Influence of family demographic factors on social communication questionnaire scores.

This study examined the effect of demographic factors on Social Communication Questionnaire (SCQ) scores in children aged 30-68 months. Diagnoses of ASD were made after a gold standard evaluation that included the Autism Diagnostic Observation Schedule (ADOS), and the Autism Diagnostic Interview Revised (ADI-R). The relationship of demographic variables to SCQ scores was compared in two source populations: (a) children recruited from clinical and educational sources serving children who have ASD or other developmental disorders (CE) and (b) children recruited from birth certificates to represent the general population (BC). The impact of the demographic variables-child sex, child age, maternal language, maternal ethnicity, maternal education, maternal race, and household income-on total SCQ score were studied to examine their impact on the SCQ's performance. Demographic factors predicting the SCQ total score were used to generate ROCs. Factors that had a significant influence on SCQ performance were identified by examining the area under the ROCs. Optimal SCQ cut-points were generated for significant factors using the Youden's Index. Overall male sex, lower household income, lower maternal education and Black race predicted higher SCQ scores. In this sample, the most common optimum value for the SCQ cut-point across the different sociodemographic groups was 11. Autism Res 2018, 11: 695-706. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Screeners are used to help identify children who are more likely to have ASD than their peers. Ideally screeners should be accurate for different groups of children and families. This study examined how well the Social Communication Questionnaire (SCQ) predicts ASD. We found that male sex, lower household income, lower maternal education and Black race were associated with higher SCQ scores. In this study an SCQ cut-point of 11 worked best across the different sociodemographic groups in our sample.

Demographic profile of families and children in the Study to Explore Early Development (SEED): Case-control study of autism spectrum disorder.

BACKGROUND: The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. OBJECTIVE: This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. METHODS: This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. RESULTS: Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. CONCLUSIONS: SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes.

Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is increasingly recognized as a public health issue. Irritability and aggression (IA) often negatively affect the lives of people with ASD and their families. Although many medications have been tested for IA in ASDs in randomized controlled trials (RCTs), critical quantitative analyses of these trials are lacking in the literature. OBJECTIVES: To systematically review and quantitatively analyze the efficacy and safety of pharmacologic treatments for IA in youth with ASD. DATA SOURCES: Studies were identified from Medline, PsycINFO, Embase, and review articles. METHODS: Original articles on placebo-controlled RCTs of pharmacologic treatments of IA in youth age 2 to 17 years with ASD were included. Data items included study design, study goals, details of study participants, details of intervention, study results, statistical methods, side effects, and risks of bias. The primary study outcome measure was the effect size of reduction in the Aberrant Behavioral Checklist-Irritability (ABC-I) scores in the medication group, as compared with placebo, in RCTs using parallel groups design. RESULTS: Forty-six RCTs were identified. Compared with placebo, 3 compounds resulted in significant improvement in ABC-I at the end of treatment. Risperidone and aripiprazole were found to be the most effective, with the largest effect sizes. Sedation, extrapyramidal sides effects, and weight gain were assessed quantitatively. CONCLUSIONS: Although risperidone and aripiprazole have the strongest evidence in reducing ABC-I in youth with ASD, a few other compounds also showed significant efficacy with fewer potential side effects and adverse reactions in single studies.

Irritability and Problem Behavior in Autism Spectrum Disorder: A Practice Pathway for Pediatric Primary Care.

OBJECTIVE: Pediatric primary care providers (PCPs) caring for patients with autism spectrum disorder (ASD) often encounter irritability (vocal or motoric outbursts expressive of anger, frustration, or distress) and problem behavior (directed acts of aggression toward other people, self, or property). The Autism Intervention Research Network on Physical Health and Autism Speaks Autism Treatment Network charged a multidisciplinary workgroup with developing a practice pathway to assist PCPs in the evaluation and treatment of irritability and problem behavior (I/PB). METHODS: The workgroup reviewed the literature on the evaluation and treatment of contributory factors for I/PB in ASD. The workgroup then achieved consensus on the content and sequence of each step in the pathway. RESULTS: The practice pathway is designed to help the PCP generate individualized treatment plans based on contributing factors identified in each patient. These factors may include medical conditions, which the PCP is in a key position to address; functional communication challenges that can be addressed at school or at home; psychosocial stressors that may be ameliorated; inadvertent reinforcement of I/PB; and co-occurring psychiatric conditions that can be treated. The pathway provides guidance on psychotropic medication use, when indicated, within an individualized treatment plan. In addition to guidance on assessment, referral, and initial treatment, the pathway includes monitoring of treatment response and periodic reassessment. CONCLUSIONS: The pediatric PCP caring for the patient with ASD is in a unique position to help generate an individualized treatment plan that targets factors contributing to I/PB and to implement this plan in collaboration with parents, schools, and other providers.

Immune mediated conditions in autism spectrum disorders.

We conducted a case-control study among members of Kaiser Permanente Northern California (KPNC) born between 1980 and 2003 to determine the prevalence of immune-mediated conditions in individuals with autism, investigate whether these conditions occur more often than expected, and explore the timing of onset relative to autism diagnosis. Cases were children and young adults with at least two autism diagnoses recorded in outpatient records (n=5565). Controls were children without autism randomly sampled at a ratio of 5 to 1, matched to cases on birth year, sex, and length of KPNC membership (n=27,825). The main outcomes - asthma, allergies, and autoimmune diseases - were identified from KPNC inpatient and outpatient databases. Chi-square tests were used to evaluate case-control differences. Allergies and autoimmune diseases were diagnosed significantly more often among children with autism than among controls (allergy: 20.6% vs. 17.7%, Crude odds ratio (OR)=1.22, 95% confidence interval (CI) 1.13-1.31; autoimmune disease: 1% vs. 0.76%, OR=1.36, 95% CI 1.01-1.83), and asthma was diagnosed significantly less often (13.7% vs. 15.9%; OR=0.83, 95% CI 0.76-0.90). Psoriasis occurred more than twice as often in cases than in controls (0.34% vs. 0.15%; OR=2.35, 95% CI 1.36-4.08). Our results support previous observations that children with autism have elevated prevalence of specific immune-related comorbidities.

Using standardized diagnostic instruments to classify children with autism in the study to explore early development.

The Study to Explore Early Development (SEED) is a multi-site case-control study designed to explore the relationship between autism spectrum disorder (ASD) phenotypes and etiologies. The goals of this paper are to (1) describe the SEED algorithm that uses the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) to classify children with ASD, (2) examine psychometric properties of different ASD classification methods, including the SEED method that incorporates rules for resolving ADI-R and ADOS discordance, and (3) determine whether restricted interests and repetitive behaviors were noted for children who had instrument discordance resolved using ADI-R social and communication scores. Results support the utility of SEED criteria when well-defined groups of children are an important clinical or research outcome.

A practice pathway for the identification, evaluation, and management of insomnia in children and adolescents with autism spectrum disorders.

OBJECTIVE: This report describes the development of a practice pathway for the identification, evaluation, and management of insomnia in children and adolescents who have autism spectrum disorders (ASDs). METHODS: The Sleep Committee of the Autism Treatment Network (ATN) developed a practice pathway, based on expert consensus, to capture best practices for an overarching approach to insomnia by a general pediatrician, primary care provider, or autism medical specialist, including identification, evaluation, and management. A field test at 4 ATN sites was used to evaluate the pathway. In addition, a systematic literature review and grading of evidence provided data regarding treatments of insomnia in children who have neurodevelopmental disabilities. RESULTS: The literature review revealed that current treatments for insomnia in children who have ASD show promise for behavioral/educational interventions and melatonin trials. However, there is a paucity of evidence, supporting the need for additional research. Consensus among the ATN sleep medicine committee experts included: (1) all children who have ASD should be screened for insomnia; (2) screening should be done for potential contributing factors, including other medical problems; (3) the need for therapeutic intervention should be determined; (4) therapeutic interventions should begin with parent education in the use of behavioral approaches as a first-line approach; (5) pharmacologic therapy may be indicated in certain situations; and (6) there should be follow-up after any intervention to evaluate effectiveness and tolerance of the therapy. Field testing of the practice pathway by autism medical specialists allowed for refinement of the practice pathway. CONCLUSIONS: The insomnia practice pathway may help health care providers to identify and manage insomnia symptoms in children and adolescents who have ASD. It may also provide a framework to evaluate the impact of contributing factors on insomnia and to test the effectiveness of nonpharmacologic and pharmacologic treatment strategies for the nighttime symptoms and daytime functioning and quality of life in ASD.

The Study to Explore Early Development (SEED): a multisite epidemiologic study of autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) network.

The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal, gastrointestinal, and sociodemographic characteristics. SEED uses a case-control design with population-based ascertainment of children aged 2-5 years with an autism spectrum disorder (ASD) and children in two control groups-one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods. SEED is a valuable resource for testing hypotheses regarding ASD characteristics and causes.

Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism.

OBJECTIVE: Exposure to thimerosal, a mercury-containing preservative that is used in vaccines and immunoglobulin preparations, has been hypothesized to be associated with increased risk of autism spectrum disorder (ASD). This study was designed to examine relationships between prenatal and infant ethylmercury exposure from thimerosal-containing vaccines and/or immunoglobulin preparations and ASD and 2 ASD subcategories: autistic disorder (AD) and ASD with regression. METHODS: A case-control study was conducted in 3 managed care organizations (MCOs) of 256 children with ASD and 752 controls matched by birth year, gender, and MCO. ASD diagnoses were validated through standardized in-person evaluations. Exposure to thimerosal in vaccines and immunoglobulin preparations was determined from electronic immunization registries, medical charts, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We used conditional logistic regression to assess associations between ASD, AD, and ASD with regression and exposure to ethylmercury during prenatal, birth-to-1 month, birth-to-7-month, and birth-to-20-month periods. RESULTS: There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83-1.51) for prenatal exposure, 0.88 (0.62-1.26) for exposure from birth to 1 month, 0.60 (0.36-0.99) for exposure from birth to 7 months, and 0.60 (0.32-0.97) for exposure from birth to 20 months. CONCLUSIONS: In our study of MCO members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk of ASDs.

[Osteoporosis in young individuals]. / Osteoporosis en individuos jóvenes.

Although there are some differential aspects related to peak bone mass acquisition and later bone loss throughout life between genders, the frequency of osteoporosis in young individuals is similar for both genders. In addition, in this population group, the development of osteoporosis is frequently associated with secondary causes. Indeed, nearly 50% of young individuals with osteoporosis have diseases or therapies related to the development of this disorder, with glucocorticoid therapy being one of the most frequently associated conditions. There are several other processes, which have also been associated with such a disorder in these individuals, but the causes differ between genders. In addition, idiopathic osteoporosis is also a frequent condition in these patients. In this subgroup of patients, a family history of osteoporosis or hypercalciuria is also a frequently associated finding. Because of that, in order to rule out secondary causes of osteoporosis, the laboratory studies performed to these patients should be extensive. Although there is few data on the treatment of these patients, basic rules such as exercise, correct calcium and vitamin D consumption, and avoiding alcohol and tobacco consumption should be advised. Drug therapy will depend on the cause of osteoporosis. However, it should be taken into account that most young women are of childbearing age, so drug therapy in these patients should be evaluated cautiously.

Multicentre physiological reference values for the concentration of creatininium in plasma and diagnostic specificity of glomerular filtration rate estimated with the MDRD equation.

BACKGROUND: The National Kidney Disease Education Program recommends that clinical laboratories, when asked for an estimation of glomerular filtration rate in a patient by means of the "four-variable" Modification of Diet in Renal Disease (MDRD) Study equation, also provide the measurement result for creatininium concentration in plasma and the appropriate reference interval. On the other hand, clinical laboratories seeking accreditation for compliance with ISO 15189:2003 need to demonstrate that the physiological reference intervals communicated to all users of laboratory services are appropriate for the patient population served, and for their measurement systems. METHODS: Ten clinical laboratories in different regions of Spain collaborated in identifying reference individuals and producing reference values for the concentration of creatininium in plasma using RD/Hitachi Modular Analytics analysers, and for the volume rate of glomerular filtrate in kidneys (glomerular filtration rate), estimated with the "four-variable" MDRD Study equation. All the logistic work was carried out in co-operation with the supplier of the reagents and analysers (Roche Diagnostics España, S.L., Sant Cugat del Vallès, Catalonia, Spain). Using all the reference values obtained by each laboratory, multicentre reference limits were estimated non-parametrically. RESULTS AND CONCLUSIONS: Reference intervals estimated in this study for concentrations of plasma creatininium are 52-85 micromol/L for women and 64-106 micromol/L for men. The diagnostic specificity of the estimated glomerular filtration rate is 99.2% when applied to healthy persons to screen for chronic kidney disease.

Multicentre physiological reference intervals for serum concentrations of immunoglobulins A, G and M, complement C3c and C4 measured with Tina-Quant reagents systems.

BACKGROUND: Clinical laboratories seeking accreditation for compliance with ISO 15189:2003 need to demonstrate that the physiological reference intervals communicated to all users of the laboratory service are appropriate for the patient population served and for the measurement systems used. In the case of immunological quantities, few articles have been published in peer-reviewed journals. METHODS: A total of 21 clinical laboratories in different regions of Spain collaborated in identifying reference individuals and determining adult reference intervals for some immunological quantities measured using RD/Hitachi Modular Analytics analysers and Tina-Quant reagent systems. These immunological quantities are the mass concentrations of immunoglobulin A, immunoglobulin G, immunoglobulin M, complement C3c and complement C4 in serum. All the logistic work was carried out in co-operation with the supplier of the reagents and analysers (Roche Diagnostics España, S.L., Sant Cugat del Vallès, Catalonia, Spain). From the set of reference values obtained by each laboratory, multicentre reference limits were estimated non-parametrically. RESULTS AND CONCLUSIONS: The reference intervals estimated in this study for concentrations of serum components under consideration are: complement C3c, 0.62-1.64 g/L for women and men; complement C4, 0.14-0.72 g/L for women and men; immunoglobulin A, 0.89-4.80 g/L for women and men; immunoglobulin G, 6.5-14.3 g/L for women and men; and immunoglobulin M, 0.48-3.38 g/L for women and 0.41-2.46 g/L for men.

A comparison of health care utilization and costs of children with and without autism spectrum disorders in a large group-model health plan.

OBJECTIVE: Data on the current costs of medical services for children with autism spectrum disorders are lacking. Our purpose for this study was to compare health care utilization and costs of children with and without autism spectrum disorders in the same health plan. PATIENTS AND METHODS: Participants included all 2- to 18-year-old children with autism spectrum disorders (n = 3053) and a random sample of children without autism spectrum disorders (n = 30529) who were continuously enrolled in the Kaiser Permanente Medical Care Program in northern California between July 1, 2003, and June 30, 2004. Data on health care utilization and costs were derived from health plan administrative databases. MAIN OUTCOME MEASURES: Outcome measures included mean annual utilization and costs of health services per child. RESULTS: Children with autism spectrum disorders had a higher annual mean number of total clinic (5.6 vs 2.8), pediatric (2.3 vs 1.6), and psychiatric (2.2 vs 0.3) outpatient visits. A higher percentage of children with autism spectrum disorders experienced inpatient (3% vs 1%) and outpatient (5% vs 2%) hospitalizations. Children with autism spectrum disorders were nearly 9 times more likely to use psychotherapeutic medications and twice as likely to use gastrointestinal agents than children without autism spectrum disorders. Mean annual member costs for hospitalizations (550 dollars vs 208 dollars), clinic visits (1373 dollars vs 540 dollars), and prescription medications (724 dollars vs 96 dollars) were more than double for children with autism spectrum disorders compared with children without autism spectrum disorders. The mean annual age- and gender-adjusted total cost per member was more than threefold higher for children with autism spectrum disorders (2757 dollars vs 892 dollars). Among the subgroup of children with other psychiatric conditions, total mean annual costs were 45% higher for children with autism spectrum disorders compared with children without autism spectrum disorders; excess costs were largely explained by the increased use of psychotherapeutic medications. CONCLUSIONS: The utilization and costs of health care are substantially higher for children with autism spectrum disorders compared with children without autism spectrum disorders. Research is needed to evaluate the impact of improvements in the management of children with autism spectrum disorders on health care utilization and costs.

An engineered plant that accumulates higher levels of heavy metals than Thlaspi caerulescens, with yields of 100 times more biomass in mine soils.

Nicotiana glauca transformed with TaPCS1 was tested for its application in phytoremediation. When plantlets were grown in mine soils containing Cu, Zn, and Pb (42, 2600, and 1500 mg kg(-1)) the plant showed high levels of accumulation especially of Zn and Pb. Adult plants growing in mine soils containing different heavy metal concentrations showed a greater accumulation as well as an extension to a wider range of elements, including Cd, Ni and B. The overexpressed gene confers up to 9 and 36 times more Cd and Pb accumulation in the shoots under hydroponic conditions, and a 3- and 6-fold increase in mining soils. When the hyperaccumulator Thlaspi caerulescens was compared, the results were higher values of heavy metal and Boron accumulation, with a yield of 100 times more biomass. Thlaspi was unable to survive in mining soils containing either a level higher than 11000 mg kg(-1) of Pb and 4500 mg kg(-1) of Zn, while engineered plants yielded an average of 0.5 kg per plant.

Brote de fiebre amarilla selvática en Colombia 2004 / Virus assembly of yellow fever in Colombia 2004

Antecedentes: el 9 de enero se confirma un caso de fiebre amarilla en la sierra nevada de Santa Marta cuya circulación viral es la continuación de la presentada en el 2003 en la región del Catatumbo. En la región no se confirmaban casos desde el año 1979 y el comportamiento del brote es similar al presentado en dicho año. Metodología: estudio descriptivo longitudinal de casos captados mediante vigilancia activa comunitaria, estudio de casos y vigilancia pasiva. Los casos son confirmados por IgM, inmunohistoquímica y patología. Se realizaron acciones del fortalecimiento de la vigilancia de febriles icterohemorrágicos, entomológica, vectorial y de epizootias. Igualmente acciones de intensificación de la inmunización de susceptibles y educación a la comunidad. Resultados: se confirmó la circulación del virus en epizootias ocurridas en tres zonas de la región (Municipios de Valledupar, La Paz y Santa Marta). Por fecha de inicio de síntomas los casos comenzaron en la semana 51 de 2003 y el pico epidémico fue en la semana 1 de 2004; el último caso se confirmó el 22 de enero de 2004. Se confirmaron 29 casos de 787 notificados (15 del distrito de Santa Marta, 8 del departamento del Cesar y 6 de La Guajira); 20% de los casos fueron captados por vigilancia activa. El 28% fue confirmado por patología e inmunohistoquímica y el restante por IgM. El grupo de edad con mayor incidencia fue 15 a 44 años (75%), hombres (72%) y agricultores (45%). La letalidad fue 28%...

Los niños del Cauca. I. Descripción de un foco de raquitismo dependiente de la vitamina D, tipo II / The children of Cauca. I. Description of a focus of vitamin D - dependent rickets, type II

Al norte del departamento del Cauca se detectó un numeroso grupo de pacientes con deformidades en miembros inferiores (genu varo, genu valgo o ambos) que correspondían clínica y radiológicamente a un cuadro de raquitismo. Ninguno de los pacientes presentaban alopecia, miopatía, tetania o aminoaciduria. La mayoría de ellos proceden de un grupo poblacional semiaislado de ancestro afromestizo, en el corregimiento de La Toma, del muncipio de Suárez. Los estudios bioquímicos comparativos entre 64 pacientes y 109 individuos no afectados, parientes en primer grado, mostraron en los pacientes una ligera hipocalcemia, niveles normales altos de fósforo sérico, un sustancial incremento de la fosfatasa alcalina, valores normales de proteínas y albúminas y niveles séricos de paratohormona aumentados. Estudios en orina de 24 horas mostraron hipocalciuria e hipofosfaturia. A un subgrupo de 8 pacientes se les determino niveles séricos de la 25 (OH)D subíndice 3 y 1 alfa,25 (OH)subíndice 2 delta subíndice 3 para establecer a qué tipo de raquitismo pertenecían nuestros pacientes. Se observó un marcado incremento de 1 alfa, 25 (OH)subíndice 2 delta subíndice 3, por lo que esta patología corresponde al raquitismo dependiente de la vitamina D, tipo II. Se trata de un tipo de raquitismo genético transmitido en forma autosómica recesiva, cuyas manifestaciones clínicas y de laboratorio se presentan por un defecto en la acción del receptor para la vitamina D. A 115 pacientes se les inició tratamiento con 1 alfa,25(OH) subíndice 2 alfa 3 µg 0,50/día, calcio 1.840 mg/día y fósforo 1.424 mg/día, administrados en dos dosis diarias. En un grupo de 21 pacientes, se analizaron los datos de laboratorio en suero, pre y post tratamiento un año después y todos los valores tendieron a normalizarse. Estudios moleculares, del mRNA y cDNA del gen del receptor de la vitamina D, obtenidos de cultivo fibroblastos de dos de los pacientes más severamente afectados, mostraron una secuencia normal de nucleótidos. Se hace una comparación entre los hallazgos clínicos y de laboratorio entre los casos informados hasta el momento en la literatura con este tipo de enfermedad y los 64 que analizamos en el presente estudio, enfatizando nuestras observaciones, como el inicio temprano de las manifestaciones clínicas, ausencia de dolor o debilidad muscular, de alopecia, de niveles normales de fósforo y leve hiperparatiroidismo secundario, lo que indica una gran heterogeneidad en este tipo de raquitismo