Recognition of early warning signs and symptoms - the first steps on the road to Autism Spectrum Disorder diagnosis.

OBJECTIVE: To identify developmental symptoms reported at firsts doctor visits by parents of children later diagnosed with Autism Spectrum Disorder (ASD). DESIGN: Cohort study. SETTING: The study was conducted in the Department of Psychiatry Research of "Prof. Dr. Alexandru Obregia" Clinical Psychiatry Hospital from Bucharest between September 2019 and May 2021. PATIENTS: 105 cases: 82 boys and 23 girls, 100 children with autism, and 5 patients with Asperger's syndrome. INTERVENTION: ASD was diagnosed according to the DSM-5 criteria, ADOS-1 (Autism Diagnostic Observation Schedule, 1st Edition) and/or ADI-R (Autism Diagnostic Interview-Revised) tests scores; features reported by the parents for which they presented to the doctor for a diagnosis were taken into consideration. MAIN OUTCOME MEASURES: The age at first presentation to the doctor; the most common early signs reported by the parents of children with ASD. RESULTS: The age at first presentation to the doctor in our group was between 9 months and 14 years. The most common early signs reported by parents were: delayed language development, deficits in understanding verbal instructions/indications, and hyperactivity and aggressivity. In the case of patients with Asperger's syndrome, the reported features were hyperactivity and aggressivity, learning difficulties, and social interaction problems. Regression and delay in language development occurred more often in boys than in girls. CONCLUSIONS: Parents, as well as family doctors or paediatricians, should pay great attention to the children's behaviour, alongside their cognitive and language development. Early detection is essential for early intervention and our results can be used to develop training programs for parents and paediatricians for early recognition of ASD.

The Phenotypic Spectrum of 15q13.3 Region Duplications: Report of 5 Patients.

Chromosome 15q13.3 microduplications are associated with a wide spectrum of clinical presentations ranging from normal to different neuropsychiatric conditions, such as developmental delay (DD), intellectual disability (ID), epilepsy, hypotonia, autism spectrum disorders (ASD), attention-deficit hyperactivity disorder, and schizophrenia. The smallest region of overlap for 15q13.3 duplications encompasses the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, a strong candidate for the behavioral abnormalities. We report on a series of five patients with 15q13.3 duplications detected by chromosomal microarray. The size of the duplications ranged from 378 to 537 kb, and involved the CHRNA7 gene in all patients. The most common clinical features, present in all patients, were speech delay, autistic behavior, and muscle hypotonia; DD/ID was present in three patients. One patient presented epileptic seizures; EEG anomalies were observed in three patients. No consistent dysmorphic features were noted. Neuroimaging studies revealed anomalies in two patients: Dandy-Walker malformation and a right temporal cyst. 15q13.3 duplications are associated with various neuropsychiatric features, including speech delay, hypotonia, ASD, and ID, also present in our patient group. Our study brings detailed clinical and molecular data from five ASD patients with 15q13.3 microduplications involving the CHRNA7 gene, contributing to the existing knowledge about the association of 15q13.3 duplications with neuropsychiatric phenotypes.

Network analysis of cases with methicillin-resistant Staphylococcus aureus and controls in a large tertiary care facility.

BACKGROUND: Despite increased awareness of infection control precautions, methicillin-resistant Staphylococcus aureus (MRSA) still spreads through patients and contaminated objects, causing a substantial burden of illness and cost. Our objective was to define risk factors for contracting MRSA in a tertiary health care facility using a historic case-control study and to validate health care network changes during pre-outbreak and outbreak periods. METHODS: We conducted a case-control study using secondary data on hospitalizations where infected or colonized cases were compared with matched controls who tested negative by age, sex, and campus over 1 year. Social networks of all cases and controls were built from links joining patients to rooms, roommates, and health care providers over time. RESULTS: Matched controls were similar to cases in comorbidity, lengths of stay, mortality, and number of roommates, rooms, and health care providers. As expected, the number of rooms and roommates increased in the outbreak by more than 50%. A timed animation of the network at one campus identified potential source patients linked to 2 rooms and many roommates, after which cases connected to those same rooms proliferated. CONCLUSIONS: Only the network animation over time revealed possible transmission of MRSA through the network, rather than attributes measured in the traditional case control study.

Oral anticoagulant re-initiation following intracerebral hemorrhage in non-valvular atrial fibrillation: Global survey of the practices of neurologists, neurosurgeons and thrombosis experts.

BACKGROUND: While oral anticoagulants (OACs) are highly effective for ischemic stroke prevention in atrial fibrillation, intracerebral hemorrhage (ICH) remains the most feared complication of OAC. Clinical controversy remains regarding OAC resumption and its timing for ICH survivors with atrial fibrillation because the balance between risks and benefits has not been investigated in randomized trials. AIMS/HYPOTHESIS: To survey the practice of stroke neurologists, thrombosis experts and neurosurgeons on OAC re-initiation following OAC-associated ICH. METHODS: An online survey was distributed to members of the International Society for Thrombosis and Haemostasis, Canadian Stroke Consortium, NAVIGATE-ESUS trial investigators (Clinicatrials.gov identifier NCT02313909) and American Association of Neurological Surgeons. Demographic factors and 11 clinical scenarios were included. RESULTS: Two hundred twenty-eight participants from 38 countries completed the survey. Majority of participants were affiliated with academic centers, and >20% managed more than 15 OAC-associated ICH patients/year. Proportion of respondents suggesting OAC anticoagulant resumption varied from 30% (for cerebral amyloid angiopathy) to 98% (for traumatic ICH). Within this group, there was wide distribution in response for timing of resumption: 21.4% preferred to re-start OACs after 1-3 weeks of incident ICH, while 25.3% opted to start after 1-3 months. Neurosurgery respondents preferred earlier OAC resumption compared to stroke neurologists or thrombosis experts in 5 scenarios (p<0.05 by Kendall's tau). CONCLUSIONS: Wide variations in current practice exist among management of OAC-associated ICH, with decisions influenced by patient- and provider-related factors. As these variations likely reflect the lack of high quality evidence, randomized trials are direly needed in this population.

Correction: Oral anticoagulant re-initiation following intracerebral hemorrhage in non-valvular atrial fibrillation: Global survey of the practices of neurologists, neurosurgeons and thrombosis experts.

[This corrects the article DOI: 10.1371/journal.pone.0191137.].

Timing of anticoagulant re-initiation following intracerebral hemorrhage in mechanical heart valves: Survey of neurosurgeons and thrombosis experts.

BACKGROUND: While oral anticoagulation (OAC) is universally indicated for patients with mechanical heart valves (MHVs), OAC resumption following anticoagulant-associated intracerebral hemorrhage (ICH) is an area of uncertainty. We sought to determine the practice preferences of North American neurosurgeons and thrombosis experts on optimal timing of OAC re-initiation. METHODS: A cross-sectional survey was disseminated to North American members of the American Association of Neurological Surgeons and the International Society for Thrombosis and Haemostasis. Demographic factors, as well as a clinical scenario with 14 modifiable clinical risk factors were included in the survey. RESULTS: 504 physicians completed our survey (response rate 34.3%). Majority of participants were affiliated with academic centres, and managed≤10 ICH patients with MHV per year. There was wide distribution in response in optimal timing for OAC resumption following an ICH: 59% and 60% preferred to re-start OAC between 3 and 14 days following the hemorrhagic event (median of 6-7 days). Smaller hemorrhages (<30cm2). CHADS2 score ≥2, concomitant venous thromboembolism, mitral valve prosthesis, caged-ball valves and multiple valves prompted earlier OAC resumption. CONCLUSION: Wide variation in the current practice of neurosurgeons and thrombosis specialists exist when they encounter patients with ICH and MHV, though decisions were influenced by patient- and valve-related factors. As our observed variation likely reflects the immense gap in current evidence, prospective randomized trials in this population are therefore urgently needed.

Timing of vitamin K antagonist re-initiation following intracranial hemorrhage in mechanical heart valves: Systematic review and meta-analysis.

BACKGROUND: While evidence supports resumption of vitamin K antagonists (VKAs) among mechanical heart valve (MHV) patients presenting with anticoagulant-associated intracranial hemorrhage (ICH), ideal timing of resumption is uncertain. OBJECTIVE: To determine the optimal timing of VKA re-initiation and its associated clinical outcomes. METHODS: We performed a systematic review and a meta-analysis of studies published from January 1950 to August 2015. We extracted data on the location of initial ICH, use of cranial surgery, presence of atrial fibrillation, MHV type and position, number of MHVs, and timing of VKA resumption. Outcomes including valve thrombosis, thromboembolic events or ICH recurrence were recorded. Meta-regression analysis was conducting with controlling for covariates. We calculated absolute risks, and assessed the effect of anticoagulant resumption timing on ICH recurrence. RESULTS: 23 case-series and case-reports were identified. Overall ICH recurrence was 13% (95% confidence interval [CI], 7%-25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3%-17%) and 12% (95% CI, 5%-23%) respectively. A trend towards lower ICH recurrence was observed with delayed VKA resumption (slope estimate -0.2154, p=0.10). Recurrence rate ranged from 50% with VKA resumption at 3days to 0% with resumption at 16days. CONCLUSION: Among patients with MHV, there is inadequate data to suggest an optimal timing of VKA re-initiation following an ICH, though delayed restart appears to be protective against recurrence but is associated with higher risk of thrombosis. Our analysis suggests 4-7days might be an ideal time with least risk of thrombosis or ICH recurrence.