Memantine for autism spectrum disorder

Background Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child's quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co‐occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness. Objectives To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours. Search methods We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found. Selection criteria We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention). Data collection and analysis We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence. Main results We included three RCTs (two double‐blind and one single‐blind) with 204 participants that examined the short‐term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview‐Revised (ADI‐R); one used ADOS, ADI‐R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child's weight and ranged from 3 mg to 15 mg per day. Comparisons Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine. Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in‐kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was –0.74 standard deviations (95% confidence interval (CI) −2.07 to 0.58; 2 studies, 181 participants; very low‐certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low‐certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low‐certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low‐certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low‐certainty evidence). Authors' conclusions It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow‐up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism

PENYELESAIAN SENGKETA KONSUMEN SECARA ONLINE BERDASARKAN UNDANG-UNDANG NO 08 TAHUN 1999 TENTANG PERLINDUNGAN KONSUMEN DAN UNDANG-UNDANG NO 30 TAHUN 1999 TENTANG ARBITRASE DAN ALTERNATIF PENYELESAIAN SENGKETA

ABSTRACT In consumer dispute resolution, there are 2 (two) forms of out-of-court trials which consumer can choose: Dispute Settlement Board (BPSK) and Online Arbitration (Online Dispute Resolution). This Problem formulations in this study are: 1. How to resolve consumer disputes through the Consumer Dispute Settlement Agency based on Law Number 8 of 1999 Concerning Consumer Protection? 2. How to Settle Consumer Disputes Through Arbitration Institutions online to protect consumer rights based on the Law Law Number 30 Year 1999 Concerning Arbitration and Alternative Dispute Resolution? This research uses Normative Juridical method —a law research which is a scientific activity to judge on decrees through primary and secondary approaches. The results of the research on Dispute Resolution by Dispute Settlement Board and Online Arbitration could give decision satisfaction to the consumer and business agency in which their rights to receive goods and/or services are aggrieved. Both forms result in strength of decisions that are final and have permanent legal force.Keywords: Consumer Dispute, Dispute Settlement Board (BPSK), Online ArbitrationABSTRAK Dalam penyelesaian sengketa kosumen ada 2 (dua) bentuk peradilan di luar pengadilan yang dapat menjadi pilihan konsumen yaitu, Badan Penyelesaian Sengketa Konsumen dan Arbitrase secara online (Online Dispute Resolution). Rumusan Masalah dalam penelitian ini yaitu: 1. Bagaimana penyelesaian sengketa konsumen melalui Badan Penyelesaian Sengketa Konsumen berdasarkan Undang-Undang Nomor 8 Tahun 1999 Tentang Perlindungan Konsumen?, 2.Bagaimana Penyelesaian Sengketa Konsumen Melalui Lembaga Arbitrase secara online untuk melindungi hak-hak konsumen berdasarkan Undang-Undang Nomor 30 Tahun 1999 Tentang Arbitrase dan Alternatif Peyelesaian Sengketa? Penelitiannya dilakukan dengan metode hukum Yuridis Normatif, penelitian hukum yang merupakan kegiatan ilmiah untuk memberikan penilaian terhadap keputusan-keputusan melalui pedekatan primer dan sekunder. Hasil Penelitian dalam Penyelesaian Sengketa Melalui Badan Penyelesaian Sengketa Konsumen dan Arbitrase secara Online dalam penyelesaian sengketanya lembaga tersebut mampu memberikan kepuasan putusan kepada konsumen dan pelaku usaha yang pihaknya dirugikan dalam hak-haknya menerima barang dan/atau jasa dalam kekuatan putusannya sama sama bersifat final dan memiliki kekuatan hukum tetap.Kata Kunci : Sengketa Konsumen, Badan Penyelesaian Sengketa Konsumen (BPSK), Arbitrase Onlin

Memantine for autism spectrum disorder

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of memantine on the core features of ASD, including, but not limited to, social functioning, communication skills and stereotypical behaviours

Is language ability associated with behaviors of concern in autism? A systematic review

This review systematically synthesized evidence on the association between structural language ability and behaviors of concern (BoC) in autism. Four databases were searched for studies that included >10 autistic participants, measures of structural language (content and/or form of language) and BoC, and an analysis of their association. BoCs included self-injurious behavior (SIB), aggression, tantrums, and externalizing behavior. Methodological quality of studies were assessed using the Newcastle Ottawa Scale. Forty-five publications (n = 11,961) were included. Forty studies were cross-sectional and five were prospective cohort studies. Over 70% of the studies investigating expressive language and SIB (n = 10), aggression (n = 5), tantrums (n = 3), and externalizing behavior (n = 17) reported an inverse association, where lower expressive language ability was associated with increased BoC. Eleven out of sixteen studies of combined expressive and receptive language reported an inverse relationship with SIB or aggression. All outcomes were rated as moderate to very low certainty of evidence. This review highlights evidence showing an inverse association between expressive or combined language ability and SIB, and externalizing behavior in autism. However, further high-quality studies that use standardized, consistent measures of language and behavior and investigate longitudinal associations are needed. Early detection and support for reduced structural language difficulties have substantial potential to assist in reducing BoC

Overall prognosis of preschool autism spectrum disorder diagnoses

Background Autism spectrum disorder is a neurodevelopmental disorder characterised by social communication difficulties, restricted interests and repetitive behaviours. The clinical pathway for children with a diagnosis of autism spectrum disorder is varied, and current research suggests some children may not continue to meet diagnostic criteria over time. Objectives The primary objective of this review was to synthesise the available evidence on the proportion of preschool children who have a diagnosis of autism spectrum disorder at baseline (diagnosed before six years of age) who continue to meet diagnostic criteria at follow‐up one or more years later (up to 19 years of age). Search methods We searched MEDLINE, Embase, PsycINFO, and eight other databases in October 2017 and ran top‐up searches up to July 2021. We also searched reference lists of relevant systematic reviews. Selection criteria Two review authors independently assessed prospective and retrospective follow‐up studies that used the same measure and process within studies to diagnose autism spectrum disorder at baseline and follow‐up. Studies were required to have at least one year of follow‐up and contain at least 10 participants. Participants were all aged less than six years at baseline assessment and followed up before 19 years of age. Data collection and analysis We extracted data on study characteristics and the proportion of children diagnosed with autism spectrum disorder at baseline and follow‐up. We also collected information on change in scores on measures that assess the dimensions of autism spectrum disorder (i.e. social communication and restricted interests and repetitive behaviours). Two review authors independently extracted data on study characteristics and assessed risk of bias using a modified quality in prognosis studies (QUIPS) tool. We conducted a random‐effects meta‐analysis or narrative synthesis, depending on the type of data available. We also conducted prognostic factor analyses to explore factors that may predict diagnostic outcome. Main results In total, 49 studies met our inclusion criteria and 42 of these (11,740 participants) had data that could be extracted. Of the 42 studies, 25 (60%) were conducted in North America, 13 (31%) were conducted in Europe and the UK, and four (10%) in Asia. Most (52%) studies were published before 2014. The mean age of the participants was 3.19 years (range 1.13 to 5.0 years) at baseline and 6.12 years (range 3.0 to 12.14 years) at follow‐up. The mean length of follow‐up was 2.86 years (range 1.0 to 12.41 years). The majority of the children were boys (81%), and just over half (60%) of the studies primarily included participants with intellectual disability (intelligence quotient < 70). The mean sample size was 272 (range 10 to 8564). Sixty‐nine per cent of studies used one diagnostic assessment tool, 24% used two tools and 7% used three or more tools. Diagnosis was decided by a multidisciplinary team in 41% of studies. No data were available for the outcomes of social communication and restricted and repetitive behaviours and interests. Of the 42 studies with available data, we were able to synthesise data from 34 studies (69% of all included studies; n = 11,129) in a meta‐analysis. In summary, 92% (95% confidence interval 89% to 95%) of participants continued to meet diagnostic criteria for autism spectrum disorder from baseline to follow‐up one or more years later; however, the quality of the evidence was judged as low due to study limitations and inconsistency. The majority of the included studies (95%) were rated at high risk of bias. We were unable to explore the outcomes of change in social communication and restricted and repetitive behaviour and interests between baseline and follow‐up as none of the included studies provided separate domain scores at baseline and follow‐up. Details on conflict of interest were reported in 24 studies. Funding support was reported by 30 studies, 12 studies omitted details on funding sources and two studies reported no funding support. Declared funding sources were categorised as government, university or non‐government organisation or charity groups. We considered it unlikely funding sources would have significantly influenced the outcomes, given the nature of prognosis studies. Authors' conclusions Overall, we found that nine out of 10 children who were diagnosed with autism spectrum disorder before six years of age continued to meet diagnostic criteria for autism spectrum disorder a year or more later, however the evidence was uncertain. Confidence in the evidence was rated low using GRADE, due to heterogeneity and risk of bias, and there were few studies that included children diagnosed using a current classification system, such as the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) or the eleventh revision of the International Classification of Diseases (ICD‐11). Future studies that are well‐designed, prospective and specifically assess prognosis of autism spectrum disorder diagnoses are needed. These studies should also include contemporary diagnostic assessment methods across a broad range of participants and investigate a range of relevant prognostic factors

Autism spectrum disorder: updated prevalence and comparison of two birth cohorts in a nationally representative Australian sample

Objectives This study aimed to (1) provide an update on the prevalence of parent-reported autism spectrum disorder (ASD) diagnosis and new information about teacher-reported ASD in two nationally representative Australian cohorts at ages 10&ndash;11 years, (2) examine differences in cohort demographic and clinical profiles and (3) compare the prevalence of teacher-reported ASD and any changes in categorisation over time across the cohorts.Design Secondary analyses were undertaken using data from the Longitudinal Study of Australian Children (LSAC).Participants Children were recruited at kindergarten age (K cohort; birth year 1999/2000) and birth (B cohort; birth year 2003/2004), with follow-up of every 2 &thinsp;years for six waves.Primary outcome measures Parent-reported and teacher-reported ASD diagnosis was ascertained at three time points (waves 4&ndash;6).Results At age 10&ndash;11 years, the adjusted prevalence of parent-reported ASD diagnosis was 3.9% (95% CI 3.2 to 4.5) and 2.4% (95% CI 1.6 to 2.9) in the B and K cohorts, respectively. Teacher-reported prevalence of ASD was 1.7% (95% CI 1.2 to 2.1) in the B cohort and 0.9% (95% CI 0.56 to 1.14) in the K cohort. Parents reported fewer conduct and peer problems and teachers more pro-social behaviour in B relative to K cohort ASD children. Children reported only by parents in the later-born B cohort had milder behaviour problems than parent-agreed and teacher-agreed cases. Although individual switching to ASD from other categories from 8&ndash;9 to 10&ndash;11 years was low (K cohort n=5, B cohort n=6), teachers reported more children with ASD in the B than K cohort at 10&ndash;11 years and fewer children with emotional/ behavioural problems.Conclusions The higher prevalence of parent-reported and teacher-reported ASD diagnosis in the later-born cohort may be partially explained by identifying children with milder behavioural problems as ASD and a change in the use of diagnostic categories in schools

A Novel Mechanism for Zika Virus Host-Cell Binding

Zika virus (ZIKV) recently emerged in the Western Hemisphere with previously unrecognized or unreported clinical presentations. Here, we identify two putative binding mechanisms of ancestral and emergent ZIKV strains featuring the envelope (E) protein residue asparagine 154 (ASN154) and viral phosphatidylserine (PS). Synthetic peptides representing the region containing ASN154 from strains PRVABC59 (Puerto Rico 2015) and MR_766 (Uganda 1947) were exposed to neuronal cells and fibroblasts to model ZIKV E protein/cell interactions and bound MDCK or Vero cells and primary neurons significantly. Peptides significantly inhibited Vero cell infectivity by ZIKV strains MR_766 and PRVABC59, indicating that this region represents a putative binding mechanism of ancestral African ZIKV strains and emergent Western Hemisphere strains. Pretreatment of ZIKV strains MR_766 and PRVABC59 with the PS-binding protein annexin V significantly inhibited replication of PRVABC59 but not MR_766, suggesting that Western hemisphere strains may additionally be capable of utilizing PS-mediated entry to infect host cells. These data indicate that the region surrounding E protein ASN154 is capable of binding fibroblasts and primary neuronal cells and that PS-mediated entry may be a secondary mechanism for infectivity utilized by Western Hemisphere strains