Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials.

BACKGROUND: Evidence for the efficacy of commonly used drugs in the treatment of childhood functional constipation (FC) is scarce, studies are often of low quality and study designs are heterogeneous. Thus, recommendations for the design of clinical trials in childhood FC are needed. PURPOSE: Members of the Rome Foundation and a member of the Pediatric Committee of the European Medicines Agency formed a committee to create recommendations for the design of clinical trials in children with FC. KEY RECOMMENDATIONS: This committee recommends conducting randomized, double-blind, placebo-controlled, parallel-group clinical trials to assess the efficacy of new drugs for the treatment of childhood FC. Pediatric study participants should be included based on fulfilling the Rome IV criteria for FC. A treatment free run-in period for baseline assessment is recommended. The trial duration should be at least 8 weeks. Treatment success is defined as no longer meeting the Rome IV criteria for FC. Stool consistency should be reported based on the Bristol Stool Scale. Endpoints of drug efficacy need to be tailored to the developmental age of the patient population.

Recommendations for pharmacological clinical trials in children with irritable bowel syndrome: the Rome foundation pediatric subcommittee on clinical trials.

BACKGROUND: There is little published evidence of efficacy for the most commonly used treatments. Thus, there is an urgent need to conduct clinical trials on existing and novel therapies. PURPOSE: In order to address these issues the Rome Foundation and members of the Pediatric Committee of the European Medicines Agency formed a subcommittee on clinical trials to develop guidelines for the design of clinical trials in children with irritable bowel syndrome (IBS). The following recommendations are based on evidence from published data when available and expert opinion. KEY RECOMMENDATIONS: The subcommittee recommends randomized, double-blind, placebo-controlled, parallel-group, clinical trials to assess the efficacy of new drugs. The combined endpoints for abdominal pain are a decrease in intensity of at least 30% compared with baseline and to meet or exceed the Reliable Change Index (RCI) for the sample. Stool consistency is measured with the Bristol Stool Scale Form (BSFS). The subcommittee recommends as entry criteria for abdominal pain a weekly average of worst abdominal pain in past 24 h of at least 3.0 on a 0-10 point scale or at least 30 mm in 100 mm Visual Analog Scale. For stool endpoints the committee recommends an average stool consistency lower than 3 in the BSFS during the run-in period for clinical trials on IBS-C and an average stool consistency greater than 5 in the BSFS during the run-in period for clinical trials on IBS-D. Changes in stool consistency are the primary endpoints for both IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C).

Abdominal pain endpoints currently recommended by the FDA and EMA for adult patients with irritable bowel syndrome may not be reliable in children.

BACKGROUND: The Food and Drug Administration (FDA) recommended ≥30% decrease on patient-reported outcomes for pain be considered clinically significant in clinical trials for adults with irritable bowel syndrome. This percent change approach may not be appropriate for children. We compared three alternate approaches to determining clinically significant reductions in pain among children. METHODS: 80 children with functional abdominal pain participated in a study of the efficacy of amitriptyline. Endpoints included patient-reported estimates of feeling better, and pain Visual Analog Scale (VAS). The minimum clinically important difference in pain report was calculated as (i) mean change in VAS score for children reporting being 'better'; (ii) percent changes in pain (≥30% and ≥50%) on the VAS; and (iii) statistically reliable changes on the VAS for 68% and 95% confidence intervals. KEY RESULTS: There was poor agreement between the three approaches. 43.6% of the children who met the FDA ≥30% criterion for clinically significant change did not achieve a reliable level of improvement (95% confidence interval). CONCLUSIONS & INFERENCES: Children's self-reported ratings of being better may not be statistically reliable. A combined approach in which children must report improvement as better and achieve a statistically significant change may be more appropriate for outcomes in clinical trials.

Oppositional defiant disorder with onset in preschool years: longitudinal stability and pathways to other disorders.

OBJECTIVE: To examine the stability and change in oppositional defiant disorder (ODD) with onset among preschool children in a pediatric sample. METHOD: A total of 510 children aged 2-5 years were enrolled initially in 1989-1990 (mean age 3.42 years); 280 participated in five waves of data collection over a period of 48 to 72 months (mean wave 5 age, 8.35 years). Test batteries varied by age, but they included the Child Behavior Checklist, developmental evaluation, Rochester Adaptive Behavior Inventory, and a play session (before age 7 years) and a structured interview (Diagnostic Interview for Children and Adolescents, parent and child versions) at ages 7+ years. Consensus diagnoses were assigned by using best-estimate procedures. RESULTS: Wave 1 single-diagnosis ODD showed a significant relationship with both single-diagnosis ODD and single-diagnosis attention-deficit hyperactivity disorder (ADHD) at subsequent waves, but not with single-diagnosis anxiety or mood disorders. Single-diagnosis ODD at wave 1 was associated with later comorbidity of ODD/ADHD, ODD/anxiety, and ODD/mood disorders. Stability across waves 2 through 5 was moderate to high for comorbid ODD/anxiety and ODD/ADHD; low to moderate stability for single-diagnosis ODD and single-diagnosis mood disorder; and low for mood disorder, single-diagnosis ADHD, and single-diagnosis anxiety disorder. CONCLUSIONS: Preschool children with ODD are likely to continue to exhibit disorder, with increasing comorbidity with ADHD, anxiety, or mood disorders.

Rational service planning in pediatric primary care: continuity and change in psychopathology among children enrolled in pediatric practices.

OBJECTIVE: To examine the stability of the occurrence of psychiatric disorders in a nonpsychiatric sample of young children. METHOD: There were 510 children ages 2-5 years enrolled through pediatric practices, with 391 children participating in the second wave, and 344 in the third wave of data collection 42-48 months later. The assessment battery administered at each wave yielded best-estimate consensus DSM-III-R diagnoses and dimensional assessments of psychopathology. RESULTS: The prevalence of disruptive disorders (DDs) decreased, while emotional disorders (EDs), other disorders, and comorbid DD increased. The DDs were associated with lower family cohesion, more maternal negative affect, stressful life events, and male gender. Comorbid DDs were associated with increasing age and family cohesion. Older children, lower family cohesion, and maternal negative affect were associated with EDs. Time trends for the dimensional assessment of psychopathology was similar to DSM-III-R disorders, but correlates differed. CONCLUSIONS: We discuss implications for service planning in pediatric primary care.

Sleep and behavior problems among preschoolers.

This study described the relationship between amount of sleep and behavior problems among preschoolers. Participants were 510 children aged 2 to 5 years who were enrolled through 68 private pediatric practices. Parents reported on the amount of sleep their child obtained at night and in 24-hour periods. With demographic variables controlled, regression models were used to determine whether sleep was associated with behavior problems. The relationship between less sleep at night and the presence of a DSM-III-R psychiatric diagnosis was significant (odds ratio = 1.23, p = .026). Less night sleep (p < .0001) and less sleep in a 24-hour period (p < .004) were associated with increased total behavior problems on the Child Behavior Checklist; less night sleep (p < .0002) and less 24-hour sleep (p < .004) were also associated with more externalizing problems on that measure. Further research is needed to ascertain whether sleep is playing a causal role in the increase of behavior problems.

A cholesterol-lowering diet does not produce adverse psychological effects in children: three-year results from the dietary intervention study in children.

The Dietary Intervention Study in Children (DISC), a 2-arm, multicenter intervention study, examined the efficacy and safety of a diet lower in total fat, saturated fatty acids, and cholesterol than the typical American child's diet. A total of 663 8- to 10-year-old children with elevated low-density lipoprotein cholesterol levels were randomly assigned to either an intervention or a usual-care group. Intervention included group and individual counseling sessions to assist participants in adopting a dietary pattern containing 28% or less of calories from total fat (<8% as saturated fat, up to 9% as polyunsaturated fat, and 11% as monounsaturated fat) and dietary cholesterol intake of less than 75 mg/1,000 kcal. The dietary intervention reduced low-density lipoprotein cholesterol levels, and 3-year results showed no adverse effects for children in the intervention group in terms of academic functioning, psychological symptoms, or family functioning.

Psychiatric disorders with onset in the preschool years: I. Stability of diagnoses.

OBJECTIVE: To examine the stability of psychiatric disorders with onset in preschool years. METHOD: Five hundred ten children aged 2 through 5 years enrolled initially, with 344 participating in a third wave of data collection 42 through 48 months later. The test batteries used for diagnoses varied by child's age, but they included the Child Behavior Checklist, developmental evaluation, Rochester Adaptive Behavior Inventory and a play session (under age 7 years), and a structured interview (Diagnostic Interview for Children and Adolescents, for parent and child) (ages 7 and older). Consensus DSM-III-R diagnoses were assigned using best-estimate procedures. RESULTS: Intraclass correlations were 0.497 for emotional disorders, 0.718 for disruptive disorders, 0.457 for other diagnoses, and 0.544 for disruptive disorders comorbid with another disorder, indicating moderate stability for all groups of disorders. More than 50% of the children who were aged 2 through 3 years at wave 1 continued to have some psychiatric disorder at wave 2 or 3. Rates were higher for children aged 4 through 5 initially; approximately two thirds were cases subsequently. Odds ratios indicate that having an emotional or disruptive disorder is a strong risk factor for later diagnoses. CONCLUSIONS: While some preschool children in primary care "grow out of" their disorder, an equally large number do not; this finding supports the need for early detection and intervention.

Psychiatric disorders with onset in the preschool years: II. Correlates and predictors of stable case status.

OBJECTIVE: To examine the correlates and predictors of stability and change in psychiatric disorder occurring among preschool children in a nonpsychiatric, primary care pediatric sample. METHOD: Five hundred ten children aged 2 through 5 years were enrolled; 344 participated in a third wave of data collection 42 through 48 months later. Consensus diagnoses were assigned using best-estimate procedures; variables of maternal psychopathology, family climate, and life stresses were the correlates/predictors studied. RESULTS: For children who were cases initially, family cohesion predicted diagnostic stability. Among initial noncases, those remaining noncases experienced increased family cohesion; for those who later became cases, family cohesion declined. Negative life events declined when children were consistently noncases. Children who were initially noncases but were cases at the two subsequent waves had the highest levels of maternal negative affect. Predictors at wave 1 for wave 2 cases status included lower socioeconomic status, less family cohesiveness, and greater family inhibition/control. Wave 2 correlates of wave 2 status included older children and negative life events. Wave 2 predictors of wave 3 status included being older, while wave 3 correlates of wave 3 case status included older children and higher maternal negative affect. CONCLUSIONS: Family context contributes to the maintenance and onset of problems beginning in the preschool years.

Mental health service use among young children receiving pediatric primary care.

OBJECTIVE: To investigate the factors associated with mental health service use among young children. METHOD: Five hundred ten preschool children aged 2 through 5 years were enrolled through 68 primary care physicians, with 388 (76% of the original sample) participating in a second wave of data collection, 12 to 40 months later. Consensus DSM-III-R diagnoses were assigned using best-estimate procedures. The test battery included the Child Behavior Checklist, a developmental evaluation, the Rochester Adaptive Behavior Inventory, and a videotaped play session (preschool children) or structured interviews (older children). At wave 2, mothers completed a survey of mental health services their child had received. RESULTS: In logistic regression models, older children, children with a wave 1 DSM-III-R diagnosis, children with more total behavior problems and family conflict, and children receiving a pediatric referral were more likely to receive mental health services. Among children with a DSM-III-R diagnosis, more mental health services were received by children who were older, white, more impaired, experiencing more family conflict, and referred by a pediatrician. CONCLUSIONS: Young children with more impairment and family conflict are more likely to enter into treatment. Services among young children of different races with diagnoses are not equally distributed. Pediatric referral is an important predictor of service use.

Emergence of childhood psychiatric disorders: a multivariate probit analysis.

We applied a computationally practical form of probit analysis for multiple response variables to data on early childhood development of four psychiatric disorders: disruptive disorders (DD-attention deficit disorders, oppositional defiant disorder, conduct disorder); adjustment disorders (ADJ); emotional disorders (ED-all anxiety disorders, depression); and other DSM-III-R Axis I disorders (OTHER). In addition to estimating the intercept slope and higher order polynomial terms for each age versus diagnosis regression, we estimated simultaneously the correlation among the four diagnostic categories. We then took into account the correlation found among these four diagnostic categories when testing the hypothesis of no age effect, which would have been ignored in a piecemeal univariate approach. Regression lines for diagnostic prevalence indicate a linear increase for OTHER disorders, and a curvilinear increase for ED. We then used expected frequencies of individual response patterns (that is, the 2(4) = 16 possible diagnostic combinations) in obtaining more precise estimates of diagnostic comorbidity and its relation to age. We further generalize the Bock and Gibbons model to alternative specification of the random-effects distribution (that is, they assumed multivariate normality), illustrate how one can estimate the random-effects distribution empirically, and study the robustness of parameter estimates to specification of the random-effects distribution.

Psychopathology and health care use among preschool children: a retrospective analysis.

OBJECTIVE: To examine the relationship between psychopathology and health care utilization beginning in the preschool (ages 2 to 5) years. METHOD: Five hundred ten preschool children were enrolled through 68 primary care physicians. The test battery used for diagnoses included the Child Behavior Checklist, a developmental evaluation, the Rochester Adaptive Behavior Inventory, and a videotaped play session. Consensus DSM-III-R diagnoses were assigned using best-estimate procedures. Frequency of primary care visits was established through 1-year retrospective record review; mothers estimated total visits and emergency department (ED) use. RESULTS: Logistic regression models showed that a DSM-III-R diagnosis was related to increased ED use but not primary care or total visits. Greater functional impairment was associated with fewer primary care visits and more ED visits. Total, internalizing, and externalizing behavior problem scores were associated with increased primary care and total visits; ED visits were associated with increased total and internalizing problems. Child's health status consistently correlated with utilization. CONCLUSION: There is a consistent relationship between health care use and child psychopathology beginning in the preschool years.

Relation between intelligence and psychopathology among preschoolers.

Examined the relation between intelligence and psychopathology in a nonclinical sample of 510 children ages 2 to 5 years. Psychopathology was measured using both quantitative, dimensional methods (Child Behavior Checklist [CBCL]) and taxonomic methods (the Diagnostic and Statistical Manual of Mental Disorders [3rd. ed., Rev.; DSM-III-R; American Psychological Association, 1987]). IQ scores were derived from either the McCarthy Scales of Children's Abilities or the Bayley Scales of Mental Development. Based on quantitative, dimensional data, results support similar findings among older children and clinical populations that lower McCarthy general, verbal, and perceptual-performance IQ scores are associated with various types of psychopathology. Results were also consistent for the DSM-III-R data. Bayley IQ scores did not predict CBCL psychopathology or DSM-III-R Disruptive Disorders, but they did predict the presence of a DSM-III-R diagnosis. Early identification of intellectual deficits among preschoolers ages 3 to 5 may help to prevent later school difficulties and severe psychopathology.

Patterns and correlates of supervision in child pedestrian injury. The Kids 'N' Cars Research Team.

Described supervision in 142 child pedestrian injuries (PI), based on presence and proximity of supervisors and/or peers. Children (5-12 years), families, sites, and PI events were described via record reviews, interviews, questionnaires, and site investigation. Supervision of PI victims varied with family size and cohesion, and with children's age, self-help skills, nearness to home, and activity (playing or journey). Peer presence was associated with more impulsive behavior among supervised (but not among unsupervised) PI victims. Definitions of supervision parameters offered here can aid research on the complex relationship between supervision and PI risk.

Supervision in childhood injury cases: a reliable taxonomy.

This paper describes the development of the "Chicago Children's Supervision Taxonomy" which operationally defines supervision based on the age of an injured child and the ages, familiarity, and proximity of that child's companions. The reliability, coverage, and utility of this taxonomy are illustrated by its application to 142 cases of urban childhood pedestrian injury. All cases were unambiguously classified with good interrater reliability. Most injured children were in unsupervised groups (42%) but 36% had supervisors nearby, thus, supervisor presence does not guarantee protection. Supervising more than one child (especially likely when the supervisor was a teenager) may increase injury risk compared with one-to-one supervision. The taxonomy provides a needed framework adaptable for describing direct supervision in most child injury situations and can facilitate studies of more complex aspects of supervision.

Prevalence rates and correlates of psychiatric disorders among preschool children.

OBJECTIVE: To determine the prevalence and correlates of psychiatric disorders among preschool children in a primary care pediatric sample. METHOD: In a two-stage design, 3,860 preschool children were screened; 510 received fuller evaluations. RESULTS: For quantitative assessment of disorder (> or = 90th percentile), prevalence of behavior problems was 8.3%. "Probable" occurrence of an Axis I DSM-III-R disorder was 21.4% (9.1%, severe). Logistic regression analyses indicated significant demographic correlates for quantitative outcomes (older age, minority status, male sex, low socio-economic status, father absence, small family size) but not for DSM-III-R diagnoses. Maternal and family characteristics were generally not significant. Child correlates included activity level, timidity, persistence, and IQ. CONCLUSIONS: Overall prevalence of disorder was consistent with rates for older children; correlates varied by approach used for classification.

Psychosocial factors in childhood pedestrian injury: a matched case-control study. Kid's'n'Cars Team.

HYPOTHESIS: Psychosocial factors--such as hyperactivity and low family cohesion--contribute to the risk for child pedestrian injury (PI), even after controlling for known demographic risk factors. PARTICIPANTS: Urban PI victims aged 5 to 12 years were recruited from one large, urban pediatric trauma center in a large city. One hundred twenty-eight cases were matched to uninjured children on age, sex, race, location of residence, and parental education. Among matched cases: 70% were male, 41% were black, 33% were Hispanic, and 66% of the mothers had a high school education or less. RESEARCH DESIGN AND MEASUREMENTS: Case-control comparisons on 19 psychosocial variables drawn from interviews and standardized tests, using one-tailed matched-pairs t tests and conditional logistic regression analyses. RESULTS: Cases had higher reported physical quotient [PQ] (P = .01), self-help quotient (P = .04), and family stress (P = .02), and lower family supportiveness (P = .03). Multivariate analyses confirmed that PQ was higher in cases (10-point increase: odds ratio (OR) = 1.32 [90% confidence interval (CI) 1.01-1.76], that stress was higher in cases (1 log increase: OR 2.13, [1.26-3.61]), and that cases had lower family supportiveness (25-point decrease: OR 1.43 [1.25-1.63]). It also identified household crowding as a factor for non-black cases (OR for increase of 0.25 people per room: 2.18, [1.31-3.62]). CONCLUSION: Even when controlling for demographic risk, several family factors and one child factor place children at risk for PI. Clinicians may choose to use these as indicators for injury prevention counseling. Research on family effects may help clarify means to protect children who are demographically at risk for PI.

Family coping with pediatric leukemia: ten years after treatment.

As part of a longitudinal study of family coping with pediatric leukemia, 28 former patients (16 male; 12 female; M age = 19.1 years) and their parents (23 mothers; 12 fathers) participated in a follow-up study at 10 years posttreatment. Measures included the Current Adjustment Rating Scale, the Brief Symptom Inventory, the Ways of Coping Scale, the Family Coping Scale, and a semistructured interview. Long-term survivors and their parents continued to be well-adjusted to life posttreatment. Coping and perceived adjustment in long-term survivors were positively related to socioeconomic status and mother's coping and negatively related to academic problems. A strong bidirectional relationship was found between survivors' and mother's adjustment. Coping strategies were variable and not significantly correlated with coping adequacy or adjustment.

Child pedestrian injury taxonomy based on visibility and action.

With data from multidisciplinary investigations of child pedestrian injuries in Chicago, a new and simpler four-category taxonomy is presented based on the process that led to the collision. Two dimensions are recognized: the visibility of the child and/or the vehicle immediately prior to the event and the rapidity of action, either movement or change in direction, of the victim or the vehicle. The taxonomy is neutral with respect to responsibility for the collision and accommodates the findings of other researchers. This classification scheme is tested empirically using objective data elements such as child gender and age and event location. It is further tested using the results of a multidisciplinary causal sequence reconstruction of each injury event, based on such factors as child's psychological character, traffic risks, driver behavior, visibility obstructions, whether the child negotiated part of the street before being struck, and child's activities immediately prior to the injury. The results show that events in the categories in this new taxonomy are distinctly different from each other, and that the structure is useful for identifying and organizing interventions.