Comparing behavioural outcomes in children born extremely preterm between 2006 and 1995: the EPICure studies.

BACKGROUND: Children born extremely preterm (EP) are at increased risk of neurocognitive and behavioural morbidity. Here, we investigate whether behavioural outcomes have changed over time concomitant with increasing survival following EP birth. METHODS: Comparison of outcomes at 11 years of age for two prospective national cohorts of children born EP in 1995 (EPICure) and 2006 (EPICure2), assessed alongside term-born children. Behavioural outcomes were assessed using the parent-completed Strengths and Difficulties Questionnaire (SDQ), DuPaul Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), and Social Communication Questionnaire (SCQ). RESULTS: In EPICure, 176 EP and 153 term-born children were assessed (mean age: 10.9 years); in EPICure2, 112 EP and 143 term-born children were assessed (mean age: 11.8 years). In both cohorts, EP children had higher mean scores and more clinically significant difficulties than term-born children on almost all measures. Comparing outcomes for EP children in the two cohorts, there were no significant differences in mean scores or in the proportion of children with clinically significant difficulties after adjustment for confounders. Using term-born children as reference, EP children in EPICure2 had significantly higher SDQ total difficulties and ADHD-RS hyperactivity impulsivity z-scores than EP children in EPICure. CONCLUSIONS: Behavioural outcomes have not improved for EP children born in 2006 compared with those born in 1995. Relative to term-born peers, EP children born in 2006 had worse outcomes than those born in 1995. There is an ongoing need for long-term clinical follow-up and psychological support for children born EP.

Practitioner Review: Pathways to care for ADHD - a systematic review of barriers and facilitators.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder starting in childhood that may persist into adulthood. It can be managed through carefully monitored medication and nonpharmacological interventions. Access to care for children at risk of ADHD varies both within and between countries. A systematic literature review was conducted to investigate the research evidence related to factors which influence children accessing services for ADHD. METHOD: Studies investigating access to care for children at risk of ADHD were identified through electronic searches of the international peer-reviewed and grey literature. Databases were searched from inception till 30th April 2012. This identified 23,156 articles which were subjected to three levels of screening (title, abstract and full text) by a minimum of two independent reviewers. Due to the heterogeneity in the study designs, a narrative approach was used to present the findings. RESULTS: Twenty-seven papers met the inclusion criteria; these were grouped into four main themes, with some papers being included in more than one. These were wider determinants (10 papers); identification of need (9 papers); entry and continuity of care (13 papers) and interventions to improve access (4 papers). Barriers and facilitators to access were found to operate at the individual, organisational and societal level. Limited evidence of effective interventions to improve access was identified. CONCLUSION: This review explored the multilayered obstacles in the pathway to care for children at risk of ADHD and the lack of evidence-based interventions designed to address these issues, thereby indicating areas for service development and further evaluative research.

A comparison of visual attention to pictures in the Autism Diagnostic Observation Schedule in children and adolescents with ADHD and/or autism.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are neurodevelopmental conditions which frequently co-occur. The Autism Diagnostic Observation Schedule (ADOS) is commonly used to aid with diagnostic assessment of ASD but was not originally designed for use in those with comorbid ADHD. Visual attention to social stimuli has been often studied in ASD using eye-tracking, to obtain quantitative indices of how attention is deployed to different parts of a social image/scene. As the ADOS includes tasks that rely on attending to and processing images of social scenes, these measures of visual attention could provide useful additional objective measurement alongside ADOS scores to enhance the characterisation of autistic symptoms in those with ADHD. Methods: Children with ASD, comorbid ASD and ADHD, ADHD and Neurotypical (NT) controls were recruited (n=84). Visual attention was measured using eye-tracking during free viewing of social scenes selected from the ADOS. The full ADOS was then administered. Stimulant medication was temporarily withdrawn during this assessment. Research diagnoses were based on the Development and Wellbeing Assessment (DAWBA), ADOS, Social Communication Questionnaire (SCQ, a measure of ASD severity) and Conners' Rating Scales (CRS-3, a measure of ADHD severity) following clinical consensus. Results: Using factorial ANOVAs to model ADHD, Autism and their interaction, we found that fixation duration to faces was reduced in those with ASD (ASD and ASD+ADHD) compared to those without ASD (ADHD and NT). Reduced visual attention to faces in the whole sample was associated with Autism symptom severity (SCQ subscale scores) but not ADHD symptom severity (CRS-3 scores). Discussion: Our findings provide preliminary evidence in support of implementing visual attention measurement during assessment of ASD in the context of comorbidity with ADHD. For example, if a child with ADHD was found to reduce attention to faces in ADOS pictures this may suggest additive difficulties on the autism spectrum. Replication across a larger sample would be informative. This work has future potential in the clinic to help with complex cases, including those with co-occurring ADHD and ASD.

Relationship between autonomic arousal and attention orienting in children and adolescents with ADHD, autism and co-occurring ADHD and autism.

INTRODUCTION: Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) may be characterized by different profiles of visual attention orienting. However, there are also many inconsistent findings emerging from the literature, probably due to the fact that the potential effect of autonomic arousal (which has been proposed to be dysregulated in these conditions) on oculomotor performance has not been investigated before. Moreover, it is not known how visual attention orienting is affected by the co-occurrence of ADHD and autism in people with a double diagnosis. METHODS: 99 children/adolescents with or without ADHD and/or autism (age 10.79 ± 2.05 years, 65% boys) completed an adapted version of the gap-overlap task (with baseline and overlap trials only). The social salience and modality of stimuli were manipulated between trials. Eye movements and pupil size were recorded. We compared saccadic reaction times (SRTs) between diagnostic groups and investigated if a trial-by-trial association existed between pre-saccadic pupil size and SRTs. RESULTS: Faster orienting (shorter SRT) was found for baseline compared to overlap trials, faces compared to non-face stimuli and-more evidently in children without ADHD and/or autism-for multi-modal compared to uni-modal stimuli. We also found a linear negative association between pre-saccadic pupil size and SRTs, in autistic participants (without ADHD), and a quadratic association in children with ADHD (without autism), for which SRTs were slower when intra-individual pre-saccadic pupil size was smallest or largest. CONCLUSION: Our findings are in line with previous literature and indicate a possible effect of dysregulated autonomic arousal on oculomotor mechanisms in autism and ADHD, which should be further investigated in future research studies with larger samples, to reliably investigate possible differences between children with single and dual diagnoses.

Indices of Heart Rate Variability and Performance During a Response-Conflict Task Are Differently Associated With ADHD and Autism.

We investigated autonomic arousal, attention and response conflict, in ADHD and autism. Heart rate variability (HRV), and behavioral/electrophysiological indices of performance, were recorded during a task with low and high levels of response conflict in 78 children/adolescents (7-15 years old) with ADHD, autism, comorbid ADHD+autism, or neurotypical. ANOVA models were used to investigate effects of ADHD and autism, while a mediation model was tested to clarify the relationship between ADHD and slower performance. Slower and less accurate performance characterized ADHD and autism; however, atypical electrophysiological indices differently characterized these conditions. The relationship between ADHD and slower task performance was mediated by reduced HRV in response to the cue stimulus. Autonomic hypo-arousal and difficulties in mobilizing energetic resources in response to sensory information (associated with ADHD), and atypical electrophysiological indices of information processing (associated with autism), might negatively affect cognitive performance in those with ADHD+autism.

What is the Effect of Stimulus Complexity on Attention to Repeating and Changing Information in Autism?

Slower habituation to repeating stimuli characterises Autism, but it is not known whether this is driven by difficulties with information processing or an attentional bias towards sameness. We conducted eye-tracking and presented looming geometrical shapes, clocks with moving arms and smiling faces, as two separate streams of stimuli (one repeating and one changing), to 7-15 years old children and adolescents (n = 103) with Autism, ADHD or co-occurring Autism+ADHD, and neurotypical children (Study-1); and to neurotypical children (n = 64) with varying levels of autistic traits (Study-2). Across both studies, autistic features were associated with longer looks to the repeating stimulus, and shorter looks to the changing stimulus, but only for more complex stimuli, indicating greater difficulty in processing complex or unpredictable information.

Heart Rate Variability in Children and Adolescents with Autism, ADHD and Co-occurring Autism and ADHD, During Passive and Active Experimental Conditions.

Despite overlaps in clinical symptomatology, autism and ADHD may be associated with opposite autonomic arousal profiles which might partly explain altered cognitive and global functioning. We investigated autonomic arousal in 106 children/adolescents with autism, ADHD, co-occurring autism/ADHD, and neurotypical controls. Heart rate variability was recorded during resting-state, a 'passive' auditory oddball task and an 'active' response conflict task. Autistic children showed hyper-arousal during the active task, while those with ADHD showed hypo-arousal during resting-state and the passive task. Irrespective of diagnosis, children characterised by hyper-arousal showed more severe autistic symptomatology, increased anxiety and reduced global functioning than those displaying hypo-arousal, suggesting the importance of considering individual autonomic arousal profiles for differential diagnosis of autism/ADHD and when developing personalised interventions.

Autism spectrum disorders in extremely preterm children.

OBJECTIVES: To investigate the prevalence, correlates, and antecedents of autism spectrum disorders (ASD) in extremely preterm children. STUDY DESIGN: We conducted a prospective study of all births <26 weeks gestation in the United Kingdom and Ireland in 1995. Of 307 survivors at 11 years, 219 (71%) were assessed and compared with 153 term-born classmates. Parents completed the Social Communication Questionnaire (SCQ) to assess autism spectrum symptoms, and ASD were diagnosed by using a psychiatric evaluation. An IQ test and clinical evaluation were also administered. Longitudinal outcome data were available for extremely preterm children. RESULTS: Extremely preterm children had significantly higher SCQ scores than classmates (mean difference, 4.6 points; 95% CI, 3.4-5.8). Sixteen extremely preterm children (8%) were assigned an ASD diagnosis, compared with none of the classmates. By hospital discharge, male sex, lower gestation, vaginal breech delivery, abnormal cerebral ultrasound scanning results, and not having had breast milk were independently associated with autism spectrum symptoms. By 6 years, independent associates were cognitive impairment, inattention and peer problems, withdrawn behavior at 2.5 years, and not having had breast milk. CONCLUSIONS: Extremely preterm children are at increased risk for autism spectrum symptoms and ASD in middle childhood. These symptoms and disorders were associated with neurocognitive outcomes, suggesting that ASD may result from abnormal brain development in this population.

Economic costs and preference-based health-related quality of life outcomes associated with childhood psychiatric disorders.

BACKGROUND: Childhood psychiatric disorders may have deleterious consequences through childhood and into adulthood. AIMS: To estimate costs and preference-based health-related quality of life outcomes (health utilities) associated with a broad range of childhood psychiatric disorders during the eleventh year of life. METHOD: Participants in a whole-population study of extremely preterm children and term-born controls (EPICure) undertook psychiatric assessment using the Development and Well Being Assessment (DAWBA) and the Kaufman-Assessment Battery for Children. Questionnaires completed by parents and teachers described the children's utilisation of health, social and education services during the eleventh year of life. Parents also described their child's health status using the Health Utilities Index Mark 2 and Mark 3 health status classification systems. Descriptive and multiple regression techniques were used to explore the association between psychiatric disorders and economic outcomes. RESULTS: The study presents detailed costs and health utilities associated with psychiatric disorders for the preterm population, term-born population and pooled study population, following appropriate controls. CONCLUSIONS: The results of this study should be used to inform future economic evaluations of interventions aimed at preventing childhood psychiatric disorders or alleviating their effects. Further research is required that identifies, measures and values the longer-term economic impacts of these disorders in a valid and reliable manner.

Atypical Electrophysiological Indices of Eyes-Open and Eyes-Closed Resting-State in Children and Adolescents with ADHD and Autism.

Investigating electrophysiological measures during resting-state might be useful to investigate brain functioning and responsivity in individuals under diagnostic assessment for attention deficit hyperactivity disorder (ADHD) and autism. EEG was recorded in 43 children with or without ADHD and autism, during a 4-min-long resting-state session which included an eyes-closed and an eyes-open condition. We calculated and analyzed occipital absolute and relative spectral power in the alpha frequency band (8-12 Hz), and alpha reactivity, conceptualized as the difference in alpha power between eyes-closed and eyes-open conditions. Alpha power was increased during eyes-closed compared to eyes-open resting-state. While absolute alpha power was reduced in children with autism, relative alpha power was reduced in children with ADHD, especially during the eyes-closed condition. Reduced relative alpha reactivity was mainly associated with lower IQ and not with ADHD or autism. Atypical brain functioning during resting-state seems differently associated with ADHD and autism, however further studies replicating these results are needed; we therefore suggest involving research groups worldwide by creating a shared and publicly available repository of resting-state EEG data collected in people with different psychological, psychiatric, or neurodevelopmental conditions, including ADHD and autism.

Neurological and psychiatric adverse effects of long-term methylphenidate treatment in ADHD: A map of the current evidence.

Methylphenidate (MPH), the most common medication for children with Attention Deficit/Hyperactivity Disorder (ADHD) in many countries, is often prescribed for long periods of time. Any long-term psychotropic treatment in childhood raises concerns about possible adverse neurological and psychiatric outcomes. We aimed to map current evidence regarding neurological and psychiatric outcomes, adverse or beneficial, of long-term MPH (> 1 year) treatment in ADHD. We coded studies using a "traffic light" system: Green: safe/favours MPH; Amber: warrants caution; Red: not safe/not well-tolerated. Un-categorisable study findings were coded as "Unclear". Although some evidence suggests an elevated risk of psychosis and tics, case reports describe remission on discontinuation. Several studies suggest that long-term MPH may reduce depression and suicide in ADHD. Evidence suggests caution in specific groups including pre-school children, those with tics, and adolescents at risk for substance misuse. We identified a need for more studies that make use of large longitudinal databases, focus on specific neuropsychiatric outcomes, and compare outcomes from long-term MPH treatment with outcomes following shorter or no pharmacological intervention.

Cost-effectiveness study comparing cefoperazone-sulbactam to a three-drug combination for treating intraabdominal infections in an Indian health-care setting.

OBJECTIVE: This article presents the methodology and results of the pharmacoeconomic analysis of the Magnex Against Standard COmbination Therapy study comparing cefoperazone-sulbactam (Magnex) versus ceftazidime+ amikacin+metronidazole, in the treatment of intra-abdominal infections. METHODS: This prospective, open label, phase IV study was conducted at 17 study sites in India and randomized subjects to receive either cefoperazone-sulbactam or the combination. Pharmacoeconomic analysis was included as a secondary objective and conducted in the clinical efficacy-evaluable (CEE) and the successfully treated patients. All comparisons between treatment groups were conducted using analysis of variance (ANOVA) or Wilcoxon Two-Sample tests. All costs were reported as Indian Rupee (INR) and actual unit costs collected in 2006 were used for the analyses [1 USD approximately 40 INR; 1 Euro approximately 56 INR]. RESULTS: In the CEE and the successfully treated subset of patients, the average cost of treatment was numerically lower in the cefoperazone-sulbactam arm (not statistically significant). The analyses found that the cost-effectiveness ratio (CER) for cefoperazone-sulbactam was INR 17,640.53 and that for the comparator group was INR 22,075.16. Additionally, the incremental CER results showed that the cost of treatment was INR 21,505.59 lower per additional successfully treated patient in the cefoperazone-sulbactam group. CONCLUSIONS: The present study was the first of its kind to be conducted in the "price sensitive" Indian health-care setting. Though study was not powered for the difference in average cost of treatments, there was a trend favoring cefoperazone sulbactam. The findings from this study should encourage further conduct of similar analyses and increase the knowledge regarding pharmacoeconomics in India.

Cefoperazone-sulbactam for treatment of intra-abdominal infections: results from a randomized, parallel group study in India.

BACKGROUND: Combinations of a third-generation cephalosporin and metronidazole, with or without an aminoglycoside, often are used for the treatment of intra-abdominal infections in surgical settings. Simpler regimens that preserve an adequate spectrum of coverage, but allow easier administration and have fewer side effects, may be a more desirable option. METHODS: This randomized, open-label, active comparator study evaluated the effectiveness (non-inferiority hypothesis) of the beta-lactam/beta-lactamase inhibitor combination cefoperazone-sulbactam (2-8 g/day), compared with ceftazidime (2-6 g/day)-amikacin (15 mg/kg/day)-metronidazole (500 mg three times daily) in 154 and 152 subjects, respectively, having intra-abdominal infections. The study was conducted at 17 centers in India. RESULTS: Non-inferiority of cefoperazone-sulbactam (91.9%) compared with ceftazidime-amikacin-metronidazole (81.8%) was demonstrated for continued resolution of clinical signs and symptoms at the 30-day follow-up (primary endpoint) with a treatment difference of 10.1% (95% confidence interval 2.1%, 18.1%; pre-defined non-inferiority limit > -12.5%). Superiority of cefoperazone-sulbactam also was demonstrated for this endpoint, with significantly more subjects achieving continued resolution at the 30-day follow-up than in the comparator group (p = 0.015). On microbiologic outcomes, cefoperazone-sulbactam had higher success rates than ceftazidime-amikacin-metronidazole (92.9% vs. 80.0%). The pathogens (202 isolated) isolated most commonly were Escherichia coli (38.6%) and Klebsiella spp. (12.9%). The incidence of treatment-related adverse events was 6.5% and 16.4% in the cefoperazone-sulbactam and ceftazidime-amikacin-metronidazole groups, respectively, with more discontinuations due to treatment-related adverse events in the comparator arm (3.2% vs. 9.9%). CONCLUSION: Empirical cefoperazone-sulbactam monotherapy could be a useful adjunct to surgical intervention for intra-abdominal infections.

Prospective randomized study of sexual function in men taking dutasteride for the treatment of androgenetic alopecia.

Treatment with 5α-reductase inhibitors has been associated with sexual adverse events such as impotence (erectile dysfunction) and decreased libido. The primary objective of this study was to evaluate adverse events related to sexual function, based on their frequency, duration, persistence and associated treatment discontinuations, in men treated with dutasteride for androgenetic alopecia. Participants were randomized to receive double-blind dutasteride 0.5 mg or placebo once daily for 24 weeks, followed by open-label dutasteride 0.5 mg for an additional 24 weeks. Sexual adverse events were followed up until resolution or for up to 24 weeks after the last dose. Overall, 117 men, 23-50 years of age, were randomized. The incidence of sexual adverse events was approximately twofold higher in the dutasteride group (16%) than the placebo group (8%) during the double-blind period; the overall incidence of sexual adverse events was lower (5%) during the open-label period. All adverse events were mild to moderate in severity and considered treatment-related. The adverse events resolved while on study treatment or after the end of treatment and did not lead to treatment discontinuation. A limitation of this study was the small sample size. The sexual adverse events of impotence, decreased libido and ejaculation disorders reported in this study were expected and reversible.

Atypical Processing of Gaze Cues and Faces Explains Comorbidity between Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD).

This study investigated the neurobiological basis of comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). We compared children with ASD, ADHD or ADHD+ASD and typically developing controls (CTRL) on behavioural and electrophysiological correlates of gaze cue and face processing. We measured effects of ASD, ADHD and their interaction on the EDAN, an ERP marker of orienting visual attention towards a spatially cued location and the N170, a right-hemisphere lateralised ERP linked to face processing. We identified atypical gaze cue and face processing in children with ASD and ADHD+ASD compared with the ADHD and CTRL groups. The findings indicate a neurobiological basis for the presence of comorbid ASD symptoms in ADHD. Further research using larger samples is needed.

Antecedents of Attention-Deficit/Hyperactivity Disorder Symptoms in Children Born Extremely Preterm.

OBJECTIVE: To investigate antecedents of attention-deficit/hyperactivity disorder (ADHD) symptoms in children born extremely preterm (EP; <26-wk gestation). METHOD: The EPICure study recruited all babies born EP in the United Kingdom and Ireland in March-December 1995. Neurodevelopmental outcomes were assessed at 2.5 (n = 283; 90%), 6 (n = 160; 78%), and 11 (n = 219; 71%) years of age. Parents and teachers completed the DuPaul Rating Scale IV to assess inattention and hyperactivity/impulsivity symptoms at 11 years. Regression analyses were used to explore the association of neonatal, neurodevelopmental, and behavioral outcomes to 6 years with ADHD symptoms at 11 years. RESULTS: Extremely preterm (EP) children had significantly more inattention (mean difference, 1.2 SD; 95% CI, 0.9-1.5) and hyperactivity/impulsivity (mean difference, 0.5 SD; 95% CI, 0.2-0.7) than controls, with a significantly greater effect size for inattention than hyperactivity/impulsivity. Significant independent predictors of inattention at 11 years included smaller head circumference, lower intelligence quotient (IQ), and pervasive peer relationship problems at 6 years, and motor development at 2.5 years. In contrast, significant independent predictors of hyperactivity/impulsivity included lower IQ, pervasive conduct problems and ADHD symptoms at 6 years, externalizing problems at 2.5 years, and non-white maternal ethnicity. CONCLUSIONS: Extremely preterm children are at increased risk for ADHD symptoms, predominantly inattention, for which the antecedents differ by symptom domain. Attention deficits after EP birth were associated with poor brain growth and neurological function. Cognitive and behavioral assessments in early and middle childhood to identify neurodevelopmental and peer relationship problems may be beneficial for identifying EP children at risk for inattention.

Amoxicillin/Clavulanic Acid for the Treatment of Odontogenic Infections: A Randomised Study Comparing Efficacy and Tolerability versus Clindamycin.

Background. Treatment of odontogenic infections includes surgical drainage and adjunctive antibiotics. This study was designed to generate efficacy and safety data to support twice daily dosing of amoxicillin/clavulanic acid compared to clindamycin in odontogenic infections. Methods. This was a phase IV, randomised, observer blind study; 472 subjects were randomised to receive amoxicillin/clavulanic acid (875 mg/125 mg BID, n = 235) or clindamycin (150 mg QID, n = 237) for 5 or 7 days based on clinical response. The primary endpoint was percentage of subjects achieving clinical success (composite measure of pain, swelling, fever, and additional antimicrobial therapy required) at the end of treatment. Results. The upper limit of two-sided 95% confidence interval for the treatment difference between the study arms (7.7%) was within protocol specified noninferiority margin of 10%, thus demonstrating noninferiority of amoxicillin/clavulanic acid to clindamycin. Secondary efficacy results showed a higher clinical success rate at Day 5 in the amoxicillin/clavulanic acid arm. Most adverse events (raised liver enzymes, diarrhoea, and headache) were similar across both arms and were of mild to moderate intensity. Conclusion. Amoxicillin/clavulanic acid was comparable to clindamycin in achieving clinical success (88.2% versus 89.7%) in acute odontogenic infections and the safety profile was consistent with the known side effects of both drugs. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT02141217.

Azithromycin in acute bacterial upper respiratory tract infections: an Indian non-interventional study.

To assess the effectiveness, safety and tolerability of azithromycin in acute bacterial upper respiratory tract infections (URTIs). In this open-label, prospective, multi-center, non-interventional study in bacterial URTI, the decision to prescribe azithromycin was independent of enrolment. Follow up was 1 week after treatment and if possible, at Week 2. Investigators' assessment of clinical outcome (Success/Failure) at the end of study was the primary endpoint for efficacy analysis. Clinical outcome of 'Success' was defined as the global response of Cure or Improvement. A pharmacoeconomic analysis of management of URTIs was also attempted. Of the 410 patients recruited, all were evaluated for safety and 278 for efficacy. The median treatment duration was 3 days. Following treatment with azithromycin, overall success rate was 98.92% (95% CI 96.88-99.78%; Clopper-Pearson method). The success rate was similar across the sub-groups of acute otitis media-100%, bacterial sinusitis-95.83%, and pharyngotonsillitis-99.38%. The success rate was 100% among children and adolescents (age ≤18 years) and 98.6% among adults (age >18 years). Most of the common signs and symptoms of URTI reported during baseline, significantly improved at the end of the study. Sixteen (3.90%) patients reported treatment emergent adverse events, the most common being diarrhea-5 (1.2%) and flatulence-2 (0.5%). The average cost of treating bacterial URTI was INR 716 per patient. Azithromycin is effective and well tolerated in Indian patients with bacterial URTIs.

Screening for autism in preterm children: diagnostic utility of the Social Communication Questionnaire.

OBJECTIVE: Preterm survivors are at high risk for autism spectrum disorders (ASD). The diagnostic utility of the Social Communication Questionnaire (SCQ) in screening for ASD was assessed in extremely preterm children at 11 years of age. DESIGN: All babies born at <26 weeks gestation in UK and Ireland from March through December 1995 were recruited to the EPICure Study. Of 307 survivors, 219 (71%) were assessed at 11 years. Parents of 173 children completed the SCQ to screen for autistic features and the Development and Well Being Assessment (DAWBA) psychiatric interview. A consensus diagnosis of ASD was assigned by two child psychiatrists following review of the DAWBA parental interview and corresponding DAWBA teacher questionnaire. SETTING: Community-based follow-up. RESULTS: Using the established SCQ cut-off (scores ≥15), 28 (16%) extremely preterm children screened positive for ASD. Eleven (6%) were assigned a diagnosis of ASD. Using this cut-off, the SCQ had 82% sensitivity and 88% specificity for identifying ASD in this population. Using a receiver operating characteristic curve, SCQ scores ≥14 had optimal diagnostic utility (area under curve: 0.94; sensitivity: 91%; specificity: 86%). Positive predictive value was relatively low (31%) resulting in numerous over-referrals. However, children with false positive screens had significantly worse neuro-developmental, cognitive and behavioural outcomes than those with true negative screens. CONCLUSION: The SCQ has good diagnostic utility for identifying ASD in extremely preterm children and is a useful screening tool in this population. Children with false positive screens represent a high-risk group in whom further diagnostic assessment would be beneficial.

Survey on perceptions of Indian investigators on research ethics.

INTRODUCTION: The last decade has witnessed globalization of drug development with early phase studies being increasingly placed in the developing world. Whether research related ethical principles around informed consent, adverse event (AE) reporting, post trial drug commitments and others are being observed, merits evaluation METHODS: A specially designed survey questionnaire was served to 29 investigators in India, having prior experience of participating in drug development studies with pharmaceutical companies. The survey included questions on investigator profile, study design, informed consent process, safety reporting, patient and physician compensation, post trial drug commitments among others RESULTS: Most respondents had nearly two decades of clinical experience. Majority believed that the research they conducted was relevant to the needs of society, but wanted common research goals established between the sponsors and the community. All investigators cited their expertise, reliability, patient pool, and low costs as the principal reasons for greater placement of studies. However, very few investigators felt that all their patients in studies were "truly autonomous". Most investigators indicated confidence in the adverse event reporting ability and expressed satisfaction with their Ethics Committees. A third of investigators accepted some form of conflict of interest between their role as a physician and researcher. Opinion was divided regarding satisfaction with the post trial drug commitments of the sponsor companies CONCLUSION: The survey revealed a good understanding of the ethical issues around conduct of clinical research in a developing country. The sooner ethical institutions and practices are fortified, the better it is for communities, patients, investigators and pharmaceutical sponsors.