Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence

Objectives: To reanalyse SmithKline Beecham’s Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine. Design: Double blind randomised placebo controlled trial. Setting: 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. Participants: 275 adolescents with major depression of at least eight weeks in duration. Exclusion criteria included a range of comorbid psychiatric and medical disorders and suicidality. Interventions: Participants were randomised to eight weeks double blind treatment with paroxetine (20-40 mg), imipramine (200-300 mg), or placebo. Main outcome measures: The prespecified primary efficacy variables were change from baseline to the end of the eight week acute treatment phase in total Hamilton depression scale (HAM-D) score and the proportion of responders (HAM-D score ≤8 or ≥50% reduction in baseline HAM-D) at acute endpoint. Prespecified secondary outcomes were changes from baseline to endpoint in depression items in K-SADS-L, clinical global impression, autonomous functioning checklist, self-perception profile, and sickness impact scale; predictors of response; and number of patients who relapse during the maintenance phase. Adverse experiences were to be compared primarily by using descriptive statistics. No coding dictionary was prespecified. Results: The efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20). There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group. Conclusions: Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.Joanna Le Noury, John M Nardo, David Healy, Jon Jureidini, Melissa Raven, Catalin Tufanaru, Elia Abi-Jaoud

Emotional health in adolescents with and without a history of specific language impairment (SLI)

Objective:  This study examined the emotional health of adolescents with and without specific language impairment (SLI). Method:  One hundred and thirty-nine adolescents with a history of SLI (15;10 years) and a peer group of 124 adolescents with normal language development (NLD) (15;11 years) participated, who were in their final year of compulsory schooling. The risk of emotional difficulties was assessed using the Moods and Feelings Questionnaire (MFQ) and the Child Manifest Anxiety Scale-R (CMAS-R). Comprehensive language and cognition data were available for all participants (NLD and SLI) concurrently and also longitudinally for those with SLI. Results:  A clear increased risk of emotional health symptoms was found for the SLI group on both self- and parental-report. Girls scored less favourably than boys when groups were combined, but these were due to the effect of the NLD group, with no gender differences found in the SLI group. Direct links with language and cognition were not obvious. Instead, more diffuse factors such as family history of emotional health difficulties may warrant further investigation. Conclusion:  There is a marked higher rate of anxiety and depression symptoms in adolescents with SLI. However, these do not appear to be a direct result of impoverished communicative experiences

Operationalising and measuring language dominance

The paper offers a new way to measure language ability in bilinguals, based on measures of lexical richness. The validity of proposed approach is tested in a variety of ways

The association between school performance at 14 years and young adults' use of cannabis: An Australian birth cohort study

This study examines, firstly, the association between school performance at 14 years and frequency of use of cannabis in early adulthood and, secondly, whether this association is explained by family and individual characteristics, including child cognitive capacity in childhood and adolescence. Data are from a cohort of 3,478 Australian young adults who were followed up from birth to age 21 years. Data on child school performance and use of cannabis were collected at the 14- and 21-year follow-ups, respectively. Child school performance was assessed at 14 years via self- and maternal-report. Potential confounding factors were measured between the child's birth and age 14 years. School performance at 14 years predicts young adults' use of cannabis. Children who had lower school performance had increased risk of frequent use of cannabis in young adulthood. Exploration of the pathway linking school performance and cannabis use in young people may help identify opportunities for preventive interventions

Orthographic depth and its impact on Universal Predictors of Reading: a cross-language investigation

Alphabetic orthographies differ in the transparency of their letter-sound mappings, with English orthography being less transparent than other alphabetic scripts. The outlier status of English has led scientists to question the generality of findings based on English-language studies. We investigated the role of phonological awareness, memory, vocabulary, rapid naming, and nonverbal intelligence in reading performance across five languages lying at differing positions along a transparency continuum (Finnish, Hungarian, Dutch, Portuguese, and French). Results from a sample of 1,265 children in Grade 2 showed that phonological awareness was the main factor associated with reading performance in each language. However, its impact was modulated by the transparency of the orthography, being stronger in less transparent orthographies. The influence of rapid naming was rather weak and limited to reading and decoding speed. Most predictors of reading performance were relatively universal across these alphabetic languages, although their precise weight varied systematically as a function of script transparenc

Residual cognitive deficits 50 years after lead poisoning during childhood

The long term neurobehavioural consequences of childhood lead poisoning are not known. In this study adult subjects with a documented history of lead poisoning before age 4 and matched controls were examined with an abbreviated battery of neuropsychological tests including measures of attention, reasoning, memory, motor speed, and current mood. The subjects exposed to lead were inferior to controls on almost all of the cognitive tasks. This pattern of widespread deficits resembles that found in children evaluated at the time of acute exposure to lead rather than the more circumscribed pattern typically seen in adults exposed to lead. Despite having completed as many years of schooling as controls, the subjects exposed to lead were lower in lifetime occupational status. Within the exposed group, performance on the neuropsychological battery and occupational status were related, consistent with the presumed impact of limitations in neuropsychological functioning on everyday life. The results suggest that many subjects exposed to lead suffered acute encephalopathy in childhood which resolved into a chronic subclinical encephalopathy with associated cognitive dysfunction still evident in adulthood. These findings lend support to efforts to limit exposure to lead in childhood

The Simple View of Reading Made Complex by Morphological Decoding Fluency in Bilingual Fourth-Grade Readers of English

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordThis study examined the complexity of the Simple View of Reading focusing on morphological decoding fluency in fourth-grade readers of English in Singapore. The participants were three groups of students who all learned to become bilingual and biliterate in the English language (EL) and their respective ethnic language in school but differed in the home language they used. The first group was ethnic Chinese students who used English as the dominant home language (Chinese EL1); the other two groups were ethnic Chinese and Malay students whose dominant home language was not English but Chinese (Chinese EL2) and Malay (Malay EL2), respectively. The measures included pseudo word decoding (phonemic decoding), timed decoding of derivational words (morphological decoding fluency), oral vocabulary, and passage comprehension. Path analysis showed that oral vocabulary significantly predicted reading comprehension across all three groups; yet a significant effect of morphological decoding fluency surfaced in the Chinese EL1 and Malay EL2 groups but not the Chinese EL2 group. Multi-group path analysis and commonality analysis further confirmed that morphological decoding played a larger role in the in the Chinese EL1 and Malay EL2 groups. These findings are discussed in light of the joint influence of target language experience and cross-linguistic influence on second language or bilingual reading development.Office of Education Research, National Institute of Education, Nanyang Technological Universit

Exploring the Underdiagnosis and Prevalence of Autism Spectrum Conditions in Beijing

Previous studies reported that the prevalence of Autism Spectrum Conditions (ASC) in mainland China is much lower than estimates from developed countries (around 1%). The aim of the study is to apply current screening and standardized diagnostic instruments to a Chinese population to establish a prevalence estimate of ASC in an undiag-nosed population in mainland China. We followed the design development used previously in the UK published in 2009 by Baron-Cohen and colleagues. The Mandarin Childhood Autism Spectrum Test (CAST) was validated by screening primary school pupils (n = 737 children age 6–10 years old) in Beijing and by conducting diagnostic assessments using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. The prevalence estimate was generated after adjusting and imputing for missing values using the inverse probability weighting. Response was high (97%). Using the UK cutoff (≥15), CAST performance has 84 % sensitivity and 96 % specificity (95 % confidence interval [CI]: 46, 98, and 96, 97, respectively). Six out of 103 children, not previously diagnosed, were found to the meet diagnostic criteria (8.5 after adjustment, 95 % CI: 1.6, 15.4). The preliminary prevalence in an undiagnosed primary school population in mainland China was 119 per 10,000 (95 % CI: 53, 265). The utility of CAST is acceptable as a screening instrument for ASC in large epidemiological studies in China. Using a comparable method, the preliminary prevalence estimate of ASC in mainland China is similar to that of those from developed countries. Autism Res 2015

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter