Faculty Bibliography

BACKGROUND AND AIMS/OBJECTIVE:STRIDE-II recommends early biomarker targets for treatment optimization to achieve treat-to-target [T2T] endoscopic remission [ER] in Crohn's disease [CD]. The predictive capabilities of intestinal ultrasound [IUS] for T2T ER remain unknown. We aimed to evaluate IUS response to predict ER in children with CD. METHODS:This was a prospective longitudinal cohort study of children with ileal [TI] CD initiating biologic therapy undergoing IUS, clinical disease activity, and C-reactive protein [CRP] assessments at baseline, week 8, 6 months, and T2T within 1 year. The primary outcome was the accuracy of optimal cut-points to predict TI ER [SES-CD ≤ 2] for change in bowel wall thickness [BWT] on IUS from baseline to week 8, and BWT at week 8. Area under the receiver operating curve [AUROC] analysis was performed and univariate analysis tested associations. RESULTS:In total, 44 children (median age 13 [IQR 12-17] years, 29 [66%] biologic naïve) were included, and 29 [66%] achieved ER. A ≥18% decrease in TI BWT at week 8 predicted ER with an AUROC of 0.99 [95% CI 0.98-1.00], 100% sensitivity, 93% specificity, 97% positive predictive value, and 100% negative predictive value, superior to a ≥46% decrease in PCDAI (AUROC 0.67 [95% CI 0.49-0.84]) and ≥84% decrease in CRP (AUROC 0.49 [95% CI 0.31-0.67]) at week 8. CONCLUSIONS:Early change in TI BWT on IUS is highly predictive of ER in children with CD and superior to symptoms and CRP. Our findings suggest that IUS could be used for treatment optimization and tight control to guide T2T strategies.

BACKGROUND AND AIMS/OBJECTIVE:Anti-tumour necrosis factor [anti-TNF] induced skin reactions are common adverse events in paediatric inflammatory bowel disease [IBD]. We aimed to report on outcomes of children with anti-TNF induced skin reactions who switched to ustekinumab [UST] vs. continued anti-TNF therapy. METHODS:Charts were reviewed for paediatric IBD patients with anti-TNF induced skin reactions. Skin reactions, including psoriasiform dermatitis [PD], were classified as mild or severe based on a severity score. Primary outcome was frequency of skin resolution at 6 months. Secondary outcomes were combined clinical remission and skin resolution at 6 months and skin resolution at latest follow-up. RESULTS:A total of 111/638 [17%] children ([85, 21%] infliximab [IFX]; [26, 11%] adalimumab [ADA]) developed skin reactions. Eighty [72%] had PD, 25 [23%] infections, and four [4%] alopecia areata; 71 [64%] continued anti-TNF; and 40 [36%] switched to UST. In all, 73 [66%] had severe reactions and were more likely to switch to UST than if mild (37 [51%] vs. 3 [8%]; p <0.0001). Switching to UST had a higher rate and odds of resolution (29 [73%] vs. 24 [34%]; p <0.0001; odds ratio [OR] = 19.7, 95% confidence interval [CI]: 5.6, 69.5; p <0.0001) and combined remission (21 [52%] vs. 22 [31%]; p = 0.03; OR = 8.5, 95% CI: 2.5, 28.4; p = 0.0005] vs. continuing anti-TNF at 6 months. CONCLUSIONS:Children who switched to UST after anti-TNF induced skin reactions were more likely to have improved outcomes than those who continued anti-TNF therapy. Future studies are needed to determine immune mechanisms of anti-TNF induced skin reactions and treatment response.

This article reports the psychometric properties of two scales for rating positive and negative schizophrenic signs and symptoms. These Positive and Negative Syndrome Scales consist of items selected from the Children's Psychiatric Rating Scale (CPRS), which contains items covering a wide range of childhood psychopathology. CPRS rating data were analyzed for 19 schizophrenic children, 16 males and 3 females, mean age 8.9 years (range 5.5-11.7), evaluated in a double-blind, placebo-controlled crossover study of haloperidol. We describe the item composition and coherence of each scale, the interrater reliabilities of clinicians using the scales, and the sensitivity of the scales for resolving treatment response. Schizophrenic children showed both positive and negative signs and symptoms, and both improved with neuroleptic treatment

This article presents data on the diagnosis and phenomenology of schizophrenia in 16 hospitalized children, ages 5.5 to 11.75 years. These 16 subjects are the first to complete an ongoing double-blind, placebo-controlled study of haloperidol in children with schizophrenia diagnosed by DSM-III-R criteria. We describe the pharmacologic treatment response of this subsample and compare our diagnostic, phenomenologic, and treatment findings with those of other investigators. Our results show that children under age 12 can be diagnosed with schizophrenia by the same criteria used for adults, that they show comparable clinical symptoms, and that on haloperidol they show improvement in target psychotic symptoms, at least in a short-term inpatient setting

This report presents preliminary findings in an ongoing double-blind, placebo-controlled study of the safety and efficacy of haloperidol in hospitalized schizophrenic children. The subjects are diagnosed schizophrenic by DSM-III-R criteria and admitted to the Bellevue Hospital Children's Inpatient Psychiatric Unit. The study is 10 weeks in duration and employs a crossover design. After a 2-week placebo baseline period, the subjects enter double-blind treatment for 8 weeks, by random assignment receiving either haloperidol for 4 weeks followed by placebo for 4 weeks, or alternatively, placebo for 4 weeks followed by haloperidol for 4 weeks. Dosage, regulated individually, ranges from 0.5 to 10.0 mg/day. To date, of an anticipated 20 subjects, 12 have completed the study. These children, 9 boys and 3 girls, were ages 5.5 to 11.75 years upon study entry. Haloperidol was superior to placebo for reduction of target symptoms with optimal haloperidol dose of 0.5 to 3.5 mg/day (0.02-0.12 mg/kg/day)

Baseline stereotypic movements in 224 autistic children were studied as well as their relationship to certain demographic variables and measures of overall symptomatology and severity of illness. Prediction of haloperidol-related dyskinesias with measures of stereotypies and demographic variables was also attempted. Stereotypies were present in at least mild form in most children, with most showing moderate severity. Most stereotypies were in the orofacial area. I.Q. was found to be negatively related to stereotypies. Furthermore, across methods of assessment, severity and frequency of stereotypies were found to be positively related to overall symptomatology and severity of illness. No significant predictors of development of dyskinesias were found.

Serum and saliva lithium levels are presented for 30 inpatients, ages 5.12 to 11.95 years, diagnosed as having conduct disorder of the undersocialized aggressive type. Maintenance doses of lithium carbonate ranged from 600 mg to 1,500 mg/day. Serum and saliva lithium levels were significantly correlated at optimal dose (r = .78, p less than .001) and overall (r = .83, p less than .001), lending support to the use of saliva lithium levels as an adjunct to serum lithium determinations. However, because saliva/serum lithium ratios reveal wide ranges between subjects, the use of saliva levels is limited, and laboratory assessments should be combined with careful clinical monitoring

Videotapes of autistic children with stereotypies and/or neuroleptic-related dyskinesias were shown to three experienced raters blind to the children's medication treatment status and history, if any, of neuroleptic exposure. Upon observation of the videotapes, stereotypies and neuroleptic-related dyskinesias were not well differentiated from each other. These results emphasize the importance of assessing and documenting baseline abnormal movements before patients receive neuroleptic therapy. Meticulous baseline evaluation, integral to all patient care, is of particular concern in treating patient populations that often show abnormal movements unrelated to neuroleptic exposure. Such movements can be mistaken clinically for neuroleptic-related dyskinesias and, in the absence of baseline data for comparison, can be misdiagnosed as such