RESEARCH Open Access

Involving consumers and the community in the development of a diagnostic instrument for fetal alcohol spectrum disorders in Australi

A modified Delphi study of screening for fetal alcohol spectrum disorders in Australia

Background: There is little reliable information on the prevalence of fetal alcohol spectrum disorders (FASD) in Australia and no coordinated national approach to facilitate case detection. The aim of this study was to identify health professionals’ perceptions about screening for FASD in Australia. Method: A modified Delphi process was used to assess perceptions of the need for, and the process of, screening for FASD in Australia. We recruited a panel of 130 Australian health professionals with experience or expertise in FASD screening or diagnosis. A systematic review of the literature was used to develop Likert statements on screening coverage, components and assessment methods which were administered using an online survey over two survey rounds. Results: Of the panel members surveyed, 95 (73%) responded to the questions on screening in the first survey round and, of these, 81 (85%) responded to the second round. Following two rounds there was consensus agreement on the need for targeted screening at birth (76%) and in childhood (84%). Participants did not reach consensus agreement on the need for universal screening at birth (55%) or in childhood (40%). Support for targeted screening was linked to perceived constraints on service provision and the need to examine the performance, costs and benefits of screening. For targeted screening of high risk groups, we found highest agreement for siblings of known cases of FASD (96%) and children of mothers attending alcohol treatment services (93%). Participants agreed that screening for FASD primarily requires assessment of prenatal alcohol exposure at birth (86%) and in childhood (88%), and that a checklist is needed to identify the components of screening and criteria for referral at birth (84%) and in childhood (90%). Conclusions: There is an agreed need for targeted but not universal screening for FASD in Australia, and sufficient consensus among health professionals to warrant development and evaluation of standardised methods for targeted screening and referral in the Australian context. Participants emphasised the need for locally-appropriate, evidence-based approaches to facilitate case detection, and the importance of ensuring that screening and referral programs are supported by adequate diagnostic and management capacity

Fetal alcohol spectrum disorder: development of concensus referral criteria for specialist diagnostic assessment in Australia

Background: Fetal alcohol spectrum disorder (FASD) is known to be under-recognised in Australia. The use of standard methods to identify when to refer individuals who may have FASD for specialist assessment could help improve the identification of this disorder. The purpose of this study was to develop referral criteria for use in Australia. Method: An online survey about FASD screening and diagnosis in Australia, which included 23 statements describing criteria for referral for fetal alcohol syndrome (FAS) and FASD based on published recommendations for referral in North America, was sent to 139 health professionals who had expertise or involvement in FASD screening or diagnosis. Survey findings and published criteria for referral were subsequently reviewed by a panel of 14 investigators at a consensus development workshop where criteria for referral were developed.Results: Among the 139 health professionals who were sent the survey, 103 (74%) responded, and 90 (65%) responded to the statements on criteria for referral. Over 80% of respondents agreed that referral for specialist evaluation should occur when there is evidence of significant prenatal alcohol exposure, defined as 7 or more standard drinks per week and at least 3 standard drinks on any one day, and more than 70% agreed with 13 of the16 statements that described criteria for referral other than prenatal alcohol exposure. Workshop participants recommended five independent criteria for referral: confirmed significant prenatal alcohol exposure; microcephaly and confirmed prenatal alcohol exposure; 2 or more significant central nervous system (CNS) abnormalities and confirmed prenatal alcohol exposure; 3 characteristic FAS facial anomalies; and 1 characteristic FAS facial anomaly, growth deficit and 1 or more CNS abnormalities .Conclusion: Referral criteria recommended for use in Australia are similar to those recommended in North America. There is a need to develop resources to raise awareness of these criteria among health professionals and evaluate their feasibility, acceptability and capacity to improve the identification of FASD in Australia

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Cefdinir for Recent-Onset Pediatric Neuropsychiatric Disorders: A Pilot Randomized Trial

Objective: Previous studies suggest that the unexplained sudden and severe onset of obsessive-compulsive disorder (OCD) and/or tics may be infection or immune precipitated. Beta lactam antibiotics may be neuroprotective beyond their antimicrobial efficacy. We examine the preliminary safety and efficacy of cefdinir in reducing obsessive-compulsive and/or tic severity in children with new-onset symptoms. Method: Twenty subjects were randomized to receive placebo or cefdinir for 30 days for the treatment of recent-onset OCD and/or tics. The placebo group received a comparable inactive treatment matched for taste, color, and consistency. The Children\u27s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) and Yale Global Tic Severity Scale (YGTSS) were the primary outcome measures utilized. Results: Subjects receiving cefdinir saw notable improvements in tic symptoms, with 44.4% showing at least a 25% reduction in YGTSS (mean decrease=9.5) scores compared with 9.1% of the placebo group (mean decrease=0.13). Despite improvements, significant group differences were not observed for YGTSS (F [1, 13]=4.03, p=0.066) although there were moderate differences between group treatment effects (d=0.72). For OCD symptoms, subjects receiving cefdinir saw improvements in OCD symptoms, with 33.3% showing at least a 25% reduction in CY-BOCS scores (mean decrease=7.8) compared with 27.3% of the placebo group (mean decrease=4.7), but there were also no significant differences for CY-BOCS (F [1, 13]=0.385, p=0.546; d=0.24). Conclusions: Subjects assigned to cefdinir exhibited notable, albeit nonstatistically significant, improvements in tic symptoms, compared with the placebo group. There were also some improvements in OCD symptoms, although these were not significant. Overall, cefdinir was well tolerated. Given these preliminary results, a fully powered study is warranted to explore the efficacy of cefdinir as a therapeutic tool for new-onset pediatric neuropsychiatric symptoms, particularly those that appear to be precipitated by infection

Cefdinir for Recent-Onset Pediatric Neuropsychiatric Disorders: A Pilot Randomized Trial

Objective: Previous studies suggest that the unexplained sudden and severe onset of obsessive-compulsive disorder (OCD) and/or tics may be infection or immune precipitated. Beta lactam antibiotics may be neuroprotective beyond their antimicrobial efficacy. We examine the preliminary safety and efficacy of cefdinir in reducing obsessive-compulsive and/or tic severity in children with new-onset symptoms. Method: Twenty subjects were randomized to receive placebo or cefdinir for 30 days for the treatment of recent-onset OCD and/or tics. The placebo group received a comparable inactive treatment matched for taste, color, and consistency. The Children\u27s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) and Yale Global Tic Severity Scale (YGTSS) were the primary outcome measures utilized. Results: Subjects receiving cefdinir saw notable improvements in tic symptoms, with 44.4% showing at least a 25% reduction in YGTSS (mean decrease=9.5) scores compared with 9.1% of the placebo group (mean decrease=0.13). Despite improvements, significant group differences were not observed for YGTSS (F [1, 13]=4.03, p=0.066) although there were moderate differences between group treatment effects (d=0.72). For OCD symptoms, subjects receiving cefdinir saw improvements in OCD symptoms, with 33.3% showing at least a 25% reduction in CY-BOCS scores (mean decrease=7.8) compared with 27.3% of the placebo group (mean decrease=4.7), but there were also no significant differences for CY-BOCS (F [1, 13]=0.385, p=0.546; d=0.24). Conclusions: Subjects assigned to cefdinir exhibited notable, albeit nonstatistically significant, improvements in tic symptoms, compared with the placebo group. There were also some improvements in OCD symptoms, although these were not significant. Overall, cefdinir was well tolerated. Given these preliminary results, a fully powered study is warranted to explore the efficacy of cefdinir as a therapeutic tool for new-onset pediatric neuropsychiatric symptoms, particularly those that appear to be precipitated by infection

Open Label Aripiprazole in the Treatment of Youth with Tic Disorders

Background: Primarily safe and efficacious treatments for chronic tic disorders are needed. Also needed are such treatments that target co-morbid conditions. Aripiprazole, a dopaminergic/serotonergic agent with partial agonist properties at the D2 dopamine receptor and 5-hydrdoxytryptamine 1A (5-HT1A) receptor and antagonist properties at the 5-HT2A receptor, holds promise in both regards. Objective: This was an open-label, flexible-dose study to evaluate the safety of aripiprazole in children and adolescents with a primary diagnosis of a chronic tic disorder with/without co-morbid disorder(s). Method: Sixteen children (15 males) aged 8–17 years participated in the 6-week trial. Ratings for tic, obsessive compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and side effects were administered weekly. Baseline and exit laboratory measures, electrocardiograms (ECGs), weight, and height were obtained. Results: The average daily aripiprazole dose was 3.3 mg (range 1.25–7.5 mg). Significant pre-and posttreatment differences were ascertained for the Yale Global Tic Severity Scale motor (p ≤ 0.0001), phonic (p ≤ 0.0001), and total tic (p ≤ 0.0001) scores. Results of other rating scales suggested significant improvements in co-morbid disorders as well, including OCD, ADHD, and depressive disorders. Although aripiprazole was well tolerated, increases in weight were found. Conclusion: In this preliminary open-label trial, aripiprazole was a well-tolerated treatment for tics and co-morbid OCD and ADHD symptoms. Improvements in co-morbid conditions may be secondary to tic reduction or to specific to aripiprazole therapy; however, further study is warranted

Open Label Aripiprazole in the Treatment of Youth with Tic Disorders

Background: Primarily safe and efficacious treatments for chronic tic disorders are needed. Also needed are such treatments that target co-morbid conditions. Aripiprazole, a dopaminergic/serotonergic agent with partial agonist properties at the D2 dopamine receptor and 5-hydrdoxytryptamine 1A (5-HT1A) receptor and antagonist properties at the 5-HT2A receptor, holds promise in both regards. Objective: This was an open-label, flexible-dose study to evaluate the safety of aripiprazole in children and adolescents with a primary diagnosis of a chronic tic disorder with/without co-morbid disorder(s). Method: Sixteen children (15 males) aged 8–17 years participated in the 6-week trial. Ratings for tic, obsessive compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and side effects were administered weekly. Baseline and exit laboratory measures, electrocardiograms (ECGs), weight, and height were obtained. Results: The average daily aripiprazole dose was 3.3 mg (range 1.25–7.5 mg). Significant pre-and posttreatment differences were ascertained for the Yale Global Tic Severity Scale motor (p ≤ 0.0001), phonic (p ≤ 0.0001), and total tic (p ≤ 0.0001) scores. Results of other rating scales suggested significant improvements in co-morbid disorders as well, including OCD, ADHD, and depressive disorders. Although aripiprazole was well tolerated, increases in weight were found. Conclusion: In this preliminary open-label trial, aripiprazole was a well-tolerated treatment for tics and co-morbid OCD and ADHD symptoms. Improvements in co-morbid conditions may be secondary to tic reduction or to specific to aripiprazole therapy; however, further study is warranted