A validated web-based tool to display individualised Crohn's disease predicted outcomes based on clinical, serologic and genetic variables.

BACKGROUND: Early treatment for Crohn's disease (CD) with immunomodulators and/or anti-TNF agents improves outcomes in comparison to a slower 'step up' algorithm. However, there remains a limited ability to identify those who would benefit most from early intensive therapy. AIM: To develop a validated, individualised, web-based tool for patients and clinicians to visualise individualised risks for developing Crohn's disease complications. METHODS: A well-characterised cohort of adult patients with CD was analysed. Available data included: demographics; clinical characteristics; serologic immune responses; NOD2 status; time from diagnosis to complication; and medication exposure. Cox proportional analyses were performed to model the probability of developing a CD complication over time. The Cox model was validated externally in two independent CD cohorts. Using system dynamics analysis (SDA), these results were transformed into a simple graphical web-based display to show patients their individualised probability of developing a complication over a 3-year period. RESULTS: Two hundered and forty three CD patients were included in the final model of which 142 experienced a complication. Significant variables in the multivariate Cox model included small bowel disease (HR 2.12, CI 1.05-4.29), left colonic disease (HR 0.73, CI 0.49-1.09), perianal disease (HR 4.12, CI 1.01-16.88), ASCA (HR 1.35, CI 1.16-1.58), Cbir (HR 1.29, CI 1.07-1.55), ANCA (HR 0.77, CI 0.62-0.95), and the NOD2 frameshift mutation/SNP13 (HR 2.13, CI 1.33-3.40). The Harrell's C (concordance index for predictive accuracy of the model) = 0.73. When applied to the two external validation cohorts (adult n = 109, pediatric n = 392), the concordance index was 0.73 and 0.75, respectively, for adult and pediatric patients. CONCLUSIONS: A validated, web-based tool has been developed to display an individualised predicted outcome for adult patients with Crohn's disease based on clinical, serologic and genetic variables. This tool can be used to help providers and patients make personalised decisions about treatment options.

A longitudinal study of a hyperlexic child: hyperlexia as a language disorder.

The longitudinal study of a hyperlexic girl, A.E., is described. Although her WISC-R IQ was 58, her reading was significantly advanced for age and level of intellectual functioning. She was socially withdrawn and displayed repetitive and self-stimulation behaviors. At birth she weighed 1000 g and was 32 weeks gestational age. She had severe respiratory distress, seizures and apnea in the perinatal period. She had a history of significantly delayed development, although the delays were more pronounced in language than in perceptual motor skills. She demonstrated difficulties with semantic and syntactic processing of language and could read words and sentences of which she had little or no comprehension. The existence of reading in spite of severely disordered language suggests that reading may occur by visual and/or phonological routes but that semantic and syntactical processing of words is not essential.

Reproductive, perinatal, and environmental variables as predictors of development of preterm (less than 1501 grams) and fullterm children at 5 years.

A risk index based on a variety of reproductive, perinatal and environmental variables was used to attempt to predict the developmental outcome of very low birthweight infants (birthweights under 1501 grams). Forty-one preterm infants and a demographically matched group of 42 fullterm infants were studied. The McCarthy Scales of Children's Abilities was administered to the children at 5 years of age. In general, the preterm children were delayed in the perceptual, memory, and motor abilities in comparison with the fullterm children. There were no significant differences between the AGA (appropriate for gestational age) and SGA (small for gestational age) preterm groups. Multiple regression and discriminant function measures were used to examine the overall relationship between the earlier measures and later development and to assess the risk for an individual child. The risk index was able to account for typically 30-40% of the variance associated with the 5 year scores and the prediction of an individual child's development was accurate for approximately 85% of the time. Severity of illness during the perinatal period, independently of social class and infant tests scores were the best predictors of outcome. This study demonstrates that developmental outcome can be predicted with a high degree of accuracy and a relatively simple system.

Ineffectiveness of 3,4-diaminopyridine as a therapy for type C botulism.

Clostridium botulinum neurotoxins inhibit acetylcholine release at neuromuscular junctions. Agents stimulating neurotransmitter efflux, such as 3,4-diaminopyridine (3,4-DAP), could be useful for botulism therapy. Treatment with 3,4-DAP (8 mg/kg hourly, beginning 3 hr after toxin injection) failed to increase the survival times of mice receiving 10, 20 or 40 LD50 type C, but did prolong the survival of those receiving 20 LD50 type A. This difference in 3,4-DAP efficacy may reflect variations in the molecular mechanism of action of types A and C botulinum neurotoxins.

Reading and language in 9- to 12-year olds prenatally exposed to cigarettes and marijuana.

Facets of reading and language were examined in 131 9- to 12-year-old children for whom prenatal exposure to marijuana and cigarettes had been ascertained. The subjects were from a low-risk, predominantly middle class sample who are participants in an ongoing longitudinal study. Discriminant Function Analysis revealed a dose-dependent association that remained after controlling for potential confounds, between prenatal cigarette exposure and lower language and lower reading scores, particularly on auditory-related aspects of this latter measure. The findings are interpreted as consistent with earlier observations of an association between cigarette smoking during pregnancy and altered auditory functioning in the offspring. Similarities and differences between the reading observations and dyslexia are discussed. Maternal prenatal passive smoke exposure did not appear to contribute to either the language or reading outcomes at this age but postnatal secondhand smoke exposure by the child was associated with poorer language scores. Prenatal marijuana exposure was not significantly related to either the reading or language outcomes.

Deep dyslexia in childhood?

Deep dyslexia is an acquired reading disorder in which semantic substitutions (e.g., city read as town) are made in reading single isolated words. In this paper, evidence for deep dyslexic-type errors is presented from the word-recognition responses of six children, aged 7 years and 0 month to 8 years and 9 months, with severe reading disorders. These semantic substitutions occur in the absence of phonological skills. Therefore, it appears that there exists a small subset of developmental dyslexics who at the beginning of acquisition of reading skills are able to engage in semantic processing, but who show severe impairment of phonological processing. The existence of these reading errors indicate that the use of a phonological code is not necessary to extract meaning from the printed word.

Left ear dichotic listening performance on consonant-vowel combinations and digits in subtypes of reading-disabled children.

Twenty reading comprehension-disabled (CD) and 20 reading comprehension and word recognition-disabled (CWRD), right-handed male children were matched with 20 normal-achieving age-matched controls and 20 normal-achieving reading level-matched controls and tested for left ear report on dichotic listening tasks using digits and consonant-vowel combinations (CVs). Left ear report for CVs and digits did not correlate for any of the groups. Both reading-disabled groups showed lower left ear report on digits. On CVs the CD group showed a high left ear report but only when there were no priming precursors, such as directions to attend right first and to process digits first. Priming effects interfered with the processing of both digits and CVs. Theoretically, the CWRD group seems to be characterized by a depressed right hemisphere, whereas the CD group may have a more labile right hemisphere, perhaps tending to overengagement for CV tasks but vulnerable to situational precursors in the form of priming effects. Implications extend to (1) subtyping practices in research with the learning-disabled, (2) inferences drawn from studies using different dichotic stimuli, and (3) the neuropsychology of reading disorders.

Peer interactions of normal and attention-deficit-disordered boys during free-play, cooperative task, and simulated classroom situations.

Groups of 30 ADD-H boys and 90 normal boys were divided into 30 mixed dyads composed of a normal and an ADD-H boy, and 30 normal dyads composed of 2 normal boys. Dyads were videotaped interacting in 15-minute free-play, 15-minute cooperative task, and 15-minute simulated classroom settings. Mixed dyads engaged in more controlling interaction than normal dyads in both free-play and simulated classroom settings. In the simulated classroom, mixed dyads completed fewer math problems and were less compliant with the commands of peers. ADD-H children spent less simulated classroom time on task and scored lower on drawing tasks than normal peers. Older dyads proved less controlling, more compliant with peer commands, more inclined to play and work independently, less active, and more likely to remain on task during the cooperative task and simulated classroom settings. Results suggest that the ADD-H child prompts a more controlling, less cooperative pattern of responses from normal peers.

Dyadic peer interaction and task orientation in attention-deficit-disordered children.

A sequential observational approach was used to compare peer interactions in 10 mixed dyads of ADD-H and non-Add-H boys and 10 dyads of non-ADD-H boys in laboratory cooperative and school classroom task analogue activities. Mixed dyads were found to have a greater frequency of aggression and less joint activity than control dyads in specific situations. No differences were found for measures of functional attention as measured by frequency, duration, and mean duration of task-oriented behavior. Lag sequential analyses revealed two major sequences that differentiated mixed from normal dyads. These were Verbal Reciprocity (a measure of reciprocal verbal interaction) and Retreat (a measure of social withdrawal following aggression).

Language intervention with children who have developmental delays: effects of an interactive approach.

The interactive model of language intervention instructs parents to use techniques that promote reciprocal social interactions and facilitate the development of communication and language abilities. In this evaluation study, 32 mothers and their preschool-age children with developmental delays were randomly assigned to treatment and control (delayed treatment) groups. Consistent with the interactive model, mothers in the treatment group became more responsive, less directive, and provided clearer linguistic models. Furthermore, these changes were maintained for at least 4 months after intervention, and involvement in the parent-centered intervention program did not increase maternal stress. More important, these changes were accompanied by concomitant increases in children's use of vocal turns. Contrary to predictions, developmental improvements in children's communicative and linguistic abilities were comparable in both groups. Findings suggest that an interactive model may afford a useful adjunct to other intervention approaches by instructing parents on how to promote children's use of existing abilities, but an interactive model may have no effect on language acquisition of at least some children with developmental delays.

Nondyslexic children with combined writing and arithmetic learning disabilities.

A common presenting problem of children in pediatric practice is the constellation of symptoms involving difficulty in completing assignments, trouble with written work, and organizational problems. Typically, these children do not have difficulty with reading but show problems with academic achievement. We have recently studied 29 children, aged 7 to 13, referred for learning problems. They were not dyslexic, that is their reading abilities were normal, but they had significant difficulty with written tests and assignments and problems with arithmetic. In addition to difficulty with eye-hand coordination as measured by a test of visual motor integration, these children showed poor performance on short-term memory tasks when compared with children who do not have writing or arithmetic problems. Suggested treatments include the use of tape recorders, typewriters, and calculators to help compensate for the writing and short-term memory difficulties associated with these learning problems. The pediatrician, acting as child advocate, can exert influence within the traditional school system to gain acceptance for use of learning aids by children with a developmental output disability.

An evaluation of the discrepancy definition of dyslexia.

The purpose of this study was to determine whether children with dyslexia, that is, children whose reading levels were significantly lower than would be predicted by their IQ scores, constituted a distinctive group when compared with poor readers, that is, children whose reading scores were consistent with their IQ scores. The performance of children with dyslexia, poor readers, and normally achieving readers was compared on a variety of reading, spelling, phonological processing, language, and memory tasks. Although the children with dyslexia had significantly higher IQ scores than the poor readers, these two groups did not differ in their performance on reading, spelling, phonological processing, or most of the language and memory tasks. In all cases, the performance of both reading disabled groups was significantly below that of nondisabled readers. The findings were similar whether absolute difference or regression scores were used. Reading disabled children, whether or not their reading is significantly below the level predicted by their IQ scores, experience significant problems in phonological processing, short-term and working memory, and syntactic awareness. On the basis of these data, there does not seem to be a need to differentiate between individuals with dyslexia and poor readers. Both of these groups are reading disabled and have deficits in phonological processing, verbal memory, and syntactic awareness.

Issues in the definition and diagnosis of learning disabilities: a perspective on Guckenberger v. Boston University.

This article reviews issues related to the definition of learning disabilities in the context of the Guckenberger v. Boston University case. Four major questions are addressed: (a) Who is learning disabled? (b) How should learning disabilities be assessed? (c) Who is qualified to make a decision about whether or not an individual has a learning disability? and (d) What accommodations should be provided by a postsecondary institution and how should they be selected? Although these are complicated and difficult questions, it is possible to develop a simple, reasonable classification system for learning disabilities, and to conduct assessments based on a coherent and relevant set of achievement tests in which individuals who score below a cutoff are considered learning disabled. Scores on IQ tests are irrelevant and not useful and may even be discriminatory. The issues of decision making regarding learning disabilities and appropriate accommodations remain significant dilemmas for the field; resolution of these issues seems virtually impossible without agreement on appropriate procedures for the definition, identification, and assessment of learning disabilities.

IQ is irrelevant to the definition of learning disabilities.

The purpose of this article was to examine the logic and the empirical data supporting the proposition that intelligence tests are not necessary for the definition of a learning disability. Four assumptions of the use of IQ test scores in the definition of learning disabilities were examined. These assumptions were (a) IQ tests measure intelligence; (b) intelligence and achievement are independent, and the presence of a learning disability will not affect IQ scores; (c) IQ scores predict reading, and children with low IQ scores should be poor readers; and (d) reading disabled children with different IQ scores have different cognitive processes and information skills. It was argued that IQ scores measure factual knowledge, expressive language abilities, and short-term memory, among other skills, and that because children with learning disabilities have deficits in these areas, their scores may be spuriously low. It was also shown that some children with low IQ scores can be good readers, indicating that low IQ scores do not necessarily result in poor reading. Empirical evidence was presented that poor readers at a variety of IQ levels show similar reading, spelling, language, and memory deficits. On logical and empirical grounds, IQ test scores are not necessary for the definition of learning disabilities.

Preference for visual scanning strategies versus phonological rehearsal in university students with reading disabilities.

This study investigated strategic preferences for visual scanning versus phonological rehearsal for recognizing words, pronounceable letter strings, and symbol strings by university students with reading disabilities (RD). Forty-seven subjects participated in this study: 20 students with reading disabilities who reported current difficulties in reading, as well as problems in learning to read at an early age; 15 students with learning disabilities (LD) who reported current difficulties in learning in areas other than reading but did not recall difficulties in learning to read; and 12 nondisabled readers (NR). The main dependent measures were response latency on a matching task for words, nonwords, and symbol strings, and posttest verbal reports of strategies used. Results showed that (a) most subjects in the NR group consistently used a strategy of phonological rehearsal for both words and nonwords, whereas most subjects with RD consistently used a strategy of visual scanning for these tasks, and (b) the NR group responded significantly faster than did the RD and LD groups to all three types of stimuli. The results indicate differences between university students who have a reading disability and nondisabled readers in strategic preferences for processing phonological information, with a clear preference by the former for using visual scanning rather than phonological rehearsal in matching tasks of words and nonwords.

Learning disabilities and adolescent suicide.

To investigate the hypothesis that learning disabilities (LD) play a part in adolescent suicide, all available suicide notes (n = 27) from 267 consecutive adolescent suicides were analyzed for spelling and handwriting errors. The suicide notes were dictated to adolescents with LD and adolescent non-LD controls. The results showed that 89% of the 27 adolescents who committed suicide had significant deficits in spelling and handwriting that were similar to those of the adolescents with LD, and they were significantly more impaired than the non-LD adolescents and older adults (65 and older) who had committed suicide in the same time period and in the same geographical area.

Subtypes of learning disabilities in adolescents and adults.

This study tested the hypothesis that a classification scheme developed for the subtyping of learning disabilities in children, when applied to a population of adolescents and adults, would result in subtyping into discrete and relatively homogeneous groups in terms of cognitive functioning and achievement. We compared three groups, arithmetic disability (AD), reading disability (RD), and reading and arithmetic disabilities (RAD), among themselves and with a comparison group with normal achievement (NA) on a variety of cognitive and achievement measures. The main findings were as follows: (a) Each of the groups differed significantly from the others on tests of reading, spelling, memory, and other cognitive measures; (b) both the RD and RAD groups showed a deficit in phonological processing, vocabulary, spelling, and STM; (c) the AD group performed similarly to the NA group on pseudoword reading and phonological processing, but did more poorly than the NA group on word reading and vocabulary; (d) on many tasks the RAD group performed more poorly than the other groups; and (e) the AD and RAD groups performed more poorly than the NA and RD groups on a visual-spatial task. This study demonstrated the validity of this classification scheme for the subtyping of learning disabilities in adolescents and adults.

Learning disability, inferential skills, and postfailure reflectivity.

Children with learning disabilities (LD) were compared with normally achieving children (NA) on two aspects of problem solving: inferential skills and response to errors in an academic content-free task. We tested 33 normally achieving children and 69 children with LD, aged 7 years 10 months to 16 years 4 months, on the PAR (PAttern Recognition) task, a computer-based, self-paced learning sequence. The children with LD were subtyped in two different ways: first, as children with only an arithmetic disability (AD), or with both arithmetic and word-recognition disabilities (AD/WRD); and second, as children with LD and attention deficit disorder (ADD), or LD without ADD. Results showed that on inferential skills, children with LD (without subtyping), children with AD/WRD, and children with LD with and without ADD scored significantly lower on the PAR task than children in the NA group. Also, an interaction was found between the NA and LD (without subtyping) groups and age, whereby children with LD improved their scores on PAR with age significantly more than normally achieving children. On attention to errors, children with both arithmetic and word-recognition disabilities scored significantly lower than children with only arithmetic disability or NA. It appears that the meta-cognitive skill of monitoring errors may be a major source of difficulty in problem solving for children with both arithmetic and word-recognition disabilities.