Is tuberous sclerosis complex-associated autism a preventable and treatable disorder?

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in the TSC1 and TSC2 genes, causing overactivation of the mechanistic (previously referred to as mammalian) target of rapamycin (mTOR) signaling pathway in fetal life. The mTOR pathway plays a crucial role in several brain processes leading to TSC-related epilepsy, intellectual disability, and autism spectrum disorder (ASD). Pre-natal or early post-natal diagnosis of TSC is now possible in a growing number of pre-symptomatic infants. DATA SOURCES: We searched PubMed for peer-reviewed publications published between January 2010 and April 2023 with the terms "tuberous sclerosis", "autism", or "autism spectrum disorder"," animal models", "preclinical studies", "neurobiology", and "treatment". RESULTS: Prospective studies have highlighted that developmental trajectories in TSC infants who were later diagnosed with ASD already show motor, visual and social communication skills in the first year of life delays. Reliable genetic, cellular, electroencephalography and magnetic resonance imaging biomarkers can identify pre-symptomatic TSC infants at high risk for having autism and epilepsy. CONCLUSIONS: Preventing epilepsy or improving therapy for seizures associated with prompt and tailored treatment strategies for autism in a sensitive developmental time window could have the potential to mitigate autistic symptoms in infants with TSC.

COVID-19 infection rate and mortality in a local health authority in Italy: Differences between home-dwelling and residential older adults.

Objectives: The health emergency following the COVID-19 pandemic has seen hospital structures collapse and put in crisis nursing homes and other long-term care facilities worldwide. Our study aims to analyze and comparing the data relating to the infection rate and mortality for COVID-19 in the elderly over 75 living in the long-term care facilities and in the home-dwelling population. Study design: The study adopts a retrospective cohort design and was conducted in Italy, in the Lazio region, in the area of the Local Health Authority (LHA) named "Azienda Sanitaria Locale Roma 6". Methods: Data were extracted from the COVID-19 surveillance system of the Lazio region. The primary outcome is the SARS-CoV-2 incidence rate in the period between 1st September 2020 and 31st May 2021. The secondary outcome is the mortality rate. Results: Living in a residential versus a home-dwelling setting was associated with a higher infection rate (OR 5.03, CI 4.67-5.43; p < 0.001). The mortality rate was higher for individuals living in a residential setting (19.3 %, CI 17.1%-21.7 %) than those living at home (13.0 %, CI 11.7%-14.5 %). Conclusions: These findings confirm the high mortality in Long-Term Care Facilities and provide new information on the infection rate. The containment measures adopted in the Long-Term Care Facilities during the COVID-19 pandemic, show limited correlation with reduced risk of contagion, but could have created unintended harm for the residents by increasing the social isolation and all other causes of mortality.

Screen exposure and sleep: How the COVID-19 pandemic influenced children and adolescents - A questionnaire-based study.

BACKGROUND: COVID-19 pandemic has drastically increased the exposure to electronic devices in children, influencing their lifestyle and their sleep. This study was conducted to explore the relationship between the augmented screen exposure and sleep habits in children during and after the pandemic. METHODS: Using the "Google Forms" tool, we created an online questionnaire addressed to parents of children and adolescents aged 2-18 years. We explored the use of screens before and during/after the lockdown and assessed the presence of sleep disturbances through the Sleep Disturbance Scale for Children (SDSC), referring to the period before and during/after COVID-19 pandemic. RESULTS: We collected 1084 valid questionnaires (median age 8.5 ± 4.1 years). We observed a significant increase in screens exposure for school (72%) and for leisure (49.7%) during the pandemic. We reported an increased sleep disturbances prevalence from 22.1% before the pandemic to 33.9% during the outbreak (p < 0.001). Even before the pandemic, the highest risks for sleep disorders were related to daily screen time for school reasons (OR 1.65, p < 0.001) and total screen time after 6 p.m. (OR 1.59, p < 0.001). The augmented exposure to screens for any reasons during the pandemic was significantly related to an increase of sleep disorders, especially regarding the increased exposure after 6 p.m. (OR 1.67, p < 0.001). CONCLUSIONS: The augmented use of electronic devices was recognized to be a significant predisposing factor in increasing the rate of sleep disorders during and after the pandemic, thus sleep hygiene recommendations should be highlighted to improve sleep habits.

Prevalence and risk factors of posttraumatic stress symptoms among Internally Displaced Christian couples in Erbil, Iraq.

Background: Research about the impact of war and displacement experiences on the mental health of Internally Displaced People (IDPs) has recently grown. However, a limited number of studies focus on minorities. The objective of the present preliminary study was to estimate the prevalence of posttraumatic stress symptoms (PTSSs) among IDPs who live outside camps and belong to the Christian minority in Iraq, and to identify possible predictors. Methods: Overall, 108 internally displaced Christians (54 married couples) participated in the study. Traumatic events and PTSSs were assessed using the Harvard Trauma Questionnaire. Multivariable linear regression models were used to investigate possible predictors of PTSSs. Multivariable logistic regression models have been developed to estimate the odds of presenting PTSSs. Results: Results demonstrated high rates of trauma exposure, with all participants having experienced at least three traumatic events. The estimated prevalence of PTSSs was 20.3%. A low economic status, the number of traumatic events, and a second experience of displacement were associated with increased PTSSs. Five traumatic events were identified as the main predictors of PTSSs. Conclusion: Findings from the current preliminary study indicated the impact of war-related traumatic events on IDPs' mental health and the negative effects of post-displacement experiences. These findings may have important implications for setting up psychosocial interventions, as well as for further promoting physical and mental health services among these populations.

A novel, integrated approach for understanding and investigating Healthcare Associated Infections: A risk factors constellation analysis.

INTRODUCTION: Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) are major public health threats in upper- and lower-middle-income countries. Electronic health records (EHRs) are an invaluable source of data for achieving different goals, including the early detection of HAIs and AMR clusters within healthcare settings; evaluation of attributable incidence, mortality, and disability-adjusted life years (DALYs); and implementation of governance policies. In Italy, the burden of HAIs is estimated to be 702.53 DALYs per 100,000 population, which has the same magnitude as the burden of ischemic heart disease. However, data in EHRs are usually not homogeneous, not properly linked and engineered, or not easily compared with other data. Moreover, without a proper epidemiological approach, the relevant information may not be detected. In this retrospective observational study, we established and engineered a new management system on the basis of the integration of microbiology laboratory data from the university hospital "Policlinico Tor Vergata" (PTV) in Italy with hospital discharge forms (HDFs) and clinical record data. All data are currently available in separate EHRs. We propose an original approach for monitoring alert microorganisms and for consequently estimating HAIs for the entire period of 2018. METHODS: Data extraction was performed by analyzing HDFs in the databases of the Hospital Information System. Data were compiled using the AREAS-ADT information system and ICD-9-CM codes. Quantitative and qualitative variables and diagnostic-related groups were produced by processing the resulting integrated databases. The results of research requests for HAI microorganisms and AMR profiles sent by the departments of PTV from 01/01/2018 to 31/12/2018 and the date of collection were extracted from the database of the Complex Operational Unit of Microbiology and then integrated. RESULTS: We were able to provide a complete and richly detailed profile of the estimated HAIs and to correlate them with the information contained in the HDFs and those available from the microbiology laboratory. We also identified the infection profile of the investigated hospital and estimated the distribution of coinfections by two or more microorganisms of concern. Our data were consistent with those in the literature, particularly the increase in mortality, length of stay, and risk of death associated with infections with Staphylococcus spp, Pseudomonas aeruginosa, Klebsiella pneumoniae, Clostridioides difficile, Candida spp., and Acinetobacter baumannii. Even though less than 10% of the detected HAIs showed at least one infection caused by an antimicrobial resistant bacterium, the contribution of AMR to the overall risk of increased mortality was extremely high. CONCLUSIONS: The increasing availability of health data stored in EHRs represents a unique opportunity for the accurate identification of any factor that contributes to the diffusion of HAIs and AMR and for the prompt implementation of effective corrective measures. That said, artificial intelligence might be the future of health data analysis because it may allow for the early identification of patients who are more exposed to the risk of HAIs and for a more efficient monitoring of HAI sources and outbreaks. However, challenges concerning codification, integration, and standardization of health data recording and analysis still need to be addressed.

Unemployment Status Subsequent to Cancer Diagnosis and Therapies: A Systematic Review and Meta-Analysis.

The purpose of our study is to examine whether cancer and treatments are associated with job loss or changes in employment status. Eight prospective studies were included in the systematic review and meta-analysis, with a population aged 18-65 years, analyzing treatment regimen and psychophysical and social status in post-cancer follow-up of at least 2 years. In the meta-analysis, a comparison was made between recovered unemployed cases and cases from a standard reference population. Results are summarized graphically using a forest plot. We showed that cancer and subsequent treatment are risk factors for unemployment with an overall relative risk of 7.24 (lnRR: 1.98, 95% CI: 1.32-2.63) or for change in employment status. Individuals undergoing chemotherapy and/or radiation treatment and those with brain and colorectal cancers are more likely to develop disabilities that negatively affect the risk of unemployment. Finally, variables such as low level education, female sex, older age, and being overweight before starting therapy are associated with higher risk of unemployment. In the future, it will be necessary for people with cancer to have access to specific health, social welfare, and employment support programs. In addition, it is desirable that they become more involved in their choice of therapeutic treatment.

Using Machine Learning to Explore Shared Genetic Pathways and Possible Endophenotypes in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a heterogeneous condition, characterized by complex genetic architectures and intertwined genetic/environmental interactions. Novel analysis approaches to disentangle its pathophysiology by computing large amounts of data are needed. We present an advanced machine learning technique, based on a clustering analysis on genotypical/phenotypical embedding spaces, to identify biological processes that might act as pathophysiological substrates for ASD. This technique was applied to the VariCarta database, which contained 187,794 variant events retrieved from 15,189 individuals with ASD. Nine clusters of ASD-related genes were identified. The 3 largest clusters included 68.6% of all individuals, consisting of 1455 (38.0%), 841 (21.9%), and 336 (8.7%) persons, respectively. Enrichment analysis was applied to isolate clinically relevant ASD-associated biological processes. Two of the identified clusters were characterized by individuals with an increased presence of variants linked to biological processes and cellular components, such as axon growth and guidance, synaptic membrane components, or transmission. The study also suggested other clusters with possible genotype-phenotype associations. Innovative methodologies, including machine learning, can improve our understanding of the underlying biological processes and gene variant networks that undergo the etiology and pathogenic mechanisms of ASD. Future work to ascertain the reproducibility of the presented methodology is warranted.

Pro-active monitoring and social interventions at community level mitigate the impact of coronavirus (COVID-19) epidemic on older adults' mortality in Italy: A retrospective cohort analysis.

BACKGROUND: The COVID-19 epidemic in Italy has severely affected people aged more than 80, especially socially isolated. Aim of this paper is to assess whether a social and health program reduced mortality associated to the epidemic. METHODS: An observational retrospective cohort analysis of deaths recorded among >80 years in three Italian cities has been carried out to compare death rate of the general population and "Long Live the Elderly!" (LLE) program. Parametric and non-parametric tests have been performed to assess differences of means between the two populations. A multivariable analysis to assess the impact of covariates on weekly mortality has been carried out by setting up a linear mixed model. RESULTS: The total number of services delivered to the LLE population (including phone calls and home visits) was 34,528, 1 every 20 day per person on average, one every 15 days during March and April. From January to April 2019, the same population received one service every 41 days on average, without differences between January-February and March-April. The January-April 2020 cumulative crude death rate was 34.8‰ (9,718 deaths out of 279,249 individuals; CI95%: 34.1-35.5) and 28.9‰ (166 deaths out of 5,727 individuals; CI95%:24.7-33.7) for the general population and the LLE sample respectively. The general population weekly death rate increased after the 11th calendar week that was not the case among the LLE program participants (p<0.001). The Standardized Mortality Ratio was 0.83; (CI95%: 0.71-0.97). Mortality adjusted for age, gender, COVID-19 weekly incidence and prevalence of people living in nursing homes was lower in the LLE program than in the general population (p<0.001). CONCLUSIONS: LLE program is likely to limit mortality associated with COVID-19. Further studies are needed to establish whether it is due to the impact of social care that allows a better clients' adherence to the recommendations of physical distancing or to an improved surveillance of older adults that prevents negative outcomes associated with COVID-19.

The Effectiveness of Intervening on Social Isolation to Reduce Mortality during Heat Waves in Aged Population: A Retrospective Ecological Study.

BACKGROUND: Heat waves are correlated with increased mortality in the aged population. Social isolation is known as a vulnerability factor. This study aims at evaluating the correlation between an intervention to reduce social isolation and the increase in mortality in the population over 80 during heat waves. METHODS: This study adopted a retrospective ecologic design. We compared the excess mortality rate (EMR) in the over-80 population during heat waves in urban areas of Rome (Italy) where a program to reduce social isolation was implemented, to others where it was not implemented. We measured the mortality of the summer periods from 2015 to 2019 compared with 2014 (a year without heat waves). Winter mortality, cadastral income, and the proportion of people over 90 were included in the multivariate Poisson regression. RESULTS: The EMR in the intervention and controls was 2.70% and 3.81%, respectively. The rate ratio was 0.70 (c.i. 0.54-0.92, p-value 0.01). The incidence rate ratio (IRR) of the interventions, with respect to the controls, was 0.76 (c.i. 0.59-0.98). After adjusting for other variables, the IRR was 0.44 (c.i. 0.32-0.60). CONCLUSIONS: Reducing social isolation could limit the impact of heat waves on the mortality of the elderly population.

Predictors of Emergency Room Access and Not Urgent Emergency Room Access by the Frail Older Adults.

Background: Emergency rooms (ERs) overcrowded by older adults have been the focus of public health policies during the recent COVID-19 outbreak too. This phenomenon needed a change in the nursing care of older frail people. Health policies have tried to mitigate the frequent use of ER by implementing community care to meet the care demands of older adults. The present study aimed to investigate the predictors of emergency room access (ERA) and not-urgent emergency room access (NUERA) of community-dwelling frail older adults in order to provide an indication for out-of-hospital care services. Method: Secondary analysis of an observational longitudinal cohort study was carried out. The cohort consisted of 1,246 community-dwelling frail older adults (over 65 years) in the Latium region in Italy. The ER admission rate was assessed over 3 years from the administration of the functional geriatric evaluation (FGE) questionnaire. The ordinal regression model was used to identify the predictors of ERA and NUERA. Moreover, the ERA and NUERA rate per 100 observations/year was analyzed. Results: The mean age was 73.6 (SD ± 7.1) years, and 53.4% were women. NUERAs were the 39.2% of the ERAs; robust and pre-frail individuals (79.3% of the sample) generated more than two-third of ERAs (68.17%), even if frails and very frails showed the higher ER rates per observation/year. The ordinal logistic regression model highlighted a predictive role on ERAs of comorbidity (OR = 1.13, p < 0.001) and frailty level (OR = 1.29; p < 0.001). Concerning NUERAs, social network (OR 0.54, P = 0.015) and a medium score of pulmo-cardio-vascular function (OR 1.50, P = 0.006) were the predictors. Conclusion: Comorbidity, lack of social support, and functional limitations increase both ERA and NUERA rates generated by the older adult population. Overall, bio-psycho-social frailty represents an indicator of the frequency of ERAs. However, to reduce the number of ERAs, intervention should focus mainly on the robust and pre-frail needs for prevention and care.

Sex Differences in Autism Spectrum Disorder: Repetitive Behaviors and Adaptive Functioning.

Sex differences in restricted and repetitive behaviors (RRBs) in individuals with Autism Spectrum Disorder (ASD) have been explored with mixed findings. We aimed to investigate sex differences in RRBs through a specific measure-i.e., the Repetitive Behavior Scale Revised (RBS-R)-in a sample of preschool-age and school-age children with ASD. Additionally, we evaluated if RRBs were differently related to adaptive functioning within the male and the female age groups. A sample of 210 ASD individuals (3-18 years; 145 males, 65 females) underwent an in-depth assessment including a cognitive, adaptive functioning evaluation (i.e., the Adaptive Behavior Assessment System, Second Edition (ABAS-II)) and RRBs assessment (i.e., RBS-R). No significant sex differences on the RBS-R total score or any RBS-R subscale emerged. Within the group of older participants, RRBs were negatively associated with all adaptive skill domains independently from sex and age. Our results suggest a lack of sex differences in RRBs in our sample. Additionally, our findings highlight the possible negative impact of RRBs on adaptive skills in older individuals with autism, emphasizing the need for autistic individuals of both sexes to undergo an early intervention targeting RRBs, in order to improve their adaptive skills.

The Impact of COVID-19 on the Adaptive Functioning, Behavioral Problems, and Repetitive Behaviors of Italian Children with Autism Spectrum Disorder: An Observational Study.

Children with autism spectrum disorder (ASD) and their families have represented a fragile population on which the extreme circumstances of the COVID-19 outbreak may have doubly impaired. Interruption of therapeutical interventions delivered in-person and routine disruption constituted some of the main challenges they had to face. This study investigated the impact of the COVID-19 lockdown on adaptive functioning, behavioral problems, and repetitive behaviors of children with ASD. In a sample of 85 Italian ASD children (mean age 7 years old; 68 males, 17 females), through a comparison with a baseline evaluation performed during the months preceding COVID-19, we evaluated whether after the compulsory home confinement any improvement or worsening was reported by parents of ASD individuals using standardized instruments (Adaptive Behavior Assessment System (Second Edition), Achenbach Child Behavior Checklist, Repetitive Behavior Scale-Revised). No significant worsening in the adaptive functioning, problematic, and repetitive behaviors emerged after the compulsory home confinement. Within the schooler children, clinical stability was found in reference to both adaptive skills and behavioral aspects, whereas within preschoolers, a significant improvement in adaptive skills emerged and was related to the subsistence of web-delivered intervention, parental work continuance, and online support during the lockdown.

Clustering Analysis Supports the Detection of Biological Processes Related to Autism Spectrum Disorder.

Genome sequencing has identified a large number of putative autism spectrum disorder (ASD) risk genes, revealing possible disrupted biological pathways; however, the genetic and environmental underpinnings of ASD remain mostly unanswered. The presented methodology aimed to identify genetically related clusters of ASD individuals. By using the VariCarta dataset, which contains data retrieved from 13,069 people with ASD, we compared patients pairwise to build "patient similarity matrices". Hierarchical-agglomerative-clustering and heatmapping were performed, followed by enrichment analysis (EA). We analyzed whole-genome sequencing retrieved from 2062 individuals, and isolated 11,609 genetic variants shared by at least two people. The analysis yielded three clusters, composed, respectively, by 574 (27.8%), 507 (24.6%), and 650 (31.5%) individuals. Overall, 4187 variants (36.1%) were common to the three clusters. The EA revealed that the biological processes related to the shared genetic variants were mainly involved in neuron projection guidance and morphogenesis, cell junctions, synapse assembly, and in observational, imitative, and vocal learning. The study highlighted genetic networks, which were more frequent in a sample of people with ASD, compared to the overall population. We suggest that itemizing not only single variants, but also gene networks, might support ASD etiopathology research. Future work on larger databases will have to ascertain the reproducibility of this methodology.

Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?

OBJECTIVE: To evaluate the relationship between age at seizure onset and neurodevelopmental outcome at age 24 months in infants with TSC, as well as the effect on neurodevelopmental outcome of early versus conventional treatment of epileptic seizures with vigabatrin (80-150 mg/kg/day). METHODS: Infants with TSC, aged ≤4 months and without previous seizures were enrolled in a prospective study and closely followed with monthly video EEG and serial standardized neurodevelopmental testing (Bayley Scales of Infant Development and Autism Diagnostic Observation Schedule). RESULTS: Eighty infants were enrolled. At the age of 24 months testing identified risk of Autism Spectrum Disorder (ASD) in 24/80 children (30.0%), and developmental delay (DD) in 26/80 (32.5%). Children with epilepsy (51/80; 63.8%) had a higher risk of ASD (P = 0.02) and DD (P = 0.001). Overall, no child presented with moderate or severe DD at 24 months (developmental quotient < 55). In 20% of children abnormal developmental trajectories were detected before the onset of seizures. Furthermore, 21% of all children with risk of ASD at 24 months had not developed seizures at that timepoint. There was no significant difference between early and conventional treatment with respect to rate of risk of ASD (P = 0.8) or DD (P = 0.9) at 24 months. INTERPRETATION: This study confirms a relationship between epilepsy and risk of ASD/DD. However, in this combined randomized/open label study, early treatment with vigabatrin did not alter the risk of ASD or DD at age 2 years.

Supporting Iraqi Kurdistan Health Authorities in Post-conflict Recovery: The Development of a Health Monitoring System.

Background: Iraq has endured several conflicts and socio-political tensions that have disrupted its public health system. Nowadays, because health data are not collected on a routine basis, the country still lacks proper statistics and, consequently, response plans to meet present and future health needs of its population. An international partnership is developing in the Iraqi Kurdistan a Health Monitoring System with the aim of supporting evidence-based health policy decisions. Methods: The pilot phase for assessing the feasibility of the programme was launched in 2015. In 2018 the implementation phase began. The first step was to choose the software platform and the coding system, as well as to identify the public hospitals (PH) and Public Health Centers (PHC) to be included in the e-health system. The technical infrastructure of each PHC or PH was updated. The staff of each center was trained in the use of the e-health system and in disease coding. Several seminars introduced regional and district health managers to the basic concepts of data-driven decision making. A local team of experts was trained to create a highly specialized staff with the objective of "training the trainers" and ensuring the future self-sufficiency of the system. Results: By September 2019, 59 PHC and PH were entering data in the Health Monitoring System, while 258 health operators (medical doctors, administrative staff, nurses, statisticians, IT and public health specialists, pharmacists) have been already trained. Currently, more than 600,000 disease events have been collected. Additionally, further 734 medical doctors, statisticians, and health managers have been trained on the basics of public health practice. The goal during the next 3 years is to reach 120 operative centers within the region, envisaging a subsequent expansion of the system to all Iraq. Conclusions: The creation of a functioning health monitoring system is feasible also in regions characterized by socio-political tensions. However, multiple stakeholder partnerships are essential. The provision of an e-health information system, coupled with the establishment of a team of local experts, allows the routinely and timely collection of health information, facilitating prompt responses to present and emerging needs, while guiding the formulation and evaluation of health policies.

Developing a Public Health Monitoring System in a War-torn Region: A Field Report From Iraqi Kurdistan.

Wars, terrorism, and embargos destroyed facilities and shattered the public health system of Iraq. Today, there is limited documented knowledge about the health situation of the Iraqi population, particularly because health data are not systematically collected. Therefore, the capacity of the health system to address the major health problems of the population is considerably reduced. This report describes the implementation, started in 2015, of an electronic system for epidemiological monitoring and health surveillance, designed to collect and manage health care data in Iraqi Kurdistan. The aim of the program is to network all of the main health centers and hospitals of the region, then of the whole country, and to train medical and administrative staff in the management and analysis of health data. In countries recovering from war, a functioning health monitoring system is essential in guiding the development of appropriate public health interventions, a key instrument to prepare the health system to respond to future emergencies.

Use of nutritional supplements based on melatonin, tryptophan and vitamin B6 (Melamil Tripto®) in children with primary chronic headache, with or without sleep disorders: a pilot study.

BACKGROUND: Headache is one of the main complaints in pediatric neurology. Exogenous melatonin has been shown to be useful and safe in improving sleep-wake cycles and sleep quality in children. Tryptophan as well plays a key role in sleep regulation. So far, no studies tried to analyze the effects of a combination of both melatonin and tryptophan in treating chronic headache in children affected also by night-time awakenings. METHODS: Thirty-four children with a diagnosis of chronic headache (with or without sleep disorders) have been enrolled. The study was articulated in two steps: 1) each child was observed for one month without any intervention; 2) children have been then randomized into two groups: the "ME-group", which received the nutritional supplement melatonin for two months and the "MET-group", which received the nutritional supplements melatonin, tryptophan, and vitamin B6 for two months. RESULTS: In terms of changes in number of headache events, responders in the ME-group were 91.7% and those in the MET-group were 66.7% (P=0.113). In terms of changes in number of night awakenings, in the ME group, mean number at baseline, after 30 days, and after 60 days were 3.6±3.2, 3.2±3.5, and 2.7±3.4 (P=0.495). In the MET group, mean number of night awakenings was 7.4±8.1, 4.0±4.4, and 3.3±2.9 (P=0.041). CONCLUSIONS: Using either nutritional supplement for two months can help in decreasing the monthly number of headache episodes and night awakenings. The addition of tryptophan and vitamin B6 appears to have stronger influence on night awakenings reduction than melatonin only.

Neurodevelopmental Disorders and Adaptive Functions: A Study of Children With Autism Spectrum Disorders (ASD) and/or Attention Deficit and Hyperactivity Disorder (ADHD).

Introduction: Autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) are the two most common neurodevelopmental disorders observed in childhood. The DSM-5 accepts a combined diagnosis of ADHD and ASD, while the DSM-IV did not. The aim of this study was to identify and evaluate the adaptive profile of children and adolescents with a diagnosis of comorbid ADHD and ASD, in comparison with adaptive functioning in subjects with a diagnosis of only ASD or ADHD. Materials and Methods: Ninety-one children (77 boys, 14 girls), aging from 3.1 to 13.4 years (mean age: 8.3 ± 7.2), who met the criteria for a diagnosis of ASD and/or ADHD were enrolled. A neuropsychological evaluation involving cognitive and adaptive assessment was conducted using the Autism Diagnostic Observation Schedule - Second Edition (ADOS-2), the Conners' Parent Rating Scale - Revised: Long Version (CPRS-R), the Wechsler Intelligence Scale - Fourth Edition or the Griffiths Mental Developmental Scales - Extended Revised, the Vineland Adaptive Behaviour Scale - Second Edition (VABS-II). Conclusion: As to the adaptive skills in the three groups evaluated, a worse general profile was ascertained in the ASD and in ASD plus ADHD groups in comparison with respect to the ADHD-only group. With VABS-II evaluation, we found significant differences among the three groups across all domains and combined scores: Communication (F = 18.960; p < 0.001), Socialization (F = 25.410; p < 0.001), Daily Living Skills (F = 19.760; p < 0.001), Motor (F = 9.615; p < 0.001), and Adaptive behavior composite [ABC] (F = 29.370; p < 0.001). Implications of neurodevelopmental double diagnosis such as ASD plus ADHD are discussed.

Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study.

Autism spectrum disorder (ASD) is highly prevalent in subjects with Tuberous Sclerosis Complex (TSC), but we are not still able to reliably predict which infants will develop ASD. This study aimed to identify the early clinical markers of ASD and/or developmental delay (DD) in infants with an early diagnosis of TSC. We prospectively evaluated 82 infants with TSC (6-24 months of age), using a detailed neuropsychological assessment (Bayley Scales of Infant Development-BSID, and Autism Diagnostic Observation Schedule-ADOS), in the context of the EPISTOP (Long-term, prospective study evaluating clinical and molecular biomarkers of EPIleptogenesiS in a genetic model of epilepsy-Tuberous SclerOsis ComPlex) project (NCT02098759). Normal cognitive developmental quotient at 12 months excluded subsequent ASD (negative predictive value 100%). The total score of ADOS at 12 months clearly differentiated children with a future diagnosis of ASD from children without (p = 0.012). Atypical socio-communication behaviors (p < 0.001) were more frequently observed than stereotyped/repetitive behaviors in children with ASD at 24 months. The combined use of BSID and ADOS can reliably identify infants with TSC with a higher risk for ASD at age 6-12 months, allowing for clinicians to target the earliest symptoms of abnormal neurodevelopment with tailored intervention strategies.