Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 84
1.
J Neurodev Disord ; 16(1): 29, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38849752

BACKGROUND: Sleep disturbances are frequently reported in children with autism spectrum disorder (ASD) and are associated with the severity of co-occurring symptoms. This study's aim was to examine the extent of healthcare utilization and clinical outcomes associated with sleep disturbances in children with ASD. STUDY DESIGN: A retrospective, cross-sectional study of 541 children with ASD from the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) whose parents completed the Children's Sleep Habits Questionnaire (CSHQ). Children with a total CSHQ score ≥ 48 were defined as having sleep disturbances. Sociodemographic characteristics, ASD diagnostic measures, chronic co-occurring conditions, medication usage, hospitalizations, visits to the emergency room (ER), and visits to specialists were compared in ASD children with and without sleep disturbances. Multivariate logistic regression models were then used to assess the independent association of sleep disturbances with clinical characteristics and healthcare utilization. RESULTS: Of the 541 children with ASD, 257 (47.5%) had sleep disturbances. Children with sleep disturbances exhibited higher rates of multiple (≥ 3) co-occurring conditions (19.1% vs. 12.7%; p = 0.0414) and prescribed medications (45.5% vs. 32.7%; p = 0.0031) than other children. Finally, ASD children with sleep disturbances were 1.72 and 2.71 times more likely to visit the ER and be hospitalized than their counterparts (aOR = 1.72; 99%CI = 1.01-2.95; and aOR = 2.71; 99%CI = 1.10-6.67, respectively). CONCLUSIONS: Our findings suggest that sleep disturbances are associated with greater healthcare utilization among children with ASD. Further studies could examine whether treating sleep disturbances in children with ASD yields additional clinical benefits beyond improvements in sleep.


Autism Spectrum Disorder , Patient Acceptance of Health Care , Sleep Wake Disorders , Humans , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/therapy , Male , Female , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Sleep Wake Disorders/therapy , Child , Cross-Sectional Studies , Retrospective Studies , Patient Acceptance of Health Care/statistics & numerical data , Child, Preschool , Comorbidity , Adolescent , Hospitalization/statistics & numerical data
2.
Autism Res ; 17(2): 410-418, 2024 02.
Article En | MEDLINE | ID: mdl-38193609

Accurate estimation of annual changes in autism spectrum disorders (ASD) prevalence is critical for planning the expansion of diagnostic, education, and intervention services at an adequate rate. Previous studies from Israel have reported that ASD prevalence among 8-year-old children has increased from estimates of 0.3% in 2008 to 0.65% in 2015 and 1.3% in 2018. Here, we analyzed data acquired from the National Insurance Institute of Israeli (NII), a governmental organization that approves and monitors all ASD children who receive welfare services in Israel, and Clalit Health Services (CHS), the largest Health Maintenance Organization in Israel that provides health services to ~52% of the population. Data from both sources included annual data files from 2017 to 2021 containing the number of ASD cases per year of birth for 1-17-year-old children. This allowed us to estimate annual ASD prevalence among 3.5 million children born between 2000 and 2020 in Israel. Both data sources revealed a nearly two-fold increase in ASD prevalence among 1-17-year-old children from 2017 to 2021. Estimated prevalence rates differed across age groups with 2-3-year-old (day-care) children increasing from 0.27% to 1.19% (>4 fold change), 4-6-year-old (pre-school) children increasing from 0.8% to 1.83%, and 8-year-old children increasing from 0.82% to 1.56% in NII data. These results demonstrate that autism prevalence continues to increase in Israel with a shift towards diagnosis at earlier ages. These findings highlight the challenge facing health and education service providers in meeting the needs of a rapidly growing autism population.


Autism Spectrum Disorder , Autistic Disorder , Child Development Disorders, Pervasive , Child , Humans , Child, Preschool , Infant , Adolescent , Autism Spectrum Disorder/epidemiology , Israel/epidemiology , Prevalence
3.
bioRxiv ; 2024 Jan 12.
Article En | MEDLINE | ID: mdl-38260528

Recent neuroimaging and eye tracking studies have suggested that children with autism spectrum disorder (ASD) may exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here we extended this research for the first time to pupillometry recordings. We successfully completed pupillometry recordings with 103 children (66 with ASD), 4.5-years-old on average, who viewed three 90 second movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group. ASD participants exhibited significantly weaker inter-subject correlations than TD participants, reliably across all three movies. Differences across groups were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. This measure enabled classification of ASD and TD children with a sensitivity of 0.82 and specificity of 0.73 when trained and tested on independent datasets. Using the largest ASD pupillometry dataset to date, we demonstrate the utility of a new technique for measuring the idiosyncrasy of pupil regulation, which can be completed even by young children with co-occurring intellectual disability. These findings reveal that a considerable subgroup of ASD children have significantly more unstable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.

4.
Sci Rep ; 13(1): 18853, 2023 11 01.
Article En | MEDLINE | ID: mdl-37914828

Autism spectrum disorder (ASD) is a heterogenous multifactorial neurodevelopmental condition with a significant genetic susceptibility component. Thus, identifying genetic variations associated with ASD is a complex task. Whole-exome sequencing (WES) is an effective approach for detecting extremely rare protein-coding single-nucleotide variants (SNVs) and short insertions/deletions (INDELs). However, interpreting these variants' functional and clinical consequences requires integrating multifaceted genomic information. We compared the concordance and effectiveness of three bioinformatics tools in detecting ASD candidate variants (SNVs and short INDELs) from WES data of 220 ASD family trios registered in the National Autism Database of Israel. We studied only rare (< 1% population frequency) proband-specific variants. According to the American College of Medical Genetics (ACMG) guidelines, the pathogenicity of variants was evaluated by the InterVar and TAPES tools. In addition, likely gene-disrupting (LGD) variants were detected based on an in-house bioinformatics tool, Psi-Variant, that integrates results from seven in-silico prediction tools. Overall, 372 variants in 311 genes distributed in 168 probands were detected by these tools. The overlap between the tools was 64.1, 22.9, and 23.1% for InterVar-TAPES, InterVar-Psi-Variant, and TAPES-Psi-Variant, respectively. The intersection between InterVar and Psi-Variant (I âˆ© P) was the most effective approach in detecting variants in known ASD genes (PPV = 0.274; OR = 7.09, 95% CI = 3.92-12.22), while the union of InterVar and Psi Variant (I U P) achieved the highest diagnostic yield (20.5%).Our results suggest that integrating different variant interpretation approaches in detecting ASD candidate variants from WES data is superior to each approach alone. The inclusion of additional criteria could further improve the detection of ASD candidate variants.


Autism Spectrum Disorder , Humans , Exome Sequencing , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/genetics , Genetic Predisposition to Disease , Computational Biology , Genomics
5.
Child Adolesc Psychiatry Ment Health ; 17(1): 123, 2023 Oct 27.
Article En | MEDLINE | ID: mdl-37891596

OBJECTIVE: Melatonin is considered an effective pharmacological treatment for the sleep disturbances that are reported in > 50% of children with autism spectrum disorder (ASD). However, real-life data about the long-term course and effectiveness of melatonin treatment in children with ASD is lacking. METHODS: In this retrospective cohort study, we assessed the adherence to melatonin treatment and parents' perspective of its effect on sleep quality and daytime behavior in children with ASD via a parental phone survey of children in the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) database. Cox regression analysis was used to assess the effect of key demographic and clinical characteristics on treatment adherence. RESULTS: Melatonin was recommended for ~ 8% of children in the ANCAN database. These children were characterized by more severe symptoms of autism. The median adherence time for melatonin treatment exceeded 88 months, with the most common reason for discontinuation being a lack of effectiveness (14%). Mild side-effects were reported in 14% of children, and 86%, 54%, and 45% experienced improvements in sleep onset, sleep duration and night awakenings, respectively. Notably, melatonin also improved the daytime behaviors of > 28% of the children. Adherence to treatment was independently associated with improvements in night awakenings and educational functioning (aHR = 0.142, 95%CI = 0.036-0.565; and aHR = 0.195, 95%CI = 0.047-0.806, respectively). CONCLUSIONS: Based on parents' report, melatonin is a safe and effective treatment that improves both sleep difficulties and daily behavior of children with ASD.

6.
Int J Rheum Dis ; 26(10): 1923-1931, 2023 Oct.
Article En | MEDLINE | ID: mdl-37443460

AIM: The cost to the healthcare system of management and treatment for fibromyalgia patients is high. The aims of the study were to identify and compare factors associated with the use of healthcare services among fibromyalgia patients in southern Israel from two ethnic groups. METHODS: A cross-sectional study of patients insured in the southern district of the Clalit Healthcare Services in Israel in 2019-2020. The data were collected from the central computerized system. Multivariable regression models were developed for healthcare services utilization. RESULTS: During the study period, 7686 members were diagnosed with fibromyalgia. The median for specialist consultations was 47 and for imaging tests was eight. About 47% made emergency room visits and 25% were hospitalized. The median of imaging tests was significantly higher in Jewish patients than in Arab patients (8 vs. 6; p = .000). In contrast, a significantly higher rate of Arab patients visited the Emergency Room at least once (51.6% vs. 46.75%; p = .000) and they had a higher median number or Emergency Room visits (2 vs. 1; p = .003), compared with Jewish patients. In the Arab group there was a strong effect coefficient for another localized pain syndrome with specialist consultations (odds ratio [OR] 1.699; 95% confidence interval [CI] 1.266-2.241) and imaging tests (OR 2.511; 95% CI 1.496-4.146). CONCLUSIONS: The utilization rate of healthcare services is high among fibromyalgia patients. The factors associated with high healthcare utilization are different in the two ethnic groups. Future studies could show if interventions designed to address modifiable factors could reduce the overutilization of healthcare services.

7.
J Neurodev Disord ; 15(1): 21, 2023 07 21.
Article En | MEDLINE | ID: mdl-37480057

BACKGROUND: Parent reports suggest that 44-84% of children with ASD exhibit sleep disturbances that are of clinical concern. Previous studies have reported that, in children with ASD, the severity of sleep disturbances is associated with the severity of either sensory problems or aberrant behaviors, but none have performed combined analyses with measures of both sensory and aberrant behaviors symptom domains from the same children. METHODS: We examined parent reports of 237 children with ASD, 1.4-8.7 years old, using the child sleep habits questionnaire (CSHQ), sensory profile (SP), and aberrant behaviors checklist (ABC). RESULTS: The analyses revealed that sleep disturbances were most strongly associated with SP sensory sensitivity and ABC irritability scores. Together these scores explained 35% of the variance in total CSHQ scores. Moreover, sensory sensitivity scores moderated the association between irritability and sleep disturbances, indicating that sleep disturbances were significantly associated with irritability only in children with moderate to severe sensory sensitivities. CONCLUSION: We suggest that the three symptom domains may interact and exacerbate each other such that successful intervention in one symptom domain may have positive impact on the others. Further intervention studies testing this hypothesis are highly warranted.


Autism Spectrum Disorder , Sleep Wake Disorders , Humans , Child , Infant , Child, Preschool , Sleep Wake Disorders/complications , Sleep Wake Disorders/epidemiology , Autism Spectrum Disorder/complications
8.
J Pharm Policy Pract ; 16(1): 78, 2023 Jun 26.
Article En | MEDLINE | ID: mdl-37365657

BACKGROUND: Our aims were to compare fibromyalgia (FM) rate, drug treatment and factors associated with the use of opiates in two ethnic sectors. METHODS: A retrospective cross-sectional study in southern district of Israel was performed on diagnosed FM patients in 2019-2020 [7686 members (1.50%)]. Descriptive analyses were conducted and multivariable models for the use of opiates were developed. RESULTS: There were significant differences between the two ethnic groups in FM prevalence at 1.63% and 0.91% in the Jewish and Arab groups, respectively. Only 32% of the patients used recommended medications and about 44% purchased opiates. Age, BMI, psychiatric co-morbidity, and treatment with a recommended drug were similarly associated with an increased risk for opiate use in both ethnic groups. However, male gender was associated with × 2 times reduced risk to use opiates only among the Bedouins (aOR = 0.552, 95%CI = 0.333-0.911). In addition, while in both of ethnic groups the existence of another localized pain syndrome was associated with an increased risk for opiates use, this risk was 4 times higher in the Bedouin group (aOR = 8.500, 95%CI = 2.023-59.293 and aOR = 2.079, 95%CI = 1.556-2.814). CONCLUSIONS: The study showed underdiagnosis of FM in the minority Arab ethnicity. Female Arab FM patients in low or high, compared to middle socio-economic status, were a risk group for excess opiate use. Increased use of opiates and very low rate of purchase of recommended drugs point to a lack of effectiveness of these drugs. Future research should assess whether the treatment of treatable factors can reduce the dangerous use of opiates.

9.
Res Child Adolesc Psychopathol ; 51(10): 1511-1520, 2023 10.
Article En | MEDLINE | ID: mdl-37231233

Early diagnosis and treatment of autism spectrum disorder (ASD) has been shown to lead to better prognosis. Here, we examined the association of commonly measured early developmental milestones (DMs) with later diagnosis of ASD. We conducted a case-control study of 280 children with ASD (cases) and 560 typically developed children (controls) matched to cases by date of birth, sex, and ethnicity in a control/case ratio of 2:1. Both cases and controls were ascertained from all children whose development was monitored at mother-child health clinics (MCHCs) in southern Israel. DM failure rates during the first 18 months of life in three developmental categories (motor, social, and verbal) were compared between cases and controls. Conditional logistic regression models were used to assess the independent association of specific DMs with the risk of ASD, while adjusting for demographic and birth characteristics.Significant case-control differences in DM failure rates were observed as early as 3 months of age (p < 0.001), and these differences increased with age. Specifically, cases were 2.4 times more likely to fail ≥ 1 DM at 3 months (aOR = 2.39; 95%CI = 1.41-4.06), and 15.3 times more likely to fail ≥ 3 DMs at 18 months (aOR = 15.32; 95%CI = 7.75-30.28). The most notable DM-ASD association was observed for social DM failure at 9-12 months (aOR = 4.59; 95%CI = 2.59-8.13). Importantly, the sex or ethnicity of the participants did not affect these DM-ASD associations. Our findings highlight the potential role of DMs as early signs of ASD that could facilitate earlier referral and diagnosis of ASD.


Autism Spectrum Disorder , Humans , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/complications , Case-Control Studies , Israel/epidemiology , Logistic Models , Time
10.
Am J Obstet Gynecol MFM ; 5(8): 101010, 2023 08.
Article En | MEDLINE | ID: mdl-37156463

BACKGROUND: Oxytocin is a neuropeptide hormone that plays a key role in social behavior, stress regulation, and mental health. Synthetic oxytocin administration is a common obstetrical practice, and importantly, previous research has suggested that intrapartum exposure may increase the risk of neurodevelopmental disorders, such as autism spectrum disorder. OBJECTIVE: This study aimed to examine the association between synthetic oxytocin exposure during labor and autism spectrum disorder diagnosis in the child. STUDY DESIGN: This population-based retrospective cohort study compared 2 cohorts of children: (1) all children born in British Columbia, Canada between April 1, 2000 and December 31, 2014 (n=414,336 births), and (2) all children delivered at Soroka University Medical Center in Be'er-Sheva, Israel between January 1, 2011 and December 31, 2019 (n=82,892 births). Nine different exposure groups were examined. Cox proportional hazards models were used to estimate crude and adjusted hazard ratios of autism spectrum disorder in both cohorts on the basis of induction and/or augmentation exposure status. To further control for confounding by indication, we conducted sensitivity analyses among a cohort of healthy, uncomplicated deliveries and among a group that was induced only for postdates. In addition, we stratified our analyses by infant sex to assess for potential sex differences. RESULTS: In the British Columbia cohort, 170,013 of 414,336 deliveries (41.0%) were not induced or augmented, 107,543 (26.0%) were exposed to oxytocin, and 136,780 (33.0%) were induced or augmented but not exposed to oxytocin. In the Israel cohort, 51,790 of 82,892 deliveries (62.5%) were not induced or augmented, 28,852 (34.8%) were exposed to oxytocin, and 2250 (2.7%) were induced or augmented but not exposed to oxytocin. On adjusting for covariates in the main analysis, significant associations were observed in the Israel cohort, including adjusted hazard ratios of 1.51 (95% confidence interval, 1.20-1.90) for oxytocin-augmented births and 2.18 (95% confidence interval, 1.32-3.57) for those induced by means other than oxytocin and not augmented. However, oxytocin induction was not significantly associated with autism spectrum disorder in the Israel cohort. In the Canadian cohort, there were no statistically significant adjusted hazard ratios. Further, no significant sex differences were observed in the fully adjusted models. CONCLUSION: This study supports that induction of labor through oxytocin administration does not increase the risk of autism spectrum disorder in the child. Our international comparison of 2 countries with differences in clinical practice regarding oxytocin administration for induction and/or augmentation suggests that previous studies reporting a significant association were likely confounded by the underlying indication for the induction.


Autism Spectrum Disorder , Oxytocin , Pregnancy , Child , Infant , Humans , Male , Female , Oxytocin/adverse effects , Autism Spectrum Disorder/chemically induced , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/epidemiology , Retrospective Studies , Labor, Induced/adverse effects , Canada
11.
PLoS One ; 18(3): e0279172, 2023.
Article En | MEDLINE | ID: mdl-36881606

BACKGROUND: The outcome of patients with chronic kidney disease (CKD) and acute kidney injury (AKI) is often dismal and measures to ameliorate their course are scarce. When admitted to the hospital, kidney patients are often hospitalized in general Medicine wards rather than in a specialized Nephrology department. In the current study, we compared the outcome of two cohorts of kidney patients (CKD and AKI) admitted either to general open-staff (with rotating physicians) Medicine wards or to a closed-staff (non-rotating Nephrologists) Nephrology ward. METHODS: In this population-based retrospective cohort study, we enrolled 352 CKD patients and 382 AKI patients admitted to either Nephrology or General Medicine wards. Short-term (< = 90 days) and long-term (>90 days) outcomes were recorded for survival, renal outcomes, cardiovascular outcomes, and dialysis complications. Multivariate analysis was performed using logistic regression and negative binomial regression adjusting to potential sociodemographic confounders as well as to a propensity score based on the association of all medical background variables to the admitted ward, to mitigate the potential admittance bias to each ward. RESULTS: One hundred and seventy-one CKD patients (48.6%) were admitted to the Nephrology ward and 181 (51.4%) were admitted to general Medicine wards. For AKI, 180 (47.1%) and 202 (52.9%) were admitted to Nephrology and general Medicine wards, respectively. Baseline age, comorbidities and the degree of renal dysfunction differed between the groups. Using propensity score analysis, a significantly reduced mortality rate was observed for kidney patients admitted to the Nephrology ward vs. general Medicine in short term mortality (but not long-term mortality) among both CKD patients admitted (OR = 0.28, CI = 0.14-0.58, p = 0.001), and AKI patients (or = 0.25, CI = 0.12-0.48, p< 0.001). Nephrology ward admission resulted in higher rates of renal replacement therapy (RRT), both during the first hospitalization and thereafter. CONCLUSIONS: Thus, a simple measure of admission to a specialized Nephrology department may improve kidney patient outcome, thereby potentially affecting future health care planning.


Acute Kidney Injury , General Practice , Nephrology , Renal Insufficiency, Chronic , Humans , Retrospective Studies , Kidney , Hospitalization , Acute Kidney Injury/therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy
12.
Autism ; 27(6): 1628-1640, 2023 08.
Article En | MEDLINE | ID: mdl-36632654

LAY ABSTRACT: Today, children with autism spectrum disorder (ASD) are placed in mainstream or special education settings somewhat arbitrarily with no clear clinical recommendations. Here, we compared changes in core ASD symptoms, as measured by the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) clinical assessment, across ASD preschool children placed in special or mainstream education. Longitudinal changes in ADOS-2 scores did not differ significantly across settings over a 1- to 2-year period. While some children improved in core ASD symptoms, others deteriorated in both settings. This highlights the need to identify specific criteria for establishing meaningful placement recommendations.


Autism Spectrum Disorder , Autistic Disorder , Child, Preschool , Humans , Autism Spectrum Disorder/diagnosis , Mainstreaming, Education , Education, Special
13.
J Autism Dev Disord ; 53(12): 4535-4544, 2023 Dec.
Article En | MEDLINE | ID: mdl-36222994

Previous studies have reported that ASD children with more severe symptoms are diagnosed earlier. However, previous studies in community settings have mostly relied on retrospective parental reports without the use of quantitative standardized test scores. Here, we evaluated the association of language, cognitive, and ASD severity standardized scores with the age of diagnosis in 1-6-year-old children diagnosed in a public healthcare setting. The results revealed that language scores were the strongest variable associated with the age of diagnosis, explaining ~ 30% of the variability across children. Indeed, all children diagnosed before 30-months of age exhibited moderate-to-severe language delays. These results further substantiate the prominence of language delay as a highly visible symptom associated with earlier ASD diagnosis in community clinical settings.


Autism Spectrum Disorder , Language Development Disorders , Child , Humans , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/psychology , Retrospective Studies , Language , Language Development Disorders/diagnosis , Language Development Disorders/psychology , Delivery of Health Care
15.
Heliyon ; 8(6): e09681, 2022 Jun.
Article En | MEDLINE | ID: mdl-35698655

Background: Studies have reported that Covid-19 home-quarantine periods have had mostly negative psychological impact on children with ASD and their families. Here we examined parent perceived impact of a 6-week quarantine period imposed in Israel at the beginning of the Covid-19 outbreak, in mid-March 2020. Methods: An anonymous online questionnaire was completed by parents of 268 children with ASD. Parents rated deterioration/improvement in their child's behaviors, abilities, mood, sleep, and anxiety along with changes in their own mood, sleep, parenting skills, and family relationships. We performed t-tests and ANOVA analyses to assess the significance of perceived impact on each domain and potential differences in the impact across families with children of different ages, genders, and levels of required support as well as families that experienced different magnitudes of economic hardships. Results: Parents reported significant deterioration in their mood and sleep along with significant improvements in relationships with their spouse and child with ASD, and in their parenting skills. Parents also reported significant increases in the severity of tantrums, anxiety, and restricted and repetitive behavior symptoms along with significant improvements in social and communication abilities of their child with ASD. Ratings were significantly lower in families of ASD children who regularly require more support and in families that experienced economic hardships. Conclusions: While periods of home-quarantine create numerous hardships for families of children with ASD, they may also offer an opportunity for improving parenting skills, family relationships, and children's social communication abilities with potential relevance for improving remote services.

16.
Front Oncol ; 12: 838911, 2022.
Article En | MEDLINE | ID: mdl-35600380

In light of the development of RAS inhibitors, a reliable assessment of the prevalence of RAS mutations and their correlation with the clinical features of patients with HNC is crucially needed. This meta-analysis compiles the findings of 149 studies with over 8500 HNC patients and assesses the global prevalence of mutations in the HRAS, KRAS and NRAS genes. The available data were stratified according to geographical region, clinical features, and tumor characteristics, including human papillomavirus (HPV) infection status and tumor stage. In addition, the distribution of codon substitutions in each RAS gene was assessed. The estimated mutation rate is highest for HRAS (7%), followed by KRAS (2.89%) and NRAS (2.20%). HRAS prevalence in South Asia (15.28%) is twice as high as the global estimate. HRAS mutations are more prevalent in oral cavity and salivary gland tumors. In contrast, KRAS mutations are found more frequently in sinonasal tumors, and NRAS mutations are found chiefly in tumors of the nasopharynx. OR analyses show a significant association between HRAS mutations and a high tumor stage (OR=3.63). In addition, there is a significant association between HPV-positive status and KRAS mutations (OR=2.09). This study highlights RAS as a potential therapeutic target in certain subsets of HNC patients.

17.
Brain ; 145(12): 4519-4530, 2022 12 19.
Article En | MEDLINE | ID: mdl-35037687

Multiple pieces of evidence support the prenatal predisposition of autism spectrum disorder (ASD). Nevertheless, robust data about abnormalities in foetuses later developing into children diagnosed with ASD are lacking. Prenatal ultrasound is an excellent tool to study abnormal foetal development as it is frequently used to monitor foetal growth and identify foetal anomalies throughout pregnancy. We conducted a retrospective case-sibling-control study of children diagnosed with ASD (cases); their own typically developing, closest-in-age siblings (TDS); and typically developing children from the general population (TDP), matched by year of birth, sex and ethnicity to investigate the association between ultrasonography foetal anomalies and ASD. The case group was drawn from all children diagnosed with ASD enrolled at the National Autism Research Center of Israel. Foetal ultrasound data from the foetal anatomy survey were obtained from prenatal ultrasound clinics of Clalit Health Services in southern Israel. The study comprised 659 children: 229 ASD, 201 TDS and 229 TDP. Ultrasonography foetal anomalies were found in 29.3% of ASD cases versus only 15.9% and 9.6% in the TDS and TDP groups [adjusted odds ratio (aOR) = 2.23, 95% confidence interval (CI) = 1.32-3.78, and aOR = 3.50, 95%CI = 2.07-5.91, respectively]. Multiple co-occurring ultrasonography foetal anomalies were significantly more prevalent among ASD cases. Ultrasonography foetal anomalies in the urinary system, heart, and head and brain were the most significantly associated with ASD diagnosis (aORUrinary = 2.08, 95%CI = 0.96-4.50 and aORUrinary = 2.90, 95%CI = 1.41-5.95; aORHeart = 3.72, 95%CI = 1.50-9.24 and aORHeart = 8.67, 95%CI = 2.62-28.63; and aORHead&Brain = 1.96, 95%CI = 0.72-5.30 and aORHead&Brain = 4.67, 95%CI = 1.34-16.24; versus TDS and TDP, respectively). ASD females had significantly more ultrasonography foetal anomalies than ASD males (43.1% versus 25.3%, P = 0.013) and a higher prevalence of multiple co-occurring ultrasonography foetal anomalies (15.7% versus 4.5%, P = 0.011). No sex differences were seen among TDS and TDP controls. ASD foetuses were characterized by a narrower head and a relatively wider ocular-distance versus TDP foetuses (ORBPD = 0.81, 95%CI = 0.70-0.94, and aOROcular distance = 1.29, 95%CI = 1.06-1.57). Ultrasonography foetal anomalies were associated with more severe ASD symptoms. Our findings shed important light on the multiorgan foetal anomalies associated with ASD.


Autism Spectrum Disorder , Child , Female , Humans , Male , Pregnancy , DNA-Binding Proteins , Retrospective Studies , Ultrasonography
18.
J Autism Dev Disord ; 52(2): 923-937, 2022 Feb.
Article En | MEDLINE | ID: mdl-33835353

Previous research has demonstrated that sleep disturbances are positively correlated with sensory sensitivities in children with ASD. Most of these studies, however, were based on cross-sectional analyses, where the relationship across symptom domains was examined at a single time-point. Here, we examined the development of 103 pre-school children with ASD over a 1-3-year period. The results revealed that spontaneous longitudinal changes in sleep disturbances were specifically correlated with changes in sensory sensitivities and not with changes in other sensory processing domains nor with changes in core ASD symptoms. These finding demonstrate a consistent longitudinal relationship between sleep disturbances and sensory sensitivities, which suggests that these symptoms may be generated by common or interacting underlying physiological mechanisms.


Autism Spectrum Disorder , Sleep Wake Disorders , Autism Spectrum Disorder/diagnosis , Child , Child, Preschool , Cross-Sectional Studies , Humans , Sensation , Sleep , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/epidemiology
19.
Autism ; 26(6): 1353-1363, 2022 08.
Article En | MEDLINE | ID: mdl-34623179

LAY ABSTRACT: It is widely believed that early diagnosis and treatment of autism spectrum disorder is essential for better outcome. This is demonstrated by the American Academy of Pediatrics recommendation to screen all 1.5-2.5-year-old toddlers for autism spectrum disorder. However, multiple longitudinal studies of children diagnosed with autism spectrum disorder at 1.5-6 years of age and treated in community settings have not reported any associations between earlier diagnosis and improved outcome in core autism spectrum disorder symptoms. In this study, we measured changes in core autism spectrum disorder symptoms over a 1-2-year period in 131 children diagnosed with autism spectrum disorder at 1.2-5 years of age, and treated in the community. The results revealed that children who were diagnosed before 2.5 years of age were three times more likely to exhibit considerable improvements in social autism spectrum disorder symptoms in comparison to children diagnosed at later ages. These results highlight the importance of early diagnosis and treatment of autism spectrum disorder even in community settings with heterogeneous services. In addition, these results motivate further prioritization of universal screening for autism spectrum disorder before 2.5 years of age.


Autism Spectrum Disorder , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/diagnosis , Autistic Disorder/complications , Child , Child, Preschool , Early Diagnosis , Humans , Infant , Longitudinal Studies , Mass Screening/methods
20.
Health Soc Care Community ; 30(4): 1391-1399, 2022 07.
Article En | MEDLINE | ID: mdl-34080739

Early autism spectrum disorder (ASD) detection is a precondition for effective intervention and facilitates significant improvements in functioning. In Israel, toddlers undergo general developmental screening by public health nurses (PHNs) at maternal and child health centres (MCHCs). Nevertheless, there are disparities among ethnic groups in the reported incidence of ASD. By means of an ecological model (EM), we identified strategies that improve ASD detection in the Bedouin community by investigating the social and policy factors that affect diagnosis. We conducted in-depth interviews with 18 policy makers and service providers and three focus groups of PHNs and paediatricians. We mapped the strategies for identifying toddlers with ASD based on the three EM levels. Correlations were established by comparing the codes within and between the EM levels. At the macro-level, the policy makers' strategy for improving ASD detection in the Bedouin community reflected the ideology, values and goals of the PHNs and included the MCHCs as the sole institution involved in detecting ASD. At the meso-level of the service providers, the key elements of the strategy consisted of actualising the professional potential of PHNs and patients' case management. At the micro-level was the population that utilises the services and complies with recommendations. A correlation was established between the PHNs' values and goals and patients' case management. Actualising their professional potential influenced the population's compliance. To reduce gaps in ASD diagnosis between Bedouin communities and the general population, it is necessary to identify and change the policy factors that influence access to services for children with ASD at every EM level while incorporating PHNs from the Bedouin community in future services. Culturally appropriate policies, screening policies and interventions must be developed to serve the needs of Bedouin children.


Autism Spectrum Disorder , Arabs , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/epidemiology , Ethnicity , Humans , Israel/epidemiology , Prevalence
...