol that includes a safety plan for the entire family. Clinicians can use this research information to assess for intimate partner violence during child health visits and inform abused mothers of the potential effects on their children's behavior. Early detection and treatment for intimate partner violence against women has the potential to interrupt and prevent behavioral problems for their children.

Adolescent↗

Effects of maternal characteristics on cesarean delivery rates among U.S. Department of Defense healthcare beneficiaries, 1996-2002.

BACKGROUND: National rates of cesarean birth continue a three decade-long escalation, despite widespread recognition that a reduction in the use of the procedure is a continuing appropriate public health goal, as evidenced by the Healthy People 2010 reduction targets. Nonclinical factors associated with cesarean delivery include maternal age, race, socioeconomic status, and insurance coverage. This study compared cesarean delivery rates and trends for the U.S. Department of Defense healthcare beneficiary population from 1996 to 2002 with those observed nationally, and assessed the association of these nonclinical factors with cesarean rate variation in the U.S. Department of Defense healthcare beneficiary population. METHODS: Hospital discharge and claims records for babies born in the military and civilian hospitals that comprise the Department of Defense healthcare network were used to calculate total and primary cesarean delivery rates and vaginal birth after cesarean (VBAC) rates from 1996 to 2002. Annual cesarean rates for subgroups defined by maternal age, race, and socioeconomic status were calculated to examine rate variations and rate trends within the study population. Pooled data from 1999 to 2002 were used to compare rates across socioeconomic status, stratified by age and race. Statistical significance of the differences calculated for subgroups was assessed using chi-square. RESULTS: Total and primary cesarean delivery rates among the U.S. Department of Defense population were lower than those reported nationally for every year examined. Cesarean delivery and VBAC rate trends in the national and Department of Defense populations were similar. Within the Department of Defense population, total cesarean delivery increased with increasing maternal age and was more highly associated with racial minorities relative to white women. The higher socioeconomic subgroup (defined as active duty, retired, and warrant officers and their families in this study) was generally associated with reduced cesarean delivery rates. CONCLUSIONS: Cesarean deliveries are performed less frequently for the U.S. Department of Defense healthcare beneficiary population relative to the national population. Associations between socioeconomic factors and cesarean rates reported for the national population were not apparent in the study population. The consistent pattern of rate variation across racial subgroups in the Department of Defense population suggests that factors beyond those examined in this study are needed to explain the elevated cesarean rates for racial minorities.

Adult↗

Is self-reported childhood abuse history associated with pain perception among healthy young women and men?

OBJECTIVE: A self-reported history of childhood physical and/or sexual abuse is frequently reported among chronic pain populations and has been associated with poorer adjustment to pain. In addition, self-reported abuse history has been related to increased pain complaints in population-based studies. One possible explanation for the association between abuse and clinical pain is that abuse victims may display enhanced sensitivity to painful stimuli, which increases the risk of developing clinical pain. However, the limited evidence addressing this issue has been mixed. The purpose of this study was to examine the association between self-reported history of childhood sexual or physical abuse and experimental pain responses in a nonclinical sample of generally healthy young adults. DESIGN: Participants were 110 (56 female, 54 male) college students who completed a series of questionnaires assessing abuse history, recent pain, health care utilization, perceived health, and psychologic variables. Also, measures of thermal and ischemic pain threshold and tolerance were obtained in all participants. In addition, a procedure assessing temporal summation of heat pain was conducted in which intensity and unpleasantness ratings of repetitive thermal stimuli were obtained. Systolic and diastolic blood pressure and heart rate were assessed at resting and during the ischemic pain task. RESULTS: Participants with a positive childhood abuse history were oversampled, yielding 21 out of 56 (37.5%) women with a positive history of abuse and 13 out of 54 (24.1%) PHA men. No abuse group differences emerged for thermal or ischemic pain thresholds or tolerances (P values>0.05). However, compared to women with no childhood abuse history, women with a positive history of abuse provided significantly lower average pain unpleasantness and peak pain unpleasantness ratings and lower unpleasantness ratings of the first trial during the temporal summation procedure, whereas no abuse group differences emerged for men. Also, compared to participants with no childhood abuse history, participants of both genders with a positive history of abuse demonstrated smaller increases (ie, less temporal summation) in pain unpleasantness ratings across trials of thermal stimulation, and participants with a positive history of abuse showed greater decreases in pain intensity and unpleasantness after reaching their peak pain level (ie, greater wind-down) compared to participants with no childhood abuse history. In addition, participants with a positive history of abuse reported more sites of recent pain, poorer perceived health, greater somatization, and more negative affect. No group differences in resting cardiovascular measures or cardiovascular reactivity were observed. CONCLUSION: These findings indicate that a self-reported history of childhood abuse is associated with decreased sensitivity to experimentally induced pain, especially among women. However, abuse history was associated with increased pain complaints, poorer self-reported health, and greater negative affect. These data highlight the complexity of the relationship between abuse history and pain and illustrate the need for further investigation of potential pain-related correlates of abuse.

Adult↗